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Sample records for vivo uraniumvi chelation

  1. New agents for in vivo chelation of uranium(VI): efficacy and toxicity in mice of multidentate catecholate and hydroxypyridinonate ligands.

    Science.gov (United States)

    Durbin, P W; Kullgren, B; Xu, J; Raymond, K N

    1997-06-01

    Soluble uranyl ion [UO2(2+), U(VI)] is a kidney poison. Uranyl ion accumulates in bone, and the high specific activity uranium isotopes induce bone cancer. Although sought since the 1940's, no multidentate ligand was identified, until now, that efficiently and stably binds U(VI) at physiological pH, promotes its excretion, and reduces deposits in kidneys and bone. Ten multidentate ligands patterned after natural siderophores and composed of sulfocatechol [CAM(S)], carboxy-catechol [CAM(C)], or hydroxypyridinone [Me-3,2-HOPO] metal-binding units have been tested for in vivo chelation of U(VI). Ligands were injected intraperitoneally (i.p.) into mice 3 min after intravenous (i.v.) injection of 233U or (232+235)U as UO2Cl2 [ligand-to-metal molar ratio 75 to 92]. Regardless of backbone structure, denticity, or binding unit, all 10 ligands significantly reduced kidney U(VI) compared with controls or with mice given CaNa3-DTPA, and four CAM(S) or CAM(C) ligands also significantly reduced skeleton U(VI). Several ligands removed U(VI) from kidneys, when injected at 1 or 24 h. Injected at molar ratios > or = 300, 5-LIO(Me-3,2-HOPO) and TREN-(Me-3,2-HOPO) reduced kidney U(VI) to about 10% of control. Given orally to fasted mice at molar ratios > or = 300, those ligands significantly reduced kidney U(VI). In mice injected i.v. with 0.42 micromol kg(-1) of 235U and given 100 micromol kg(-1) of one of those Me-3,2-HOPO ligands i.p. daily for 10 d starting at 1 h after the U(VI)) loss of kidney U(VI) was greatly accelerated, and the kidneys of treated mice showed no microscopic evidence of renal injury. Crystals of uranyl chelates with linear tetradentate ligands containing bidentate Me-3,2-HOPO groups demonstrate a 1:1 structure. Considering low toxicity, effectiveness, and reasonable cost, the structurally simple linear tetradentate ligands based on the 5-LI backbone (diaminopentane) offer the most promising approach to a clinically acceptable therapeutic agent for U(VI). Work

  2. Chelating agents for uranium(VI): 2. Efficacy and toxicity of tetradentate catecholate and hydroxypyridinonate ligands in mice.

    Science.gov (United States)

    Durbin, P W; Kullgren, B; Ebbe, S N; Xu, J; Raymond, K N

    2000-05-01

    Uranium(VI) (UO2(2+), uranyl) is nephrotoxic. Depending on isotopic composition and dosage, U(VI) is also chemically toxic and carcinogenic in bone. Several ligands containing two, three, or four bidentate catecholate or hydroxypyridinonate metal binding groups, developed for in vivo chelation of other actinides, were found, on evaluation in mice, to be effective for in vivo chelation of U(VI). The most promising ligands contained two bidentate groups per chelator molecule (tetradentate) attached to linear 4- or 5-carbon backbones (4-LI, butylene; 5-LI, pentylene; 5-LIO, diethyl ether). New ligands were then prepared to optimize ligand affinity for U(VI) in vivo and low acute toxicity. Five bidentate binding groups--sulfocatechol [CAM(S)], carboxycatechol [CAM(C)], methylterephthalamide (MeTAM), 1,2-hydroxypyridinone (1,2-HOPO), or 3,2-hydroxypyridinone (Me-3,2-HOPO)--were each attached to two linear backbones (4-LI and 5-LI or 5-LIO). Those ten tetradentate ligands and octadentate 3,4,3-LI(1,2-HOPO), an effective actinide chelator, were evaluated in mice for in vivo chelation of 233U(VI) (injection at 3 min, 1 h, or 24 h or oral administration at 3 min after intravenous injection of 233UO2Cl2) and for acute toxicity (100 micromol kg(-1) injected daily for 10 d). The combined efficacy and toxicity screening identified 5-LIO(Me-3,2-HOPO) and 5-LICAM(S) as the most effective low-toxicity agents. They chelate circulating U(VI) efficiently at ligand:uranium molar ratios > or = 20, remove useful amounts of newly deposited U(VI) from kidney and bone at molar ratios > or = 100, and reduce kidney U(VI) levels significantly when given orally at molar ratios > or = 100. 5-LIO(Me-3,2-HOPO) has greater affinity for kidney U(VI) while 5-LICAM(S) has greater affinity for bone U(VI), and a 1:1 mixture (total molar ratio = 91) reduced kidney and bone U(VI) to 15 and 58% of control, respectively--more than an equimolar amount of either ligand alone.

  3. A Zinc Chelator TPEN Attenuates Airway Hyperresponsiveness Airway Inflammation in Mice In Vivo

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    Satoru Fukuyama

    2011-01-01

    Conclusions: In pulmonary allergic inflammation induced in mice immunized with antigen without alum, zinc chelator inhibits airway inflammation and hyperresponsiveness. These findings suggest that zinc may be a therapeutic target of allergic asthma.

  4. Iron Chelation

    Science.gov (United States)

    Skip to main content Menu Donate Treatments Therapies Iron Chelation Iron chelation therapy is the main treatment ... have iron overload and need treatment. What is iron overload? Iron chelation therapy is used when you ...

  5. The Iron Chelator, Dp44mT, Effectively Inhibits Human Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo

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    Jehn-Chuan Lee

    2016-08-01

    Full Text Available Oral squamous cell carcinoma (OSCC is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO, and deferasirox all significantly inhibit SAS cell growth. Flow cytometry further indicated that Dp44mT inhibition of SAS cells growth was partly due to induction of G1 cell cycle arrest. Iron chelators enhanced expressions of NDRG1 and NDRG3 while repressing cyclin D1 expression in OSCC cells. The in vivo antitumor effect on OSCC and safety of Dp44mT were further confirmed through a xenograft animal model. The Dp44mT treatment also increased Maspin protein levels in SAS and OECM-1 cells. NDRG3 knockdown enhanced the growth of OECM-1 cells in vitro and in vivo. Our results indicated that NDRG3 is a tumor suppressor gene in OSCC cells, and Dp44mT could be a promising therapeutic agent for OSCC treatment.

  6. Ga(III) chelates of amphiphilic DOTA-based ligands: synthetic route and in vitro and in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Fontes, Andre [Centro de Quimica, Campus de Gualtar, Universidade do Minho, 4710-057, Braga (Portugal); Prata, M. Isabel M. [IBILI, Faculdade de Medicina, Universidade de Coimbra, 3548, Coimbra (Portugal); Geraldes, Carlos F.G.C. [Departamento de Ciencias da Vida, Faculdade de Ciencias e Tecnologia, Universidade de Coimbra, 3001-401, Coimbra (Portugal); Centro de Neurociencias e Biologia Celular, Universidade de Coimbra, 3001-401, Coimbra (Portugal); Andre, Joao P., E-mail: jandre@quimica.uminho.p [Centro de Quimica, Campus de Gualtar, Universidade do Minho, 4710-057, Braga (Portugal)

    2011-04-15

    In this work, we report on a synthetic strategy using amphiphilic DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based chelators bearing a variable-sized {alpha}-alkyl chain at one of the pendant acetate arms (from 6 to 14 carbon atoms), compatible with their covalent coupling to amine-bearing biomolecules. The amphiphilic behavior of the micelles-forming Ga(III) chelates (critical micellar concentration), their stability in blood serum and their lipophilicity (logP) were investigated. Biodistribution studies with the {sup 67}Ga-labeled chelates were performed in Wistar rats, which showed a predominant liver uptake with almost no traces of the radiochelates in the body after 24 h.

  7. Cyclotron Production of High–Specific Activity 55Co and In Vivo Evaluation of the Stability of 55Co Metal-Chelate-Peptide Complexes

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    Tara Mastren

    2015-10-01

    Full Text Available This work describes the production of high–specific activity 55Co and the evaluation of the stability of 55Co-metal-chelate-peptide complexes in vivo. 55Co was produced via the 58Ni(p,α55Co reaction and purified using anion exchange chromatography with an average recovery of 92% and an average specific activity of 1.96 GBq/μmol. 55Co-DO3A and 55Co-NO2A peptide complexes were radiolabeled at 3.7 MBq/μg and injected into HCT-116 tumor xenografted mice. Positron emission tomography (PET and biodistribution studies were performed at 24 and 48 hours postinjection and compared to those of 55CoCl2. Both 55Co-metal-chelate complexes demonstrated good in vivo stability by reducing the radiotracers’ uptake in the liver by sixfold at 24 hours with ˜ 1% ID/g and at 48 hours with ˜ 0.5% ID/g and reducing uptake in the heart by fourfold at 24 hours with ˜ 0.7% ID/g and sevenfold at 48 hours with ˜ 0.35% ID/g. These results support the use of 55Co as a promising new radiotracer for PET imaging of cancer and other diseases.

  8. Cyclotron production of high specific activity 55Co and in vivo evaluation of the stability of 55Co metal-chelate-peptide complexes

    Science.gov (United States)

    Mastren, Tara; Marquez, Bernadette V.; Sultan, Deborah E.; Bollinger, Elizabeth; Eisenbeis, Paul; Voller, Tom; Lapi, Suzanne E.

    2016-01-01

    This work describes the production of high-specific activity 55Co and the evaluation of the stability of 55Co-metal-chelate-peptide complexes in vivo. 55Co was produced via the 58Ni(p,α)55Co reaction and purified using anion exchange chromatography with an average recovery of 92% and an average specific activity of 1.96GBq/µmol. 55Co-DO3A and 55Co-NO2A peptide complexes were radiolabelled at 3.7MBq/µg and injected into HCT-116 tumor xenografted mice. PET imaging and biodistribution studies were performed at 24 and 48 hours post injection and compared with that of 55CoCl2. Both 55Co-metal-chelate complexes demonstrated good in vivo stability by reducing the radiotracers’ uptake in the liver by 6-fold at 24 with ~1% ID/g and at 48 hours with ~0.5% ID/g, and reducing uptake in the heart by 4-fold at 24 hours with ~0.7% ID/g and 7-fold at 48 hours with ~0.35% ID/g. These results support the use of 55Co as a promising new radiotracer for Positron Emission Tomography (PET) imaging of cancer and other diseases. PMID:26505224

  9. A Copper Chelate of Thiosemicarbazone NSC 689534 induces Oxidative/ER Stress and Inhibits Tumor Growth In Vitro and In Vivo

    Science.gov (United States)

    Hancock, Chad N.; Stockwin, Luke H.; Han, Bingnan; Divelbiss, Raymond D.; Jun, Jung Ho; Malhotra, Sanjay V.; Hollingshead, Melinda G.; Newton, Dianne L.

    2010-01-01

    In this study, a Cu2+ chelate of the novel thiosemicarbazone NSC 689534 was evaluated for in vitro and in vivo anti-cancer activity. Results demonstrated that NSC 689534 activity (low µM range) was enhanced 4–5 fold by copper chelation and completely attenuated by iron. Importantly, once formed, the NSC 689534/Cu2+ complex retained activity in the presence of additional iron or iron-containing biomolecules. NSC 689534/Cu2+ mediated its effects primarily through the induction of ROS, with depletion of cellular glutathione and protein thiols. Pre-treatment of cells with the antioxidant L-NAC impaired activity, whereas NSC 689534/Cu2+ effectively synergized with the glutathione biosynthesis inhibitor, buthionine sulphoximine. Microarray analysis of NSC 689534/Cu2+-treated cells highlighted activation of pathways involved in oxidative and ER-stress/UPR, autophagy and metal metabolism. Further scrutiny of the role of ER-stress and autophagy indicated that NSC 689534/Cu2+ -induced cell death was ER-stress dependent and autophagy-independent. Lastly, NSC 689534/Cu2+ was shown to have activity in an HL60 xenograft model. These data suggest that NSC 689534/Cu2+ is a potent oxidative stress inducer worthy of further preclinical investigation. PMID:20971185

  10. Exploiting the Metal-Chelating Properties of the Drug Cargo for In Vivo Positron Emission Tomography Imaging of Liposomal Nanomedicines.

    Science.gov (United States)

    Edmonds, Scott; Volpe, Alessia; Shmeeda, Hilary; Parente-Pereira, Ana C; Radia, Riya; Baguña-Torres, Julia; Szanda, Istvan; Severin, Gregory W; Livieratos, Lefteris; Blower, Philip J; Maher, John; Fruhwirth, Gilbert O; Gabizon, Alberto; T M de Rosales, Rafael

    2016-11-22

    The clinical value of current and future nanomedicines can be improved by introducing patient selection strategies based on noninvasive sensitive whole-body imaging techniques such as positron emission tomography (PET). Thus, a broad method to radiolabel and track preformed nanomedicines such as liposomal drugs with PET radionuclides will have a wide impact in nanomedicine. Here, we introduce a simple and efficient PET radiolabeling method that exploits the metal-chelating properties of certain drugs (e.g., bisphosphonates such as alendronate and anthracyclines such as doxorubicin) and widely used ionophores to achieve excellent radiolabeling yields, purities, and stabilities with (89)Zr, (52)Mn, and (64)Cu, and without the requirement of modification of the nanomedicine components. In a model of metastatic breast cancer, we demonstrate that this technique allows quantification of the biodistribution of a radiolabeled stealth liposomal nanomedicine containing alendronate that shows high uptake in primary tumors and metastatic organs. The versatility, efficiency, simplicity, and GMP compatibility of this method may enable submicrodosing imaging studies of liposomal nanomedicines containing chelating drugs in humans and may have clinical impact by facilitating the introduction of image-guided therapeutic strategies in current and future nanomedicine clinical studies.

  11. Manganese-induced hydroxyl radical formation in rat striatum is not attenuated by dopamine depletion or iron chelation in vivo

    NARCIS (Netherlands)

    W.N. Sloot (W.); J. Korf (Jakob); J.F. Koster (Johan); L.E.A. de Wit (Elly); J.-B.P. Gramsbergen (J. B P)

    1996-01-01

    textabstractThe present studies were aimed at investigating the possible roles of dopamine (DA) and iron in production of hydroxyl radicals (.OH) in rat striatum after Mn2+ intoxication. For this purpose, DA depletions were assessed concomitant with in vivo 2,3- and 2,5-dihydroxybenzoic acid (DHBA)

  12. Manganese-induced hydroxyl radical formation in rat striatum is not attenuated by dopamine depletion or iron chelation in vivo

    NARCIS (Netherlands)

    Sloot, WN; Korf, J; Koster, JF; DeWit, LEA; Gramsbergen, JBP

    The present studies were aimed at investigating the possible roles of dopamine (DA) and iron in production of hydroxyl radicals ((OH)-O-.) in rat striatum after Mn2+ intoxication. For this purpose, DA depletions were assessed concomitant with in vivo 2,3- and 2,5-dihydroxybenzoic acid (DHBA)

  13. In vivo chelation of Am(III), Pu(IV), Np(V), and U(VI) in mice by TREN-(Me-3,2-HOPO)

    Energy Technology Data Exchange (ETDEWEB)

    Durbin, P.W.; Kullgren, B.; Xu, J.; Raymond, K.N.

    1993-08-01

    Octadentate 3,4,3-LI(1,2-HOPO), composed of the acidic hydroxypyridine isomer, 1,2-HOPO, is the most effective ligand yet prepared for in vivo chelation of Pu(IV) and Am(III), but it is difficult to prepare and acutely toxic. Hexadentate TREN-(Me-3,2-HOPO), composed of the less acidic Me-3,2-HOPO isomer, can be produced in relatively large quantities. TREN-(Me-3,2-HOPO) (30 {mu}mol.kg{sup {minus}1} injected intraperitoneally in mice 3 min to 1 h after intravenous injection of an actinide) removed significant body Pu(IV), Am(III), Np(V), or U(VI) (compared with controls), and those actinide reductions were significantly greater than were obtained with CaNa{sub 3}-DTPA. TREN-(Me-3,2-HOPO) was almost as effective for reducing body PU(IV) as 3,4,3-LI(1,2-HOPO). TREN-(Me-3,2-HOPO) is of low acute toxicity in mice and its clinical potential, as a practical compromise between the effectiveness of 3,4,3-LI(1,2-HOPO) and the safety of CaNa{sub 3}-DTPA, merits further investigation.

  14. Metal chelate surfactants. Kinzoku chelate kaimen kasseizai

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, S. (Kagoshima Univ., Kagoshima (Japan). Faculty of Engineering); Takeshita, T. (Sendai Polytechnic College, Kagoshima (Japan))

    1990-10-20

    The chelating agent which forms soluble metal chelates by combining with metal ions and masks metal irons, is one of builder added in order to improve the efficiency of surface activity. This report reviews the compounds having chelating ligands and surface activity. Hydrophobic groups have been introduced into the chelate ligands such as ethylenediamine, polyethylene-polyimines, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), aminophosphonic acids, and 2-salicylic acid. Carbon- and nitrogen-substitution products or ester- and amide-derivatives of EDTA and DTPA were found to form metal chelates and have excellent surface activities. Some of them were applied to additives for coatings, coal slurry fuels and anti-tumor drugs. 32 refs., 29 figs.

  15. Solvothermal synthesis of uranium(VI) phases with aromatic carboxylate ligands: A dinuclear complex with 4-hydroxybenzoic acid and a 3D framework with terephthalic acid

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yingjie, E-mail: yzx@ansto.gov.au [Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Karatchevtseva, Inna [Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Bhadbhade, Mohan [Mark Wainwright Analytical Centre, University of New South Wales, Kensington, NSW 2052 (Australia); Tran, Toan Trong; Aharonovich, Igor [School of Physics and Advanced Materials, University of Technology Sydney, Ultimo, NSW 2007 (Australia); Fanna, Daniel J.; Shepherd, Nicholas D. [School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751 (Australia); Lu, Kim [Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Li, Feng [School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751 (Australia); Lumpkin, Gregory R. [Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia)

    2016-02-15

    With the coordination of dimethylformamide (DMF), two new uranium(VI) complexes with either 4-hydroxybenzoic acid (H{sub 2}phb) or terephthalic acid (H{sub 2}tph) have been synthesized under solvothermal conditions and structurally characterized. [(UO{sub 2}){sub 2}(Hphb){sub 2}(phb)(DMF)(H{sub 2}O){sub 3}]·4H{sub 2}O (1) has a dinuclear structure constructed with both pentagonal and hexagonal bipyramidal uranium polyhedra linked through a µ{sub 2}-bridging ligand via both chelating carboxylate arm and alcohol oxygen bonding, first observation of such a coordination mode of 4-hydroxybenzoate for 5 f ions. [(UO{sub 2})(tph)(DMF)] (2) has a three-dimensional (3D) framework built with pentagonal bipyramidal uranium polyhedra linked with µ{sub 4}-terephthalate ligands. The 3D channeled structure is facilitated by the unique carboxylate bonding with nearly linear C–O–U angles and the coordination of DMF molecules. The presence of phb ligands in different coordination modes, uranyl ions in diverse environments and DMF in complex 1, and tph ligand, DMF and uranyl ion in complex 2 has been confirmed by Raman spectroscopy. In addition, their thermal stability and photoluminescence properties have been investigated. - Graphical abstract: With the coordination of dimethylformamide, two new uranyl complexes with either 4-hydroxybenzoate or terephthalate have been synthesized under solvothermal conditions and structurally characterized. - Highlights: • Solvent facilitates the synthesis of two new uranium(VI) complexes. • A dinuclear complex with both penta- and hexagonal bipyramidal uranium polyhedral. • A unique µ{sub 2}-bridging mode of 4-hydroxybenzoate via alcohol oxygen for 5 f ions. • A 3D framework with uranium polyhedra and µ{sub 4}-terephthalate ligands. • Vibration modes and photoluminescence properties are reported.

  16. The Extracellular Domain of Human High Affinity Copper Transporter (hNdCTR1, Synthesized by E. coli Cells, Chelates Silver and Copper Ions In Vivo

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    Tatiana P. Sankova

    2017-11-01

    Full Text Available There is much interest in effective copper chelators to correct copper dyshomeostasis in neurodegenerative and oncological diseases. In this study, a recombinant fusion protein for expression in Escherichia coli cells was constructed from glutathione-S-transferase (GST and the N-terminal domain (ectodomain of human high affinity copper transporter CTR1 (hNdCTR1, which has three metal-bound motifs. Several biological properties of the GST-hNdCTR1 fusion protein were assessed. It was demonstrated that in cells, the protein was prone to oligomerization, formed inclusion bodies and displayed no toxicity. Treatment of E. coli cells with copper and silver ions reduced cell viability in a dose- and time-dependent manner. Cells expressing GST-hNdCTR1 protein demonstrated resistance to the metal treatments. These cells accumulated silver ions and formed nanoparticles that contained AgCl and metallic silver. In this bacterial population, filamentous bacteria with a length of about 10 µm were often observed. The possibility for the fusion protein carrying extracellular metal binding motifs to integrate into the cell’s copper metabolism and its chelating properties are discussed.

  17. Chelation in Metal Intoxication

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    Swaran J.S. Flora

    2010-06-01

    Full Text Available Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.

  18. Uranium(VI adsorption on surfactant modified heulandite/clinoptilolite rich tuff

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    SRDJAN MATIJASEVIC

    2006-12-01

    Full Text Available The adsorption of uranium(VI on heulandite/clinoptilolite rich zeolitic tuff modified with diferent amounts (2, 5 and 10 meq/100 g of hexadecyltrimethyl ammonium (HDTMA ion was investigated. The organozeolites were prepared by ion exchange of inorganic cations at the zeolite surface with HDTMA ions, and the three prepared samples were denoted as OA-2, OA-5 and OA-10. The maximal amount of HDTMAin the organozeolite OA-10 (10 meq/100 g was equal to the external cation exchange capacity of the starting material. The results showed that uranium( VI adsorption on unmodified zeolitic tuff was low (0.34 mg uranium(VI/g adsorbent, while for the organozeolites, the adsorption increased with increasing amount of HDTMA at the zeolitic surface. The highest adsorption indexes were achieved for the organozeolite OA-10, in which all the surface inorganic cations had been replaced with HDTMA. An investigation of the adsorption of uranium(VI ions onto organozeolite OA-10 at different pH values (3, 6 and 8 showed that the adsorption index increased with increasing amount of adsorbent in the suspension. Since uranium(VI speciation is highly dependent on pH, from the adsorption isotherms, it can be seen that uranium(VI adsorption on organozeolite OA-10 at pH 6 and 8 is well described by a Langmuir type of isotherm, while at pH 3, it corresponds to a Type III isotherm.

  19. Iron chelators: correlation between effects on Plasmodium spp. and immune functions.

    NARCIS (Netherlands)

    Golenser, J.; Domb, A.; Mordechai-Daniel, T.; Leshem, B.; Luty, J.F.; Kremsner, P.

    2006-01-01

    Iron chelating agents, which permeate through erythrocytic and parasite membranes, are effective against Plasmodium falciparum in vitro. However, the protective effect in humans is transient. We examined the antiplasmodial capacity of several iron chelators in vitro and in vivo. The chelators

  20. Chelation in metal intoxication

    DEFF Research Database (Denmark)

    Aaseth, Jan; Skaug, Marit Aralt; Cao, yang

    2015-01-01

    The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due...... to the inconvenience of parenteral administration, their own toxicity and tendency to increase the neurotoxicity of several metals. The hydrophilic dithiol chelators DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-propanesulphonate) are less toxic and more efficient than BAL in the clinical treatment...... of heavy metal poisoning, and available as capsules for oral use. In copper overload, DMSA appears to be a potent antidote, although d-penicillamine is still widely used. In the chelation of iron, the thiols are inefficient, since iron has higher affinity for ligands with nitrogen and oxygen, but the new...

  1. Chelating polymeric membranes

    KAUST Repository

    Peinemann, Klaus-Viktor

    2015-01-22

    The present application offers a solution to the current problems associated with recovery and recycling of precious metals from scrap material, discard articles, and other items comprising one or more precious metals. The solution is premised on a microporous chelating polymeric membrane. Embodiments include, but are not limited to, microporous chelating polymeric membranes, device comprising the membranes, and methods of using and making the same.

  2. Sorption of Uranium(VI and Thorium(IV by Jordanian Bentonite

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    Fawwaz I. Khalili

    2013-01-01

    Full Text Available Purification of raw bentonite was done to remove quartz. This includes mixing the raw bentonite with water and then centrifuge it at 750 rpm; this process is repeated until white purified bentonite is obtained. XRD, XRF, FTIR, and SEM techniques will be used for the characterization of purified bentonite. The sorption behavior of purified Jordanian bentonite towards and Th4+ metal ions in aqueous solutions was studied by batch experiment as a function of pH, contact time, temperature, and column techniques at 25.0∘C and . The highest rate of metal ions uptake was observed after 18 h of shaking, and the uptake has increased with increasing pH and reached a maximum at . Bentonite has shown high metal ion uptake capacity toward uranium(VI than thorium(IV. Sorption data were evaluated according to the pseudo- second-order reaction kinetic. Sorption isotherms were studied at temperatures 25.0∘C, 35.0∘C, and 45.0∘C. The Langmuir, Freundlich, and Dubinin-Radushkevich (D-R sorption models equations were applied and the proper constants were derived. It was found that the sorption process is enthalpy driven for uranium(VI and thorium(IV. Recovery of uranium(VI and thorium(IV ions after sorption was carried out by treatment of the loaded bentonite with different concentrations of HNO3 1.0 M, 0.5 M, 0.1 M, and 0.01 M. The best percent recovery for uranium(VI and thorium(IV was obtained when 1.0 M HNO3 was used.

  3. MoS2-Gd Chelate Magnetic Nanomaterials with Core-Shell Structure Used as Contrast Agents in in Vivo Magnetic Resonance Imaging.

    Science.gov (United States)

    Anbazhagan, Rajeshkumar; Su, Yu-An; Tsai, Hsieh-Chih; Jeng, Ru-Jong

    2016-01-27

    Despite their frequent usages as contrast agents for in vivo MRI imaging, paramagnetic molecules continue to suffer from low resolution, physicochemical instability, and high toxicity. Herein, we present a molybdenum disulfide and gadolinium complex, as an alternative core-shell magnetic nanomaterial that exhibits enhanced paramagnetic property; 4.5-times longer water proton spin-lattice relaxation time (T1) when compared to commercial gadolinium contrast agents; as well as lowered toxicity, extended blood circulation time, increased stability, and desirable excretion characteristic. Transmission electron microscopy (TEM) revealed smooth core-shell nanoparticles 100 nm in size with a shell width of approximately 10 nm. These findings suggest that the synthesized nanomaterial possesses high potential as a positive contrast agent for the enhancement of MRI imaging.

  4. Chelation Therapy for Mercury Poisoning

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    Rong Guan

    2009-01-01

    Full Text Available Chelation therapy has been the major treatment for heavy metal poisoning. Various chelating agents have been developed and tested for treatment of heavy metal intoxications, including mercury poisoning. It has been clearly shown that chelating agents could rescue the toxicity caused by heavy metal intoxication, but the potential preventive role of chelating agents against heavy metal poisoning has not been explored much. Recent paper by Siddiqi and colleagues has suggested a protective role of chelating agents against mercury poisoning, which provides a promising research direction for broader application of chelation therapy in prevention and treatment of mercury poisoning.

  5. Fluorescent Europium Chelate Stain

    Science.gov (United States)

    Scaff, W. L.; Dyer, D. L.; Mori, K.

    1969-01-01

    The europium chelate of 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedione (thenoyl-trifluoroacetone; TTA) is firmly bound to microorganisms. It fluoresces brightly at 613 nm with activation at 340 nm. Cells may be stained with 10−3m chelate in 50% ethyl alcohol, followed by washing with 50% ethyl alcohol. Equal or better stains are produced with 10−3m aqueous europium salt, water wash, and 10−2m aqueous TTA. A noncomplexing buffer should be used to maintain the pH at 6.5 to 6.8. Images PMID:4181107

  6. Chelation Therapy for Mercury Poisoning

    OpenAIRE

    Rong Guan; Han Dai

    2009-01-01

    Chelation therapy has been the major treatment for heavy metal poisoning. Various chelating agents have been developed and tested for treatment of heavy metal intoxications, including mercury poisoning. It has been clearly shown that chelating agents could rescue the toxicity caused by heavy metal intoxication, but the potential preventive role of chelating agents against heavy metal poisoning has not been explored much. Recent paper by Siddiqi and colleagues has suggested a protective role o...

  7. Electroreduction of uranium(VI) to uranium(IV) in strip product solutions

    Science.gov (United States)

    Skripchenko, S. Yu.; Chernyshov, M. V.; Smirnov, A. L.

    2017-09-01

    The electrochemical reduction of uranium(VI) to uranium(IV) in strip product solutions on a carbon electrode was investigated. The maximal tetravalent uranium yield as well as a high current efficiency could be achieved during the electrolysis at current densities of 8-10 mA/cm2. The use of solutions with fluoride ions addition for electrolysis resulted in increased process efficiency due to formation of fluoride complexes. The efficiency of the electrochemical reduction also increased with increasing uranium content in the strip product solutions. The addition of hydrazine in solution was very effective for preventing nitric acid reduction at cathode, oxidation of uranium ions and anode destruction.

  8. EXAFS investigation of uranium(VI) complexes formed at Bacillus cereus and Bacillus sphaericus surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Hennig, C.; Panak, P.J.; Reich, T.; Rossberg, A.; Raff, J.; Selenska-Pobell, S.; Bernhard, G.; Nitsche, H. [Inst. of Radiochemistry, Forschungszentrum Rossendorf, Dresden (Germany); Matz, W. [Inst. of Ion Beam Physics and Materials Research, Forschungszentrum Rossendorf, Dresden (Germany); Bucher, J.J. [Lawrence Berkeley National Lab., CA (United States)

    2001-07-01

    Uranium(VI) complex formation at vegetative cells and spores of Bacillus cereus and Bacillus sphaericus was studied using uranium L{sub II}-edge and L{sub III}-edge extended X-ray absorption fine structure (EXAFS) spectroscopy. A comparison of the measured equatorial U-O distances and other EXAFS structural parameters of uranyl species formed at the Bacillus strains with those of the uranyl structure family indicates that the uranium is predominantly bound as uranyl complexes with phosphoryl residues. (orig.)

  9. Biosorption characteristics of uranium(VI) from aqueous medium onto Catenella repens, a red alga

    Energy Technology Data Exchange (ETDEWEB)

    Bhat, Suman Vikas [Nuclear Agriculture and Biotechnology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Department of Botany, University of Pune, Ganeshkhind, Pune 411007 (India); Melo, J.S. [Nuclear Agriculture and Biotechnology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Chaugule, B.B. [Department of Botany, University of Pune, Ganeshkhind, Pune 411007 (India); D' Souza, S.F. [Nuclear Agriculture and Biotechnology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India)], E-mail: sfdsouza@barc.gov.in

    2008-10-30

    The biosorption characteristics of uranium(VI) onto Catenella repens (a red alga), were evaluated as a function of pH, biosorbent size, time, biomass dosage, initial uranium concentration and temperature. Within the pH range studied (1.5-7.5), 4.5 was the optimum pH for the uptake of uranium(VI) by C. repens. Reduction in particle size did not increase the biosorption capacity. The metal removal was rapid, with more than 90% of total biosorption taking place in 30 min, and equilibrium was attained in 45 min. The maximum metal loading capacity of the alga was 303 mg/g. Within the temperature range studied (15-55 deg. C), there was no significant change in biosorption, under optimal conditions. Adsorption process could be well defined by both the Langmuir and Freundlich isotherms with r{sup 2} of 0.94 and 0.96, respectively. The kinetic data fitted the pseudo-second-order kinetic model with the r{sup 2} value of 0.99. At a low pH of 2.5, where most of the biomasses show either no or less metal uptake, a good (>15%) metal loading capacity of 25% was achieved. Therefore biosorption characteristics were also evaluated at pH 2.5.

  10. Quantum chemistry study of uranium(VI), neptunium(V), and plutonium(IV,VI) complexes with preorganized tetradentate phenanthrolineamide ligands.

    Science.gov (United States)

    Xiao, Cheng-Liang; Wu, Qun-Yan; Wang, Cong-Zhi; Zhao, Yu-Liang; Chai, Zhi-Fang; Shi, Wei-Qun

    2014-10-20

    The preorganized tetradentate 2,9-diamido-1,10-phenanthroline ligand with hard-soft donors combined in the same molecule has been found to possess high selectivity toward actinides in an acidic aqueous solution. In this work, density functional theory (DFT) coupled with the quasi-relativistic small-core pseudopotential method was used to investigate the structures, bonding nature, and thermodynamic behavior of uranium(VI), neptunium(V), and plutonium(IV,VI) with phenanthrolineamides. Theoretical optimization shows that Et-Tol-DAPhen and Et-Et-DAPhen ligands are both coordinated with actinides in a tetradentate chelating mode through two N donors of the phenanthroline moiety and two O donors of the amide moieties. It is found that [AnO2L(NO3)](n+) (An = U(VI), Np(V), Pu(VI); n = 0, 1) and PuL(NO3)4 are the main 1:1 complexes. With respect to 1:2 complexes, the reaction [Pu(H2O)9](4+)(aq) + 2L(org) + 2NO3(-)(aq) → [PuL2(NO3)2](2+)(org) + 9H2O(aq) might be another probable extraction mechanism for Pu(IV). From the viewpoint of energy, the phenanthrolineamides extract actinides in the order of Pu(IV) > U(VI) > Pu(VI) > Np(V), which agrees well with the experimental results. Additionally, all of the thermodynamic reactions are more energetically favorable for the Et-Tol-DAPhen ligand than the Et-Et-DAPhen ligand, indicating that substitution of one ethyl group with one tolyl group can enhance the complexation abilities toward actinide cations (anomalous aryl strengthening).

  11. Effect of humic acid on the uranium(VI) sorption onto phyllite and its mineralogical constituents

    Energy Technology Data Exchange (ETDEWEB)

    Schmeide, K.; Jander, R.; Heise, K.H.; Bernhard, G. [Forschungszentrum Rossendorf e.V. (FZR) (Germany). Inst. fuer Radiochemie

    1999-06-01

    The effect of humic acid (HA) on the uranium(VI) sorption onto phyllite and onto its individual main mineralogical constituents, muscovite, albite, and quartz was studied in air-equilibrated batch experiments in the pH range of 3.5 to 9.5. The uranyl(VI) and HA concentration was 1 x 10{sup -6}M and 5 mg/L, respectively. The ionic strength was held constant at 0.1 M (NaClO{sub 4} solution). A size fraction of 63 to 200 {mu}m of the solids was used, the mass loading was 12.5 g/L, and the experimental volume was 40 mL. (orig.)

  12. Interaction of uranium(VI) with bioligands present in human biological fluids. The case study of urea and uric acid

    Energy Technology Data Exchange (ETDEWEB)

    Osman, A.A.A.; Geipel, G.; Bernhard, G. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany). Inst. of Resource Ecology

    2013-05-01

    The complexation of uranium(VI) with bioligands found in human biological fluids, viz, urea and uric acid in aqueous solutions, has been investigated using time-resolved laser-induced fluorescence spectroscopy (TRLFS) at room temperature, I = 0.1 M (NaClO4) and pH (3 for uric acid; 4 for urea). In both complex systems a static quench effect with increasing ligand concentration and no peaks shift upon complexation were observed. With uranium(VI) both ligands formed a fairly weak 1:1 complex with average stability constants of log {beta}{sub 110} = 4.67 {+-} 0.29 for uric acid and log {beta}{sub 110} = 3.79 {+-} 0.15 and 2.12 {+-} 0.18 for relatively low and relatively high urea concentrations, respectively. Application of the newly generated data on the U(VI) speciation modelling in biofluids, e.g., human urine was also discussed.

  13. Uranium(VI) coordination polymers with pyromellitate ligand: Unique 1D channel structures and diverse fluorescence

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yingjie, E-mail: yzx@ansto.gov.au [Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Bhadbhade, Mohan [Mark Wainwright Analytical Centre, University of New South Wales, Kensington, NSW 2052 (Australia); Karatchevtseva, Inna [Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Price, Jason R. [Australian Synchrotron, 800 Blackburn Road, Clayton, VIC 3168 (Australia); Liu, Hao [Centre for Clean Energy Technology, School of Chemistry and Forensic Science, University of Technology Sydney, PO Box 123, Broadway, Sydney, NSW 2007 (Australia); Zhang, Zhaoming; Kong, Linggen [Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Čejka, Jiří [Department of Mineralogy, National Museum, Václavské náměstí, 68, Prague 1, 115 79-CZ (Czech Republic); Lu, Kim; Lumpkin, Gregory R. [Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia)

    2015-03-15

    Three new coordination polymers of uranium(VI) with pyromellitic acid (H{sub 4}btca) have been synthesized and structurally characterized. (ED)[(UO{sub 2})(btca)]·(DMSO)·3H{sub 2}O (1) (ED=ethylenediammonium; DMSO=dimethylsulfoxide) has a lamellar structure with intercalation of ED and DMSO. (NH{sub 4}){sub 2}[(UO{sub 2}){sub 6}O{sub 2}(OH){sub 6}(btca)]·~6H{sub 2}O (2) has a 3D framework built from 7-fold coordinated uranyl trinuclear units and btca ligands with 1D diamond-shaped channels (~8.5 Å×~8.6 Å). [(UO{sub 2}){sub 2}(H{sub 2}O)(btca)]·4H{sub 2}O (3) has a 3D network constructed by two types of 7-fold coordinated uranium polyhedron. The unique μ{sub 5}-coordination mode of btca in 3 enables the formation of 1D olive-shaped large channels (~4.5 Å×~19 Å). Vibrational modes, thermal stabilities and fluorescence properties have been investigated. - Graphical abstract: Table of content: three new uranium(VI) coordination polymers with pyromellitic acid (H{sub 4}btca) have been synthesized via room temperature and hydrothermal synthesis methods, and structurally characterized. Two to three dimensional (3D) frameworks are revealed. All 3D frameworks have unique 1D large channels. Their vibrational modes, thermal stabilities and photoluminescence properties have been investigated. - Highlights: • Three new coordination polymers of U(VI) with pyromellitic acid (H{sub 4}btca). • Structures from a 2D layer to 3D frameworks with unique 1D channels. • Unusual µ{sub 5}-(η{sub 1}:η{sub 2}:η{sub 1}:η{sub 2:}η{sub 1}) coordination mode of btca ligand. • Vibrational modes, thermal stabilities and luminescent properties reported.

  14. Removal of uranium(VI) from aqueous solutions by manganese oxide coated zeolite: discussion of adsorption isotherms and pH effect.

    Science.gov (United States)

    Han, Runping; Zou, Weihua; Wang, Yi; Zhu, Lu

    2007-01-01

    This paper discusses the adsorption properties for uranium(VI) by manganese oxide coated zeolite (MOCZ). The removal of uranium(VI) from aqueous solution by adsorption onto MOCZ in a single-component system with various contact times, pH, competitive ions, temperatures and initial concentrations of uranium(VI) was investigated. The experimental results were fitted to the Langmuir, Freundlich and the three-parameter Redlich-Peterson model isotherms to obtain the characteristic parameters of each model. Both the Langmuir and Redlich-Peterson isotherms were found to best represent the measured adsorption data. According to the evaluation using the Langmuir equation, the maximum adsorption capacity of uranium(VI) ions onto MOCZ was 15.1 mg g(-1) at 293K and pH 4.0. Using the thermodynamic equilibrium constants obtained at different temperatures, various thermodynamic parameters, such as DeltaG(0), DeltaH(0) and DeltaS(0), have been calculated. The thermodynamics of uranium(VI) ion/MOCZ system indicates the spontaneous and endothermic nature of the process. It was noted that an increase in temperature resulted in a higher uranium loading per unit weight of the adsorbent.

  15. Chelation for Coronary Heart Disease

    Science.gov (United States)

    ... procedures, and cardiac rehabilitation (a program consisting of education, counseling, and exercise training) are among the mainstays of conventional treatment . Some heart patients also turn to chelation therapy using disodium EDTA ( ...

  16. Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89.

    Directory of Open Access Journals (Sweden)

    Nikunj B Bhatt

    Full Text Available The development of bifunctional chelators (BFCs for zirconium-89 immuno-PET applications is an area of active research. Herein we report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2 as zirconium-89 chelators. While both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. Differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation.

  17. Article Commentary: Chelation Therapy for Mercury Poisoning

    Directory of Open Access Journals (Sweden)

    Rong Guan

    2009-01-01

    Full Text Available Chelation therapy has been the major treatment for heavy metal poisoning. Various chelating agents have been developed and tested for treatment of heavy metal intoxications, including mercury poisoning. It has been clearly shown that chelating agents could rescue the toxicity caused by heavy metal intoxication, but the potential preventive role of chelating agents against heavy metal poisoning has not been explored much. Recent paper by Siddiqi and colleagues has suggested a protective role of chelating agents against mercury poisoning, which provides a promising research direction for broader application of chelation therapy in prevention and treatment of mercury poisoning.

  18. Sorption of uranium(VI) using oxime-grafted ordered mesoporous carbon CMK-5

    Energy Technology Data Exchange (ETDEWEB)

    Tian Gan; Geng Junxia; Jin Yongdong; Wang Chunli; Li Shuqiong; Chen Zhen; Wang Hang; Zhao Yongsheng [College of Chemistry, Sichuan University, Chengdu 610064 (China); Li Shoujian, E-mail: sjli000616@scu.edu.cn [College of Chemistry, Sichuan University, Chengdu 610064 (China)

    2011-06-15

    A new sorbent for uranium(VI) has been developed by functionalizing ordered mesoporous carbon CMK-5 with 4-acetophenone oxime via thermally initiated diazotization. The sorption of U(VI) ions onto the functionalized CMK-5 (Oxime-CMK-5) was investigated as a function of sorbent dosage, pH value, contact time, ionic strength and temperature using batch sorption techniques. The results showed that U(VI) sorption onto Oxime-CMK-5 was strongly dependent on pH, but to a lesser extent, on ionic strength. Kinetic studies revealed that the sorption process achieved equilibrium within 30 min and followed a pseudo-first-order rate equation. The isothermal data correlated with the Langmuir model better than the Freundlich model. Thermodynamic data indicated the spontaneous and endothermic nature of the process. Under current experimental conditions, a maximum U(VI) sorption capacity was found to be 65.18 mg/g. Quantitative recovery of uranium was achieved by desorbing the U(VI)-loaded Oxime-CMK-5 with 1.0 mol/L HCl and no significant decrease in U(VI) sorption capability of Oxime-CMK-5 was observed after five consecutive sorption-desorption cycles. The sorption study performed in a simulated nuclear industry effluent demonstrated that the new sorbent showed a desirable selectivity for U(VI) ions over a range of competing metal ions.

  19. Overview of current chelation practices

    Directory of Open Access Journals (Sweden)

    Y. Aydinok

    2011-12-01

    Full Text Available Deferoxamine (DFO is reference standard therapy for transfusional iron overload since the 1980s. Although it is a highly effective iron chelator, the compliance problem to subcutaneous administration of DFO remains as the major problem. The oral chelator Deferiprone (DFP has no marketing licence in North America, however, it has been licensed in India since 1994 and the European Union (EU granted marketing approval for DFP in 1999, specifically for patients with thalassemia major when DFO is inadequate, intolerable or unacceptable. There are still limited data available on the use of DFP in children between 6 and 10 years of age, and no data on DFP use in children under 6 years of age. Subsequently the oral chelator Deferasirox (DFX was approved by FDA and EMA for the treatment of patients with transfusional iron overload -older than 2 years of age- as first line therapy, in 2005 and 2006 respectively. The primary objective of iron chelation is to maintain body iron at safe levels at all times but once iron is accumulated, the objective of iron chelation is to reduce tissue iron to safe levels which is a slow process. The chelation regimen, dose and frequency of administration, of the chelator(s are mainly determined based on body iron burden, presence of myocardial iron and the transfusional iron loading rate. A proper monitoring of chelation is of importance for measuring the response rate to a particular regimen and providing dose adjustments to enhance chelation efficacy and to avoid toxicity. Efficacy of a chelation regimen may exhibit individual variability resulting from factors such as absorbtion and metabolism of the chelator. Tolerability and compliance are also individual variables effecting the response to chelation. Understanding of advantages and limitations of chelators, accurately determining chelation needs of patients with iron overload and designing individualized chelation regimens with less toxicity but optimum efficacy

  20. AAZTA: an ideal chelating agent for the development of {sup 44}Sc PET imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Gabor; Szikra, Dezso; Trencsenyi, Gyoergy [Scanomed Ltd., Debrecen (Hungary); University of Debrecen, Medical Imaging Clinic (Hungary); Fekete, Aniko [University of Debrecen, Medical Imaging Clinic (Hungary); Garai, Ildiko [Scanomed Ltd., Debrecen (Hungary); Giani, Arianna M.; Negri, Roberto [Dipartimento di Scienze del Farmaco, Universita del Piemonte Orientale, Novara (Italy); Masciocchi, Norberto [Dipartimento di Scienza e Alta Tecnologia e To.Sca.Lab, Universita degli Studi dell' Insubria, Como (Italy); Maiocchi, Alessandro; Uggeri, Fulvio [Bracco Imaging spa, Bracco Research Centre, Colleretto Giacosa (Italy); Toth, Imre [Department of Inorganic and Analytical Chemistry, University of Debrecen (Hungary); Aime, Silvio [Dipartimento di Biotecnologie Molecolari e Scienze della Salute, Centro di Imaging Molecolare e Preclinico, Universita degli Studi di Torino (Italy); Giovenzana, Giovanni B. [Dipartimento di Scienze del Farmaco, Universita del Piemonte Orientale, Novara (Italy); CAGE Chemicals srl, Novara (Italy); Baranyai, Zsolt [Bracco Imaging spa, Bracco Research Centre, Colleretto Giacosa (Italy); Department of Inorganic and Analytical Chemistry, University of Debrecen (Hungary)

    2017-02-13

    Unprecedented fast and efficient complexation of Sc{sup III} was demonstrated with the chelating agent AAZTA (AAZTA=1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)] amino-6-methylperhydro-1,4-d iazepine) under mild experimental conditions. The robustness of the {sup 44}Sc(AAZTA){sup -} chelate and conjugated biomolecules thereof is further shown by in vivo PET imaging in healthy and tumor mice models. The new results pave the way towards development of efficient Sc-based radiopharmaceuticals using the AAZTA chelator. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Quercetin glycosides and chlorogenic acid in highbush blueberry leaf decoction prevent cataractogenesis in vivo and in vitro: Investigation of the effect on calpains, antioxidant and metal chelating properties.

    Science.gov (United States)

    Ferlemi, Anastasia-Varvara; Makri, Olga E; Mermigki, Penelope G; Lamari, Fotini N; Georgakopoulos, Constantinos D

    2016-04-01

    The present study investigates whether highbush blueberry leaf polyphenols prevent cataractogenesis and the underlying mechanisms. Chlorogenic acid, quercetin, rutin, isoquercetin and hyperoside were quantified in Vaccinium corymbosum leaf decoction (BBL) using HPLC-DAD. Wistar rats were injected subcutaneously with 20 μmol selenite (Na2SeO3)/kg body weight on postnatal (PN) day 10 (Se, n = 8-10/group) only or also intraperitoneally with 100 mg dry BBL/kg body weight on PN days 11 and 12 (SeBBL group, n = 10). Control group received only normal saline (C). Cataract evaluation revealed that BBL significantly prevented lens opacification. It, also, protected lens from selenite oxidative attack and prevented calpain activation, as well as protein loss and aggregation. In vitro studies showed that quercetin attenuated porcine lens turbidity caused by [Formula: see text] or Ca(2+) and interacted efficiently with those ions according to UV-Vis titration experiments. Finally, rutin, isoquercetin and hyperoside moderately inhibited pure human μ-calpain. Conclusively, blueberry leaf extract, a rich source of bioactive polyphenols, prevents cataractogenesis by their strong antioxidant, chelating properties and through direct/indirect inhibition of lens calpains. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Binuclear uranium(VI) complexes with a "pacman" expanded porphyrin: computational evidence for highly unusual bis-actinyl structures.

    Science.gov (United States)

    Pan, Qing-Jiang; Shamov, Grigory A; Schreckenbach, Georg

    2010-02-15

    On the basis of uranyl complexes reacting with a polypyrrolic ligand (H(4)L), we explored structures and reaction energies of a series of new binuclear uranium(VI) complexes using relativistic density functional theory. Full geometry optimizations on [(UO(2))(2)(L)], in which two uranyl groups were initially placed into the pacman ligand cavity, led to two minimum-energy structures. These complexes with cation-cation interactions (CCI) exhibit unusual coordination modes of uranyls: one is a T-shaped (T) skeleton formed by two linear uranyls {O(exo)=U(2)=O(endo)-->U(1)(=O(exo))(2)}, and another is a butterfly-like (B) unit with one linear uranyl coordinating side-by-side to a second cis-uranyl. The CCI in T was confirmed by the calculated longest distance and lowest stretching vibrational frequency of U(2)=O(endo) among the four U=O bonds. Isomer B is more stable than T, for which experimental tetrameric analogues are known. The formation of B and T complexes from the mononuclear [(UO(2))(H(2)L)(thf)] (M) was found to be endothermic. The further protonation and dehydration of B and T are thermodynamically favorable. As a possible product, we have found a trianglelike binuclear uranium(VI) complex having a O=U=O=U=O unit.

  3. Uranium(VI) interactions with mackinawite in the presence and absence of bicarbonate and oxygen

    Science.gov (United States)

    Gallegos, Tanya J.; Fuller, Christopher C.; Webb, Samuel M.; Betterton, William J.

    2013-01-01

    Mackinawite, Fe(II)S, samples loaded with uranium (10-5, 10-4, and 10-3 mol U/g FeS) at pH 5, 7, and 9, were characterized using X-ray absorption spectroscopy and X-ray diffraction to determine the effects of pH, bicarbonate, and oxidation on uptake. Under anoxic conditions, a 5 g/L suspension of mackinawite lowered 5 × 10-5 M uranium(VI) to below 30 ppb (1.26 × 10-7 M) U. Between 82 and 88% of the uranium removed from solution by mackinawite was U(IV) and was nearly completely reduced to U(IV) when 0.012 M bicarbonate was added. Near-neighbor coordination consisting of uranium–oxygen and uranium-uranium distances indicates the formation of uraninite in the presence and absence of bicarbonate, suggesting reductive precipitation as the dominant removal mechanism. Following equilibration in air, mackinawite was oxidized to mainly goethite and sulfur and about 76% of U(IV) was reoxidized to U(VI) with coordination of uranium to axial and equatorial oxygen, similar to uranyl. Additionally, uranium-iron distances, typical of coprecipitation of uranium with iron oxides, and uranium-sulfur distances indicating bidentate coordination of U(VI) to sulfate were evident. The affinity of mackinawite and its oxidation products for U(VI) provides impetus for further study of mackinawite as a potential reactive medium for remediation of uranium-contaminated water.

  4. Luminescent lanthanide chelates and methods of use

    Science.gov (United States)

    Selvin, Paul R.; Hearst, John

    1997-01-01

    The invention provides lanthanide chelates capable of intense luminescence. The celates comprise a lanthanide chelator covalently joined to a coumarin-like or quinolone-like sensitizer. Exemplary sensitzers include 2- or 4-quinolones, 2- or 4-coumarins, or derivatives thereof e.g. carbostyril 124 (7-amino-4-methyl-2-quinolone), coumarin 120 (7-amino-4-methyl-2-coumarin), coumarin 124 (7-amino-4-(trifluoromethyl)-2-coumarin), aminomethyltrimethylpsoralen, etc. The chelates form high affinity complexes with lanthanides, such as terbium or europium, through chelator groups, such as DTPA. The chelates may be coupled to a wide variety of compounds to create specific labels, probes, diagnostic and/or therapeutic reagents, etc. The chelates find particular use in resonance energy transfer between chelate-lanthanide complexes and another luminescent agent, often a fluorescent non-metal based resonance energy acceptor. The methods provide useful information about the structure, conformation, relative location and/or interactions of macromolecules.

  5. Some Linguistic Detail on Chelation

    Science.gov (United States)

    Haworth, Daniel T.

    1998-01-01

    The term chelate was first applied by Morgan and Drew in 1920 to describe the heterocyclic rings formed from bidentate ligands bonding to a central atom. The history of the word ch_l_ is traced from its original Greek meaning through the Latin language to its anglicized form, chela. This word has a very rich history and has been cited by both Greek (Aristotle) and Latin (Cicero, Vergil) philosophers and poets.

  6. MULTIDENTATE TEREPHTHALAMIDATE AND HYDROXYPYRIDONATE LIGANDS: TOWARDS NEW ORALLY ACTIVE CHELATORS

    Energy Technology Data Exchange (ETDEWEB)

    Abergel, Rebecca J.; Raymond, Kenneth N.

    2011-07-13

    The limitations of current therapies for the treatment of iron overload or radioisotope contamination have stimulated efforts to develop new orally bioavailable iron and actinide chelators. Siderophore-inspired tetradentate, hexadentate and octadentate terephthalamidate and hydroxypyridonate ligands were evaluated in vivo as selective and efficacious iron or actinide chelating agents, with several metal loading and ligand assessment procedures, using {sup 59}Fe, {sup 238}Pu, and {sup 241}Am as radioactive tracers. The compounds presented in this study were compared to commercially available therapeutic sequestering agents [deferoxamine (DFO) for iron and diethylenetriaminepentaacetic acid (DPTA) for actinides] and are unrivaled in terms of affinity, selectivity and decorporation efficacy, which attests to the fact that high metal affinity may overcome the low bioavailability properties commonly associated to multidenticity.

  7. Real-world use of iron chelators

    National Research Council Canada - National Science Library

    Kwiatkowski, Janet L

    2011-01-01

    .... Three chelators are currently available worldwide-deferoxamine, deferasirox, and deferiprone, although the latter is available in North America only in research protocols and compassionate use programs...

  8. Iron Chelation Nanoparticles with Delayed Saturation as an Effective Therapy for Parkinson Disease.

    Science.gov (United States)

    Wang, Nan; Jin, Xin; Guo, Dongbo; Tong, Gangsheng; Zhu, Xinyuan

    2017-02-13

    Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson's diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We explored and investigated whether the Parkinsonian neurodegeneration and the corresponding symptoms in behaviors and physiologies could be prevented or reversed both in vitro and in vivo. The results demonstrated that iron chelator loaded therapeutic nanoparticles could reverse functional deficits in Parkinsonian mice not only physiologically but also behaviorally. On the contrary, both untreated PD mice and non-TAT anchored nanoparticle treated PD mice showed similar loss in DA neurons and difficulties in behaviors. Therefore, with protection of zwitterionic polymer and prolonged in vivo lifetime, iron chelator loaded nanoparticles with delayed saturation provide a PD phenotype reversion therapy and significantly improve the living quality of the Parkinsonian mice.

  9. Theoretical study of the reduction of uranium(VI) aquo complexes on titania particles and by alcohols

    Energy Technology Data Exchange (ETDEWEB)

    Odoh, Samuel O.; Schreckenbach, Georg [Department of Chemistry, University of Manitoba, Winnipeg, MB (Canada); Pan, Qing-Jiang [Department of Chemistry, University of Manitoba, Winnipeg, MB (Canada); Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education, School of Chemistry and Materials Science, Heilongjiang University, Harbin (China); Shamov, Grigory A. [Department of Chemistry, University of Manitoba, Winnipeg, MB (Canada); Division of Information Technologies, Kazan National Research Technological University, Kazan (Russian Federation); Wang, Feiyue [Department of Chemistry, University of Manitoba, Winnipeg, MB (Canada); Centre for Earth Observation Science, Department of Environment and Geography, University of Manitoba, Winnipeg, MB (Canada); Fayek, Mostafa [Department of Geological Sciences, University of Manitoba, Winnipeg, MB (Canada)

    2012-06-04

    To provide insights into the adsorption and photoreduction of uranium(VI) on TiO{sub 2}, we have studied the structural and electronic properties of uranium(VI) aquo complexes adsorbed on stoichiometric and defected TiO{sub 2} surfaces and nanoparticles. Plane wave calculations with the pure PBE density functional and the PBE+U approach were used to study U{sup VI} complexes on a periodic rutile (110) slab. In addition, a nanoparticulate Ti{sub 38}O{sub 76} cluster was used to simulate anatase nanoparticles. The electronic structures of the adsorbed U{sup VI} complexes indicate that the photoreduction process is a consequence of the photocatalytic properties of TiO{sub 2}. The reduction of the adsorbed complexes can only occur if the energy of the incident photon exceeds the semiconductor band gap. The gap states induced by single or neighboring hydrogen atoms and oxygen vacancies at the rutile (110) surface cannot reduce adsorbed U{sup VI} complexes as the unoccupied 5f orbitals are found deeper in the conduction band. In the absence of a solid substrate, photoreduction proceeds by abstraction of a hydrogen atom from water or organic molecules present in solution. Photoreduction by chlorophenol results in lower product yield than reduction by aliphatic alcohols. This is because the triplet uranyl-chlorophenol complex is much more stable than similar complexes formed with methanol and ethanol. In the case of water, the hydroxyl photoproduct easily re-oxidizes the pentavalent species formed. In addition, it is easier for the triplet uranyl-water complex to decompose to the photoreactants. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  10. Theoretical study of the reduction of uranium(VI) aquo complexes on titania particles and by alcohols.

    Science.gov (United States)

    Odoh, Samuel O; Pan, Qing-Jiang; Shamov, Grigory A; Wang, Feiyue; Fayek, Mostafa; Schreckenbach, Georg

    2012-06-04

    To provide insights into the adsorption and photoreduction of uranium(VI) on TiO(2), we have studied the structural and electronic properties of uranium(VI) aquo complexes adsorbed on stoichiometric and defected TiO(2) surfaces and nanoparticles. Plane wave calculations with the pure PBE density functional and the PBE+U approach were used to study U(VI) complexes on a periodic rutile (110) slab. In addition, a nanoparticulate Ti(38)O(76) cluster was used to simulate anatase nanoparticles. The electronic structures of the adsorbed U(VI) complexes indicate that the photoreduction process is a consequence of the photocatalytic properties of TiO(2). The reduction of the adsorbed complexes can only occur if the energy of the incident photon exceeds the semiconductor band gap. The gap states induced by single or neighboring hydrogen atoms and oxygen vacancies at the rutile (110) surface cannot reduce adsorbed U(VI) complexes as the unoccupied 5f  orbitals are found deeper in the conduction band. In the absence of a solid substrate, photoreduction proceeds by abstraction of a hydrogen atom from water or organic molecules present in solution. Photoreduction by chlorophenol results in lower product yield than reduction by aliphatic alcohols. This is because the triplet uranyl-chlorophenol complex is much more stable than similar complexes formed with methanol and ethanol. In the case of water, the hydroxyl photoproduct easily re-oxidizes the pentavalent species formed. In addition, it is easier for the triplet uranyl-water complex to decompose to the photoreactants. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Importance of iron chelation therapy

    Directory of Open Access Journals (Sweden)

    A. Varoğlu

    2011-12-01

    Full Text Available It is necessary to remember that today patients have different options of chelation treatment, as desferrioxamine, deferiprone and deferasirox are available. However, a patient has to be compliant with treatments. They have always to remember that too much iron causes different complications and could be a barrier for a definitive cure from thalassemia. 由于出现了去铁胺、去铁酮和去铁斯若等药物,病人现在可以选择不同的螯合治疗方式。 然而,病人必须适应这几种治疗方式。 他们必须时刻记住太多的铁元素会引发多种并发症,并对地中海贫血的彻底治疗造成阻碍。

  12. Functionalization of hydroxy compounds with nitrilotriacetic acid for technetium-99m chelation: excretory properties of the radiolabelled chelates.

    Science.gov (United States)

    Chatterjee, M; Banerjee, S

    1991-01-01

    Substituted monoanilides of nitrilotriacetic acid (NTA) have gained much popularity in recent years as an important class of ligands for technetium-99m (99mTc) radiopharmaceutical preparations used in liver imaging and function studies. We were interested in investigating the properties of the corresponding ester analogues of this important class of ligands and for this study cyclohexanol was selected as a hydroxy component, which on condensation with nitrilotriacetic acid in the presence of acetic anhydride, furnished the monoester, N-cyclohexyloxycarbonylmethyl iminodiacetic acid 4 and the corresponding diester 5. Phenol on similar condensation produced mainly the diester, N,N-di(phenyloxycarbonylmethyl) aminoacetic acid 2, with traces of the corresponding monoester 7. A reinvestigation of the well known condensation reaction of aniline with nitrilotriacetic acid revealed that in addition to the reported monoanilide, N-phenylcarbamoylmethyl imino diacetic acid 3, the corresponding dianilide 6 was also produced in appreciable amount. The ester ligands 2, 4, 5 after 99mTc chelation exhibited good in vitro and in vivo stabilities. The biodistribution characteristics of these radiolabelled esters and amides were very similar showing thereby that esterification with NTA could be an effective method for converting alcohols to 99mTc-radiopharmaceuticals without generating any unusual properties because of the ester linkage. Residual radiopharmaceutical concentration after i.v. administration of these amide and ester 99mTc chelates at 30 min in blood, urine, liver, kidney and intestine were correlated with their lipophilicities and during this correlation it was observed that in addition to lipophilicity the anionic strength of these chelates is also an important determinant in governing their biodistribution. The ester ligand 4 after 99mTc chelation showed ultrafast hepatobiliary kinetics and was therefore compared in a rabbit model with a standard hepatobiliary

  13. Metal ions, Alzheimer's disease and chelation therapy

    National Research Council Canada - National Science Library

    Budimir, Ana

    2011-01-01

    .... In contrast to the direct chelation approach in metal ion overload disorders, in neurodegeneration the goal seems to be a better and subtle modulation of metal ion homeostasis, aimed at restoring ionic balance...

  14. Optimized and validated spectrophotometric method for the determination of uranium(VI) via complexation with meloxicam

    Energy Technology Data Exchange (ETDEWEB)

    Lutfullah [Department of Chemistry, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh (India)], E-mail: lutfullah786@gmail.com; Alam, Mohd Noor; Rahman, Nafisur; Azmi, Syed Najmul Hejaz [Department of Chemistry, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh (India)

    2008-06-30

    An optimized and validated spectrophotometric method has been developed for the determination of uranyl ion in the presence of other metal ions. The method is based on the chelation of uranyl ion with meloxicam via {beta}-diketone moiety to produce a yellow colored complex, which absorbs maximally at 398 nm. Beer's law is obeyed in the concentration range of 5-60 {mu}g/mL with apparent molar absorptivity and Sandell's sensitivity of 5.02 x 10{sup 4} L/mol/cm and 0.1 {mu}g/cm{sup 2}/0.001 absorbance unit, respectively. The method has been successfully applied for the determination of uranyl ion in synthetic mixture and soil samples. Results of analysis were statistically compared with those obtained by Currah's spectrophotometric method showing acceptable recovery and precision.

  15. Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of MPP+/MPTP-Lesioned Dopaminergic Neurons.

    Directory of Open Access Journals (Sweden)

    Pabla Aguirre

    Full Text Available Neuronal death in Parkinson's disease (PD is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2'-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death.

  16. Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Jun-Peng Guo

    Full Text Available Patients of Alzheimer's disease (AD frequently have lower bone mineral density and higher rate of hip fracture. Tg2576, a well characterized AD animal model that ubiquitously express Swedish mutant amyloid precursor protein (APPswe, displays not only AD-relevant neuropathology, but also age-dependent bone deficits. However, the underlying mechanisms remain poorly understood. As APP is implicated as a regulator of iron export, and the metal chelation is considered as a potential therapeutic strategy for AD, we examined iron chelation's effect on the osteoporotic deficit in Tg2576 mice. Remarkably, in vivo treatment with iron chelator, clinoquinol (CQ, increased both trabecular and cortical bone-mass, selectively in Tg2576, but not wild type (WT mice. Further in vitro studies showed that low concentrations of CQ as well as deferoxamine (DFO, another iron chelator, selectively inhibited osteoclast (OC differentiation, without an obvious effect on osteoblast (OB differentiation. Intriguingly, both CQ and DFO's inhibitory effect on OC was more potent in bone marrow macrophages (BMMs from Tg2576 mice than that of wild type controls. The reduction of intracellular iron levels in BMMs by CQ was also more dramatic in APPswe-expressing BMMs. Taken together, these results demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits.

  17. Effect of chelate-ring over the stabilization of copper-dioxygen adducts

    Indian Academy of Sciences (India)

    Administrator

    Effect of chelate-ring over the stabilization of copper-dioxygen adducts. RAJEEV GUPTA and RABINDRANATH MUKHERJEE. Department of Chemistry, Indian Institute of Technology,. Kanpur 208 016, India. Copper-dioxygen adducts are very important in biological systems as well as in synthetic oxidation chemistry.

  18. Complexation study of a tert-butyl-calix[4]arene-based 2-hydroxynaphthalene ligand with uranium(VI) in non-aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, Anne; Schmeide, Katja [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Surface Processes

    2017-06-01

    The actinide uranium, well known from nuclear power cycle, plays also a role in rare earth production as it is an undesired constituent of the respective ores. To facilitate the production of rare earth elements, uranium has to be removed. Due to their modifiable selectivity and solubility calix[n]arenes are interesting compounds for the extraction of actinides and lanthanides. The mechanism of uranium(VI) interaction with a tert-butyl-calix[4]arene-based 2-hydroxynaphthalene ligand (L1) was studied by TRLFS, UV-vis spectroscopy and isothermal calorimetry.

  19. Copper Chelation in Alzheimer's Disease Protein

    Science.gov (United States)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2013-03-01

    Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions of people in the U.S. AD is primarily characterized at the cellular level by densely tangled fibrils of amyloid- β protein. These protein clusters have been found in association with elevated levels of multiple transition metals, with copper being the most egregious. Interestingly, metal chelation has shown promise in attenuating the symptoms of AD in recent clinical studies. We investigate this process by constructing an atomistic model of the amyloid- β-copper complex and profile the energetic viability in each of its subsequent disassociation stages. Our results indicate that five energetic barriers must be overcome for full metal chelation. The energy barriers are biologically viable in the presence water mediated bond and proton transfer between the metal and the protein. We model the chelation reaction using a consecutive path nudged elastic band method implemented in our ab initio real-space multi-grid code to obtain a viable sequence. This reaction model details a physically consistent explanation of the chelation process that could lead to the discovery of more effective chelation agents in the treatment of AD.

  20. Uranium(VI) solubility and speciation in simulated elemental human biological fluids.

    Science.gov (United States)

    Sutton, Mark; Burastero, Stephen R

    2004-11-01

    The complete understanding of the human body response to uranium contamination exposure is vital to the development of exposure analysis and subsequent treatments for overexposure. Thermodynamic modeling has traditionally been used to study environmental metal contaminant migration (especially uranium and other radionuclides), allowing examination of chemical processes difficult to study experimentally. However, such techniques are rarely used in the study of metal toxicology. Chemical thermodynamics has a unique and valuable role in developing models to explain metal metabolism and toxicology. Previous computational models of beryllium in simulated biological fluids have been shown to be useful in predicting metal behavior in the human body. However, previous studies utilizing chemical thermodynamics in understanding uranium chemistry in body fluids are limited. Here, a chemical thermodynamic speciation code has been used to model and understand the chemistry of uranium in simulated human biological fluids such as intracellular, interstitial, and plasma fluids, saliva, sweat, urine, bile, gastric juice, pancreatic fluid, and a number of airway surface fluids from patients with acute lung conditions. The results show predicted uranium solubility, and speciation varies markedly between each biological fluid due to differences in fluid composition, ionic strength, and pH. The formation of uranium hydroxide, phosphate (sodium/potassium autunite), and calcium uranate was observed in most of the fluids. The results of this work, supported by experimental validation, can aid in understanding the metabolism and toxic effects of uranium with potential applications to biological monitoring as well as chelation treatment of uranium body burden.

  1. Trypanotoxic activity of thiosemicarbazone iron chelators.

    Science.gov (United States)

    Ellis, Samuel; Sexton, Darren W; Steverding, Dietmar

    2015-03-01

    Only a few drugs are available for treating sleeping sickness and nagana disease; parasitic infections caused by protozoans of the genus Trypanosoma in sub-Saharan Africa. There is an urgent need for the development of new medicines for chemotherapy of these devastating diseases. In this study, three newly designed thiosemicarbazone iron chelators, TSC24, Dp44mT and 3-AP, were tested for in vitro activity against bloodstream forms of Trypanosoma brucei and human leukaemia HL-60 cells. In addition to their iron chelating properties, TSC24 and Dp44mT inhibit topoisomerase IIα while 3-AP inactivates ribonucleotide reductase. All three compounds exhibited anti-trypanosomal activity, with minimum inhibitory concentration (MIC) values ranging between 1 and 100 µM and 50% growth inhibition (GI50) values of around 250 nM. Although the compounds did not kill HL-60 cells (MIC values >100 µM), TSC24 and Dp44mT displayed considerable cytotoxicity based on their GI50 values. Iron supplementation partly reversed the trypanotoxic and cytotoxic activity of TSC24 and Dp44mT but not of 3-AP. This finding suggests possible synergy between the iron chelating and topoisomerase IIα inhibiting activity of the compounds. However, further investigation using separate agents, the iron chelator deferoxamine and the topoisomerase II inhibitor epirubicin, did not support any synergy for the interaction of iron chelation and topoisomerase II inhibition. Furthermore, TSC24 was shown to induce DNA degradation in bloodstream forms of T. brucei indicating that the mechanism of trypanotoxic activity of the compound is topoisomerase II independent. In conclusion, the data support further investigation of thiosemicarbazone iron chelators with dual activity as lead compounds for anti-trypanosomal drug development. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy.

    Science.gov (United States)

    Liu, Renfa; Jing, Lijia; Peng, Dong; Li, Yong; Tian, Jie; Dai, Zhifei

    2015-01-01

    The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy. In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method. The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity. Besides, the high loading content of Mn(II) chelates makes the nanoparticles attractive T1 contrast agent in magnetic resonance imaging (MRI). In vivo photoacoustic imaging (PAI) results showed that the nanoparticles could be efficiently accumulated in tumor site in 24 h after systematic administration, which was further validated by MRI tests. The subsequent photothermal therapy of cancer in vivo was achieved without inducing any observed side effects. Therefore, the copper sulfide nanoparticles functionalized with Mn(II) chelate hold great promise as a theranostic nanomedicine for MR/PA dual-modal imaging guided photothermal therapy of cancer.

  3. Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy

    Science.gov (United States)

    Liu, Renfa; Jing, Lijia; Peng, Dong; Li, Yong; Tian, Jie; Dai, Zhifei

    2015-01-01

    The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy. In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method. The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity. Besides, the high loading content of Mn(II) chelates makes the nanoparticles attractive T1 contrast agent in magnetic resonance imaging (MRI). In vivo photoacoustic imaging (PAI) results showed that the nanoparticles could be efficiently accumulated in tumor site in 24 h after systematic administration, which was further validated by MRI tests. The subsequent photothermal therapy of cancer in vivo was achieved without inducing any observed side effects. Therefore, the copper sulfide nanoparticles functionalized with Mn(II) chelate hold great promise as a theranostic nanomedicine for MR/PA dual-modal imaging guided photothermal therapy of cancer. PMID:26284144

  4. Automated determination of uranium(VI) at ultra trace levels exploiting flow techniques and spectrophotometric detection using a liquid waveguide capillary cell

    Energy Technology Data Exchange (ETDEWEB)

    Avivar, Jessica; Ferrer, Laura; Cerda, Victor [University of the Balearic Islands, Chemistry Department, Palma (Spain); Casas, Montserrat [University of the Balearic Islands Cra, Physics Department and IFISC-CSIC, Palma (Spain)

    2010-05-15

    Rapid and fully automated multisyringe flow-injection analysis (MSFIA) with a multi-pumping flow system (MPFS) coupled to a long path-length liquid waveguide capillary cell (LWCC) is proposed for the determination of uranium(VI) at ultra trace levels. On-line separation and pre-concentration of uranium is carried out by means of a TRU resin. After elution, uranium(VI) is spectrophotometrically detected after reaction with arsenazo-III. Combination of the MSFIA and MPFS techniques with the TRU-resin enables the analysis to be performed in a short time, using large sample volumes and achieving high selectivity and sensitivity levels. A detection limit of 12.6 ng L{sup -1} (ppt) is reached for a 100-mL sample volume. The versatility of the proposed method also enables pre-concentration of variable sample volumes, enabling application of the analysis to a wide concentration range. Reproducibility of better than 5% and a resin durability of 40 injections should be emphasized. The developed method was successfully applied to different types of environmental sample matrices with recoveries between 95 and 108%. (orig.)

  5. Changes in the Kinetics of Uranium(VI) Sorption Reactions to Mineral Surfaces in the Presence of Fulvic Acid

    Science.gov (United States)

    Honeyman, B. D.; Tinnacher, R. M.

    2010-12-01

    In this study, we investigate changes in the kinetics of uranium(VI) sorption reactions to silica sand due to the presence of fulvic acid, a recalcitrant natural organic matter fraction. On the field scale, local contact times between metal contaminants and bulk mineral phases may often be too short to attain full sorption equilibria. Hence, kinetic limitations for surface reactions need to be included in predictive transport models. Natural organic matter is ubiquitous in the environment and can substantially influence metal sorption and transport behavior in saturated porous media. However, at this point little is known about potential effects of organic matter on metal sorption kinetics. Therefore, we investigated the kinetics of uranium(VI) (U(VI)) sorption onto a pretreated silica sand in the absence and presence of fulvic acid in lab-scale experiments. Furthermore, experimental data were simulated in pseudo-first order kinetic models in order to determine the characteristic times for U(VI) sorption reactions under various chemical conditions. Last, speciation modeling allowed for a qualitative assessment of dominant U(VI) solution species as a function of organic ligand concentrations and pH. Results indicate that U(VI) surface reactions are slowed down in the presence of low concentrations of fulvic acid (0.4 and 4.3 mg/l TOC), at conditions where U(VI)-fulvic acid solution complexes can be neglected. This kinetic behavior can be attributed to the competition of U(VI) and fulvic acid for a limited number of fast-sorbing surface sites. In contrast, metal sorption reactions seem to be faster relative to the binary metal-mineral system at a high FA concentration (26 mg/l TOC) and pH conditions where a substantial fraction of U(VI)-FA solution complexes is expected. In this case, U(VI) and fulvic acid sorption kinetics appear to be very similar, which suggests the formation of ternary U(VI)-FA-surface complexes. Hence, kinetic sorption data indicate a change in

  6. Effects of novel neuroprotective and neurorestorative multifunctional drugs on iron chelation and glucose metabolism.

    Science.gov (United States)

    Pollak, Yulia; Mechlovich, Danit; Amit, Tamar; Bar-Am, Orit; Manov, Irena; Mandel, Silvia A; Weinreb, Orly; Meyron-Holtz, Esther G; Iancu, Theodore C; Youdim, Moussa B H

    2013-01-01

    Iron accumulation and iron-related oxidative stress are involved in several pathological conditions and provide a rationale for the development of iron chelators as novel promising therapeutic strategies. Thus, we have recently synthesized multifunctional non-toxic, brain permeable iron chelating compounds, M30 and HLA20, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase (MAO)-B inhibitor, rasagiline and the antioxidant-iron chelating moiety of an 8-hydroxyquinoline derivative of the iron chelator, VK28. Here, we examined the hepatic regulatory effects of these novel compounds using two experimental approaches: chelation activity and glucose metabolism parameters. The present study demonstrated that M30 and HLA20 significantly decreased intracellular iron content and reduced ferritin expression levels in iron-loaded hepatoma Hep3B cells. In electron microscopy analysis, M30 was shown to reduce the electron-dense deposits of siderosomes by ~30 %, as well as down-regulate cytosolic ferritin particles observed in iron-overloaded cells. In vivo studies demonstrated that M30 administration (1 mg/kg, P.O. three times a week) reduced hepatic ferritin levels; increased hepatic insulin receptor and glucose transporter-1 levels and improved glucose tolerance in C57BL/6 mice and in a mouse model of type-2 diabetes, the ob/ob (leptin(-/-)). The results clearly indicate that the novel multifunctional drugs, especially M30, display significant capacity of chelating intracellular iron and regulating glucose metabolism parameters. Such effects can have therapeutic significance in conditions with abnormal local or systemic iron metabolism, including neurological diseases.

  7. Recent developments centered on orally active iron chelators

    Directory of Open Access Journals (Sweden)

    Robert Hider

    2014-09-01

    Full Text Available Over the past twenty years there has been a growing interest in the orally active iron chelators, deferiprone and deferasirox, both have been extensively studied. The ability of these compounds to mobilize iron from the heart and endocrine tissue has presented the clinician with some advantages over desferrioxamine, the first therapeutic iron chelator. Other orally active iron chelators are currently under development. The critical features necessary for the design of therapeutically useful orally active iron chelators are presented in this review, together with recent studies devoted to the design of such chelators. This newly emerging range of iron chelators will enable clinicians to apply iron chelation methodology to other disease states and to begin to design personalized chelation regimes.

  8. Chelates for Micronutrient Nutrition among Crops

    Indian Academy of Sciences (India)

    playa major role in bringing stability and sustainability in the production of food grains, pulses and oilseeds in the coming decade. The three main classes of micronutrient sources are inorganic, synthetic chelates and organic complexes. Inorganic sources such as sulphates of Cu, Mn, Fe and Zn are the most common.

  9. Chelates for Micronutrient Nutrition among Crops

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 7. Chelates for Micronutrient Nutrition among Crops. B S Sekhon. General Article Volume 8 Issue 7 July 2003 pp 46-53. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/008/07/0046-0053. Keywords.

  10. CHELATING LIGANDS: ENHANCERS OF QUALITY AND PURITY ...

    African Journals Online (AJOL)

    Nwokem et al.

    ABSTRACT. The quality of biogas depends largely on the percentage of methane and hydrogen sulphide gas present. High concentration of hydrogen sulphide results in low quality biogas. This work employed the use of chelating ligands in scrubbing hydrogen sulphide gas while improving the yield of methane gas.

  11. Complexation of Gluconate with Uranium(VI) in Acidic Solutions: Thermodynamic Study with Structural Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhicheng; Helms, G.; Clark, S. B.; Tian, Guoxin; Zanonato, PierLuigi; Rao, Linfeng

    2009-01-05

    Within the pC{sub H} range of 2.5 to 4.2, gluconate forms three uranyl complexes UO{sub 2}(GH{sub 4}){sup +}, UO{sub 2}(GH{sub 3})(aq), and UO{sub 2}(GH{sub 3})(GH{sub 4}){sup -}, through the following reactions: (1) UO{sub 2}{sup 2+} + GH{sub 4}{sup -} = UO{sub 2}(GH{sub 4}){sup +}, (2) UO{sub 2}{sup 2+} + GH{sub 4}{sup -} = UO{sub 2}(GH{sub 3})(aq) + H{sup +}, and (3) UO{sub 2}{sup 2+} + 2GH{sub 4}{sup -} = UO{sub 2}(GH{sub 3})(GH{sub 4}){sup -} + H{sup +}. Complexes were inferred from potentiometric, calorimetric, NMR, and EXAFS studies. Correspondingly, the stability constants and enthalpies were determined to be log {Beta}{sub 1} = 2.2 {+-} 0.3 and {Delta}H{sub 1} = 7.5 {+-} 1.3 kJ mol{sup -1} for reaction (1), log {Beta}{sub 2} = -(0.38 {+-} 0.05) and {Delta}H{sub 2} = 15.4 {+-} 0.3 kJ mol{sup -1} for reaction (2), and log {Beta}{sub 3} = 1.3 {+-} 0.2 and {Delta}H{sub 3} = 14.6 {+-} 0.3 kJ mol{sup -1} for reaction (3), at I = 1.0 M NaClO{sub 4} and t = 25 C. The UO{sub 2}(GH{sub 4}){sup +} complex forms through the bidentate carboxylate binding to U(VI). In the UO{sub 2}(GH{sub 3})(aq) complex, hydroxyl-deprotonated gluconate (GH{sub 3}{sup 2-}) coordinates to U(VI) through the five-membered ring chelation. For the UO{sub 2}(GH{sub 3})(GH{sub 4}){sup -} complex, multiple coordination modes are suggested. These results are discussed in the context of trivalent and pentavalent actinide complexation by gluconate.

  12. Searching for new aluminium chelating agents: a family of hydroxypyrone ligands.

    Science.gov (United States)

    Toso, Leonardo; Crisponi, Guido; Nurchi, Valeria M; Crespo-Alonso, Miriam; Lachowicz, Joanna I; Mansoori, Delara; Arca, Massimiliano; Santos, M Amélia; Marques, Sérgio M; Gano, Lurdes; Niclós-Gutíerrez, Juan; González-Pérez, Josefa M; Domínguez-Martín, Alicia; Choquesillo-Lazarte, Duane; Szewczuk, Zbigniew

    2014-01-01

    Attention is devoted to the role of chelating agents in the treatment of aluminium related diseases. In fact, in spite of the efforts that have drastically reduced the occurrence of aluminium dialysis diseases, they so far constitute a cause of great medical concern. The use of chelating agents for iron and aluminium in different clinical applications has found increasing attention in the last thirty years. With the aim of designing new chelators, we synthesized a series of kojic acid derivatives containing two kojic units joined by different linkers. A huge advantage of these molecules is that they are cheap and easy to produce. Previous works on complex formation equilibria of a first group of these ligands with iron and aluminium highlighted extremely good pMe values and gave evidence of the ability to scavenge iron from inside cells. On these bases a second set of bis-kojic ligands, whose linkers between the kojic chelating moieties are differentiated both in terms of type and size, has been designed, synthesized and characterized. The aluminium(III) complex formation equilibria studied by potentiometry, electrospray ionization mass spectroscopy (ESI-MS), quantum-mechanical calculations and (1)H NMR spectroscopy are here described and discussed, and the structural characterization of one of these new ligands is presented. The in vivo studies show that these new bis-kojic derivatives induce faster clearance from main organs as compared with the monomeric analog. © 2013.

  13. Salivary proline-rich protein may reduce tannin-iron chelation: a systematic narrative review.

    Science.gov (United States)

    Delimont, Nicole M; Rosenkranz, Sara K; Haub, Mark D; Lindshield, Brian L

    2017-01-01

    Tannins are often cited for antinutritional effects, including chelation of non-heme iron. Despite this, studies exploring non-heme iron bioavailability inhibition with long-term consumption have reported mixed results. Salivary proline-rich proteins (PRPs) may mediate tannin-antinutritional effects on non-heme iron bioavailability. To review evidence regarding biochemical binding mechanisms and affinity states between PRPs and tannins, as well as effects of PRPs on non-heme iron bioavailability with tannin consumption in vivo. Narrative systematic review and meta-analysis. Common themes in biochemical modeling and affinity studies were collated for summary and synthesis; data were extracted from in vivo experiments for meta-analysis. Thirty-two studies were included in analysis. Common themes that positively influenced tannin-PRP binding included specificity of tannin-PRP binding, PRP and tannin stereochemistry. Hydrolyzable tannins have different affinities than condensed tannins when binding to PRPs. In vivo, hepatic iron stores and non-heme iron absorption are not significantly affected by tannin consumption ( d  = -0.64-1.84; -2.7-0.13 respectively), and PRP expression may increase non-heme iron bioavailability with tannin consumption. In vitro modeling suggests that tannins favor PRP binding over iron chelation throughout digestion. Hydrolyzable tannins are not representative of tannin impact on non-heme iron bioavailability in food tannins because of their unique structural properties and PRP affinities. With tannin consumption, PRP production is increased, and may be an initial line of defense against tannin-non-heme iron chelation in vivo . More research is needed to compare competitive binding of tannin-PRP to tannin-non-heme iron complexes, and elucidate PRPs' role in adaption to non-heme iron bioavailability in vivo.

  14. IRON CHELATION THERAPY IN THALASSEMIA SYNDROMES

    Directory of Open Access Journals (Sweden)

    Paolo Cianciulli

    2009-06-01

    Full Text Available Transfusional hemosiderosis is a frequent complication in patients with transfusion dependent chronic diseases such as  thalassemias and severe type of sickle cell diseases. As there are no physiological mechanisms to excrete the iron contained in transfused red cells (1 unit of blood contains approximately 200 mg of iron the excess of iron is stored in various organs. Cardiomyopathy is the most severe complication covering more than 70% of the causes of death of thalassemic patients. Although the current reference standard iron chelator deferoxamine (DFO has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Despite poor compliance, because of the inconvenience of subcutaneous infusion, DFO improved considerably the survival and quality of life of patients with thalassemia. Deferiprone since 1998 and Deferasirox since 2005 were licensed for clinical use. The oral chelators have a better compliance because of oral use, a comparable efficacy to DFO in iron excretion and probably a better penetration to myocardial cells. Considerable increase in iron excretion was documented with combination therapy of DFO and Deferiprone. The proper use of the three chelators will improve the prevention and treatment of iron overload, it will reduce  complications, and improve survival and quality of life of transfused patients

  15. Investigations on the molecular structure of water dissolved and hematite-sorbed uranium(VI) complexes with aliphatic (hydroxo-) carboxylic acids. Combination of several spectroscopic techniques with factor analysis and quantum chemical calculations; Untersuchungen zur Struktur von wassergeloesten und an Haematit sorbierten Uran(VI)-Komplexen mit aliphatischen (Hydroxy-) Carbonsaeuren. Kombination verschiedener spektroskopischer Methoden mit Faktorenanalyse und quantenchemischen Berechnungen

    Energy Technology Data Exchange (ETDEWEB)

    Lucks, Christian

    2013-04-23

    This study is focussed on throwing light on the structures of uranium(VI) complexes with aliphatic (hydroxy-) carboxylic acids and on the structures of the sorption complexes on the iron mineral hematite in presence and absence of organic acids. The ternary system of hematite, uranium(VI), and organic ligand is very complicated, thus it is necessary to decompose it in binary systems. The results within these binary systems are used to better understand the complicated ternary system. Based on the comprehensive investigations on the aqueous uranium(VI) complexes, it is now possible to draw inferences from the structure of the carboxylic acid about the structure of the formed uranium(VI) complex in dependence of the pH. At first it has to be mentioned that uranium(VI) commonly gives pentagonal bipyramidal complexes. The pentaaquauranylion is formed by two axial oxygen atoms (O{sub ax}) at a distance of 1.76 Aa and five equatorial oxygen atoms (O{sub eq}) at 2.40 Aa stemming from coordinated water molecules. Due to complexation with organic ligands water is replaced by the ligand, thus the interatomic distances change. The results gained during all these investigations can help to better understand the interaction of uranium(VI) and carboxylic acids, and beyond that the sorption of uranium(VI) on hematite in the presence of carboxylic acids. Structures of the aqueous and sorption complexes are proposed. All these findings support the ongoing research on the transport behaviour of radioactive matter and may lead to more reliable risk assessment in connection with the permanent disposal of nuclear waste and the residues of uranium mining.

  16. Bp44mT: an orally active iron chelator of the thiosemicarbazone class with potent anti-tumour efficacy

    Science.gov (United States)

    Yu, Y; Rahmanto, Y Suryo; Richardson, DR

    2012-01-01

    BACKGROUND AND PURPOSE Our previous studies demonstrated that a thiosemicarbazone iron chelator (di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone; Dp44mT) possesses potent and selective anti-cancer activity but led to cardiotoxicity at non-optimal doses. In this study, we examined the in vivo anti-tumour efficacy and tolerability of a new-generation 2-benzoylpyridine thiosemicarbazone iron chelator (2-benzoylpyridine-4,4-dimethyl-3-thiosemicarbazone; Bp44mT) administered via the oral or i.v. routes. EXPERIMENTAL APPROACH BpT chelators were tested in vitro against human lung cancer cells (DMS-53) and in vivo in DMS-53 tumour xenografts in mice. The toxicity of Bp44mT in vivo and its effects on the expression of iron-regulated molecules involved in growth and cell cycle control were investigated. KEY RESULTS Administration of Bp44mT by either route resulted in marked dose-dependent inhibition of tumour growth. When administered at 50 mg·kg−1 via oral gavage three times per week for 23 days, the net xenograft growth was inhibited by 75%, compared with vehicle-treated mice. Toxicological examination showed reversible alterations including slight reduction of RBC count, with a decrease of liver and splenic iron levels, which confirmed iron chelation in vivo. Importantly, in contrast to Dp44mT, the chelator-treated mice did not show cardiac histological abnormalities. There was also no significant weight loss in mice, suggesting oral administration of Bp44mT was well tolerated. CONCLUSIONS AND IMPLICATIONS This is the first study to show that Bp44mT can be given orally with potent anti-tumour efficacy. Oral administration of a novel and effective chemotherapeutic agent provides the benefits of convenience for chronic dosing regimens. PMID:21658021

  17. Formation of a third phase in the extraction of uranium(VI) and plutonium(IV) nitrates into various diluents by bis(2-ethylhexyl)sulfoxide

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, J.P. (Radiochemistry Div., Bhabha Atomic Research Centre, Bombay (India)); Kedari, C.S. (Radiochemistry Div., Bhabha Atomic Research Centre, Bombay (India))

    1994-01-01

    The formation of a third phase in the extraction of large amounts of uranium(VI) and plutonium(IV) by bis(2-ethylhexyl)sulfoxide (BESO) into various hydrocarbon diluents was investigated over a wide range of experimental conditions. Solubility of both the extracted solvates UO[sub 2](NO[sub 3])[sub 2].2BESO and Pu(NO[sub 3])[sub 4].2BESO was maximum in polarizable benzene and the tendency to form third phase increased in the order: benzene < n-hexane < SST < dodecane. Usefulness of some commonly employed polar modifiers like tributylphosphate (TBP), 2-ethylhexanol and isodecanol on improving the metal solvate solubility was also assessed. (orig.)

  18. Neuroprotection of brain-permeable iron chelator VK-28 against intracerebral hemorrhage in mice.

    Science.gov (United States)

    Li, Qian; Wan, Jieru; Lan, Xi; Han, Xiaoning; Wang, Zhongyu; Wang, Jian

    2017-09-01

    Iron overload plays a key role in the secondary brain damage that develops after intracerebral hemorrhage (ICH). The significant increase in iron deposition is associated with the generation of reactive oxygen species (ROS), which leads to oxidative brain damage. In this study, we examined the protective effects of VK-28, a brain-permeable iron chelator, against hemoglobin toxicity in an ex vivo organotypic hippocampal slice culture (OHSC) model and in middle-aged mice subjected to an in vivo, collagenase-induced ICH model. We found that the effects of VK-28 were similar to those of deferoxamine (DFX), a well-studied iron chelator. Both decreased cell death and ROS production in OHSCs and in vivo, decreased iron-deposition and microglial activation around hematoma in vivo, and improved neurologic function. Moreover, compared with DFX, VK-28 polarized microglia to an M2-like phenotype, reduced brain water content, deceased white matter injury, improved neurobehavioral performance, and reduced overall death rate after ICH. The protection of VK-28 was confirmed in a blood-injection ICH model and in aged-male and young female mice. Our findings indicate that VK-28 is protective against iron toxicity after ICH and that, at the dosage tested, it has better efficacy and less toxicity than DFX does.

  19. Chelation therapy in intoxications with mercury, lead and copper

    DEFF Research Database (Denmark)

    Cao, yang; Skaug, Marit Aralt; Andersen, Ole

    2015-01-01

    In the present review we provide an update of the appropriate use of chelating agents in the treatment of intoxications with compounds of mercury, lead and copper. The relatively new chelators meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-propanesulphonate (DMPS) can effectively...... or tetrathiomolybdate may be more suitable alternatives today. In copper-toxicity, a free radical scavenger might be recommended as adjuvant to the chelator therapy...

  20. MYELODYSPLASTIC SYNDROMES AND IRON CHELATION THERAPY

    Directory of Open Access Journals (Sweden)

    Emanuele Angelucci

    2017-03-01

    Full Text Available Over recent decades we have been fortunate to witness the advent of new technologies and of an expanded knowledge and application of chelation therapies to the benefit of patients with iron overload. However, extrapolation of learnings from thalassemia to the myelodysplastic syndromes (MDS has resulted in a fragmented and uncoordinated clinical evidence base. We’re therefore forced to change our understanding of MDS, looking with other eyes to observational studies that inform us about the relationship between iron and tissue damage in these subjects. The available evidence suggests that iron accumulation is prognostically significant in MDS, but levels of accumulation historically associated with organ damage (based on data generated in the thalassemias are infrequent. Emerging experimental data have provided some insight into this paradox, as our understanding of iron-induced tissue damage has evolved from a process of progressive bulking of organs through high-volumes iron deposition, to one of ‘toxic’ damage inflicted through multiple cellular pathways. Damage from iron may therefore occur prior to reaching reference thresholds, and similarly, chelation may be of benefit before overt iron overload is seen. In this review, we revisit the science and clinical evidence for iron overload in MDS to better characterise the iron overload phenotype in these patients, which is distinct from the classical transfusional and non-transfusional iron overload syndrome. We hope this will provide a conceptual framework to better understand the complex associations between anemia, iron and clinical outcomes, to accelerate progress in this area.

  1. Potentials and drawbacks of chelate-enhanced phytoremediation of soils

    NARCIS (Netherlands)

    Römkens, P.F.A.M.; Bouwman, L.A.; Japenga, J.; Draaisma, C.

    2002-01-01

    Chelate-enhanced phytoremediation has been proposed as an effective tool for the extraction of heavy metals from soils by plants. However, side-effects related to the addition of chelates, e.g. metal leaching and effects on soil micro-organisms, were usually neglected. Therefore, greenhouse and

  2. Chelated ruthenium catalysts for Z-selective olefin metathesis.

    Science.gov (United States)

    Endo, Koji; Grubbs, Robert H

    2011-06-08

    We report the development of ruthenium-based metathesis catalysts with chelating N-heterocyclic carbene (NHC) ligands that catalyze highly Z-selective olefin metathesis. A very simple and convenient procedure for the synthesis of such catalysts has been developed. Intramolecular C-H bond activation of the NHC ligand, promoted by anion ligand substitution, forms the appropriate chelate for stereocontrolled olefin metathesis.

  3. Chelation Treatment for Autism Spectrum Disorders: A Systematic Review

    Science.gov (United States)

    Davis, Tonya N.; O'Reilly, Mark; Kang, Soyeon; Lang, Russell; Rispoli, Mandy; Sigafoos, Jeff; Lancioni, Giulio; Copeland, Daelynn; Attai, Shanna; Mulloy, Austin

    2013-01-01

    Chelation treatment is used to eliminate specific metals from the body, such as mercury. It has been hypothesized that mercury poisoning may be a factor in autism and data suggest that perhaps 7% of individuals with autism spectrum disorder (ASD) have received chelation treatment. It would therefore seem timely to review studies investigating the…

  4. Uranium(VI) speciation: modelling, uncertainty and relevance to bioavailability models. Application to uranium uptake by the gills of a freshwater bivalve; Speciation de l'uranium(6), modelisation, incertitude et implication pour les modeles de biodisponibilite. Application a l'accumulation dans les branchies d'un bivalve d'eau douce

    Energy Technology Data Exchange (ETDEWEB)

    Denison, F.H

    2004-07-01

    The effects of varying solution composition on the interactions between uranium(VI) and excised gills of the freshwater bivalve Corbicula fluminea have been investigated in well defined solution media. A significant reduction in the uptake of uranium was observed on increasing the concentrations of the uranium complexing ligands citrate and carbonate. Saturation kinetics as a function of uranium concentration at a pH value of 5.0 were observed, indicating that the uptake of uranium is a facilitated process, probably involving one or several trans-membrane transport systems. A relatively small change in the uptake of uranium was found as a function of pH (factor of ca. 2), despite the extremely large changes to the solution speciation of uranium within the range of pH investigated (5.0 - 7.5). A comprehensive review of the thermodynamic data relevant to the solution composition domain employed for this study was performed. Estimates of the uncertainties for the formation constants of aqueous uranium(VI) species were integrated into a thermodynamic database. A computer program was written to predict the equilibrium distribution of uranium(VI) in simple aqueous systems, using thermodynamic parameter mean-values. The program was extended to perform Monte Carlo and Quasi Monte Carlo uncertainty analyses, incorporating the thermodynamic database uncertainty estimates, to quantitatively predict the uncertainties inherent in predicting the solution speciation of uranium. The use of thermodynamic equilibrium modelling as a tool for interpreting the bioavailability of uranium(VI) was investigated. Observed uranium(VI) uptake behaviour was interpreted as a function of the predicted changes to the solution speciation of uranium. Different steady-state or pre-equilibrium approaches to modelling uranium uptake were tested. Alternative modelling approaches were also tested, considering the potential changes to membrane transport system activity or sorption characteristics on

  5. Quantitative measurement of metal chelation by fourier transform infrared spectroscopy

    Directory of Open Access Journals (Sweden)

    Monika E. Miller

    2015-12-01

    Full Text Available Nutritionally important minerals are more readily absorbed by living systems when complexed with organic acids, resulting in higher consumer demand and premium prices for these products. These chelated metals are produced by reaction of metal oxides and acids in aqueous solution. However, unreacted dry blends are sometimes misrepresented as metal chelates, when in reality they are only simple mixtures of the reactants typically used to synthesize them. This practice has increased interest in developing analytical methods that are capable of measuring the extent of metal chelation for quality control and regulatory compliance. We describe a novel method to rapidly measure the percent chelation of citric and malic acids with calcium, magnesium, and zinc. Utilization of attenuated total reflectance (FTIR-ATR provides for the direct, rapid measurement of solid samples. The inclusion of an internal standard allows independent determination of either free or chelated acids from integrated areas in a single spectrum.

  6. Treating Lead Toxicity: Possibilities beyond Synthetic Chelation

    Directory of Open Access Journals (Sweden)

    Shambhavi Tannir

    2013-01-01

    Full Text Available Lead, a ubiquitous metal, is one of the most abundant elements present on earth. Its easy availability and cost effectiveness made it an extremely popular component in the industrial revolution. However, its hazardous health effects were not considered at the time. Over the last few decades, with the adverse effects of lead coming to the forefront, nations across the world have started to recognize and treat lead toxicity. The most reliable and used method until now has been chelation therapy. Recent research has suggested the use of natural products and sources to treat lead poisoning with minimal or no side effects. This review has tried to summarize a few of the natural products/sources being investigated by various groups.

  7. Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment.

    LENUS (Irish Health Repository)

    Byrne, A T

    2009-11-03

    Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF(2)-chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06.

  8. Chelating ionic liquids for reversible zinc electrochemistry.

    Science.gov (United States)

    Kar, Mega; Winther-Jensen, Bjorn; Forsyth, Maria; MacFarlane, Douglas R

    2013-05-21

    Advanced, high energy-density, metal-air rechargeable batteries, such as zinc-air, are of intense international interest due to their important role in energy storage applications such as electric and hybrid vehicles, and to their ability to deal with the intermittency of renewable energy sources such as solar and wind. Ionic liquids offer a number of ideal thermal and physical properties as potential electrolytes in such large-scale energy storage applications. We describe here the synthesis and characterisation of a family of novel "chelating" ILs designed to chelate and solubilize the zinc ions to create electrolytes for this type of battery. These are based on quaternary alkoxy alkyl ammonium cations of varying oligo-ether side chains and anions such as p-toluene sulfonate, bis(trifluoromethylsulfonyl)amide and dicyanoamides. This work shows that increasing the ether chain length in the cation from two to four oxygens can increase the ionic conductivity and reduce the melting point from 67 °C to 15 °C for the tosylate system. Changing the anion also plays a significant role in the nature of the zinc deposition electrochemistry. We show that zinc can be reversibly deposited from [N(222(20201))][NTf2] and [N(222(202020201))][NTf2] beginning at -1.4 V and -1.7 V vs. SHE, respectively, but not in the case of tosylate based ILs. This indicates that the [NTf2] is a weaker coordinating anion with the zinc cation, compared to the tosylate anion, allowing the coordination of the ether chain to dominate the behavior of the deposition and stripping of zinc ions.

  9. Fixation kinetics of chelated and non-chelated zinc in semi-arid alkaline soils: application to zinc management

    Science.gov (United States)

    Udeigwe, Theophilus K.; Eichmann, Madeleine; Menkiti, Matthew C.

    2016-07-01

    This study was designed to examine the fixation pattern and kinetics of zinc (Zn) in chelated (ethylenediaminetetraacetic acid, EDTA) and non-chelated mixed micronutrient systems of semi-arid alkaline soils from the Southern High Plains, USA. Soils were characterized for a suite of chemical and physical properties and data obtained from extraction experiments fitted to various kinetic models. About 30 % more plant-available Zn was fixed in the non-chelated system within the first 14 days with only about 18 % difference observed between the two systems by day 90, suggesting that the effectiveness of the chelated compounds tended to decrease over time. The strengths of the relationships of change in available Zn with respect to other micronutrients (copper, iron, and manganese) were higher and more significant in the non-chelated system (average R2 of 0.83), compared to the chelated (average R2 of 0.42). Fixation of plant-available Zn was best described by the power-function model (R2 = 0.94, SE = 0.076) in the non-chelated system, and was poorly described by all the models examined in the chelated system. Reaction rate constants and relationships generated from this study can serve as important tools for micronutrient management and for future micronutrient modeling studies on these soils and other semi-arid regions of the world.

  10. Chelation: Harnessing and Enhancing Heavy Metal Detoxification—A Review

    Directory of Open Access Journals (Sweden)

    Margaret E. Sears

    2013-01-01

    Full Text Available Toxic metals such as arsenic, cadmium, lead, and mercury are ubiquitous, have no beneficial role in human homeostasis, and contribute to noncommunicable chronic diseases. While novel drug targets for chronic disease are eagerly sought, potentially helpful agents that aid in detoxification of toxic elements, chelators, have largely been restricted to overt acute poisoning. Chelation, that is multiple coordination bonds between organic molecules and metals, is very common in the body and at the heart of enzymes with a metal cofactor such as copper or zinc. Peptides glutathione and metallothionein chelate both essential and toxic elements as they are sequestered, transported, and excreted. Enhancing natural chelation detoxification pathways, as well as use of pharmaceutical chelators against heavy metals are reviewed. Historical adverse outcomes with chelators, lessons learned in the art of using them, and successes using chelation to ameliorate renal, cardiovascular, and neurological conditions highlight the need for renewed attention to simple, safe, inexpensive interventions that offer potential to stem the tide of debilitating, expensive chronic disease.

  11. Glyphosate, a chelating agent-relevant for ecological risk assessment?

    Science.gov (United States)

    Mertens, Martha; Höss, Sebastian; Neumann, Günter; Afzal, Joshua; Reichenbecher, Wolfram

    2018-01-02

    Glyphosate-based herbicides (GBHs), consisting of glyphosate and formulants, are the most frequently applied herbicides worldwide. The declared active ingredient glyphosate does not only inhibit the EPSPS but is also a chelating agent that binds macro- and micronutrients, essential for many plant processes and pathogen resistance. GBH treatment may thus impede uptake and availability of macro- and micronutrients in plants. The present study investigated whether this characteristic of glyphosate could contribute to adverse effects of GBH application in the environment and to human health. According to the results, it has not been fully elucidated whether the chelating activity of glyphosate contributes to the toxic effects on plants and potentially on plant-microorganism interactions, e.g., nitrogen fixation of leguminous plants. It is also still open whether the chelating property of glyphosate is involved in the toxic effects on organisms other than plants, described in many papers. By changing the availability of essential as well as toxic metals that are bound to soil particles, the herbicide might also impact soil life, although the occurrence of natural chelators with considerably higher chelating potentials makes an additional impact of glyphosate for most metals less likely. Further research should elucidate the role of glyphosate (and GBH) as a chelator, in particular, as this is a non-specific property potentially affecting many organisms and processes. In the process of reevaluation of glyphosate its chelating activity has hardly been discussed.

  12. Preparation of magnetic core-shell iron oxide@silica@nickel-ethylene glycol microspheres for highly efficient sorption of uranium(VI).

    Science.gov (United States)

    Tan, Lichao; Zhang, Xiaofei; Liu, Qi; Wang, Jun; Sun, Yanbo; Jing, Xiaoyan; Liu, Jingyuan; Song, Dalei; Liu, Lianhe

    2015-04-21

    We report a facile approach for the formation of magnetic core-shell iron oxide@silica@nickel-ethylene glycol (Fe3O4@SiO2@Ni-L) microspheres. The structure and morphology of Fe3O4@SiO2@Ni-L are characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen sorption isotherm. The composite possesses a high specific surface area of 382 m(2) g(-1). The obtained core/shell structure is composed of a superparamagnetic core with a strong response to external fields, which are recovered readily from aqueous solutions by magnetic separation. When used as the adsorbent for uranium(vi) in water, the as-prepared Fe3O4@SiO2@Ni-L multi-structural microspheres exhibit a high adsorption capacity, which is mainly attributed to the large specific surface area and typical mesoporous characteristics of Fe3O4@SiO2@Ni-L microspheres. This work provides a promising approach for the design and synthesis of multifunctional microspheres, which can be used for water treatment, as well as having other potential applications in a variety of biomedical fields including drug delivery and biosensors.

  13. Aminothiol multidentate chelators against Chagas disease.

    Science.gov (United States)

    Deharo, E; Loyevsky, M; John, C; Balanza, E; Ruiz, G; Muñoz, V; Gordeuk, V R

    2000-03-01

    Three compounds of an aminothiol family of iron chelators were examined for activity against trypomastigote (human) and epimastigote (vector) forms of Trypanosoma cruzi: tetraethyl and tetramethyl derivatives of ethane-1,2-bis (N-1-amino-3-ethyl butyl-3-thiol) (BAT-TE and BAT-TM) and N',N',N'-tris-(2-methyl-2-mercaptopriopyl)- 1,4,7-triazacyclonane (TAT). BAT-TE at 270 microM completely arrested the growth of trypomastigote forms in mouse blood stored at 4 degrees C for 24 h (IC(50) 67.7+/-7 microM), while BAT-TM arrested growth at 630 microM (IC(50) 158+/-17 microM) and TAT at concentrations >800 microM (IC(50) 415+/-55 microM). In T. cruzi-infected mice, BAT-TE and BAT-TM had no anti-trypanosomal activity in doses up to 200 mg/kg, whether the route of administration was intraperitoneal or oral, and TAT was not tested due to insufficient quantity. TAT had an IC(50) of 52+/-7 microM against the epimastigote forms while BAT-TM and BAT-TE were inhibitory only at concentrations >250 microM. The trypanocidal activity of BAT derivatives in blood stored at 4 degrees C makes these compounds potential candidates for the purpose of clearing donated blood of trypomastigotes. Copyright 2000 Academic Press.

  14. New Chelators for Low Temperature Al(18)F-Labeling of Biomolecules.

    Science.gov (United States)

    Cleeren, Frederik; Lecina, Joan; Billaud, Emilie M F; Ahamed, Muneer; Verbruggen, Alfons; Bormans, Guy M

    2016-03-16

    The Al(18)F labeling method is a relatively new approach that allows radiofluorination of biomolecules such as peptides and proteins in a one-step procedure and in aqueous solution. However, the chelation of the {Al(18)F}(2+) core with the macrocyclic chelators NOTA or NODA requires heating to 100-120 °C. Therefore, we have developed new polydentate ligands for the complexation of {Al(18)F}(2+) with good radiochemical yields at a temperature of 40 °C. The stability of the new Al(18)F-complexes was tested in phosphate buffered saline (PBS) at pH 7.4 and in rat serum. The stability of the Al(18)F-L3 complex was found to be comparable to that of the previously reported Al(18)F-NODA complex up to 60 min in rat serum. Moreover, the biodistribution of Al(18)F-L3 in healthy mice showed the absence of in vivo defluorination since no significant bone uptake was observed, whereas the major fraction of activity at 60 min p.i. was observed in liver and intestines, indicating hepatobiliary clearance of the radiolabeled ligand. The acyclic chelator H3L3 proved to be a good lead candidate for labeling of heat-sensitive biomolecules with fluorine-18. In order to obtain a better understanding of the different factors influencing the formation and stability of the complex, we carried out more in-depth experiments with ligand H3L3. As a proof of concept, we successfully conjugated the new AlF-chelator with the urea-based PSMA inhibitor Glu-NH-CO-NH-Lys to form Glu-NH-CO-NH-Lys(Ahx)L3, and a biodistribution study in healthy mice was performed with the Al(18)F-labeled construct. This new class of AlF-chelators may have a great impact on PET radiochemical space as it will stimulate the rapid development of new fluorine-18 labeled peptides and other heat-sensitive biomolecules.

  15. Chelation in metal intoxication XVI. Influence of chelating agents on chromate poisoned rats

    Energy Technology Data Exchange (ETDEWEB)

    Tandon, S.K.; Srivastava, L.

    1985-01-01

    The ability of selective polyaminocarboxylic acids and common drugs to reduce the body burden of chromium and restore Cr induced biochemical alterations in chromate intoxicated rats was investigated. 1,2 Cychlohexylene dinitrilotetraacetic acid (CDTA) and triethylenetetramine hexacetic acid (TTHA) were more effective than p-aminosalicylic acid (PAS) and isoniazid (INH) in enhancing urinary excretion of Cr, lowering hepatic and blood levels of Cr and restoring inhibited activity of hepatic aldolase. The chromate antidotal property of chelators seem to be related to the combination of nitrogen and oxygen as the electron donating centres.

  16. Chelation: Harnessing and Enhancing Heavy Metal Detoxification—A Review

    National Research Council Canada - National Science Library

    Sears, Margaret E

    2013-01-01

    .... While novel drug targets for chronic disease are eagerly sought, potentially helpful agents that aid in detoxification of toxic elements, chelators, have largely been restricted to overt acute poisoning...

  17. Comparing potential copper chelation mechanisms in Parkinson's disease protein

    Science.gov (United States)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2011-03-01

    We have implemented the nudged elastic band (NEB) as a guided dynamics framework for our real-space multigrid method of DFT-based quantum simulations. This highly parallel approach resolves a minimum energy pathway (MEP) on the energy hypersurface by relaxing intermediates in a chain-of-states. As an initial application we present an investigation of chelating agents acting on copper ion bound to α -synuclein, whose misfolding is implicated in Parkinson's disease (PD). Copper ions are known to act as highly effective misfolding agents in a-synuclein and are thus an important target in understanding PD. Furthermore, chelation therapy has shown promise in the treatment of Alzheimer's and other neuro-degenerative diseases with similar metal-correlated pathologies. At present, our candidate chelating agents include nicotine, curcumin and clioquinol. We examine their MEP activation barriers in the context of a PD onset mechanism to assess the viability of various chelators for PD remediation.

  18. Chelated Ruthenium Catalysts for Z-Selective Olefin Metathesis

    OpenAIRE

    Endo, Koji; Grubbs, Robert H

    2011-01-01

    We report the development of ruthenium-based metathesis catalysts with chelating N-heterocyclic carbene (NHC) ligands which catalyze highly Z-selective olefin metathesis. A very simple and convenient synthetic procedure of such a catalyst has been developed. An intramolecular C-H bond activation of the NHC ligand, which is promoted by anion ligand substitution, forms the appropriate chelate for stereo- controlled olefin metathesis.

  19. Removal of Fe3+ and Zn2+ from plasma metalloproteins by iron chelating therapeutics depicted with SEC-ICP-AES.

    Science.gov (United States)

    Sooriyaarachchi, Melani; Gailer, Jürgen

    2010-08-28

    The iron chelation therapy drugs desferrioxamine B (DFO) and deferiprone (DFP) are used to treat iron overload patients, but not much is known about their adverse effects on other essential metals in vivo. After the addition of a clinically relevant dose of DFP or an equimolar dose of DFO to human plasma in vitro, the mixtures were analyzed by size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES). Simultaneous detection of the emission lines of copper, iron and zinc allowed the visualization of changes that these drugs exerted at the metalloprotein level. After the addition of DFP, a AES can simultaneously provide insight into the efficacy of chelation therapy drugs and their adverse health effects at the metalloprotein level. Thus, SEC-ICP-AES emerges as a useful analytical tool to visualize health-relevant bioinorganic chemistry-related reactions of medicinal drugs in blood plasma in vitro.

  20. The Effect of Different Tea Varieties on Iron Chelation

    Science.gov (United States)

    Truong, S. K.; Karim, R.

    2016-12-01

    The chief objectives of this experiment are to distinguish which type of tea of four variants, pomegranate blackberry green, green, lemon chamomile (herbal), and earl grey (black), are capable of chelating the most iron (III) chloride (FeCl3) through titration. We hypothesized that if each tea variety chelates differing amounts of iron chloride, and if we conduct an experiment in which four different teas are mixed in the same amount of water, iron chloride, and iron chloride indicator EDTA, then the pomegranate blackberry green tea will bind to the most iron due to its large amount of fruit antioxidants. To summarize our methodology, we prepared three solutions of each tea, dissolved with 1 gram of FeCl3 to test three trials per tea variety. The chelation process took place overnight as teas cooled. Six drops of iron chloride indicator added to each solution began the titration. The necessary amount of 0.1M EDTA (ethylenediaminetetraacetic acid) drops required for each solution to turn to a universal amber color from its original dark tone indicates how many free iron molecules were left unbound by the tea solution. After careful analysis of the data, we discovered that blackberry pomegranate green tea possessed the best chelating abilities with 97.48% of FeCl3 adsorbed. Green tea followed with 96.67%. Herbal tea chelated 94.24% of the iron while earl grey absorbed the least amount at 93.43%. From our conclusion, we drew that since blackberry pomegranate green tea contained the highest amount of polyphenols and antioxidants as well as epigallocatechin gallate (EGCG) found in green teas, it was able to chelate the most amount of iron. The substances mentioned in blackberry pomegranate green tea possess the ability to form strong bonds with multiple heavy metals, such as iron (III) chloride atoms. Overall, each variety of tea contains different organic substances. Each of these substances possesses a unique chelating ability, determining how well the type of tea can

  1. A comparative evaluation of the chelators H4octapa and CHX-A″-DTPA with the therapeutic radiometal 90Y☆

    Science.gov (United States)

    Price, Eric W.; Edwards, Kimberly J.; Carnazza, Kathryn E.; Carlin, Sean D.; Zeglis, Brian M.; Adam, Michael J.; Orvig, Chris; Lewis, Jason S.

    2016-01-01

    Objectives To compare the radiolabeling performance, stability, and practical efficacy of the chelators CHX-A″-DTPA and H4octapa with the therapeutic radiometal 90Y. Methods The bifunctional chelators p-SCN-Bn-H4octapa and p-SCN-Bn-CHX-A″-DTPA were conjugated to the HER2-targeting antibody trastuzumab. The resulting immunoconjugates were radiolabeled with 90Y to compare radiolabeling efficiency, in vitro and in vivo stability, and in vivo performance in a murine model of ovarian cancer. Results High radiochemical yields (>95%) were obtained with 90Y-CHX-A′-DTPA-trastuzumab and 90Y-octapa-trastuzumab after 15 min at room temperature. Both 90Y-CHX-A″-DTPA-trastuzumab and 90Y-octapa-trastuzumab exhibited excellent in vitro and in vivo stability. Furthermore, the radioimmunoconjugates displayed high tumoral uptake values (42.3 ± 4.0%ID/g for 90Y-CHX-A″-DTPA-trastuzumab and 30.1 ± 7.4%ID/g for 90Y-octapa-trastuzumab at 72 h post-injection) in mice bearing HER2-expressing SKOV3 ovarian cancer xenografts. Finally, 90Y radioimmunotherapy studies performed in tumor-bearing mice demonstrated that 90Y-CHX-A″-DTPA-trastuzumab and 90Y-octapa-trastuzumab are equally effective therapeutic agents, as treatment with both radioimmunoconjugates yielded substantially decreased tumor growth compared to controls. Conclusions Ultimately, this work demonstrates that the acyclic chelators CHX-A″-DTPA and H4octapa have comparable radiolabeling, stability, and in vivo performance, making them both suitable choices for applications requiring 90Y. PMID:27419360

  2. Chelation therapy for the management of diabetic complications: a hypothesis and a proposal for clinical laboratory assessment of metal ion homeostasis in plasma.

    Science.gov (United States)

    Frizzell, Norma; Baynes, John W

    2014-01-01

    In a recent article, we presented the hypothesis that decompartmentalized metal ions are a major contributor to the development of diabetic complications and supported the use of chelation therapy for the treatment of diabetic complications [Nagai R, Murray DB, Metz TO, Baynes JW. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications. Diabetes 2012;61:549-59]. Evidence in support of this hypothesis included the observation that many drugs used in the treatment of diabetes are chelators, that advanced glycation end product (AGE) inhibitors and AGE breakers lack carbonyl-trapping or AGE-breaker activity but are potent chelators, and that simple copper chelators inhibit vascular pathology in diabetes and aging. In the present article, we extend this hypothesis, proposing the interplay between copper and iron in the development of pathology in diabetes and other chronic age-related diseases, including atherosclerosis and neurodegenerative diseases. We also discuss the need and provide a framework for the development of a clinical laboratory test to assess plasma autoxidative catalytic activity and transition metal homeostasis in vivo.

  3. Chemical speciation of uranium(VI) in marine environments: complexation of calcium and magnesium ions with [(UO{sub 2})(CO{sub 3}){sub 3}]{sup 4-} and the effect on the extraction of uranium from seawater

    Energy Technology Data Exchange (ETDEWEB)

    Endrizzi, Francesco; Rao, Linfeng [Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States)

    2014-10-27

    The interactions of Ca{sup 2+} and Mg{sup 2+} with [UO{sub 2}(CO{sub 3}){sub 3}]{sup 4-} were studied by calcium ion selective electrode potentiometry and spectrophotometry. The stability constants of ternary Ca-UO{sub 2}-CO{sub 3} and Mg-UO{sub 2}-CO{sub 3} complexes were determined with calcium ion selective electrode potentiometry and optical absorption spectrophotometry, respectively. The enthalpies of complexation for two successive complexes, [CaUO{sub 2}(CO{sub 3}){sub 3}]{sup 2-} and [Ca{sub 2}UO{sub 2}(CO{sub 3}){sub 3}](aq), were determined for the first time by microcalorimetry. The data help to revise the speciation of uranium(VI) species under seawater conditions. In contrast to the previously accepted assumption that the highly negatively charged [UO{sub 2}(CO{sub 3}){sub 3}]{sup 4-} is the dominant species, the revised speciation indicates that the dominant aqueous uranium(VI) species under seawater conditions is the neutral [Ca{sub 2}UO{sub 2}(CO{sub 3}){sub 3}](aq). The results have a significant impact on the strategies for developing efficient sorption processes to extract uranium from seawater. (copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. REGIONAL SIDEROSIS: A NEW CHALLENGE FOR IRON CHELATION THERAPY

    Directory of Open Access Journals (Sweden)

    Zvi Ioav Cabantchik

    2013-12-01

    Full Text Available The traditional role of iron chelation therapy has been to reduce body iron burden via chelation of excess metal from organs and fluids and its excretion via biliary-fecal and/or urinary routes. In their present use for hemosiderosis, chelation regimens might not be suitable for treating disorders of iron maldistribution, as those are characterized by toxic islands of siderosis appearing in a background of normal or subnormal iron levels (e.g. sideroblastic anemias, neuro- and cardio-siderosis in Friedreich ataxia- and neurosiderosis in Parkinson’s disease. We aimed at clearing local siderosis from aberrant labile metal that promotes oxidative damage, without interfering with essential local functions or with hematological iron-associated properties. For this purpose we introduced a conservative mode of iron chelation based on dual activity based on scavenging labile metal but also redeploying it to cell acceptors or to physiological transferrin. The scavenging and redeployment mode of action was designed both for correcting aberrant iron distribution and also for minimizing/preventing systemic loss of chelated metal. We first examine cell models that recapitulate iron maldistribution and associated dysfunctions identified with Friedreich ataxia and Parkinson’s disease and use them to explore the ability of the double-acting agent deferiprone, an orally active chelator, to mediate iron scavenging and redeployment and thereby causing functional improvement. We subsequently evaluate the concept in translational models of disease and finally assess its therapeutic potential in prospective double-blind pilot clinical trials. We claim that any chelator applied to diseases of regional siderosis, cardiac, neuronal or endocrine ought to preserve both systemic and regional iron levels. The proposed deferiprone-based therapy has provided a paradigm for treating regional types of siderosis without affecting hematological parameters and systemic

  5. Nanoencapsulation of DMSA monoester for better therapeutic efficacy of the chelating agent against arsenic toxicity.

    Science.gov (United States)

    Yadav, Abhishek; Mathur, Rashi; Samim, Mohammed; Lomash, Vinay; Kushwaha, Pramod; Pathak, Uma; Babbar, Anil Kumar; Flora, Swaran Jeet Singh; Mishra, Anil Kumar; Kaushik, Mahabir Parshad

    2014-04-01

    Exposure to toxic metals remains a widespread occupational and environmental problem in world. Chelation therapy is a mainstream treatment used to treat heavy metal poisoning. This paper describes the synthesis, characterization and therapeutic evaluation of monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)-encapsulated polymeric nanoparticles as a detoxifying agent for arsenic poisoning. Polymeric nanoparticles entrapping the DMSA monoester, which can evade the reticulo-endothelial system and have a long circulation time in the blood, were prepared. Particle characterization was carried out by transmission electron microscopy and dynamic light scattering. An in vivo study was conducted to investigate the therapeutic efficacy of MiADMSA-encapsulated polymeric nanoparticles (nano- MiADMSA; 50 mg/kg orally for 5 days) and comparison drawn with bulk MiADMSA. Swiss albino mice exposed to sodium arsenite for 4 weeks were treated for 5 days to evaluate alterations in blood, brain, kidney and liver oxidative stress variables. The study also evaluated the histopathological changes in tissues and the chelating potential of the nanoformulation. Our results show that nano-MiADMSA have a narrow size distribution in the 50-nm range. We observed an enhanced chelating potential of nano-MiADMSA compared with bulk MiADMSA as evident in the reversal of biochemical changes indicative of oxidative stress and efficient removal of arsenic from the blood and tissues. Histopathological changes and urinary 8-OHdG levels also prove better therapeutic efficacy of the novel formulation for arsenic toxicity. The results from our study show better therapeutic efficacy of nano-MiADMSA in removing arsenic burden from the brain and liver.

  6. Combined use of flow cytometry and microscopy to study the interactions between the gram-negative betaproteobacterium Acidovorax facilis and uranium(VI)

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, U., E-mail: u.gerber@hzdr.de [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Resource Ecology, P.O. Box 510119, 01314 Dresden (Germany); Zirnstein, I. [Research Institute of Leather and Plastic Sheeting (FILK) gGmbH, Meissner Ring 1-5, 09599 Freiberg (Germany); Krawczyk-Bärsch, E. [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Resource Ecology, P.O. Box 510119, 01314 Dresden (Germany); Lünsdorf, H. [Helmholtz Centre for Infection Research, Central Facility for Microscopy, Inhoffenstr. 7, D-38124 Braunschweig (Germany); Arnold, T. [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Resource Ecology, P.O. Box 510119, 01314 Dresden (Germany); Merroun, M.L. [University of Granada, Department of Microbiology, Campus Fuentenueva, E-18071 Granada (Spain)

    2016-11-05

    Highlights: • Acidovorax facilis is able to remove 130 mg U/g dry biomass from solution. • Kinetically temperature-dependent uranium removal was studied. • Cell viability and metabolic activity was tested by flow cytometry. • Uranium was removed by active biosorption and passive bioaccumulation. - Abstract: The former uranium mine Königstein (Saxony, Germany) is currently in the process of remediation by means of controlled underground flooding. Nevertheless, the flooding water has to be cleaned up by a conventional wastewater treatment plant. In this study, the uranium(VI) removal and tolerance mechanisms of the gram-negative betaproteobacterium Acidovorax facilis were investigated by a multidisciplinary approach combining wet chemistry, flow cytometry, and microscopy. The kinetics of uranium removal and the corresponding mechanisms were investigated. The results showed a biphasic process of uranium removal characterized by a first phase where 95% of uranium was removed within the first 8 h followed by a second phase that reached equilibrium after 24 h. The bacterial cells displayed a total uranium removal capacity of 130 mg U/g dry biomass. The removal of uranium was also temperature-dependent, indicating that metabolic activity heavily influenced bacterial interactions with uranium. TEM analyses showed biosorption on the cell surface and intracellular accumulation of uranium. Uranium tolerance tests showed that A. facilis was able to withstand concentrations up to 0.1 mM. This work demonstrates that A. facilis is a suitable candidate for in situ bioremediation of flooding water in Königstein as well as for other contaminated waste waters.

  7. Ab initio coordination chemistry for nickel chelation motifs.

    Science.gov (United States)

    Sudan, R Jesu Jaya; Kumari, J Lesitha Jeeva; Sudandiradoss, C

    2015-01-01

    Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition. Coordination chemistry provides a way to understand metal association in biological structures. In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences. This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences. Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture. The analysis revealed histidine as the most favored residue in nickel coordination. The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals. Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination. The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture. In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns. Nickel binding sequence motifs were noted to be organism specific and protein class specific. As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins. The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies.

  8. Ab initio coordination chemistry for nickel chelation motifs.

    Directory of Open Access Journals (Sweden)

    R Jesu Jaya Sudan

    Full Text Available Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition. Coordination chemistry provides a way to understand metal association in biological structures. In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences. This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences. Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture. The analysis revealed histidine as the most favored residue in nickel coordination. The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals. Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination. The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture. In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns. Nickel binding sequence motifs were noted to be organism specific and protein class specific. As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins. The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies.

  9. Supercritical Fluid Extraction of Metal Chelate: A Review.

    Science.gov (United States)

    Ding, Xin; Liu, Qinli; Hou, Xiongpo; Fang, Tao

    2017-03-04

    Supercritical fluid extraction (SFE), as a new green extraction technology, has been used in extracting various metal species. The solubilities of chelating agents and corresponding metal chelates are the key factors which influence the efficiency of SFE. Other main properties of them such as stability and selectivity are also reviewed. The extraction mechanisms of mainly used chelating agents are explained by typical examples in this paper. This is the important aspect of SFE of metal ions. Moreover, the extraction efficiencies of metal species also depend on other factors such as temperature, pressure, extraction time and matrix effect. The two main complexation methods namely in-situ and on-line chelating SFE are described in detail. As an efficient chelating agent, tributyl phosphate-nitric acid (TBP-HNO 3 ) complex attracts much attention. The SFE of metal ions, lanthanides and actinides as well as organometallic compounds are also summarized. With the proper selection of ligands, high efficient extraction of metal species can be obtained. As an efficient sample analysis method, supercritical fluid chromatography (SFC) is introduced in this paper. Recently, the extraction method combining ionic liquids (ILs) with supercritical fluid has been becoming a novel technology for treating metal ions. The kinetics related to SFE of metal species is discussed with some specific examples.

  10. Neuroprotective Role of a Novel Copper Chelator against Aβ42 Induced Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Sandeep Kumar Singh

    2013-01-01

    Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disease and associated with the extracellular deposits of amyloid-β peptide in hippocampus region. Metal ions like Cu, Fe and Zn are known to associate with the amyloid beta (Aβ at high concentration and interaction of these ions with soluble and aggregated forms of Aβ peptide help in development of AD. Here we showed Cu mediated neurotoxicity in the eye tissues of transgenic Drosophila expressing human amyloid β and its rescue through a novel Cu chelator. In this context, we have synthesised and characterized the compound L 2,6-Pyridinedicarboxylic acid, 2,6-bis[2-[(4-carboxyphenyl methylene] hydrazide] by Mass spectra (MS and Elemental analysis (EA. The Cu chelation potential of the compound L is tested in vivo in Drosophila. Oral administration of Copper to the transgenic larvae resulted in severe degeneration in eye tissues, which was rescued by the supplementation of compound L. The levels of anti-oxidant markers like SOD and MDA were measured in compound L treated flies and found a significant rescue (P<0.001. Further rescue of the eye degeneration phenotypes as revealed by SEM affirm the role of copper in Aβ toxicity. Hence, use of compound L, an amidoamine derivative, could be a possible therapeutic measure for Aβ induced neurotoxicity.

  11. Zinc and zinc chelators modify taurine transport in rat retinal cells.

    Science.gov (United States)

    Márquez, Asarí; Urbina, Mary; Lima, Lucimey

    2014-11-01

    Zinc regulates Na(+)/Cl(-)-dependent transporters, similar to taurine one, such as those for dopamine, serotonin and norepinephrine. This study examined the ex vivo effect of zinc (ZnSO4), N,N,N,N-tetraquis-(2-piridilmetil)etilendiamino (TPEN) and diethylenetriaminepenta-acetic acid (DTPA), intracellular and extracellular zinc chelators, respectively, on rat retina [(3)H]taurine transport. Isolated cells were incubated in Locke solution with 100 nM of [(3)H]taurine for 25 s. Different concentrations of ZnSO4 (0.5-200 μM) were used. Low concentrations of ZnSO4 (30 and 40 μM) increased the transport, while higher concentrations (100, 150 and 200 μM) decreased it. Various concentrations of TPEN (1-200 μM) were added. Intermediate concentrations of TPEN (10-60 μM) significantly decreased [(3)H]taurine transport. The presence of TPEN, 20 μM, plus ZnSO4 reversed the effect of TPEN alone. Several concentrations of DTPA (1-500 μM) were also investigated. Reduction of transport took place at high concentrations of the chelator (100, 250 and 500 μM). DTPA, 500 μM, plus ZnSO4, did not modify the effect of it. These results indicate that zinc modulates taurine transport in a concentration-dependent manner, directly acting on the transporter or by forming taurine-zinc complexes in cell membranes.

  12. Comparison of bifunctional chelates for {sup 64}Cu antibody imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Cara L.; Crisp, Sarah; Bensimon, Corinne [MDS Nordion, Vancouver, BC (Canada); Yapp, Donald T.T.; Ng, Sylvia S.W. [British Columbia Cancer Agency Research Centre, Vancouver, BC (Canada); University of British Columba, The Faculty of Pharmaceutical Sciences, Vancouver, BC (Canada); Sutherland, Brent W. [British Columbia Cancer Agency Research Centre, Vancouver, BC (Canada); Gleave, Martin [Prostate Centre at Vancouver General Hospital, Vancouver, BC (Canada); Jurek, Paul; Kiefer, Garry E. [Macrocyclics Inc., Dallas, TX (United States)

    2010-11-15

    Improved bifunctional chelates (BFCs) are needed to facilitate efficient {sup 64}Cu radiolabeling of monoclonal antibodies (mAbs) under mild conditions and to yield stable, target-specific agents. The utility of two novel BFCs, 1-Oxa-4,7,10-triazacyclododecane-5-S-(4-isothiocyanatobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA), for mAb imaging with {sup 64}Cu were compared to the commonly used S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (p-SCN-Bn-DOTA). The BFCs were conjugated to trastuzumab, which targets the HER2/neu receptor. {sup 64}Cu radiolabeling of the conjugates was optimized. Receptor binding was analyzed using flow cytometry and radioassays. Finally, PET imaging and biodistribution studies were done in mice bearing either HER2/neu-positive or HER2/neu-negative tumors. {sup 64}Cu-Oxo-DO3A- and PCTA-trastuzumab were prepared at room temperature in >95% radiochemical yield (RCY) in <30 min, compared to only 88% RCY after 2 h for the preparation of {sup 64}Cu-DOTA-trastuzumab under the same conditions. Cell studies confirmed that the immunoreactivity of the mAb was retained for each of the bioconjugates. In vivo studies showed that {sup 64}Cu-Oxo-DO3A- and PCTA-trastuzumab had higher uptake than the {sup 64}Cu-DOTA-trastuzumab at 24 h in HER2/neu-positive tumors, resulting in higher tumor to background ratios and better tumor images. By 40 h all three of the {sup 64}Cu-BFC-trastuzumab conjugates allowed for clear visualization of the HER2/neu-positive tumors but not the negative control tumor. The antibody conjugates of PCTA and Oxo-DO3A were shown to have superior {sup 64}Cu radiolabeling efficiency and stability compared to the analogous DOTA conjugate. In addition, {sup 64}Cu-PCTA and Oxo-DO3A antibody conjugates may facilitate earlier imaging with greater target to background ratios than

  13. Eltrombopag: a powerful chelator of cellular or extracellular iron(III) alone or combined with a second chelator.

    Science.gov (United States)

    Vlachodimitropoulou, Evangelia; Chen, Yu-Lin; Garbowski, Maciej; Koonyosying, Pimpisid; Psaila, Bethan; Sola-Visner, Martha; Cooper, Nichola; Hider, Robert; Porter, John

    2017-10-26

    Eltrombopag (ELT) is a thrombopoietin receptor agonist reported to decrease labile iron in leukemia cells. Here we examine the previously undescribed iron(III)-coordinating and cellular iron-mobilizing properties of ELT. We find a high binding constant for iron(III) (log β 2 =35). Clinically achievable concentrations (1 µM) progressively mobilized cellular iron from hepatocyte, cardiomyocyte, and pancreatic cell lines, rapidly decreasing intracellular reactive oxygen species (ROS) and also restoring insulin secretion in pancreatic cells. Decrements in cellular ferritin paralleled total cellular iron removal, particularly in hepatocytes. Iron mobilization from cardiomyocytes exceeded that obtained with deferiprone, desferrioxamine, or deferasirox at similar iron-binding equivalents. When combined with these chelators, ELT enhanced cellular iron mobilization more than additive (synergistic) with deferasirox. Iron-binding speciation plots are consistent with ELT donating iron to deferasirox at clinically relevant concentrations. ELT scavenges iron citrate species faster than deferasirox, but rapidly donates the chelated iron to deferasirox, consistent with a shuttling mechanism. Shuttling is also suggested by enhanced cellular iron mobilization by ELT when combined with the otherwise ineffective extracellular hydroxypyridinone chelator, CP40. We conclude that ELT is a powerful iron chelator that decreases cellular iron and further enhances iron mobilization when combined with clinically available chelators. © 2017 by The American Society of Hematology.

  14. NHS-MAS{sub 3}: a bifunctional chelator alternative to NHS-MAG{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Chang, F.; Qu, T.; Rusckowski, M.; Hnatowich, D.J

    1999-04-01

    This laboratory uses an N-hydroxysuccinimide derivative of S-acetylmercaptoacetyltriglycine (NHS-MAG{sub 3}) to conjugate amines for subsequent labeling with {sup 99m}Tc. However, the synthesis from triglycerine is general and not restricted to this tripeptide. We had earlier selected a small number of alternative tripeptides and synthesized the corresponding NHS derivatives. Each was then evaluated in a search for bifunctional chelators with properties superior to NHS-MAG{sub 3}, such as lower serum protein binding or improved stability to cysteine challenge. Based on these preliminary results, NHS-S-acetylmercaptoacetyltriserine (NHS-MAS{sub 3}) was selected for further investigation. We have now conjugated this bifunctional chelator to biocytin and to an amine-derivatized peptide nucleic acid (PNA). Both carriers were also conjugated with NHS-MAG{sub 3} under identical conditions and all were labeled with {sup 99m}Tc at neutral pH and at boiling temperature while the conjugated PNAs were radiolabelled at neutral pH and at room temperature. Regardless of the chelator, reverse phase HPLC radiochromatograms of the labeled biotins and PNAs after purification showed a single peak. However, by size exclusion HPLC, the radiochromatograms always showed several peaks even after purification, but the MAS{sub 3} radiochromatograms were less complicated. For biotin and PNA both, radiolabeling via MAS{sub 3} showed improved {sup 99m}Tc stability in 37 deg. C serum and in cysteine solution. The four preparations were administered to mice implanted in one thigh with avidin beads (biotins) or complementary PNA beads (PNAs). At 5 h post-administration, no significant differences were observed in the targeting of PNA beads between the two chelators, however the target thigh/normal thigh ratio was significantly higher for MAS{sub 3}-biotin compared to MAG{sub 3}-biotin. We conclude that labeling biocytin and amine-derivatized PNA with NHS-MAS{sub 3} compared to NHS-MAG{sub 3

  15. Efficacy of chelation therapy to remove aluminium intoxication.

    Science.gov (United States)

    Fulgenzi, Alessandro; De Giuseppe, Rachele; Bamonti, Fabrizia; Vietti, Daniele; Ferrero, Maria Elena

    2015-11-01

    There is a distinct correlation between aluminium (Al) intoxication and neurodegenerative diseases (ND). We demonstrated how patients affected by ND showing Al intoxication benefit from short-term treatment with calcium disodium ethylene diamine tetraacetic acid (EDTA) (chelation therapy). Such therapy further improved through daily treatment with the antioxidant Cellfood. In the present study we examined the efficacy of long-term treatment, using both EDTA and Cellfood. Slow intravenous treatment with the chelating agent EDTA (2 g/10 mL diluted in 500 mL physiological saline administered in 2 h) (chelation test) removed Al, which was detected (using inductively coupled plasma mass spectrometry) in urine samples collected from patients over 12 h. Patients that revealed Al intoxication (expressed in μg per g creatinine) underwent EDTA chelation therapy once a week for ten weeks, then once every two weeks for a further six or twelve months. At the end of treatment (a total of 22 or 34 chelation therapies, respectively), associated with daily assumption of Cellfood, Al levels in the urine samples were analysed. In addition, the following blood parameters were determined: homocysteine, vitamin B12, and folate, as well as the oxidative status e.g. reactive oxygen species (ROS), total antioxidant capacity (TAC), oxidized LDL (oxLDL), and glutathione. Our results showed that Al intoxication reduced significantly following EDTA and Cellfood treatment, and clinical symptoms improved. After treatment, ROS, oxLDL, and homocysteine decreased significantly, whereas vitamin B12, folate and TAC improved significantly. In conclusion, our data show the efficacy of chelation therapy associated with Cellfood in subjects affected by Al intoxication who have developed ND.

  16. Development of a new radiolabel (lead-203) and new chelating agents for labeling monoclonal anntibodies for imaging

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.; Mease, R.C.; Meinken, G.E.; Mausner, L.F.; Steplewski, Z.

    1988-01-01

    High liver uptake and slow body clearance presently limit the usefulness of /sup 111/In labeled antibodies for tumor imaging. We have investigated /sup 203/Pb as an alternate and better antibody label. The DTPA and cyclohexyl EDTA (CDTA) conjugates of an anticolon carcinoma antibody, 17-1A were labeled (bicyclic anhydride method) with /sup 203/Pb and /sup 111/In with 60 and 90% labeling yields, respectively. The biodistribution of /sup 203/Pb-17-1A conjugates was compared with the corresponding /sup 111/In-labeled preparations and with /sup 203/Pb-DTPA, /sup 203/Pb-nitrate and nonrelevant antibody controls in normal and human tumor (SW948) xenografted nude mice at 24, and 96 hr. Lead-203-labeled CDTA and DTPA antibody conjugates gave similar in vivo distributions. Even though the lead bound to these chelate-antibody conjugates was more labile in serum and in vivo, compared to indium, it cleared much faster from the liver and the whole body. A new series of chelating agents based on the incorporation of a trans-1,2- diaminocyclohexane moiety into the carbon backbone of polyaminocarboxylates is being synthesized. These are expected to provide stronger complexing ability for lead and produce greater in vivo stability. These ligands are also expected to be superior to EDTA and DTPA for labeling antibodies with other radiometals, including indium. 32 refs., 3 tabs.

  17. Thiourea derivatives as chelating agents for bioconjugation of rhenium and technetium.

    Science.gov (United States)

    Gomez, J D Castillo; Hagenbach, A; Gerling-Driessen, U I M; Koksch, B; Beindorff, N; Brenner, W; Abram, U

    2017-10-31

    Potential tetradentate thiocarbamoylbenzamidine derivatives H4L have been synthesized from the corresponding benzimidoyl chlorides and triglycine. They are suitable chelating agents for the oxidotechnetium(v) and oxidorhenium(v) cores and form stable, neutral [MO(HL)] complexes with an equatorial SN3 coordination sphere and an additional, uncoordinated carboxylic group, which can be used for bioconjugation. Representatives of the rhenium and (99)Tc products have been isolated and analyzed with spectroscopic methods and X-ray diffraction. Bioconjugates of these complexes with angiotensin-II have been synthesized and structurally characterized. Analogous (99m)Tc complexes have been produced and tested in vitro and in vivo. The experiments confirm a considerable stability for the [(99m)Tc(HL)] product as well as for its bioconjugate and recommend this class of compounds for further bioconjugation studies towards clinical applications.

  18. Comparison of the octadentate bifunctional chelator DFO*-pPhe-NCS and the clinically used hexadentate bifunctional chelator DFO-pPhe-NCS for {sup 89}Zr-immuno-PET

    Energy Technology Data Exchange (ETDEWEB)

    Vugts, Danielle J.; Klaver, Chris; Sewing, Claudia; Poot, Alex J.; Adamzek, Kevin; Visser, Gerard W.M.; Dongen, Guus A.M.S. van [VU University Medical Center, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Huegli, Seraina; Mari, Cristina; Gasser, Gilles [University of Zurich, Department of Chemistry, Zurich (Switzerland); Valverde, Ibai E. [University of Basel Hospital, Division of Radiopharmaceutical Chemistry, Basel (Switzerland); Mindt, Thomas L. [Institute of Pharmaceutical Sciences, ETH Zurich, Zurich (Switzerland); General Hospital of Vienna, Ludwig Boltzmann Institute for Applied Diagnostics, Vienna (Austria)

    2017-02-15

    All clinical {sup 89}Zr-immuno-PET studies are currently performed with the chelator desferrioxamine (DFO). This chelator provides hexadentate coordination to zirconium, leaving two coordination sites available for coordination with, e.g., water molecules, which are relatively labile ligands. The unsaturated coordination of DFO to zirconium has been suggested to result in impaired stability of the complex in vivo and consequently in unwanted bone uptake of {sup 89}Zr. Aiming at clinical improvements, we report here on a bifunctional isothiocyanate variant of the octadentate chelator DFO* and the in vitro and in vivo comparison of its {sup 89}Zr-DFO*-mAb complex with {sup 89}Zr-DFO-mAb. The bifunctional chelator DFO*-pPhe-NCS was prepared from previously reported DFO* and p-phenylenediisothiocyanate. Subsequently, trastuzumab was conjugated with either DFO*-pPhe-NCS or commercial DFO-pPhe-NCS and radiolabeled with Zr-89 according to published procedures. In vitro stability experiments were carried out in saline, a histidine/sucrose buffer, and blood serum. The in vivo performance of the chelators was compared in N87 tumor-bearing mice by biodistribution studies and PET imaging. In 0.9 % NaCl {sup 89}Zr-DFO*-trastuzumab was more stable than {sup 89}Zr-DFO-trastuzumab; after 72 h incubation at 2-8 C 95 % and 58 % intact tracer were left, respectively, while in a histidine-sucrose buffer no difference was observed, both products were ≥ 92 % intact. In vivo uptake at 144 h post injection (p.i.) in tumors, blood, and most normal organs was similar for both conjugates, except for skin, liver, spleen, ileum, and bone. Tumor uptake was 32.59 ± 11.95 and 29.06 ± 8.66 % ID/g for {sup 89}Zr-DFO*-trastuzumab and {sup 89}Zr-DFO-trastuzumab, respectively. The bone uptake was significantly lower for {sup 89}Zr-DFO*-trastuzumab compared to {sup 89}Zr-DFO-trastuzumab. At 144 h p.i. for {sup 89}Zr-DFO*-trastuzumab and {sup 89}Zr-DFO-trastuzumab, the uptake in sternum was 0.92

  19. Antioxidant properties of modified rutin esters by DPPH, reducing power, iron chelation and human low density lipoprotein assays

    DEFF Research Database (Denmark)

    Lue, Bena-Marie; Nielsen, Nina Skall; Jacobsen, Charlotte

    2010-01-01

    system. With regards to in vivo considerations, a pre-treatment step confirmed that the ester bond linking rutin and acyl moieties was most susceptible to hydrolysis by digestive enzymes, while rutin itself was not degraded. Thus, acylation of rutin with medium or long chain fatty acids may result...... rutin compounds exhibited decreased reducing power and metal chelating abilities as compared to rutin. Conversely, investigations on the oxidation of human low density lipoprotein (LDL) revealed that rutin laurate was most effective in inhibiting oxidation by prolonging LDL lag time for an in vitro...

  20. Characterization of Tumor-Avid Antibody Fragments Genetically Engineered for Mono-Specific Radionuclide Chelation

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, T.P.

    2003-12-31

    The successful clinical application of targeted-radiopharmaceuticals depends on the development of molecules that optimize tumor specific radionuclide deposition and minimize non-specific organ irradiation. To this end, this proposal outlines a research effort to identify and evaluate novel antibodies and antibody fragments that bind breast tumors. The tumor-avid antibodies will be investigated for as imaging and therapeutic agents and to gain a better understanding of the pharmacokinetics and metabolism of radiolabeled tumor-avid antibody fragments through the use of site-specifically labeled molecules. Antibodies or antibody fragments, that bind breast carcinoma carbohydrate antigens, will be obtained from hybridoma or bacteriophage library screening. More specifically, antibody fragments that bind the carcinoma-associated Thomsen-Friedenreich (T) antigen will be radiolabeled with {sup 99m}Tc and {sup 188}Re at a natural amino acid chelation site and will be investigated in vivo for their abilities to target human breast tumors. In addition, site-specific radiolabeled antibody fragments will be biosynthesized using misacylated suppressor tRNAs. Homogeneously radiolabeled populations of antibody fragments will be used to investigate the effects of radionuclide location and chelation chemistries on their biodistribution and metabolism. It is hypothesized that site-specifically radiolabeled antibody fragments will possess enhanced tumor imaging and therapeutic properties due to optimal label location and conjugation chemistries. New insights into the factors that govern antibody metabolism in vivo are also expected from this work. Results from these studies should enhance our ability to design and synthesize radiolabeled antibody fragments that have improved pharmacokinetic properties. The studies in this proposal involve basic research into the development of antibody-based radiopharmaceuticals, with the ultimate goal of application in humans. This type of basic

  1. Cellular growth and mitochondrial ultrastructure of leishmania (Viannia braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.

    Directory of Open Access Journals (Sweden)

    Camila Mesquita-Rodrigues

    Full Text Available Iron is an essential element for the survival of microorganisms in vitro and in vivo, acting as a cofactor of several enzymes and playing a critical role in host-parasite relationships. Leishmania (Viannia braziliensis is a parasite that is widespread in the new world and considered the major etiological agent of American tegumentary leishmaniasis. Although iron depletion leads to promastigote and amastigote growth inhibition, little is known about the role of iron in the biology of Leishmania. Furthermore, there are no reports regarding the importance of iron for L. (V. braziliensis.In this study, the effect of iron on the growth, ultrastructure and protein expression of L. (V. braziliensis was analyzed by the use of the chelator 2,2-dipyridyl. Treatment with 2,2-dipyridyl affected parasites' growth in a dose- and time-dependent manner. Multiplication of the parasites was recovered after reinoculation in fresh culture medium. Ultrastructural analysis of treated promastigotes revealed marked mitochondrial swelling with loss of cristae and matrix and the presence of concentric membranar structures inside the organelle. Iron depletion also induced Golgi disruption and intense cytoplasmic vacuolization. Fluorescence-activated cell sorting analysis of tetramethylrhodamine ester-stained parasites showed that 2,2-dipyridyl collapsed the mitochondrial membrane potential. The incubation of parasites with propidium iodide demonstrated that disruption of mitochondrial membrane potential was not associated with plasma membrane permeabilization. TUNEL assays indicated no DNA fragmentation in chelator-treated promastigotes. In addition, two-dimensional electrophoresis showed that treatment with the iron chelator induced up- or down-regulation of proteins involved in metabolism of nucleic acids and coordination of post-translational modifications, without altering their mRNA levels.Iron chelation leads to a multifactorial response that results in cellular

  2. Anti-oxidative, metal chelating and radical scavenging effects of ...

    African Journals Online (AJOL)

    Purpose: To evaluate protein hydrolysates and membrane ultrafiltration fractions of blue-spotted stingray for metal chelating and radical scavenging activities, as well as protection against oxidative protein damage. Methods: Stingray protein isolates were hydrolysed with alcalase, papain and trypsin for 3 h. Alcalase ...

  3. Chelating ligands: enhancers of quality and purity of biogas ...

    African Journals Online (AJOL)

    The quality of biogas depends largely on the percentage of methane and hydrogen sulphide gas present. High concentration of hydrogen sulphide results in low quality biogas. This work employed the use of chelating ligands in scrubbing hydrogen sulphide gas while improving the yield of methane gas. Experimental ...

  4. Evaluation of the chelating effect of methanolic extract of ...

    African Journals Online (AJOL)

    Background: The rate of lead poisoning has decreased in recent years due to increased health control in industries that use this metal. However, it is still a public health problem worldwide. The use of various plants with chelating properties has been a topic of research today. In traditional medicine, it is said that Coriandrum ...

  5. Iron chelating activity, phenol and flavonoid content of some ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-17

    Sep 17, 2008 ... Thalassemia major is characterized by anemia, iron overload, further potentiation of reactive oxygen species (ROS) and damage to major organs, especially the cardiovascular system. Antioxidant and other supportive therapies protect red blood cells (RBC) against antioxidant damage. Chelation therapy.

  6. Physiological response of Moringa oleifera to stigmasterol and chelated zinc

    Directory of Open Access Journals (Sweden)

    KARIMA GAMAL EL-DIN

    2012-11-01

    Full Text Available El-Moursi A, Talaat IM, Bekheta MA, Gamal El-Din K. 2012. Physiological response of Moringa oleifera to stigmasterol and chelated zinc. Nusantara Bioscience 4: 118-123. Two pot experiments were carried out in the screen of the National Research Centre, Dokki, Giza, Egypt, during two successive seasons (2009/2010 and 2010/2011, respectively to study the effect of foliar spray with chelated zinc (100, 200 and 300 mg/L and stigmasterol (50, 100 and 150 mg/L on growth and chemical constituents of moringa plants. The results indicated that treatment of plants with 300 mg/L chelated zinc or 150 mg/L stigmasterol significantly influenced the vegetative growth of moringa plants. The same treatments also significantly increased total sugars%, total protein%, total phosphorous and microelements contents in the leaves. The changes in the pattern of protein electrophoresis (SDS-PAGE extracted from the newly formed leaves of moringa plants treated with different concentrations of chelated Zinc (Zn or stigmasterol showed beneficial influences for improving plant growth, leaves quality and quantity.

  7. Iron chelation excludes protein synthesis inhibition in the ...

    African Journals Online (AJOL)

    We have compared the trypanocidal properties of four antibiotics that show bactericidal activities by destabilizing ribosome-mRNA complex to inhibit protein synthesis. Tetracycline and oxytetracycline that have iron chelating properties extended the lifespan of trypanosome infected rats from 6 and 5 days of control to 15 and ...

  8. Laccase Immobilization by Chelated Metal Ion Coordination Chemistry

    Directory of Open Access Journals (Sweden)

    Qingqing Wang

    2014-09-01

    Full Text Available In this work, amidoxime polyacrylonitrile (AOPAN nanofibrous membrane was prepared by a reaction between PAN nanofibers and hydroxylamine hydrochloride. The AOPAN nanofibrous membranes were used for four metal ions (Fe3+, Cu2+, Ni2+, Cd2+ chelation under different conditions. Further, the competition of different metal ions coordinating with AOPAN nanofibrous membrane was also studied. The AOPAN chelated with individual metal ion (Fe3+, Cu2+, Ni2+, Cd2+ and also the four mixed metal ions were further used for laccase (Lac immobilization. Compared with free laccase, the immobilized laccase showed better resistance to pH and temperature changes as well as improved storage stability. Among the four individual metal ion chelated membranes, the stability of the immobilized enzymes generally followed the order as Fe–AOPAN–Lac > Cu–AOPAN–Lac > Ni–AOPAN–Lac > Cd–AOPAN–Lac. In addition, the immobilized enzyme on the carrier of AOPAN chelated with four mixed metal ions showed the best properties.

  9. Sequestration of zinc oxide by fimbrial designer chelators

    DEFF Research Database (Denmark)

    Kjærgaard, Kristian; Sørensen, Jack K; Schembri, Mark

    2000-01-01

    Type 1 fimbriae are surface organelles of Escherichia coli. By engineering a structural component of the fimbriae, FimH, to display a random peptide library, we were able to isolate metal-chelating bacteria. A library consisting of 4 x 10(7) independent clones was screened for binding to Zn...

  10. Chelator induced phytoextraction and in situ soil washing of Cu

    Energy Technology Data Exchange (ETDEWEB)

    Kos, Bostjan; Lestan, Domen

    2004-11-01

    In a soil column experiment, we investigated the effect of 5 mmol kg{sup -1} soil addition of citric acid, ethylenediamine tetraacetate (EDTA), diethylenetriamine-pentaacetate (DTPA) and [S,S]-stereoisomer of ethylenediamine-disuccinate (EDDS) on phytoextraction of Cu from a vineyard soil with 162.6 mg kg{sup -1} Cu, into the test plant Brassica rapa var. pekinensis. We also examined the use of a horizontal permeable barrier, composed of layers of nutrient enriched sawdust and apatite, for reduction of chelator induced Cu leaching. The addition of all chelators, except citric acid, enhanced Cu mobility and caused leaching of 19.5-23% of initial total Cu from the soil column. However, Cu plant uptake did not increase accordingly; the most effective was the EDDS treatment, in which plant Cu concentration reached 37.8{+-}1.3 mg kg{sup -1} Cu and increased by 3.3-times over the control treatment. The addition of none of the chelators in the concentration range from 5 to 15 mmol kg{sup -1} exerted any toxic effect on respiratory soil microorganisms. When EDDS was applied into the columns with horizontal permeable barriers, only 0.53{+-}0.32% of the initial total Cu was leached. Cu (36.7%) was washed from the 18 cm soil layer above the barrier and accumulated in the barrier. Our results indicate that rather than for a reduction of Cu leaching during rather ineffective chelate induced Cu phytoextraction, horizontal permeable barriers could be more effective in a new remediation technique of controlled in situ soil washing of Cu with biodegradable chelates.

  11. Unexpected effect of dry olive leaf extract on the level of DNA damage in lymphocytes of lead intoxicated workers, before and after CaNa2EDTA chelation therapy.

    Science.gov (United States)

    Čabarkapa, Andrea; Dekanski, Dragana; Živković, Lada; Milanović-Čabarkapa, Mirjana; Bajić, Vladan; Topalović, Dijana; Giampieri, Francesca; Gasparrini, Massimiliano; Battino, Maurizio; Spremo-Potparević, Biljana

    2017-08-01

    The CaNa2EDTA chelation therapy is often practiced with antioxidant supplementation. Dry olive leaf extract (DOLE) is natural product with antioxidant and DNA protective properties. The effects of DOLE on the levels of DNA damage were investigated ex vivo in peripheral blood lymphocytes (PBLs) of 19 workers occupationally exposed to lead (Pb), before and after CaNa2EDTA chelation therapy. DOLE demonstrated pronounced radical scavenging activity in concentrations ≥1 mg/mL, and showed no genotoxicity per se, in concentrations 0.125-1 mg/mL. The level of DNA damage in PBLs of workers before chelation therapy was elevated (24.21 ± 14.26) compared to controls (6.0 ± 3.37). The incubation of PBLs before chelation therapy with selected concentration of DOLE lead to a severe increase of DNA damage (64.03 ± 20.96), exhibiting prooxidant rather than antioxidant effect. After the five-day CaNa2EDTA chelation regimen, DNA damage in PBLs of workers decreased (8.26 ± 4.62) significantly compared to baseline. Treatment of PBLs with DOLE after chelation, again produced high level of damage (41.82 ± 23.17) and the acute prooxidant effects of DOLE remained, but, DNA damage was less severe than before chelation. The DOLE exhibits prooxidant effect in presence of Pb in lymphocytes of exposed workers, and its effect is less pronounced following the removal of Pb after standard chelation therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Iron Binding and Iron Removal Efficiency of Desferrioxamine Based Polymeric Iron Chelators: Influence of Molecular Size and Chelator Density.

    Science.gov (United States)

    Hamilton, Jasmine L; Ul-Haq, Muhammad Imran; Creagh, A Louise; Haynes, Charles A; Kizhakkedathu, Jayachandran N

    2017-03-01

    Desferrioxamine (DFO) is a clinically approved, high affinity iron chelator used for the treatment of iron overload. Due to its short half-life and toxicity, DFO is administered for 8-12 h per day, 5-7 d per week. In this manuscript, the influence of molecular properties of hyperbranched polyglycerol (HPG)-DFO conjugates on their iron binding by isothermal titration calorimetry, iron removal efficiency from ferritin in presence and absence of a low molecular weight (MW) iron chelator, and protection against iron mediated oxidation of proteins is reported. The iron binding properties of HPG-DFO are slightly altered with size and DFO density of conjugates. The lower MW conjugate shows greater iron removal efficiency at room temperature, however, the efficacy of high MW conjugates increases at physiological temperature. The iron removal from ferritin by HPG-DFO conjugates increases significantly in presence of a low MW chelator, suggesting the potential of combination therapy. The molecular properties of the polymer scaffold also have influence on the prevention of iron mediated oxidation of proteins by the conjugates. The results therefore help to define the iron binding thermodynamics of HPG-DFO and their dependence on MW, and can be extended to improve the general understanding of polymeric chelator-iron interactions in situ. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Iron(III)-chelating resins. X. Iron detoxification of human plasma with iron(III)-chelating resins

    NARCIS (Netherlands)

    Feng, M.; Feng, M.H.; van der Does, L.; Bantjes, A.; Bantjes, A.

    1994-01-01

    Iron detoxification of human blood plasma was studied with resins containing desferrioxamine B (DFO) or 3-hydroxy-2-methyl-4(1H)-pyridinone (HMP) as iron(III)-chelating groups. The behaviour of four resins was investigated: DFO-Sepharose, HMP-Sepharose and crosslinked copolymers of

  14. Chelator-Free and Biocompatible Melanin Nanoplatform with Facile-Loading Gadolinium and Copper-64 for Bioimaging.

    Science.gov (United States)

    Hong, Su Hyun; Sun, Yao; Tang, Chu; Cheng, Kai; Zhang, Ruiping; Fan, Quli; Xu, Liying; Huang, Daijuan; Zhao, Anthony; Cheng, Zhen

    2017-07-19

    Development of a chelator-free and biocompatible platform for the facile construction of gadolinium 3+ (Gd 3+ )-loaded nanoparticle based probes for in vivo magentic resonance imaging (MRI) is still challenging. Herein, biocompatible Gd 3+ -loading melanin dots (Gd-M-dots) have been easily prepared and have exhibited good loading efficiency for Gd 3+ , high stability, and higher T 1 relaxivity compared to the commercial Gd-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) agent. Furthermore, Gd-M-dots showed unique photoacoustic (PA) properties, and a high PA imaging signal could be observed in vivo 1 h after injection. Compared to the traditional Gd 3+ -loaded nanoparticles for single-modal MRI, Gd-M-dots can also be radiolabeled with 64 Cu 2+ for positron emission tomography. Overall, these attractive properties of Gd-M-dots render them a promising imaging agent for various biomedical applications.

  15. Removal of cadmium from fish sauce using chelate resin.

    Science.gov (United States)

    Sasaki, Tetsuya; Araki, Ryohei; Michihata, Toshihide; Kozawa, Miyuki; Tokuda, Koji; Koyanagi, Takashi; Enomoto, Toshiki

    2015-04-15

    Fish sauce that is prepared from squid organs contains cadmium (Cd), which may be present at hazardous concentrations. Cd molecules are predominantly protein bound in freshly manufactured fish sauce, but are present in a liberated form in air-exposed fish sauce. In the present study, we developed a new method for removing both Cd forms from fish sauce using chelate resin and a previously reported tannin treatment. Sixteen-fold decreases in Cd concentrations were observed (0.78-0.05 mg/100 mL) following the removal of liberated Cd using chelate resin treatment, and the removal of protein-bound Cd using tannin treatment. Major nutritional components of fish sauce were maintained, including free amino acids and peptides, and angiotensin I-converting enzyme inhibitory and antioxidant activities. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Encapsulation and retention of chelated-copper inside hydrophobic nanoparticles

    DEFF Research Database (Denmark)

    Hervella, Pablo; Ortiz, Elisa Parra; Needham, David

    2016-01-01

    that our endogenous-inspired nanoparticle strategies for imaging and therapeutics are focused on encapsulating and retaining imaging ions such as copper inside novel hydrophobic nanoparticles. In this paper, we describe a new approach to label the core of hydrophobic nanoparticles composed of Glyceryl...... Trioleate (Triolein) with copper using the hydrophobic chelator Octaethyl porphyrin (OEP). RESEARCH PLAN AND METHODS: The research plan for this study was to (1) Formulate nanoparticles and control nanoparticle size using a modification of the solvent injection technique, named fast ethanol injection; (2...... to nanoparticles was >95% at low OEP-Cu concentrations. In the absence of OEP, copper was not detected in nanoparticles demonstrating the role of the hydrophobic chelator OEP in the encapsulation of the otherwise water-soluble copper inside lipid nanoparticles. (4) The in vitro retention upon incubation at 37°C...

  17. CITRIC ACID FERMENTATION OF SUGARS PURIFIED WITH CHELATING RESIN1

    Science.gov (United States)

    Noguchi, Yuichi; Johnson, Marvin J.

    1961-01-01

    Noguchi, Yuichi (University of Wisconsin, Madison), and Marvin J. Johnson. Citric acid fermentation of sugars purified with chelating resin. J. Bacteriol. 82:538–541. 1961.—A new, independently isolated strain of Aspergillus niger capable of giving high yields of citric acid in submerged culture was found to show the same behavior toward iron, zinc, and manganese as a previously studied strain. Citric acid accumulation did not occur in the presence of manganese. Best citric acid production was obtained in the presence of limited amounts of iron and zinc. Use of a chelating ion exchange resin was found to be an excellent method of removing polyvalent metals from sugars, either for analytical purposes or for fermentation. Commercial glucose, after resin treatment, gave citric acid yields of more than 80% when supplemented with iron and zinc. Unpurified glucose was converted to citric acid in good yields by mycelium grown on resin-treated glucose. PMID:14480219

  18. Macrocyclic chelator-coupled gastrin-based radiopharmaceuticals for targeting of gastrin receptor-expressing tumours

    Energy Technology Data Exchange (ETDEWEB)

    Good, Stephan; Wang, Xuejuan; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Walter, Martin A.; Mueller-Brand, Jan [University Hospital, Institute of Nuclear Medicine, Basel (Switzerland); Waser, Beatrice; Reubi, Jean-Claude [University of Berne, Department of Pathology, Bern (Switzerland); Behe, Martin P. [Philipps-University of Marburg, Department of Nuclear Medicine, Marburg (Germany)

    2008-10-15

    Diethylenetriamine-pentaacetic acid (DTPA)-coupled minigastrins are unsuitable for therapeutic application with the available {beta}-emitting radiometals due to low complex stability. Low tumour-to-kidney ratio of the known radiopharmaceuticals is further limiting their potency. We used macrocyclic chelators for coupling to increase complex stability, modified the peptide sequence to enhance radiolytic stability and studied tumour-to-kidney ratio and metabolic stability using {sup 111}In-labelled derivatives. Gastrin derivatives with decreasing numbers of glutamic acids were synthesised using {sup 111}In as surrogate for therapeutic radiometals for in vitro and in vivo studies. Gastrin receptor affinities of the {sup nat}In-metallated compounds were determined by receptor autoradiography using {sup 125}I-CCK as radioligand. Internalisation was evaluated in AR4-2J cells. Enzymatic stability was determined by incubating the {sup 111}In-labelled peptides in human serum. Biodistribution was performed in AR4-2J-bearing Lewis rats. IC{sub 50} values of the {sup nat}In-metallated gastrin derivatives vary between 1.2 and 4.8 nmol/L for all methionine-containing derivatives. Replacement of methionine by norleucine, isoleucine, methionine-sulfoxide and methionine-sulfone resulted in significant decrease of receptor affinity (IC{sub 50} between 9.9 and 1,195 nmol/L). All cholecystokinin receptor affinities were >100 nmol/L. All {sup 111}In-labelled radiopeptides showed receptor-specific internalisation. Serum mean-life times varied between 2.0 and 72.6 h, positively correlating with the number of Glu residues. All {sup 111}In-labelled macrocyclic chelator conjugates showed higher tumour-to-kidney ratios after 24 h (0.37-0.99) compared to {sup 111}In-DTPA-minigastrin 0(0.05). Tumour wash out between 4 and 24 h was low. Imaging studies confirmed receptor-specific blocking of the tumour uptake. Reducing the number of glutamates increased tumour-to-kidney ratio but resulted in

  19. Decontamination of process equipment using recyclable chelating solvent

    Energy Technology Data Exchange (ETDEWEB)

    Jevec, J.; Lenore, C.; Ulbricht, S. [Babcock & Wilcox, Co., R& DD, Alliance, OH (United States)

    1995-10-01

    The Department of Energy (DOE) is now faced with the task of meeting decontamination and decommissioning obligations at numerous facilities by the year 2019. Due to the tremendous volume of material involved, innovative decontamination technologies are being sought that can reduce the volumes of contaminated waste materials and secondary wastes requiring disposal. This report describes the results of the performance testing of chelates and solvents for the dissolution of uranium.

  20. Targeted Iron Chelation Will Improve Recovery after Spinal Cord Injury

    Science.gov (United States)

    2014-10-01

    life. Even though sub- stantial improvements in care have increased survival rates, people with SCI now live with significant deficits for many...can re- duce tissue damage and promote functional improvement (Klapka et al., 2005; Paterniti et al., 2010; Rathore et al., 2008; Schultke et al...attenuate post-SCI pathology ( Paterniti et al., 2010). A caveat, however, is that the drug was given 30 min prior to injury. The iron chelator

  1. Reducing power and iron chelating property of Terminalia chebula (Retz. alleviates iron induced liver toxicity in mice

    Directory of Open Access Journals (Sweden)

    Sarkar Rhitajit

    2012-08-01

    Full Text Available Abstract Background The 70% methanol extract of Terminalia chebula Retz. fruit (TCME was investigated for its in vitro iron chelating property and in vivo ameliorating effect on hepatic injury of iron overloaded mice. Methods The effect of fruit extract on Fe2+-ferrozine complex formation and Fe2+ mediated pUC-18 DNA breakdown was studied in order to find the in vitro iron chelating activity. Thirty-six Swiss Albino mice were divided into six groups of: blank, patient control and treated with 50, 100, 200 mg/kg b.w. of TCME and desirox (standard iron chelator drug with Deferasirox as parent compound. Evaluations were made for serum markers of hepatic damage, antioxidant enzyme, lipid per oxidation and liver fibrosis levels. The reductive release of ferritin iron by the extract was further studied. Results In vitro results showed considerable iron chelation with IC50 of 27.19 ± 2.80 μg/ml, and a significant DNA protection with [P]50 of 1.07 ± 0.03 μg/ml along with about 86% retention of supercoiled DNA. Iron-dextran injection (i.p. caused significant increase in the levels of the serum enzymes, viz., alanine aminotransferase (ALAT, aspartate aminotransferase (ASAT, alkaline phosphatase (ALP and Bilirubin, which were subsequently lowered by oral administration of 200 mg/kg b.w. dose of the fruit extract by 81.5%, 105.88%, 188.08% and 128.31%, respectively. Similarly, treatment with the same dose of the extract was shown to alleviate the reduced levels of liver antioxidant enzyme superoxide dismutase, catalase, glutathione S-transferase and non-enzymatic reduced glutathione, by 49.8%, 53.5%, 35.4% and 11% respectively, in comparison to the iron overloaded mice. At the same time, the fruit extract effectively lowered the iron-overload induced raised levels of lipid per oxidation, protein carbonyl, hydroxyproline and liver iron by 49%, 67%, 67% and 26%, respectively, with oral treatment of 200 mg/kg b.w. dose of TCME. The fruit extract

  2. Chelate-free metal ion binding and heat-induced radiolabeling of iron oxide nanoparticles.

    Science.gov (United States)

    Boros, Eszter; Bowen, Alice M; Josephson, Lee; Vasdev, Neil; Holland, Jason P

    2015-01-01

    A novel reaction for chelate-free, heat-induced metal ion binding and radiolabeling of ultra-small paramagnetic iron oxide nanoparticles (USPIOs) has been established. Radiochemical and non-radioactive labeling studies demonstrated that the reaction has a wide chemical scope and is applicable to p-, d- and f-block metal ions with varying ionic sizes and formal oxidation states from 2+ to 4+. Radiolabeling studies found that 89Zr-Feraheme (89Zr-FH or 89Zr-ferumoxytol) can be isolated in 93 ± 3% radiochemical yield (RCY) and >98% radiochemical purity using size-exclusion chromatography. 89Zr-FH was found to be thermodynamically and kinetically stable in vitro using a series of ligand challenge and plasma stability tests, and in vivo using PET/CT imaging and biodistribution studies in mice. Remarkably, ICP-MS and radiochemistry experiments showed that the same reaction conditions used to produce 89Zr-FH can be employed with different radionuclides to yield 64Cu-FH (66 ± 6% RCY) and 111In-FH (91 ± 2% RCY). Electron magnetic resonance studies support a mechanism of binding involving metal ion association with the surface of the magnetite crystal core. Collectively, these data suggest that chelate-free labeling methods can be employed to facilitate clinical translation of a new class of multimodality PET/MRI radiotracers derived from metal-based nanoparticles. Further, this discovery is likely to have broader implications in drug delivery, metal separation science, ecotoxicology of nanoparticles and beyond.

  3. The removal of strontium from the mouse by chelating agents

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, A.; Gomez, M.; Domingo, J.L.; Corbella, J.

    1989-07-01

    The effects of the chelating agents monosodium glutamate, Tiron, tartaric acid, ascorbic acid, 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6), 2,3-dimercaptosuccinic acid (DMSA), succinic acid, malic acid, ethylendiaminetetraacetic acid (EDTA), ethylenglycol-bis-(beta-amino-ethylether)-N,N'tetraacetic acid (EGTA), cyclohexane-diaminetetraacetic acid (CDTA) and diethylentria-minepentaacetic acid (DTPA) on the distribution and excretion of intraperitoneally injected strontium were investigated in male Swiss mice. Strontium nitrate was given at a dose equal to 3.78 mmol/kg and ten minutes after, chelators were administered intraperitoneally at doses approximately equal to one-fourth of their respective LD50 values. DTPA, followed by CDTA, EDTA and tartaric acid, was consistently the most effective in increasing the urinary excretion of strontium. Only ascorbic acid increased significantly the fecal excretion of strontium. CDTA, DTPA and ascorbic acid were also the most effective chelators in reducing the concentration of strontium found in various tissues. CDTA, DTPA and tartaric acid are the most effective agents of those tested in the removal of strontium after a single administration.

  4. Copper and Zinc Chelation as a Treatment of Alzheimer's Disease

    Science.gov (United States)

    Hodak, Miroslav; Bernholc, Jerry

    2014-03-01

    Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions of people in the U.S. The cause of the disease remains unknown, but amyloid- β (A β), a short peptide, is considered causal its pathogenesis. At cellular level, AD is characterized by deposits mainly composed of A β that also contain elevated levels of transition metals ions. Targeting metals is a promising new strategy for AD treatment, which uses moderately strong metal chelators to sequester them from A β or the environment. PBT2 is a chelating compound that has been the most promising in clinical trials. In our work, we use computer simulations to investigate complexes of a close analog of PBT2 with Cu2+ and Zn2+ ions. The calculations employ KS/FD DFT method, which combines Kohn-Sham DFT with the frozen-density DFT to achieve efficient description of explicit solvent beyond the first solvation shell. Our work is based on recent experiments and examines both 1:1 and 2:1 chelator-metal stochiometries detected experimentally. The results show that copper attaches more strongly than zinc, find that 1:1 complexes involve water in the first coordination shell and determine which one of several possible 2:1 geometries is the most preferable.

  5. Chelate forms of biometalls. Theoretical aspects of obtaining and characteristics

    Directory of Open Access Journals (Sweden)

    A. Kapustyan

    2017-04-01

    Full Text Available The problem of microelements bioavailability is highlighted and the correct ways of its solution are substantiated as a result of generalization of theoretical aspects of obtaining of the biometals chelate forms. The characteristics of the main biogenic elements, their physiological significance, electrochemical properties are presented. The main examples of the participation of biometals in various biological processes are given. The properties and the structure peculiarities of biometals coordination complexes are considered in detail. It is shown that in obtaining of biometals chelate forms, there is the mutual selectivity and the affinity of biometals and ligands. The main factors of obtaining a hard metal complex are given. Potential bioligands for obtaining bioavailable forms of microelements are detailed. Among them there are amino acids, peptides, proteins, nucleic acids, carbohydrates. The possible character of complexation depending on the nature of the bioligand is indicated. Practical examples of preparation of biometals mixed ligand complexes are given. The expediency of using metabolic products and processing of lactic acid bacteria as promising components of mixed ligand chelate complexes is substantiated. These substances contain in their composition a mass of potential donor atoms that are capable to form covalent and coordination bonds with biomethalles, and also possess high biological and immunotropic activities. The use of this system in the biocoordination compounds of the "metals of life" can provide a synergistic effect of the components, significantly to expand the range of their physiological activity and to increase the degree of assimilation by the body.

  6. Hydroxyurea could be a good clinically relevant iron chelator.

    Directory of Open Access Journals (Sweden)

    Khushnooma Italia

    Full Text Available Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.

  7. Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model.

    Science.gov (United States)

    Ferrer, Patricia; Tripathi, Abhai K; Clark, Martha A; Hand, Carla Cerami; Rienhoff, Hugh Young; Sullivan, David J

    2012-01-01

    Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S)3"-(HO)-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC(50)) of 6 µM for Plasmodium falciparum in contrast to the IC(50) for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials.

  8. Chelation therapy in Wilson's disease: from D-penicillamine to the design of selective bioinspired intracellular Cu(I) chelators.

    Science.gov (United States)

    Delangle, Pascale; Mintz, Elisabeth

    2012-06-07

    Wilson's disease is an orphan disease due to copper homeostasis dysfunction. Mutations of the ATP7B gene induces an impaired functioning of a Cu-ATPase, impaired Cu detoxification in the liver and copper overload in the body. Indeed, even though copper is an essential element, which is used as cofactor by many enzymes playing vital roles, it becomes toxic when in excess as it promotes cytotoxic reactions leading to oxidative stress. In this perspective, human copper homeostasis is first described in order to explain the mechanisms promoting copper overload in Wilson's disease. We will see that the liver is the main organ for copper distribution and detoxification in the body. Nowadays this disease is treated life-long by systemic chelation therapy, which is not satisfactory in many cases. Therefore the design of more selective and efficient drugs is of great interest. A strategy to design more specific chelators to treat localized copper accumulation in the liver will then be presented. In particular we will show how bioinorganic chemistry may help in the design of such novel chelators by taking inspiration from the biological copper cell transporters.

  9. In vitro and in vivo biological activities of iron chelators and gallium nitrate against Acinetobacter baumannii.

    Science.gov (United States)

    de Léséleuc, Louis; Harris, Greg; KuoLee, Rhonda; Chen, Wangxue

    2012-10-01

    We investigated the ability of compounds interfering with iron metabolism to inhibit the growth of Acinetobacter baumannii. Iron restriction with transferrin or 2,2-bipyridyl significantly inhibited A. baumannii growth in vitro. Gallium nitrate alone was moderately effective at reducing A. baumannii growth but became bacteriostatic in the presence of serum or transferrin. More importantly, gallium nitrate treatment reduced lung bacterial burdens in mice. The use of gallium-based therapies shows promise for the control of multidrug-resistant A. baumannii.

  10. Engineered Recognition of Tetravalent Zirconium and Thorium by Chelator-Protein Systems: Toward Flexible Radiotherapy and Imaging Platforms.

    Science.gov (United States)

    Captain, Ilya; Deblonde, Gauthier J-P; Rupert, Peter B; An, Dahlia D; Illy, Marie-Claire; Rostan, Emeline; Ralston, Corie Y; Strong, Roland K; Abergel, Rebecca J

    2016-11-21

    Targeted α therapy holds tremendous potential as a cancer treatment: it offers the possibility of delivering a highly cytotoxic dose to targeted cells while minimizing damage to surrounding healthy tissue. The metallic α-generating radioisotopes 225Ac and 227Th are promising radionuclides for therapeutic use, provided adequate chelation and targeting. Here we demonstrate a new chelating platform composed of a multidentate high-affinity oxygen-donating ligand 3,4,3-LI(CAM) bound to the mammalian protein siderocalin. Respective stability constants log β110 = 29.65 ± 0.65, 57.26 ± 0.20, and 47.71 ± 0.08, determined for the EuIII (a lanthanide surrogate for AcIII), ZrIV, and ThIV complexes of 3,4,3-LI(CAM) through spectrophotometric titrations, reveal this ligand to be one of the most powerful chelators for both trivalent and tetravalent metal ions at physiological pH. The resulting metal-ligand complexes are also recognized with extremely high affinity by the siderophore-binding protein siderocalin, with dissociation constants below 40 nM and tight electrostatic interactions, as evidenced by X-ray structures of the protein:ligand:metal adducts with ZrIV and ThIV. Finally, differences in biodistribution profiles between free and siderocalin-bound 238PuIV-3,4,3-LI(CAM) complexes confirm in vivo stability of the protein construct. The siderocalin:3,4,3-LI(CAM) assembly can therefore serve as a "lock" to consolidate binding to the therapeutic 225Ac and 227Th isotopes or to the positron emission tomography emitter 89Zr, independent of metal valence state.

  11. Uranium(VI) reduction by nanoscale zero-valent iron in anoxic batch systems: The role of Fe(II) and Fe(III)

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Sen; Chen, Yongheng; Xiang, Wu; Bao, Zhengyu; Liu, Chongxuan; Deng, Baolin

    2014-12-01

    The role of Fe(II) and Fe(III) on U(VI) reduction by nanoscale zerovalent iron (nanoFe0) was investigated using two iron chelators 1,10-phenanthroline and triethanolamine (TEA) under a CO2-free anoxic condition. The results showed U(VI) reduction was strongly inhibited by 1,10-phenanthroline and TEA in a pH range from 6.92 to 9.03. For instance, at pH 6.92 the observed U(VI) reduction rates decreased by 80.7% and 82.3% in the presence of 1,10-phenanthroline and TEA, respectively. The inhibition was attributed to the formation of stable complexes between 1,10-phenanthroline and Fe(II) or TEA and Fe(III). In the absence of iron chelators, U(VI) reduction can be enhanced by surface-bound Fe(II) on nanoFe0. Our results suggested that Fe(III) and Fe(II) probably acted as an electron shuttle to mediate the transfer of electrons from nanoFe0 to U(VI), therefore a combined system with Fe(II), Fe(III) and nanoFe0 can facilitate the U(VI) reductive immobilization in the contaminated groundwater.

  12. Complexation and Antimicrobial Studies of Some Divalent Metal Chelates

    Directory of Open Access Journals (Sweden)

    Suparna Ghosh

    2010-01-01

    Full Text Available Metal chelates of Ni(II and Cu(II with the ligand 5-acetamido-1,3,4-thiadiazole-2-sulphonamide have been synthesized. The isolated compounds have been characterized by elemental analysis, molar conductivity, magnetic moment, electronic and IR spectral studies. The analytical data reflects the metal to ligand stoichiometry to be 1: 2. The conductivity data of the complexes also suggests their non-electrolytic nature. The stability constants and free energy change for the complexes have been calculated.. Ligand and their complexes have been screened for their biological activity and the data show good activity of these complexes and ligands.

  13. Thesis The effect of flavoinoids and chosen chelators on the oxidation of natural substances

    OpenAIRE

    Malá, Marie

    2014-01-01

    Mgr. Marie Malá, Thesis The effect of flavoinoids and chosen chelators on the oxidation of natural substances, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, 2014, 67 pages. Thesis "The effect of flavonoids and chosen chelators on the oxidation of natural substances" deals with Fenton's reaction. For the needs of this work it means the effect of chosen flavonoids and chelators on oxidation of salicylic acid in presence of peroxide and ferrous ions. Chelators were efficie...

  14. Intrinsically Mn2+-Chelated Polydopamine Nanoparticles for Simultaneous Magnetic Resonance Imaging and Photothermal Ablation of Cancer Cells.

    Science.gov (United States)

    Miao, Zhao-Hua; Wang, Hui; Yang, Huanjie; Li, Zheng-Lin; Zhen, Liang; Xu, Cheng-Yan

    2015-08-12

    Theranostic agents for magnetic resonance imaging (MRI) guided photothermal therapy have attracted intensive interest in cancer diagnosis and treatment. However, the development of biocompatible theranostic agents with high photothermal conversion efficiency and good MRI contrast effect remains a challenge. Herein, PEGylated Mn2+-chelated polydopamine (PMPDA) nanoparticles were successfully developed as novel theranostic agents for simultaneous MRI signal enhancement and photothermal ablation of cancer cells, based on intrinsic manganese-chelating properties and strong near-infrared absorption of polydopamine nanomaterials. The obtained PMPDA nanoparticles showed significant MRI signal enhancement for both in vitro and in vivo imaging. Highly effective photothermal ablation of HeLa cells exposed to PMPDA nanoparticles was then achieved upon laser irradiation for 10 min. Furthermore, the excellent biocompatibility of PMPDA nanoparticles, because of the use of Mn2+ ions as diagnostic agents and biocompatible polydopamine as photothermal agents, was confirmed by a standard MTT assay. Therefore, the developed PMPDA nanoparticles could be used as a promising theranostic agent for MRI-guided photothermal therapy of cancer cells.

  15. Influence of a novel, versatile bifunctional chelator on theranostic properties of a minigastrin analogue.

    Science.gov (United States)

    Pfister, Joachim; Summer, Dominik; Rangger, Christine; Petrik, Milos; von Guggenberg, Elisabeth; Minazzi, Paolo; Giovenzana, Giovanni B; Aloj, Luigi; Decristoforo, Clemens

    2015-12-01

    6-[Bis(carboxymethyl)amino]-1,4-bis(carboxymethyl)-6-methyl-1,4-diazepane (AAZTA ) is a promising chelator with potential advantages over 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for radiopharmaceutical applications. Its mesocyclic structure enables fast radiolabelling under mild conditions with trivalent metals including not only (68)Ga for positron emission tomography (PET) but also (177)Lu and (111)In for single-photon emission computed tomography (SPECT) and radionuclide therapy. Here, we describe the evaluation of a bifunctional AAZTA derivative conjugated to a model minigastrin derivative as a potential theranostic agent. An AAZTA derivative with an aliphatic C9 chain as linker was coupled to a minigastrin, namely [AAZTA(0), D-Glu(1), desGlu(2-6)]-minigastrin (AAZTA-MG), and labelled with (68)Ga, (177)Lu and (111)In. The characterisation in vitro included stability studies in different media and determination of logD (octanol/PBS). Affinity determination (IC50) and cell uptake studies were performed in A431-CCK2R cells expressing the human CCK2 receptor. μPET/CT and ex vivo biodistribution studies were performed in CCK2 tumour xenograft-bearing nude mice and normal mice. AAZTA-MG showed high radiochemical yields for (68)Ga (>95 %), (177)Lu (>98 %) and (111)In (>98 %). The logD value of -3.7 for both [(68)Ga]- and [(177)Lu]-AAZTA-MG indicates a highly hydrophilic character. Stability tests showed overall high stability in solution with some degradation in human plasma for [(68)Ga]- and transchelation towards DTPA for and [(177)Lu]-AAZTA-MG. An IC50 value of 10.0 nM was determined, which indicates a high affinity for the CCK2 receptor. Specific cell uptake after 60 min was >7.5 % for [(68)Ga]-AAZTA-MG and >9.5 % for [(177)Lu]-AAZTA-MG, comparable to other DOTA-MG-analogues. μPET/CT studies in CCK2 receptor tumour xenografted mice not only revealed high selective accumulation in A431-CCK2R positive tumours of (68)Ga-labelled AAZTA

  16. Antiradical, Chelating and Antioxidant Activities of Hydroxamic Acids and Hydroxyureas

    Directory of Open Access Journals (Sweden)

    Branka Zorc

    2011-07-01

    Full Text Available Reactive oxygen species, along with reactive nitrogen species, may play an important role in the pathogenesis and progress of many diseases, including cancer, diabetes and sickle cell disease. It has been postulated that hydroxyurea, one of the main treatments in sickle cell disease, achieves its activity partly also through its antioxidant properties. A series of hydroxyurea derivatives of L- and D-amino acid amides and cycloalkyl-N-aryl-hydroxamic acids was synthesized and investigated for their radical scavenging activity, chelating properties and antioxidant activity. All the compounds showed exceptional antiradical activities. For example, free radical scavenging activities of investigated hydroxyureas were higher than the activity of standard antioxidant, butylated hydroxyanisole (BHA. Moreover, most of the investigated hydroxamic acids were stronger Fe2+ ion chelators than quercetin. In addition, the investigated compounds, especially hydroxamic acids, were proven to be excellent antioxidants. They were as effective as BHA in inhibiting b-carotene-linoleic acid coupled oxidation. It is reasonable to assume that the antioxidant activity of the investigated compounds could contribute to their previously proven biological properties as cytostatic and antiviral agents.

  17. Using iron chelating agents to enhance dermatological PDT

    Science.gov (United States)

    Curnow, Alison; Dogra, Yuktee; Winyard, Paul; Campbell, Sandra

    2009-06-01

    Topical protoporphyrin IX (PPIX) induced photodynamic therapy (PDT) of basal cell carcinoma (BCC) produces good clinical outcomes with excellent cosmesis as long as the disease remains superficial. Efficacy for nodular BCC however appears inferior to standard treatment unless repeat treatments are performed. Enhancement is therefore required and is possible by employing iron chelating agents to temporarily increase PPIX accumulation above the levels normally obtained using aminolevulinic acid (ALA) or the methyl ester of ALA (MAL) alone. In vitro studies investigated the effect of the novel iron chelator, CP94 on necrotic or apoptotic cell death in cultured human skin fibroblasts and epidermal carcinoma cells incubated with MAL. Furthermore, following a dose escalating safety study conducted with ALA in patients, an additional twelve nodular BCCs were recruited for topical treatment with standard MAL-PDT +/- increasing doses of CP94. Six weeks later following clinical assessment, the whole treatment site was excised for histological analysis. CP94 produced greater cell death in vitro when administered in conjunction with MAL than this porphyrin precursor could produce when administered alone. Clinically, PDT treatment using Metvix + CP94 was a simple and safe modification associated with a trend of reduced tumor thickness with increasing CP94 dose.

  18. Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents

    Science.gov (United States)

    Katti, Kattesh V.; Gali, Hariprasad; Volkert, Wynn A.

    2004-08-24

    This invention describes a novel strategy to produce phosphine-functionalized biomolecules (e.g. peptides or proteins) for potential use in the design and development of site-specific radiopharmaceuticals for diagnosis or therapy of specific cancers. Hydrophilic alkyl phosphines, in general, tend to be oxidatively unstable. Therefore, incorporation of such phosphine functionalities on peptide (and other biomolecule) backbones, without oxidizing the P.sup.III centers, is difficult. In this context this discovery reports on a new technology by which phosphines, in the form of bifunctional chelating agents, can be directly incorporated on biomolecular backbones using manual synthetic or solid phase peptide synthesis methodologies. The superior ligating abilities of phosphine ligands, with various diagnostically (e.g. TC-99m) or therapeutically (e.g. Re186/188, Rh-105, Au-199) useful radiometals, coupled with the findings that the resulting complexes demonstrate high in vivo stability makes this approach useful in the development of radiolabeled biomolecules for applications in the design of tumor-specific radiopharmaceuticals.

  19. DOTA-Functionalized Polylysine: A High Number of DOTA Chelates Positively Influences the Biodistribution of Enzymatic Conjugated Anti-Tumor Antibody chCE7agl

    OpenAIRE

    Gr?nberg, J?rgen; Jeger, Simone; Sarko, Dikran; Dennler, Patrick; Zimmermann, Kurt; Mier, Walter; Schibli, Roger

    2013-01-01

    Site-specific enzymatic reactions with microbial transglutaminase (mTGase) lead to a homogenous species of immunoconjugates with a defined ligand/antibody ratio. In the present study, we have investigated the influence of different numbers of 1,4,7,10-tetraazacyclododecane-N-N'-N''-N'''-tetraacetic acid (DOTA) chelats coupled to a decalysine backbone on the in vivo behavior of the chimeric monoclonal anti-L1CAM antibody chCE7agl. The enzymatic conjugation of (DOTA)1-decalysine, (DOTA)3-decaly...

  20. The mechanism of activation of amidobenzylidene ruthenium chelates - latent catalysts of olefin metathesis.

    Science.gov (United States)

    Rogalski, Szymon; Żak, Patrycja; Tadeuszyk, Natalia; Pyta, Krystian; Przybylski, Piotr; Pietraszuk, Cezary

    2017-01-24

    Amidobenzylidene ruthenium chelates - latent catalysts of olefin metathesis can be easily activated by the addition of Brønsted or Lewis acids. Their activation in the presence of hydrogen chloride involves the formation of catalytically active trans-dichloro carbamatobenzylidene ruthenium chelates.

  1. Antioxidant, Iron-chelating and Anti-glucosidase Activities of Typha ...

    African Journals Online (AJOL)

    Antioxidant, Iron-chelating and Anti-glucosidase Activities of Typha domingensis Pers (Typhaceae). T Chai, M Mohan, H Ong, F Wong. Abstract. Purpose: To evaluate the phytochemical profile as well as in vitro antioxidant, iron-chelating, and antiglucosidase activities of Typha domingensis Pers. (Typhaceae) Methods: Total ...

  2. A novel BF2-chelated azadipyrromethene-fullerene dyad: synthesis, electrochemistry and photodynamics.

    Science.gov (United States)

    Amin, Anu N; El-Khouly, Mohamed E; Subbaiyan, Navaneetha K; Zandler, Melvin E; Fukuzumi, Shunichi; D'Souza, Francis

    2012-01-07

    The synthesis, structure, electrochemistry and photodynamics of a BF(2)-chelated azadipyrromethene-fullerene dyad are reported in comparison with BF(2)-chelated azadipyrromethene without fullerene. The attachment of fullerene resulted in efficient generation of the triplet excited state of the azadipyrromethene via photoinduced electron transfer. This journal is © The Royal Society of Chemistry 2012

  3. Liquid-liquid extraction of uranium(VI) with Aliquat® 336 from HCl media in microfluidic devices: Combination of micro-unit operations and online ICP-MS determination.

    Science.gov (United States)

    Hellé, Gwendolyne; Mariet, Clarisse; Cote, Gérard

    2015-07-01

    The analysis of radionuclides is carried out according to operating protocols which include a series of chemical operations such as separation/purification steps and therefore is usually time-consuming, complex and difficult to put in place in a hostile environment (gloves box). In the present work, the liquid-liquid extraction of uranium in HCl media by Aliquat® 336 was performed in microsystem to demonstrate the potential of miniaturization in radiochemistry compared to classical protocols (decrease in volumes, analysis time, radiations received and feasibility of automation). Through the investigation of the influence of different parameters (flow rates, length of the microchannel, specific interfacial area), it was shown that the same performances of liquid-liquid extraction can be obtained in microsystem and in batch. Then, the coupling of different micro-unit operations for continuous process was performed to highlight the advantages of the miniaturized analytical techniques. The online ICP-MS determination of uranium(VI) was successfully coupled with the stripping of the latter from pre-loaded organic phases in microsystem, which constitutes a proof of concept and a first step towards a global analytical process with continuous flow. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Ex vivo

    Science.gov (United States)

    Matsuda, Kant M; Lopes-Calcas, Ana; Honke, Michael L; O'Brien-Moran, Zoe; Buist, Richard; West, Michael; Martin, Melanie

    2017-07-01

    To advance magnetic resonance imaging (MRI) technologies further for in vivo tissue characterization with histopathologic validation, we investigated the feasibility of ex vivo tissue imaging of a surgically removed human brain tumor as a comprehensive approach for radiology-pathology correlation in histoanatomically identical fashion in a rare case of pigmented ganglioglioma with complex paramagnetic properties. Pieces of surgically removed ganglioglioma, containing melanin and hemosiderin pigments, were imaged with a small bore 7-T MRI scanner to obtain T1-, T2-, and T2*-weighted image and diffusion tensor imaging (DTI). Corresponding histopathological slides were prepared for routine hematoxylin and eosin stain and special stains for melanin and iron/hemosiderin to correlate with MRI signal characteristics. Furthermore, mean diffusivity (MD) maps were generated from DTI data and correlated with cellularity using image analysis. While the presence of melanin was difficult to interpret in in vivo MRI with certainty due to concomitant hemosiderin pigments and calcium depositions, ex vivo tissue imaging clearly demonstrated pieces of tissue exhibiting the characteristic MR signal pattern for melanin with pathologic confirmation in a histoanatomically identical location. There was also concordant correlation between MD and cellularity. Although it is still in an initial phase of development, ex vivo tissue imaging is a promising approach, which offers radiology-pathology correlation in a straightforward and comprehensive manner.

  5. Low-Molecular-Weight Iron Chelates May Be an Alternative to Gadolinium-based Contrast Agents for T1-weighted Contrast-enhanced MR Imaging.

    Science.gov (United States)

    Boehm-Sturm, Philipp; Haeckel, Akvile; Hauptmann, Ralf; Mueller, Susanne; Kuhl, Christiane K; Schellenberger, Eyk A

    2017-01-07

    Purpose To synthesize two low-molecular-weight iron chelates and compare their T1 contrast effects with those of a commercial gadolinium-based contrast agent for their applicability in dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging. Materials and Methods The animal experiments were approved by the local ethics committee. Two previously described iron (Fe) chelates of pentetic acid (Fe-DTPA) and of trans-cyclohexane diamine tetraacetic acid (Fe-tCDTA) were synthesized with stability constants several orders of magnitude higher than those of gadolinium-based contrast agents. The T1 contrast effects of the two chelates were compared with those of gadopentetate dimeglumine in blood serum phantoms at 1.5 T, 3 T, and 7 T. For in vivo studies, a human breast cancer cell line (MDA-231) was implanted in five mice per group. The dynamic contrast effects of the chelates were compared by performing DCE MR imaging with intravenous application of Fe-DTPA or Fe-tCDTA on day 1 and DCE MR imaging in the same tumors with gadopentetate dimeglumine on day 2. Quantitative DCE maps were generated with software and were compared by means of a one-tailed Pearson correlation test. Results Relaxivities in serum (0.94 T at room temperature) of Fe-tCDTA (r1 = 2.2 mmol(-1) · sec(-1), r2 = 2.5 mmol(-1) · sec(-1)) and Fe-DTPA (r1 = 0.9 mmol(-1) · sec(-1), r2 = 0.9 mmol(-1) · sec(-1)) were approximately twofold and fivefold lower, respectively, compared with those of gadopentetate dimeglumine (r1 = 4.1 mmol(-1) · sec(-1), r2 = 4.8 mmol(-1) · sec(-1)). Used at moderately higher concentrations, however, iron chelates generated similar contrast effects at T1-weighted MR imaging in vitro in serum, in vivo in blood, and for DCE MR imaging of breast cancer xenografts. The volume transfer constant values for Fe-DTPA and Fe-tCDTA in the same tumors correlated well with those observed for gadopentetate dimeglumine (Fe-tCDTA Pearson R, 0.99; P = .0003; Fe-DTPA Pearson R, 0

  6. Development of iron chelators for Cooley's anemia. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Crosby, W.H.; Green, R.

    1982-01-26

    Iron chelators were screened in an iron-loaded rat model using selective radioiron probes. In all experiments, chelators D and F, in that order, induced significant loss of radioiron compared with controls. However, use of chelator D was associated with side effects, and resulted in the death of some animals. There was some evidence that chelator A also caused iron loss significantly greater than controls. Chelators B, C and E were without apparent enhancing effect on radioiron excretion. This was a blind study and the compounds used were A - 2,3-Dihydroxybenzoic acid; B - N,N1-Dimethyladipohydroxamic acid; C - DL-Phenylalanine hydroxamic acid; D - Ethylenediamine-N,N1-bis(2-hydroxphenylacetic acid); E - Propionohydroxamic acid; and F - Deferrioxamine B.

  7. Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

    Energy Technology Data Exchange (ETDEWEB)

    Fatimah, Soja Siti, E-mail: soja-sf@upi.edu [Departemen Pendidikan Kimia, Universitas Pendidikan Indonesia, Jl. Dr. Setiabudhi No. 229, Bandung 40154 (Indonesia); Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jl. Raya Bandung-Sumedang, Km. 21, Jatinangor (Indonesia); Bahti, Husein H.; Hastiawan, Iwan [Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jl. Raya Bandung-Sumedang, Km. 21, Jatinangor (Indonesia); Permanasari, Anna [Departemen Pendidikan Kimia, Universitas Pendidikan Indonesia, Jl. Dr. Setiabudhi No. 229, Bandung 40154 (Indonesia)

    2016-02-08

    The use of dialkyldithiocarbamates as chelating agents of transition metals have been developing for decades. Many chelating agents have been synthesized and used in the extraction of the metals. Studies on particular aspects of extraction of the metals, such as the effect of increasing hydrophobicity of chelating agents on the effectiveness of the extraction, have been done. However, despite the many studies on the synthesis and applications of this type of chelating agents, interests in the aspect of molecular structure of the synthesized ligands and of their complexes, have been limited. This study aimed at synthesizing and characterizing dihexylthiocarbamate, and using the ligand for the extraction of gold III). Characterization of the ligand and of its metal complex were done by using elemental analysis, DTG, and spectroscopic methods to include NMR, ({sup 1}H, and {sup 13}C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.

  8. Conversion of agonist site to metal-ion chelator site in the beta(2)-adrenergic receptor

    DEFF Research Database (Denmark)

    Elling, C E; Thirstrup, K; Holst, Birgitte

    1999-01-01

    effect of, for example Cu(2+), and in several cases increased the affinity of the ions for the agonistic site. Wash-out experiments and structure-activity analysis indicated, that the high-affinity chelators and the metal ions bind and activate the mutant receptor as metal ion guided ligand complexes...... in the mutant receptors not by normal catecholamine ligands but instead either by free zinc ions or by zinc or copper ions in complex with small hydrophobic metal-ion chelators. Chelation of the metal ions by small hydrophobic chelators such as phenanthroline or bipyridine protected the cells from the toxic....... Because of the well-understood binding geometry of the small metal ions, an important distance constraint has here been imposed between TM-III and -VII in the active, signaling conformation of 7TM receptors. It is suggested that atoxic metal-ion chelator complexes could possibly in the future be used...

  9. Convection-aided collection of metal ions using chelating porous flat-sheet membranes.

    Science.gov (United States)

    Saito, Kaori; Saito, Kyoichi; Sugita, Kazuyuki; Tamada, Masao; Sugo, Takanobu

    2002-04-19

    Chelating porous membranes were prepared by radiation-induced graft polymerization of an epoxy-group-containing monomer onto a polyethylene flat sheet and subsequent conversion of the epoxy group to an iminodiacetate group as a chelate-forming group. The chelating group density on the resultant porous flat-sheet membrane of 1.0 mol/kg was comparable to that of commercially available chelating beads. The pure water permeability of the membrane was 40% that of the trunk porous membrane, which was used for microfiltration. During the permeation of a copper chloride solution through the membrane, diffusional mass-transfer resistance of copper ion was negligible, since the ion was transported by convective flow through the pore. The tensile strength and elongation at break of the membranes were measured as a function of dose of electron-beam irradiation, the degree of grafting, and the chelating group density to determine an applicable range for practical use.

  10. Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Maha A. Badawi

    2010-01-01

    Full Text Available Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC. A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the same time course, ferritin levels decreased but did not normalize. There have been eighteen other MDS patients reported showing improvement in hemoglobin level with iron chelation; nine became transfusion independent, nine had decreased transfusion requirements, and some showed improved trilineage myelopoiesis. The clinical features of these patients are summarized and possible mechanisms for such an effect of iron chelation on cytopenias are discussed.

  11. Chelation and stabilization of berkelium in oxidation state +IV

    Science.gov (United States)

    Deblonde, Gauthier J.-P.; Sturzbecher-Hoehne, Manuel; Rupert, Peter B.; An, Dahlia D.; Illy, Marie-Claire; Ralston, Corie Y.; Brabec, Jiri; de Jong, Wibe A.; Strong, Roland K.; Abergel, Rebecca J.

    2017-09-01

    Berkelium (Bk) has been predicted to be the only transplutonium element able to exhibit both +III and +IV oxidation states in solution, but evidence of a stable oxidized Bk chelate has so far remained elusive. Here we describe the stabilization of the heaviest 4+ ion of the periodic table, under mild aqueous conditions, using a siderophore derivative. The resulting Bk(IV) complex exhibits luminescence via sensitization through an intramolecular antenna effect. This neutral Bk(IV) coordination compound is not sequestered by the protein siderocalin—a mammalian metal transporter—in contrast to the negatively charged species obtained with neighbouring trivalent actinides americium, curium and californium (Cf). The corresponding Cf(III)-ligand-protein ternary adduct was characterized by X-ray diffraction analysis. Combined with theoretical predictions, these data add significant insight to the field of transplutonium chemistry, and may lead to innovative Bk separation and purification processes.

  12. Beryllium Chelation by Dicarboxylic Acids in Aqueous Solution.

    Science.gov (United States)

    Schmidt, Michael; Bauer, Andreas; Schmidbaur, Hubert

    1997-05-07

    Maleic and phthalic acids are found to react with Be(OH)(2), generated in situ from BeSO(4)(aq) and Ba(OH)(2)(aq), in aqueous solution at pH 3.0 or 4.4, respectively (25 degrees C), to give solutions containing the complexes (H(2)O)(2)Be[(OOCCH)(2)] (1) and (H(2)O)(2)Be[(OOC)(2)C(6)H(4)] (3). The products can be isolated in high yield and identified by microanalytical data. With 2 equiv of the dicarboxylic acids and the pH adjusted to 5.5 and 5.9, respectively, by addition of ammonia, the bis-chelate complexes [(NH(4))(+)](2){[Be[(OOCCH)(2)](2)}(2)(-) (2) and [(NH(4))(+)](2){Be[(OOC)(2)C(6)H(4)](2)}(2)(-) (4) are obtained, which can also be isolated. The compounds show distinct (9)Be, (1)H, and (13)C resonances in their NMR spectra in aqueous solutions. Layering of an aqueous solution of compound 4 with acetone at ambient temperature leads to the precipitation of single crystals suitable for an X-ray structure determination. This salt (5) was found to contain the bis-chelated dianion {Be[(OOC)(2)C(6)H(4)](2)}(2)(-) with the beryllium atom in the spiro center of two seven-membered rings and an overall geometry approaching closely C(2) symmetry. These anions are associated with two crystallographically independent but structurally similar counterions [MeC(O)CH(2)CMe(2)NH(3)](+), which are the product of a condensation reaction of the ammonium cation with the acetone solvent. In the crystal the ammonium hydrogen atoms of the cations form N-H.O hydrogen bonds with the oxo functions of the dianion.

  13. MRI marrow observations in thalassemia: the effects of the primary disease, transfusional therapy, and chelation

    Energy Technology Data Exchange (ETDEWEB)

    Levin, T.L. [Department of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, New York, NY (United States); Sheth, S.S. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, 3959 Broadway, New York, NY 10032 (United States); Ruzal-Shapiro, C. [Department of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, New York, NY (United States); Abramson, S. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Piomelli, S. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, 3959 Broadway, New York, NY 10032 (United States); Berdon, W.E. [Department of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, New York, NY (United States)

    1995-11-01

    The magnetic resonance bone marrow patterns in thalassemia were evaluated to determine changes produced by transfusion and chelation therapy. Thirteen patients had T1- and T2-weighted images of the spine, pelvis and femurs. Three received no therapy (age range 2.5-3 years). Three were ``hypertransfused`` (transfused to maintain a hemoglobin greater than 10 g/dl) and not chelated because of age (age range 6 months-8 years). Seven were ``hypertransfused`` and chelated (age range 12-35 years). Signal characteristics of marrow were compared with those of surrounding muscle and fat. Fatty marrow (isointense with subcutaneous fat) was compared with red marrow (hypointense to fat and slightly hyperintense to muscle). Marrow hypointense to muscle was identified as iron deposition within red marrow. The untreated group demonstrated signal consistent with red marrow throughout the central and peripheral skeleton. Hypertransfused but not chelated patients demonstrated marked iron deposition in the central and peripheral skeleton. Hypertransfused and chelated patients demonstrated iron deposition in the central skeleton and a mixed appearance of marrow in the peripheral skeleton. The MR appearance of marrow in thalassemia is a reflection of the patient`s transfusion and chelation therapy. Iron deposition occurs despite chelation therapy in sites of active red marrow. As red marrow retreats centrally with age, so does the pattern of iron deposition. The long-term biological effects of this iron deposition are unknown. (orig.). With 8 figs., 1 tab.

  14. The effect of ferrous-chelating hairtail peptides on iron deficiency and intestinal flora in rats.

    Science.gov (United States)

    Lin, Hui-Min; Deng, Shang-Gui; Huang, Sai-Bo; Li, Ying-Jie; Song, Ru

    2016-06-01

    Chelating agents, such as small peptides, can decrease free iron content and increase iron bioavailability. They may have promising therapeutic potential and may prevent the pro-oxidant effects of low molecular weight iron. Hairtail is a species of fish that is rich in easily digestible proteins. We extended this strategy for iron delivery by using an enzymatic hydrolysate of hairtail as the chelating agent and found that the ferrous-chelating hairtail peptides have anti-anaemic activity in Sprague-Dawley rats with anaemia. The anti-anaemic activity of ferrous-chelating hairtail peptides prepared by enzymatic hydrolysis of the hairtail and ferrous chelation was studied in rat models of iron deficiency anaemia. After the end of the 35 d experiment, we noted significant differences in haemoglobin, mean corpuscular volume, haemoglobin distribution width, and ferritin concentrations between those animals supplemented with ferrous-chelating hairtail peptides and FeSO4 and healthy animals. There were no negative side effects on the animals' growth or behaviour. There was no obvious inflammation in the intestinal mucosa lamina propria and no unbalance of intestinal flora. The novel ferrous-chelating hairtail peptides may be a suitable fortificant for improving iron-deficiency status. Our findings demonstrated that this multi-tracer technique has many applications in nutritional research. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  15. Chelating properties of alpha-oximinocarboxamides-I alpha-Oximinophenylacetamide isomers.

    Science.gov (United States)

    Coviello, D A; El-Fatatry, H M

    1971-06-01

    Various polyfunctional oximes chelate with metals pro vided that the other functional group is proximal to the oxime and contains a good donor atom or is a good donor itself. Thus alpha-oximinocarboxamides are potential chelating agents of analytical value since the amide function attached to the carbon atom bearing the oxime has two groups capable of functioning as donors (ketone and amine). Two isomers of alpha-oximinophenylacetamide (AOPA) were obtained by two different synthetic routes, and structures were assigned by spectrometric methods. syn-AOPA was found to have chelating properties, but the anti-isomer did not. The synthesis and details of structure assignments are reported here.

  16. Inhibitor Ranking Through QM based Chelation Calculations for Virtual Screening of HIV-1 RNase H inhibition

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Svendsen, Casper Steinmann; Kongsted, Jacob

    2014-01-01

    Quantum mechanical (QM) calculations have been used to predict the binding affinity of a set of ligands towards HIV-1 RT associated RNase H (RNH). The QM based chelation calculations show improved binding affinity prediction for the inhibitors compared to using an empirical scoring function...... of the methods based on the use of a training set of molecules, QM based chelation calculations were used as filter in virtual screening of compounds in the ZINC database. By this, we find, compared to regular docking, QM based chelation calculations to significantly reduce the large number of false positives...

  17. In vivo

    Science.gov (United States)

    Berkowitz, Bruce A; Lenning, Jacob; Khetarpal, Nikita; Tran, Catherine; Wu, Johnny Y; Berri, Ali M; Dernay, Kristin; Haacke, E Mark; Shafie-Khorassani, Fatema; Podolsky, Robert H; Gant, John C; Maimaiti, Shaniya; Thibault, Olivier; Murphy, Geoffrey G; Bennett, Brian M; Roberts, Robin

    2017-09-01

    Hippocampus oxidative stress is considered pathogenic in neurodegenerative diseases, such as Alzheimer disease (AD), and in neurodevelopmental disorders, such as Angelman syndrome (AS). Yet clinical benefits of antioxidant treatment for these diseases remain unclear because conventional imaging methods are unable to guide management of therapies in specific hippocampus subfields in vivo that underlie abnormal behavior. Excessive production of paramagnetic free radicals in nonhippocampus brain tissue can be measured in vivo as a greater-than-normal 1/ T 1 that is quenchable with antioxidant as measured by quench-assisted (Quest) MRI. Here, we further test this approach in phantoms, and we present proof-of-concept data in models of AD-like and AS hippocampus oxidative stress that also exhibit impaired spatial learning and memory. AD-like models showed an abnormal gradient along the CA1 dorsal-ventral axis of excessive free radical production as measured by Quest MRI, and redox-sensitive calcium dysregulation as measured by manganese-enhanced MRI and electrophysiology. In the AS model, abnormally high free radical levels were observed in dorsal and ventral CA1. Quest MRI is a promising in vivo paradigm for bridging brain subfield oxidative stress and behavior in animal models and in human patients to better manage antioxidant therapy in devastating neurodegenerative and neurodevelopmental diseases.-Berkowitz, B. A., Lenning, J., Khetarpal, N., Tran, C., Wu, J. Y., Berri, A. M., Dernay, K., Haacke, E. M., Shafie-Khorassani, F., Podolsky, R. H., Gant, J. C., Maimaiti, S., Thibault, O., Murphy, G. G., Bennett, B. M., Roberts, R. In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome. © FASEB.

  18. Radiolabeled technetium chelates for use in renal function determinations

    Science.gov (United States)

    Fritzberg, Alan; Kasina, Sudhakar; Johnson, Dennis L.

    1990-01-01

    The present invention is directed to novel radiopharmaceutical imaging agents incorporating Tc-99m as a radiolabel. In particular, the novel imaging agents disclosed herein have relatively high renal extraction efficiencies, and hence are useful for conducting renal function imaging procedures. The novel Tc-99m compounds of a present invention have the following general formula: ##STR1## wherein X is S or N; and wherein Y is--H or wherein Y is ##STR2## and where R.sub.1 is --H, --CH.sub.3, or --CH.sub.2 CH.sub.3 ; R.sub.2 is --H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.3, --CH.sub.2 CH.sub.3, CH.sub.2 C.sub.6 H.sub.5, or --CH.sub.2 OH; and Z is --H, --CO.sub.2 H, --CONH.sub.2, --SO.sub.3 H, --SO.sub.2 NH.sub.2, or --CONHCH.sub.2 CO.sub.2 H; and the Tc is Tc-99m; and water-soluble salts thereof. Of the foregoing, the presently preferred Tc-99m compound of the present invention is Tc-99m-mercaptoacetylglycylglycylglycine (Tc-99m-MAGGG). The present invention is also directed to novel chelating agents that may be reacted with Tc-99m to form the foregoing compounds. Such novel chelating agents have the following general formula. ##STR3## where X and Y have the same definitions as above, and wherein Y' is --H.sub.2 when X is N, or wherein Y' is --H, or a suitable protective group such as --COCH.sub.3, --COC.sub.6 H.sub.5, --CH.sub.2 NHCOCH.sub.3, --COCF.sub.3, or --COCH.sub.2 OH when X is S. The present invention also provides methods for preparing and using the novel Tc-99m compounds.

  19. Model-Based Optimisation of Deferoxamine Chelation Therapy.

    Science.gov (United States)

    Bellanti, Francesco; Del Vecchio, Giovanni C; Putti, Maria C; Cosmi, Carlo; Fotzi, Ilaria; Bakshi, Suruchi D; Danhof, Meindert; Della Pasqua, Oscar

    2016-02-01

    Here we show how a model-based approach may be used to provide further insight into the role of clinical and demographic covariates on the progression of iron overload. The therapeutic effect of deferoxamine is used to illustrate the application of disease modelling as a means to characterising treatment response in individual patients. Serum ferritin, demographic characteristics and individual treatment data from clinical routine practice on 27 patients affected by β-thalassaemia major were used for the purposes of this analysis. The time course of serum ferritin was described by a hierarchical nonlinear mixed effects model, in which compliance was parameterised as a covariate factor. Modelling and simulation procedures were implemented in NONMEM (7.2.0). A turnover model best described serum ferritin changes over time, with the effect of blood transfusions introduced on the ferritin conversion rate and the effect of deferoxamine on the elimination parameter (Kout) in a proportional manner. The results of the simulations showed that poor quality of execution is preferable over drug holidays; and that independently of the compliance pattern, the therapeutic intervention is not effective if >60% of the doses are missed. Modelling of ferritin response enables characterisation of the dynamics of iron overload due to chronic transfusion. The approach can be used to support decision making in clinical practice, including personalisation of the dose for existing and novel chelating agents.

  20. Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model.

    Directory of Open Access Journals (Sweden)

    Patricia Ferrer

    Full Text Available Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S3"-(HO-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC(50 of 6 µM for Plasmodium falciparum in contrast to the IC(50 for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials.

  1. Imaging cancer using PET--the effect of the bifunctional chelator on the biodistribution of a (64)Cu-labeled antibody.

    Science.gov (United States)

    Dearling, Jason L J; Voss, Stephan D; Dunning, Patricia; Snay, Erin; Fahey, Frederic; Smith, Suzanne V; Huston, James S; Meares, Claude F; Treves, S Ted; Packard, Alan B

    2011-01-01

    Use of copper radioisotopes in antibody radiolabeling is challenged by reported loss of the radionuclide from the bifunctional chelator used to label the protein. The objective of this study was to investigate the relationship between the thermodynamic stability of the (64)Cu-complexes of five commonly used bifunctional chelators (BFCs) and the biodistribution of an antibody labeled with (64)Cu using these chelators in tumor-bearing mice. The chelators [S-2-(aminobenzyl)1,4,7-triazacyclononane-1,4,7-triacetic acid (p-NH(2)-Bn-NOTA): 6-[p-(bromoacetamido)benzyl]-1, 4, 8, 11-tetraazacyclotetradecane-N, N', N'', N'''-tetraacetic acid (BAT-6): S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododocane tetraacetic acid (p-NH(2)-Bn-DOTA): 1,4,7,10-tetraazacyclododocane-N, N', N", N"'-tetraacetic acid (DOTA): and 1-N-(4-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (SarAr)] were conjugated to the anti-GD2 antibody ch14.18, and the modified antibody was labeled with (64)Cu and injected into mice bearing subcutaneous human melanoma tumors (M21) (n = 3-5 for each study). Biodistribution data were obtained from positron emission tomography images acquired at 1, 24 and 48 hours post-injection, and at 48 hours post-injection a full ex vivo biodistribution study was carried out. The biodistribution, including tumor targeting, was similar for all the radioimmunoconjugates. At 48 h post-injection, the only statistically significant differences in radionuclide uptake (p < 0.05) were between blood, liver, spleen and kidney. For example, liver uptake of [(64)Cu]ch14.18-p-NH(2)-Bn-NOTA was 4.74 ± 0.77 per cent of the injected dose per gram of tissue (%ID/g), and for [(64)Cu]ch14.18-SarAr was 8.06 ± 0.77 %ID/g. Differences in tumor targeting correlated with variations in tumor size rather than which BFC was used. The results of this study indicate that differences in the thermodynamic stability of these chelator-Cu(II) complexes were not associated with significant

  2. Bifunctional chelates of RH-105 and AU199 as potential radiotherapeutic agents

    Energy Technology Data Exchange (ETDEWEB)

    Droege, P.

    1997-03-01

    Research is presented on new bifunctional chelating ligand systems with stability on the macroscopic and radiochemical levels. The synthesis of the following complexes are described: rhodium 105, palladium 109, and gold 198.

  3. Photocatalysts Based on Cobalt-chelating Conjugated Polymers for Hydrogen Evolution from Water

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lianwei; Hadt, Ryan G.; Yao, Shiyu; Lo, Waiyip; Cai, Zhengxu; Wu, Qingliu; Pandit, Bill; Chen, Lin X.; Yu, Luping

    2016-08-09

    Developing photocatalytic systems for water splitting to generate oxygen and hydrogen is one of the biggest chemical challenges in solar energy utilization. In this work, we report the first example of heterogeneous photocatalysts for hydrogen evolution based on in-chain cobalt-chelating conjugated polymers. Four conjugated polymers chelated with earth abundant cobalt ions were synthesized and found to evolve hydrogen photocatalytically from water. These polymers are designed to combine functions of the conjugated backbone as light-harvesting antenna and electron transfer conduit with the in-chain bipyridyl chelated transition metal centers as catalytic active sites. In addition, these polymers are soluble in organic solvents, enabling effective interactions with the substrates as well as detailed characterization. We also found a polymer-dependent optimal cobalt chelating concentration at which the highest photocatalytic hydrogen production (PHP) activity can be achieved.

  4. Absorption of nitric oxide into aqueous solutions of ferrous chelates accompanied by instantaneous reaction

    NARCIS (Netherlands)

    Demmink, J.F; vanGils, I.C.F.; Beenackers, A.A C M

    1997-01-01

    The absorption of nitric oxide (NO) into aqueous solutions of ferrous chelates of nitrilotriacetic acid (NTA), ethylene diaminetetraacetic acid (EDTA), hydroxyethylenediaminetriacetic acid (HEDTA), and diethylenetriaminepentaacetic acid (DTPA) was studied in a stirred cell reactor. Experimental

  5. Influence of chelation ratio of metal alkoxides on aging of PZT 53/47 ...

    Indian Academy of Sciences (India)

    Administrator

    gel-based synthesis routes, generally demands the use of chelating agents in order to avoid fast hydrolysis and also to allow an easier manipulation of intermediates as well as final solutions. Under these conditions, stability issues sometimes ...

  6. The Management of Iron Chelation Therapy: Preliminary Data from a National Registry of Thalassaemic Patients

    Directory of Open Access Journals (Sweden)

    Adriana Ceci

    2011-01-01

    Full Text Available Thalassaemia and other haemoglobinopathies constitute an important health problem in Mediterranean countries, placing a tremendous emotional, psychological, and economic burden on their National Health systems. The development of new chelators in the most recent years had a major impact on the treatment of thalassaemia and on the quality of life of thalassaemic patients. A new initiative was promoted by the Italian Ministry of Health, establishing a Registry for thalassaemic patients to serve as a tool for the development of cost-effective diagnostic and therapeutic approaches and for the definition of guidelines supporting the most appropriate management of the iron-chelating therapy and a correct use of the available iron-chelating agents. This study represents the analysis of the preliminary data collected for the evaluation of current status of the iron chelation practice in the Italian thalassaemic population and describes how therapeutic interventions can widely differ in the different patients' age groups.

  7. Effect of calcium chelators on physical changes in casein micelles in concentrated micellar casein solutions

    NARCIS (Netherlands)

    Kort, de E.J.P.; Minor, M.; Snoeren, T.H.M.; Hooijdonk, van A.C.M.; Linden, van der E.

    2011-01-01

    The effect of calcium chelators on physical changes of casein micelles in concentrated micellar casein solutions was investigated by measuring calcium-ion activity, viscosity and turbidity, and performing ultracentrifugation. The highest viscosities were measured on addition of sodium

  8. Click-to-Chelate: Development of Technetium and Rhenium-Tricarbonyl Labeled Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Thomas L. Mindt

    2013-03-01

    Full Text Available The Click-to-Chelate approach is a highly efficient strategy for the radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction enables the simultaneous synthesis and conjugation of tridentate chelating systems for the stable complexation of the radiometals. In many cases, the functionalization of (biomolecules with the ligand system and radiolabeling can be achieved by convenient one-pot procedures. Since its first report in 2006, Click-to-Chelate has been applied to the development of numerous novel radiotracers with promising potential for translation into the clinic. This review summarizes the use of the Click-to-Chelate approach in radiopharmaceutical sciences and provides a perspective for future applications.

  9. Combined therapy of iron chelator and antioxidant completely restores brain dysfunction induced by iron toxicity

    National Research Council Canada - National Science Library

    Sripetchwandee, Jirapas; Pipatpiboon, Noppamas; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-01-01

    .... We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine...

  10. Intracellular reduction/activation of a disulfide switch in thiosemicarbazone iron chelators

    OpenAIRE

    Akam, Eman A.; Chang, Tsuhen M.; Astashkin, Andrei V.; Tomat, Elisa

    2014-01-01

    Iron scavengers (chelators) offer therapeutic opportunities in anticancer drug design by targeting the increased demand for iron in cancer cells as compared to normal cells. Prochelation approaches are expected to avoid systemic iron depletion as chelators are liberated under specific intracellular conditions. In the strategy described herein, a disulfide linkage is employed as a redox-directed switch within the binding unit of an antiproliferative thiosemicarbazone prochelator, which is acti...

  11. Synthesis, Characterization and Chelating Properties of 4-Butyrylsemicarbazone-1-phenyl-3-methyl-2-pyrazolin-5-one

    Directory of Open Access Journals (Sweden)

    J. D. Patel

    2010-01-01

    Full Text Available 4-Butyrylsemicarbazone-1-phenyl-3-methyl-2-pyrazolin-5-one (BUMP-SC was prepared and its metal chelates of Cu2+, Ni2+, Co2+, Mn2+, Fe2+, Fe3+, Cr3+, UO2 and OV were prepared. The ligands and its chelates were characterized by elemental analysis, metal:ligand (M:L stoichiometry, IR-electronic spectral studies and magnetic properties. The compounds also were screened for their antimicrobial activity.

  12. Rapid anaerobic benzene oxidation with a variety of chelated Fe(III) forms

    Science.gov (United States)

    Lovley, D.R.; Woodward, J.C.; Chapelle, F.H.

    1996-01-01

    Fe(III) chelated to such compounds as EDTA, N-methyliminodiacetie acid, ethanol diglycine, humic acids, and phosphates stimulated benzene oxidation coupled to Fe(III) reduction in anaerobic sediments from a petroleum- contaminated aquifer as effectively as or more effectively than nitrilotriacetic acid did in a previously demonstrated stimulation experiment. These results indicate that many forms of chelated Fe(III) might be applicable to aquifer remediation.

  13. Influence of chelation ratio of metal alkoxides on aging of PZT 53/47 ...

    Indian Academy of Sciences (India)

    In this work, we explore the sol–gel-based synthesis route of lead zirconate titanate (Pb(Zr0.53Ti0.47)O3 or PZT 53/47) using acetylacetone-chelated propoxides as intermediate reactants. Our main purpose here is to analyse the influence of the alkoxides:acetylacetone chelation ratio on the time evolution of mean particle ...

  14. Response of soybean plants to the application of synthetic and biodegradable Fe chelates and Fe complexes.

    Science.gov (United States)

    Martín-Fernández, Clara; Solti, Ádám; Czech, Viktória; Kovács, Krisztina; Fodor, Ferenc; Gárate, Agustín; Hernández-Apaolaza, Lourdes; Lucena, Juan J

    2017-09-01

    The growing concern over the environmental risk of synthetic chelate application promotes the search for alternatives in Fe fertilization, such as biodegradable chelating agents and natural complexing agents. In this work, plant responses to the application of several Fe treatments (chelates and complexes) was analyzed to study their potential use in Fe fertilization under calcareous conditions. Thus, the root ferric chelate reductase (FCR) activity of soybean (Glycine max cv. Klaxon) plants was determined, and the effectiveness of the Fe chelates and complexes assessed in a pot experiment, by SPAD and fluorescence induction measurements, and the determination of Fe distribution in plant and soil. Additionally, (57)Fe Mössbauer spectroscopy was conducted to identify the Fe forms present in the soybean roots. The highest FCR activity was observed for the chelates EDDS/Fe(3+) and IDHA/Fe(3+); while no activity was observed when using complexes as Fe substrates. In contrast to the FCR data, the pot experiment confirmed that the o,oEDDHA/Fe(3+) is the most effective treatment, and the complexes LS/Fe(3+) and GA/Fe(3+) are able to alleviate Fe chlorosis, also indicated by SPAD data and the maximal quantum efficiency of photosystem II reaction centers as vitality parameters, and the enhanced plant uptake of Fe from natural sources. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. ELECTED PROBLEMS RELATED TO ENVIRONMENTAL HEAVY METALS EXPOSURE AND CHELATION THERAPY

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    Anna Skoczyńska

    2010-09-01

    Full Text Available Background: Exposure to heavy metals leads to functional and metabolic disturbances and many of them are included in pathogenesis of common diseases (arterial hypertension, atherosclerosis, neurodegenerative processes. In this context new therapeutic and prophylactic strategies are necessary. Patients diagnosed with chronic heavy metals intoxication usually require chelation to increase mobilisation of metals from tissues and elimination of them via urine. Acute poisoning with toxic metal may be difficult to diagnosis, especially in case of accidental intoxication or suicidal intention. Patients also require chelation after causative factor is identified. Objectives: To describe some problems connected with toxicity of metals poisoning and to review pharmacologic therapies that could have a role in poisoning with metals. Methods: A review of the literature was carried out and expert opinion expressed. Results/conclusion: Chelation is a common therapy in case of poisoning with toxic metals but it is satisfied only partially. A combined therapy with structurally different chelators or long-term acting chelators could become viable alternatives in the future. A combined therapy with an antioxidant plus chelator may be a good choice in patients chronically poisoned with metals. Exposure to lead should be taken into account during estimation of global cardiovascular risk.

  16. Effect of roasting on properties of the zinc-chelating substance in coffee brews.

    Science.gov (United States)

    Wen, Xu; Enokizo, Akiko; Hattori, Harumi; Kobayashi, Satiko; Murata, Masatsune; Homma, Seiichi

    2005-04-06

    ApV is a brownish polymer with zinc-chelating activity in brewed coffee. We investigated in this study the effects of roasting on the zinc-chelating, reducing, and antioxidative activities of ApV from light-, medium-, and dark-roasted coffee. We also discuss the effect on the zinc-chelating activity of adding milk to the brewed coffee. The chelating activities of ApVs were evaluated by the tetramethyl murexide method. As the intensity of roasting increased, the yield of ApV increased, and the brown color and molecular weight of ApV respectively became darker and higher. Increasing the degree of roasting also decreased the zinc-chelating activity of ApV. The reducing activities of ApVs estimated by the indophenol method were stronger than those of ascorbic acid. Both the antioxidative activity estimated by the ABTS assay and the reducing activity of ApV increased with roasting. When milk was added to instant coffee and its ApV was prepared, the zinc-chelating activity of ApV was not changed.

  17. Wood impregnated with metal chelates dissolved in organic media tested for termite resistance

    Directory of Open Access Journals (Sweden)

    Lara Maistrello

    2011-08-01

    Full Text Available Wood manufactured products are subjected to biological decay due to fungi and insects. The use of copper chelates as biocides was proposed, due to their high stability which minimizes copper leaching into the environment. Considering the remarkable effectiveness showed by copper chelates on brown rot fungi, zinc and copper salicylate complexes were prepared in order to have metal chelates soluble in organic media available. The present study aimed at evaluating these metal chelates complexes as preservative agents for wood treatment against termites. Trials were performed on Reticulitermes lucifugus (Rossi and Kalotermes flavicollis (Fabricius. Results showed that in both termite species wood consumption was significantly lower on Cu-chelates treated samples compared to untreated wood, whereas the wood slices impregnated with Zn-chelates and the organic media alone gave an intermediate response. Interestingly, in one case solvent-impregnated wood was significantly more attractive than untreated wood for both species and further investigations are being carried out to clarify this behaviour.

  18. The role of chelation in the treatment of arsenic and mercury poisoning.

    Science.gov (United States)

    Kosnett, Michael J

    2013-12-01

    Chelation for heavy metal intoxication began more than 70 years ago with the development of British anti-lewisite (BAL; dimercaprol) in wartime Britain as a potential antidote the arsenical warfare agent lewisite (dichloro[2-chlorovinyl]arsine). DMPS (unithiol) and DMSA (succimer), dithiol water-soluble analogs of BAL, were developed in the Soviet Union and China in the late 1950s. These three agents have remained the mainstay of chelation treatment of arsenic and mercury intoxication for more than half a century. Animal experiments and in some instances human data indicate that the dithiol chelators enhance arsenic and mercury excretion. Controlled animal experiments support a therapeutic role for these chelators in the prompt treatment of acute poisoning by arsenic and inorganic mercury salts. Treatment should be initiated as rapidly as possible (within minutes to a few hours), as efficacy declines or disappears as the time interval between metal exposure and onset of chelation increases. DMPS and DMSA, which have a higher therapeutic index than BAL and do not redistribute arsenic or mercury to the brain, offer advantages in clinical practice. Although chelation following chronic exposure to inorganic arsenic and inorganic mercury may accelerate metal excretion and diminish metal burden in some organs, potential therapeutic efficacy in terms of decreased morbidity and mortality is largely unestablished in cases of chronic metal intoxication.

  19. Chelating effect of silver nitrate by chitosan on its toxicity and growth performance in broiler chickens

    Directory of Open Access Journals (Sweden)

    Yemdjie Mane Divine Doriane

    2017-06-01

    Full Text Available Objective: This study was conducted to investigate the chelating effect of silver nitrate (AgNO3 by chitosan on growth performances, hematological and biochemical parameters, and the histopathological structure of the liver and the kidney in broiler chicken. Materials and methods: A total of 192 day-old Cobb 500 strain chicks were randomly assigned to 3 treatments of 64 chicks each. Control group was fed on basal diet without supplement (R0 and the two others groups were fed on rations supplemented with 10 mg of unchelated (RAg or chelated (RCs-Ag AgNO3 per Kg of feed, respectively. Parameters that have been studied consisted of feed intake, weight gain, blood and serum biochemical, and histopathological analyses of liver and kidney. Results: Results revealed that chelation of AgNO3 by chitosan did not have any effect on growth performances and hematological parameters in chicken. However, chelated and unchelated AgNO3 increased the serum content in triglyceride, and cholesterol and decreased the serum content in creatinin, albumin and alanine aminotransferase (ALAT. Chelating AgNO3 with chitosan prevented and corrected the toxicity induced on the histological structure of liver and kidney. Conclusion: Chitosan can be used as a chelating agent to alleviate the harmful effects of AgNO3 as silver ion for poultry. [J Adv Vet Anim Res 2017; 4(2.000: 187-193

  20. Detection of biothiols in cells by a terbium chelate-Hg (II) system

    Science.gov (United States)

    Tan, Hongliang; Chen, Yang

    2012-01-01

    Great efforts have been devoted to the development of sensitive and specific analysis methods for biothiols because of their important roles in biological systems. We present a new detection system for biothiols that is based on the reversible quenching and restoration of fluorescence of terbium chelate caused by Hg2+ and thiol species. In the presence of biothiols, a restoration of fluorescence of terbium chelate after quenching by Hg2+ was observed due to the interaction of Hg2+ with thiol groups, and the restored fluorescence increased with the concentration of biothiols. This method was sensitive and selective for biothiols. The detection limit was 80 nM for glutathione, 100 nM for Hcy, and 400 nM for Cysteine, respectively. The terbium chelate-Hg (II) system was successfully applied to determine the levels of biothiols in cancer cells and urine samples. Further, it was also shown to be comparable to Ellman's assay. Compared to other fluorescence methods, the terbium chelate probe is advantageous because interference from short-lived nonspecific fluorescence can be efficiently eliminated due to the long fluorescence lifetime of terbium chelate, which allows for detection by time-resolved fluorescence. The terbium chelate probe can serve as a diagnostic tool for the detection of abnormal levels of biothiols in disease.

  1. Advances in iron chelation therapy: transitioning to a new oral formulation

    Directory of Open Access Journals (Sweden)

    Nirmish R Shah

    2017-06-01

    Full Text Available Iron overload is a concern for patients who require repeated red-blood-cell transfusions due to conditions such as sickle cell disease, thalassemia, or myelodysplastic syndromes. The recommended treatment for removing excess iron in these patients is iron chelation therapy. Currently available iron chelators include deferoxamine, which is administered by injection, and deferasirox and deferiprone, both of which are administered orally. Adherence to iron chelator therapy is an important consideration and may be affected by side effects. A new formulation of deferasirox, a film-coated tablet (FCT, has the potential to improve adherence by offering greater flexibility in administration compared with the original formulation of deferasirox, a dispersible tablet (DT for oral suspension. This review provides an overview of the currently available iron chelator formulations, with a focus on a comparison between deferasirox DT for oral suspension and deferasirox FCT. The new formulation may be associated with fewer side effects and has increased bioavailability. In addition, alternative strategies for iron chelation, such as combining two different iron chelators, will be discussed.

  2. Resinas quelantes amidoxímicas Amidoxime chelating resins

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    Fernanda M. B. Coutinho

    1999-12-01

    Full Text Available Resinas quelantes com grupos amidoxima foram sintetizadas por copolimerização em suspensão de acrilonitrila (AN e divinilbenzeno (DVB e subsequente modificação química dos grupos ciano por reação com hidroxilamina. Na copolimerização, a proporção de divinilbenzeno e o grau de diluição foram variados. Gelatina e carbonato de cálcio foram usados como estabilizadores de suspensão e sulfato de sódio foi adicionado para reduzir a solubilidade da acrilonitrila em água, por meio do efeito salting out. Os copolímeros de AN/DVB e as resinas amidoxímicas obtidos foram caracterizados por meio de densidade aparente, área específica, volume de poros e teor de nitrogênio. As resinas amidoxímicas foram também avaliadas em relação a capacidade de complexação de íons cobre.Chelating resins with amidoxime groups were synthesized by suspension copolymerization of acrylonitrile (AN and divinylbenzene (DVB and subsequent chemical modification of cyano groups by reaction with hydroxylamine. In the copolymerization, the proportion of divinylbenzene and the dilution degree were varied. Gelatin and calcium carbonate were used as suspension stabilizers and sodium sulphate was added in order to reduce acrylonitrile solubility in water, by salting out effect. The AN/DVB copolymers and amidoxime resins obtained were characterized by apparent density, surface area, pore volume and by the content of nitrogen. The amidoxime resins were also evaluated in relation to the complexation capacity of copper ion.

  3. The effect of an EDTA-based chelation regimen on patients with diabetes mellitus and prior myocardial infarction in the Trial to Assess Chelation Therapy (TACT).

    Science.gov (United States)

    Escolar, Esteban; Lamas, Gervasio A; Mark, Daniel B; Boineau, Robin; Goertz, Christine; Rosenberg, Yves; Nahin, Richard L; Ouyang, Pamela; Rozema, Theodore; Magaziner, Allan; Nahas, Richard; Lewis, Eldrin F; Lindblad, Lauren; Lee, Kerry L

    2014-01-01

    The Trial to Assess Chelation Therapy (TACT) showed clinical benefit of an EDTA-based infusion regimen in patients aged ≥50 years with prior myocardial infarction. Diabetes mellitus before enrollment was a prespecified subgroup. Patients received 40 infusions of EDTA chelation or placebo. A total of 633 (37%) patients had diabetes mellitus (322 EDTA and 311 placebo). EDTA reduced the primary end point (death, reinfarction, stroke, coronary revascularization, or hospitalization for angina; 25% versus 38%; hazard ratio, 0.59; 95% confidence interval [CI], 0.44-0.79; Pdiabetes mellitus (n=1075; P=0.877), resulting in a treatment by diabetes mellitus interaction (P=0.004). Post-myocardial infarction patients with diabetes mellitus aged ≥50 demonstrated a marked reduction in cardiovascular events with EDTA chelation. These findings support efforts to replicate these findings and define the mechanisms of benefit. However, they do not constitute sufficient evidence to indicate the routine use of chelation therapy for all post-myocardial infarction patients with diabetes mellitus. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00044213.

  4. CARDIAC FUNCTION AND IRON CHELATION IN THALASSEMIA MAJOR AND INTERMEDIA: A REVIEW OF THE UNDERLYING PATHOPHYSIOLOGY AND APPROACH TO CHELATION MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Athanasios Aessopos

    2009-07-01

    Full Text Available Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. Patients with homozygous thalassemia may have either a severe phenotype which is usually transfusion dependent or a milder form that is thalassemia intermedia.  The two main factors that determine cardiac disease in homozygous β thalassemia are the high output state that results from chronic tissue hypoxia, hypoxia-induced compensatory reactions and iron overload.  The high output state playing a major role in thalassaemia intermedia and the iron load being more significant in the major form. Arrhythmias, vascular involvement that leads to an increased pulmonary vascular resistance and an increased systemic vascular stiffness and valvular abnormalities also contribute to the cardiac dysfunction in varying degrees according to the severity of the phenotype.  Endocrine abnormalities, infections, renal function and medications can also play a role in the overall cardiac function.  For thalassaemia major, regular and adequate blood transfusions and iron chelation therapy are the mainstays of management. The approach to thalassaemia intermedia, today, is aimed at monitoring for complications and initiating, timely, regular transfusions and/or iron chelation therapy.  Once the patients are on transfusions, then they should be managed in the same way as the thalassaemia major patients.  If cardiac manifestations of dysfunction are present in either form of thalassaemia, high pre transfusion Hb levels need to be maintained in order to reduce cardiac output and appropriate intensive chelation therapy needs to be instituted.  In general recommendations on chelation, today, are usually made according to the Cardiac Magnetic Resonance findings, if available.  With the advances in the latter technology and the ability to tailor chelation therapy according to the MRI findings as well as the availability of three iron chelators, together with

  5. Imaging tumor vasculature noninvasively with positron emission tomography and RGD peptides labeled with copper 64 using the bifunctonal chelates DOTA, oxo-DO3a. and PCTA.

    Science.gov (United States)

    Yapp, Donald T T; Ferreira, Cara L; Gill, Rajanvir K; Boros, Eszter; Wong, May Q; Mandel, Derek; Jurek, Paul; Kiefer, Garry E

    2013-06-01

    Two novel bifunctional chelates, 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA) and 1-oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid (Oxo-DO3A), were found to radiolabel antibodies with copper 64 (64Cu) well for positron emission tomography (PET). In this study, the same chelators were used to radiolabel peptides with 64Cu for PET imaging of angiogenesis. PCTA, Oxo-DO3A, and 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) were conjugated to cyclic-(RGDyK), and their binding affinities were confirmed. Conditions for 64Cu radiolabeling were optimized for maximum yield and specific activity. The in vitro stability of the radiolabeled compounds was challenged with serum incubation. PET studies were carried out in a non-αvβ3-expressing tumor model to evaluate the compounds' specificity for proliferating tumor vasculature and their in vivo pharmacokinetics. The PCTA and Oxo-DO3A bioconjugates were labeled with 64Cu at higher effective specific activity and radiochemical yield than the DOTA bioconjugate. In the imaging studies, all the 64Cu bioconjugates could be used to visualize the tumor and the radiotracer uptake was blocked with cyclic-(RGDyK). Target uptake of each bioconjugate was similar, but differences in other tissues were observed. 64Cu-PCTA-RGD showed the best clearance from nontarget tissue and the highest tumor to nontarget ratios. PCTA was the most promising bifunctional chelate for 64Cu peptide imaging and warrants further investigation.

  6. Imaging Tumor Vasculature Noninvasively with Positron Emission Tomography and RGD Peptides Labeled with Copper 64 Using the Bifunctonal Chelates DOTA, Oxo-DO3A. and PCTA

    Directory of Open Access Journals (Sweden)

    Donald T.T. Yapp

    2013-06-01

    Full Text Available Two novel bifunctional chelates, 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15,11,13-triene-3,6,9-triacetic acid (PCTA and 1-oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid (Oxo-DO3A, were found to radiolabel antibodies with copper 64 (64Cu well for positron emission tomography (PET. In this study, the same chelators were used to radiolabel peptides with 64Cu for PET imaging of angiogenesis. PCTA, Oxo-DO3A, and 1,4,7,10-tetraazacyclododecane-N,N‘,N“,N”’-tetraacetic acid (DOTA were conjugated to cyclic-(RGDyK, and their binding affinities were confirmed. Conditions for 64Cu radiolabeling were optimized for maximum yield and specific activity. The in vitro stability of the radiolabeled compounds was challenged with serum incubation. PET studies were carried out in a non-αvβ3-expressing tumor model to evaluate the compounds' specificity for proliferating tumor vasculature and their in vivo pharmacokinetics. The PCTA and Oxo-DO3A bioconjugates were labeled with 64Cu at higher effective specific activity and radiochemical yield than the DOTA bioconjugate. In the imaging studies, all the 64Cu bioconjugates could be used to visualize the tumor and the radiotracer uptake was blocked with cyclic-(RGDyK. Target uptake of each bioconjugate was similar, but differences in other tissues were observed. 64Cu-PCTA-RGD showed the best clearance from nontarget tissue and the highest tumor to nontarget ratios. PCTA was the most promising bifunctional chelate for 64Cu peptide imaging and warrants further investigation.

  7. Antimicrobial Properties of Copper Nanoparticles and Amino Acid Chelated Copper Nanoparticles Produced by Using a Soya Extract

    OpenAIRE

    DeAlba-Montero, I.; Guajardo-Pacheco, Jesús; Morales-Sánchez, Elpidio; Araujo-Martínez, Rene; Loredo-Becerra, G. M.; Martínez-Castañón, Gabriel-Alejandro; Ruiz, Facundo; Compeán Jasso, M. E.

    2017-01-01

    This paper reports a comparison of the antibacterial properties of copper-amino acids chelates and copper nanoparticles against Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis. These copper-amino acids chelates were synthesized by using a soybean aqueous extract and copper nanoparticles were produced using as a starting material the copper-amino acids chelates species. The antibacterial activity of the samples was evaluated by using the standard microdilution method (CLSI M...

  8. In vivo

    Science.gov (United States)

    Freudenblum, Julia; Iglesias, José A; Hermann, Martin; Walsen, Tanja; Wilfinger, Armin; Meyer, Dirk; Kimmel, Robin A

    2018-02-08

    The three-dimensional architecture of the pancreatic islet is integral to beta cell function, but the process of islet formation remains poorly understood due to the difficulties of imaging internal organs with cellular resolution. Within transparent zebrafish larvae, the developing pancreas is relatively superficial and thus amenable to live imaging approaches. We performed in vivo time-lapse and longitudinal imaging studies to follow islet development, visualizing both naturally occurring islet cells and cells arising with an accelerated timecourse following an induction approach. These studies revealed previously unappreciated fine dynamic protrusions projecting between neighboring and distant endocrine cells. Using pharmacological compound and toxin interference approaches, and single-cell analysis of morphology and cell dynamics, we determined that endocrine cell motility is regulated by phosphoinositide 3-kinase (PI3K) and G-protein-coupled receptor (GPCR) signaling. Linking cell dynamics to islet formation, perturbation of protrusion formation disrupted endocrine cell coalescence, and correlated with decreased islet cell differentiation. These studies identified novel cell behaviors contributing to islet morphogenesis, and suggest a model in which dynamic exploratory filopodia establish cell-cell contacts that subsequently promote cell clustering. © 2018. Published by The Company of Biologists Ltd.

  9. In Vivo

    Science.gov (United States)

    Lau, Melissa; Li, Jianli; Cline, Hollis T

    2017-01-01

    The neurovascular niche is a specialized microenvironment formed by the interactions between neural progenitor cells (NPCs) and the vasculature. While it is thought to regulate adult neurogenesis by signaling through vascular-derived soluble cues or contacted-mediated cues, less is known about the neurovascular niche during development. In Xenopus laevis tadpole brain, NPCs line the ventricle and extend radial processes tipped with endfeet to the vascularized pial surface. Using in vivo labeling and time-lapse imaging in tadpoles, we find that intracardial injection of fluorescent tracers rapidly labels Sox2/3-expressing NPCs and that vascular-circulating molecules are endocytosed by NPC endfeet. Confocal imaging indicates that about half of the endfeet appear to appose the vasculature, and time-lapse analysis of NPC proliferation and endfeet-vascular interactions suggest that proliferative activity does not correlate with stable vascular apposition. Together, these findings characterize the neurovascular niche in the developing brain and suggest that, while signaling to NPCs may occur through vascular-derived soluble cues, stable contact between NPC endfeet and the vasculature is not required for developmental neurogenesis.

  10. IN VIVO

    Science.gov (United States)

    Jamila, Nargis; Khan, Naeem; Khan, Amir Atlas; Khan, Imran; Khan, Sadiq Noor; Zakaria, Zainal Amiruddin; Khairuddean, Melati; Osman, Hasnah; Kim, Kyong Su

    2017-01-01

    Garcinia hombroniana , known as "manggis hutan" (jungle mangosteen) in Malaysia, is distributed in tropical Asia, Borneo, Thailand, Andaman, Nicobar Islands, Vietnam and India. In Malaysia, its ripened crimson sour fruit rind is used as a seasoning agent in curries and culinary dishes. Its roots and leaves decoction is used against skin infections and after child birth. This study aimed to evaluate in vivo hepatoprotective and in vitro cytotoxic activities of 20% methanolic ethyl acetate (MEA) G. hombroniana bark extract. In hepatoprotective activity, liver damage was induced by treating rats with 1.0 mL carbon tetrachloride (CCl 4 )/kg and MEA extract was administered at a dose of 50, 250 and 500 mg/kg 24 h before intoxication with CCl 4 . Cytotoxicity study was performed on MCF-7 (human breast cancer), DBTRG (human glioblastoma), PC-3 (human prostate cancer) and U2OS (human osteosarcoma) cell lines. 1 H, 13 C-NMR (nuclear magnetic resonance), and IR (infrared) spectral analyses were also conducted for MEA extract. In hepatoprotective activity evaluation, MEA extract at a higher dose level of 500 mg/kg showed significant (pIR spectra exhibited bands, signals and J (coupling constant) values representing aromatic/phenolic constituents. From the results, it could be concluded that MEA extract has potency to inhibit hepatotoxicity and MCF-7 and DBTRG cancer cell lines which might be due to the phenolic compounds depicted from NMR and IR spectra.

  11. N-acetylcysteine protects rats with chronic renal failure from gadolinium-chelate nephrotoxicity.

    Directory of Open Access Journals (Sweden)

    Leonardo Victor Barbosa Pereira

    Full Text Available The aim of this study was to evaluate the effect of Gd-chelate on renal function, iron parameters and oxidative stress in rats with CRF and a possible protective effect of the antioxidant N-Acetylcysteine (NAC. Male Wistar rats were submitted to 5/6 nephrectomy (Nx to induced CRF. An ionic-cyclic Gd (Gadoterate Meglumine was administrated (1.5 mM/KgBW, intravenously 21 days after Nx. Clearance studies were performed in 4 groups of anesthetized animals 48 hours following Gd- chelate administration: 1--Nx (n = 7; 2--Nx+NAC (n = 6; 3--Nx+Gd (n = 7; 4--Nx+NAC+Gd (4.8 g/L in drinking water, initiated 2 days before Gd-chelate administration and maintained during 4 days (n = 6. This group was compared with a control. We measured glomerular filtration rate, GFR (inulin clearance, ml/min/kg BW, proteinuria (mg/24 hs, serum iron (µg/dL; serum ferritin (ng/mL; transferrin saturation (%, TIBC (µg/dL and TBARS (nmles/ml. Normal rats treated with the same dose of Gd-chelate presented similar GFR and proteinuria when compared with normal controls, indicating that at this dose Gd-chelate is not nephrotoxic to normal rats. Gd-chelate administration to Nx-rats results in a decrease of GFR and increased proteinuria associated with a decrease in TIBC, elevation of ferritin serum levels, transferrin oversaturation and plasmatic TBARS compared with Nx-rats. The prophylactic treatment with NAC reversed the decrease in GFR and the increase in proteinuria and all alterations in iron parameters and TBARS induced by Gd-chelate. NAC administration to Nx rat did not modify the inulin clearance and iron kinetics, indicating that the ameliorating effect of NAC was specific to Gd-chelate. These results suggest that NAC can prevent Gd-chelate nephrotoxicity in patients with chronic renal failure.

  12. Intracellular reduction/activation of a disulfide switch in thiosemicarbazone iron chelators.

    Science.gov (United States)

    Akam, Eman A; Chang, Tsuhen M; Astashkin, Andrei V; Tomat, Elisa

    2014-10-01

    Iron scavengers (chelators) offer therapeutic opportunities in anticancer drug design by targeting the increased demand for iron in cancer cells as compared to normal cells. Prochelation approaches are expected to avoid systemic iron depletion as chelators are liberated under specific intracellular conditions. In the strategy described herein, a disulfide linkage is employed as a redox-directed switch within the binding unit of an antiproliferative thiosemicarbazone prochelator, which is activated for iron coordination following reduction to the thiolate chelator. In glutathione redox buffer, this reduction event occurs at physiological concentrations and half-cell potentials. Consistent with concurrent reduction and activation, higher intracellular thiol concentrations increase cell susceptibility to prochelator toxicity in cultured cancer cells. The reduction of the disulfide switch and intracellular iron chelation are confirmed in cell-based assays using calcein as a fluorescent probe for paramagnetic ions. The resulting low-spin Fe(III) complex is identified in intact Jurkat cells by EPR spectroscopy measurements, which also document a decreased concentration of active ribonucleotide reductase following exposure to the prochelator. Cell viability and fluorescence-based assays show that the iron complex presents low cytotoxicity and does not participate in intracellular redox chemistry, indicating that this antiproliferative chelation strategy does not rely on the generation of reactive oxygen species.

  13. Increased Uptake of Chelated Copper Ions by Lolium perenne Attributed to Amplified Membrane and Endodermal Damage

    Directory of Open Access Journals (Sweden)

    Anthea Johnson

    2015-10-01

    Full Text Available The contributions of mechanisms by which chelators influence metal translocation to plant shoot tissues are analyzed using a combination of numerical modelling and physical experiments. The model distinguishes between apoplastic and symplastic pathways of water and solute movement. It also includes the barrier effects of the endodermis and plasma membrane. Simulations are used to assess transport pathways for free and chelated metals, identifying mechanisms involved in chelate-enhanced phytoextraction. Hypothesized transport mechanisms and parameters specific to amendment treatments are estimated, with simulated results compared to experimental data. Parameter values for each amendment treatment are estimated based on literature and experimental values, and used for model calibration and simulation of amendment influences on solute transport pathways and mechanisms. Modeling indicates that chelation alters the pathways for Cu transport. For free ions, Cu transport to leaf tissue can be described using purely apoplastic or transcellular pathways. For strong chelators (ethylenediaminetetraacetic acid (EDTA and diethylenetriaminepentaacetic acid (DTPA, transport by the purely apoplastic pathway is insufficient to represent measured Cu transport to leaf tissue. Consistent with experimental observations, increased membrane permeability is required for simulating translocation in EDTA and DTPA treatments. Increasing the membrane permeability is key to enhancing phytoextraction efficiency.

  14. Reversible adsorption of catalase onto Fe(3+) chelated poly(AAm-GMA)-IDA cryogels.

    Science.gov (United States)

    Aktaş Uygun, Deniz; Uygun, Murat; Akgöl, Sinan; Denizli, Adil

    2015-05-01

    In this presented study, poly(acrylamide-glycidyl methacrylate) [poly(AAm-GMA)] cryogels were synthesized by cryopolymerization technique at sub-zero temperature. Prepared cryogels were then functionalized with iminodiacetic acid (IDA) and chelated with Fe(3+) ions in order produce the metal chelate affinity matrix. Synthesized cryogels were characterized with FTIR, ESEM and EDX analysis, and it was found that the cryogel had sponge like structure with interconnected pores and their pore diameter was about 200 μm. Fe(3+) chelated poly(AAm-GMA)-IDA cryogels were used for the adsorption of catalase and optimum adsorption conditions were determined by varying the medium pH, initial catalase concentration, temperature and ionic strength. Maximum catalase adsorption onto Fe(3+) chelated poly(AAm-GMA)-IDA cryogel was found to be 12.99 mg/g cryogel at 25 °C, by using pH 5.0 acetate buffer. Adsorbed catalase was removed from the cryogel by using 1.0M of NaCl solution and desorption yield was found to be 96%. Additionally, reusability profile of the Fe(3+) chelated poly(AAm-GMA)-IDA cryogel was also investigated and it was found that, adsorption capacity of the cryogels didn't decrease significantly at the end of the 40 reuses. Catalase activity studies were also tested and it was demonstrated that desorbed catalase retained 70% of its initial activity. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Effect of different chelated zinc sources on the growth and yield of maize (Zea mays L.

    Directory of Open Access Journals (Sweden)

    M. Tahir

    2009-05-01

    Full Text Available A field study was conducted at Agronomic Research Area, University of Agriculture, Faisalabad during spring, 2007 to evaluate the effect of different chelated zinc sources on growth and yield of maize (Zea mays L.. Crop was sown on well prepared soil in 1st week of March, 2007. The experiment was laid out according to randomized complete block design. The treatments comprised of different chelated zinc sources: ZnSO4-DTPA, ZnSO4-Fulvate, ZnSO4-Lignosulphonate, ZnSO4-EDTA and ZnSO4-H2O along with control (no zinc, repeated three times. Results showed that number of cobs plant-1, grain rows cob-1 and oil contents did not differ significantly. However, differences among treatments for plant height at harvest (cm, leaf area plant-1 (cm2, stem diameter (cm, cob length (cm, cob diameter (cm, 100-grains weight (g, number of grains cob-1, grains weight cob-1(g, biological yield (tons ha-1, grain yield (tons ha-1 and protein contents (% were significantly higher. Moreover, results also revealed that ZnSO4-DPTA was found the most effective Zn chelated source among all the treatments. Rest of the chelating agents were not too impressive as they showed varied response for different variables. The result of this experiment suggest further experimentation to explore behaviour of Zn-DTPA with other macro and micro nutrients and to calculate cost benefit ratio for use ofZn chelated compounds.

  16. Assessment of iron chelates efficiency for photo-Fenton at neutral pH.

    Science.gov (United States)

    De Luca, Antonella; Dantas, Renato F; Esplugas, Santiago

    2014-09-15

    In this study, homogeneous photo-Fenton like at neutral pH was applied to remove sulfamethoxazole from water. The process was performed using different chelating agents in order to solubilize iron in a neutral water solution. The chelating agents tested were: ethylenediaminetetraacetic acid (EDTA); nitrilotriacetic acid (NTA); oxalic acid (OA) and tartaric acid (TA). The iron leaching was monitored over reaction time to evaluate the chelates stability and their resistance to HO· and UV-A radiation. Chelates of EDTA and NTA presented more stability than OA and TA, which also confirmed their higher efficiency. Total Organic Carbon (TOC) analyses were also performed to evaluate the contribution in terms of solution contamination related to the use of chelating agents. The better properties of biodegradability in respect of EDTA combined with better efficiency in terms of microcontaminant removal and the smallest TOC contribution indicate that NTA could represent a useful option to perform photo-Fenton processes at neutral pH. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Metal-chelating compounds produced by ectomycorrhizal fungi collected from pine plantations.

    Science.gov (United States)

    Machuca, A; Pereira, G; Aguiar, A; Milagres, A M F

    2007-01-01

    To investigate the in vitro production of metal-chelating compounds by ectomycorrhizal fungi collected from pine plantations in southern Chile. Scleroderma verrucosum, Suillus luteus and two isolates of Rhizopogon luteolus were grown in solid and liquid modified Melin-Norkans (MMN) media with and without iron addition and the production of iron-chelating compounds was determined by Chrome Azurol S (CAS) assay. The presence of hydroxamate and catecholate-type compounds and organic acids was also investigated in liquid medium. All isolates produced iron-chelating compounds as detected by CAS assay, and catecholates, hydroxamates as well as oxalic, citric and succinic acids were also detected in all fungal cultures. Scleroderma verrucosum produced the greatest amounts of catecholates and hydroxamates whereas the highest amounts of organic acids were detected in S. luteus. Nevertheless, the highest catecholate, hydroxamate and organic acid concentrations did not correlate with the highest CAS reaction which was observed in R. luteolus (Yum isolate). Ectomycorrhizal fungi produced a variety of metal-chelating compounds when grown in liquid MMN medium. However, the addition of iron to all fungi cultures reduced the CAS reaction, hydroxamate and organic acid concentrations. Catecholate production was affected differently by iron, depending on the fungal isolate. The ectomycorrhizal fungi described in this study have never been reported to produce metal-chelating compound production. Moreover, apart from some wood-rotting fungi, this is the first evidence of the presence of catecholates in R. luteolus, S. luteus and S. verrucosum cultures.

  18. Structure-activity relationships of novel salicylaldehyde isonicotinoyl hydrazone (SIH) analogs: iron chelation, anti-oxidant and cytotoxic properties

    National Research Council Canada - National Science Library

    Potůčková, Eliška; Hrušková, Kateřina; Bureš, Jan; Kovaříková, Petra; Špirková, Iva A; Pravdíková, Kateřina; Kolbabová, Lucie; Hergeselová, Tereza; Hašková, Pavlína; Jansová, Hana; Macháček, Miloslav; Jirkovská, Anna; Richardson, Vera; Lane, Darius J R; Kalinowski, Danuta S; Richardson, Des R; Vávrová, Kateřina; Šimůnek, Tomáš

    2014-01-01

    ...). Their structure-activity relationships were assessed with respect to their stability in plasma, iron chelation efficacy, redox effects and cytotoxic activity against MCF-7 breast adenocarcinoma cells...

  19. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications.

    Science.gov (United States)

    Nagai, Ryoji; Murray, David B; Metz, Thomas O; Baynes, John W

    2012-03-01

    This article outlines evidence that advanced glycation end product (AGE) inhibitors and breakers act primarily as chelators, inhibiting metal-catalyzed oxidation reactions that catalyze AGE formation. We then present evidence that chelation is the most likely mechanism by which ACE inhibitors, angiotensin receptor blockers, and aldose reductase inhibitors inhibit AGE formation in diabetes. Finally, we note several recent studies demonstrating therapeutic benefits of chelators for diabetic cardiovascular and renal disease. We conclude that chronic, low-dose chelation therapy deserves serious consideration as a clinical tool for prevention and treatment of diabetes complications.

  20. Detection of decontamination solution chelating agents using ion selective coated-wire electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Banks, Mark Lavior [Arizona Univ., Tucson, AZ (United States)

    1992-01-01

    This thesis explores feasibility of using coated-wire electrodes to measure chelating agent concentration. Chelating agents are often found in radioactive decontamination solutions because they aid in the removal of radionuclides from contaminated surfaces by increasing their solubility. However, this characteristic will also enhance the mobility of the radionuclide and thus its transport out of a waste disposal site. Coated-wire ion selective electrodes, based on a polyvinylchloride membrane using dioctylphthalate as a plasticizer and dinonylnaphthalenesulfonic acid as a counterion, were constructed for five commonly utilized chelating agents (ethylenediaminetetracetic acid (EDTA), nitrilotriacetic acid (NTA), citric acid, oxalic acid and tartaric add). The EDTA and NTA electrodes` calibration characteristics exhibited acceptable behavior in pure standard solutions. From data obtained while using the EDTA and NTA electrodes in a cement environment, further research needs to be done in the area of ion interference.

  1. Renal handling of amino acid /sup 99m/technetium chelates

    Energy Technology Data Exchange (ETDEWEB)

    Chattopadhyay, M.; Banerjee, S.

    1988-09-01

    Four amino acids--alanine, 2,3-diaminopropionic acid, cystine, and cystein--and also one diamine, ethylenediamine, were chelated with /sup 99m/-technetium (/sup 99m/Tc), and their renal excretion patterns were studied in rabbits in the presence and absence of two renal tubular transport inhibitors, probenecid and 2,4-dinitrophenol. From the depression of renal excretion for the first three amino acid chelates, in the presence of the inhibitors, a renal tubular excretory pathway of elimination was suggested for these compounds. The renal excretions of /sup 99m/Tc-cystein and /sup 99m/Tc-ethylenediamine however, remained undepressed under similar experimental conditions. An explanation of these observations was forwarded from the possible chemical structures of these chelates.

  2. Antioxidant and mercury chelating activity of Psidium guajava var. pomifera L. leaves hydroalcoholic extract.

    Science.gov (United States)

    Pinho, Antonio Ivanildo; Oliveira, Cláudia Sirlene; Lovato, Fabricio Luís; Waczuk, Emily Pansera; Piccoli, Bruna Candia; Boligon, Aline Augusti; Leite, Nadghia Figueredo; Coutinho, Henrique Douglas Melo; Posser, Thais; Da Rocha, João Batista Teixeira; Franco, Jeferson Luis

    2017-01-01

    Mercury (Hg) is widely distributed in the environment and is known to produce several adverse effects in organisms. The aim of the present study was to examine the in vitro antioxidant activity and Hg chelating ability of the hydroalcoholic extract of Psidium guajava leaves (HEPG). In addition, the potential protective effects of HEPG against Hg(II) were evaluated using a yeast model (Saccharomyces cerevisiae). HEPG was found to exert significant antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenger and inhibition of lipid peroxidation induced by Fe(II) assays in a concentration-dependent manner. The extract also exhibited significant Hg(II) chelating activity. In yeast, Hg(II) induced a significant decrease in cell viability. In contrast, HEPG partially prevented the fall in cell viability induced by Hg(II). In conclusion, HEPG exhibited protective effects against Hg(II)-mediated toxicity, which may be related to both antioxidant and Hg(II)-chelating activities.

  3. REVIEW ARTICLE:Future of Lead Chelation – Distribution and Treatment

    Directory of Open Access Journals (Sweden)

    Venkatesh Thuppil

    2012-01-01

    Full Text Available Lead is the major environmental toxin resulting in the ill health and deleterious effect on almost all organs in the human body in a slow and effective manner. The best treatment for lead poisoning is chelation therapy which is next only to prevention. The authors describe the disruption of homeostasis of the human body by lead in various tissues like blood, bones, liver, kidneys and brain; and the ability of lead to enter the cell using calcium channels and calcium receptors like Ca++ dependant K+ ion channels, transient receptor potential channels, T-tubules, calmodulin receptors, inositol trisphosphate receptors and ryanodine receptors. We report a few novel chelating agents like ionophores, decadentate ligands, picolinate ligands, octadentate ligand, allicin, thiamine, that show good potential for being used in chelation therapy. Future of leadpoisoning is a challenge to all and it needs to be meticulously studies to have an economic and health approach.

  4. Chelating agents improve enzymatic solubilization of pectinaceous co-processing streams

    DEFF Research Database (Denmark)

    Ravn, Helle Christine; Meyer, Anne S.

    2014-01-01

    /substrate] at 60 °C, pH 6.0 for 1 min. Characterization of the released fractions demonstrated a significantly improved effect of chelating agents for polysaccharide solubilization from FiberBind 400, PUF, and citrus peel, whereas only low amounts of polysaccharides were solubilized from the sugar beet pulp...... solubilization yields. The effect of the chelating agents correlated to their dissociation constants (pKa values) and calcium binding constants and citric acid and EDTA exerted highest effects. Maximum polysaccharide yield was obtained for FiberBind 400 where the enzymatic treatment in presence of citric acid......This study investigates the hypothesis that loosening of the egg-box structure by presence of divalent ion chelating agents during enzymatic degradation of homogalacturonan (HG) can improve enzymatic polysaccharide solubilization on pectinaceous, agro-industrial co-processing streams. The influence...

  5. Classification of the Electronic Properties of Chelating Ligands in cis-[LL'Rh(CO)2] Complexes.

    Science.gov (United States)

    Canac, Yves; Lepetit, Christine

    2017-01-03

    By analogy to the Tolman electronic parameter, a ligand electronic parameter, referred to as L2EP, is introduced here for estimating the donating ability of chelating ligands, featuring two coordinating extremities. It is based on the average of the computed infrared stretching frequencies of CO in a series of isostructural rhodium(I)-dicarbonyl complexes, that is linearly correlated to the number x of N-heterocyclic carbene coordinating ends (x = 0, 1, or 2). The L2EP values allow the design of an unified scale for the classification of the electron donation of chelating ligands, based on an ortho-phenylene bridge substituted by two coordinating extremities, which may have a different donating character. Strengths and limitations of the L2EP scale are illustrated for a large diversity of bidentate chelating ligands with coordinating ends ranging from extremely electron-rich phosphonium yldiides to extremely electron-poor amidiniophosphonites.

  6. Controlling lipid oxidation via a biomimetic iron chelating active packaging material.

    Science.gov (United States)

    Tian, Fang; Decker, Eric A; Goddard, Julie M

    2013-12-18

    Previously, a siderophore-mimetic metal chelating active packaging film was developed by grafting poly(hydroxamic acid) (PHA) from the surface of polypropylene (PP) films. The objective of the current work was to demonstrate the potential applicability of this PP-g-PHA film to control iron-promoted lipid oxidation in food emulsions. The iron chelating activity of this film was investigated, and the surface chemistry and color intensity of films were also analyzed after iron chelation. In comparison to the iron chelating activity in the free Fe(3+) solution, the PP-g-PHA film retained approximately 50 and 30% of its activity in nitrilotriacetic acid (NTA)/Fe(3+) and citric acid/Fe(3+) solutions, respectively (pH 5.0), indicating a strong chelating strength for iron. The ability of PP-g-PHA films to control lipid oxidation was demonstrated in a model emulsion system (pH 3.0). PP-g-PHA films performed even better than ethylenediaminetetraacetic acid (EDTA) in preventing the formation of volatile oxidation products. The particle size and ζ potential results of emulsions indicated that PP-g-PHA films had no adverse effects on the stability of the emulsion system. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis suggested a non-migratory nature of the PP-g-PHA film surface. These results suggest that such biomimetic, non-migratory metal chelating active packaging films have commercial potential in protecting foods against iron-promoted lipid oxidation.

  7. The preparation and characterization of novel human-like collagen metal chelates

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Chenhui; Sun, Yan [Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering Northwest University, Xi' an 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Xi' an 710069 (China); Wang, Yaoyu [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, Xi' an 710069 (China); Luo, Yane, E-mail: luoyane@nwu.edu.cn [Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering Northwest University, Xi' an 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Xi' an 710069 (China); Fan, Daidi, E-mail: fandaidi@nwu.edu.cn [Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering Northwest University, Xi' an 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Xi' an 710069 (China)

    2013-07-01

    In order to develop the nutritional trace elements which could be absorbed and utilized effectively, protein chelates were adopted. Calcium, copper and manganese were considered based on their physiological functions, and the new chelates of HLC-Ca, HLC-Cu and HLC-Mn were formed in MOPS or MES buffer and purified by gel chromatography, and then freeze-dried. And they were detected and analyzed by atomic absorption spectrophotometry, ultraviolet–visible absorption (UV–vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, fluorescence quenching method, circular dichroism (CD) and differential scanning calorimetry (DSC). The results showed that some chemical reactions happened between HLC and the three metal ions to form new chemical compounds. The thermodynamic parameters, ∆H, ∆G and ∆S, showed that the chelation process between HLC and metal ions was performed spontaneously. Fluorescence quenching spectra of HLC indicated that the quenching mechanism was static in nature. According to the data of DSC, the new chelates were more stable than the free HLC. And HLC-metal complex was non-toxic to the BHK21 cell through MTT assay. - Highlights: ► HLC-Ca, HLC-Cu and HLC-Mn were new chemical compounds and different to free HLC. ► Possible sites for Ca{sup 2+}, Cu{sup 2+} and Mn{sup 2+} to bind with HLC were presented. ► The chelation process between HLC and metal ions was performed spontaneously. ► The thermodynamic stability of the new chelates was higher than that of free HLC.

  8. Heavy metal induced oxidative stress & its possible reversal by chelation therapy.

    Science.gov (United States)

    Flora, S J S; Mittal, Megha; Mehta, Ashish

    2008-10-01

    Exposure to heavy metals is a common phenomenon due to their environmental pervasiveness. Metal intoxication particularly neurotoxicity, genotoxicity, or carcinogenicity is widely known. This review summarizes our current understanding about the mechanism by which metalloids or heavy metals (particularly arsenic, lead, cadmium and mercury) induce their toxic effects. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. The toxic manifestations of these metals are caused primarily due to imbalance between pro-oxidant and antioxidant homeostasis which is termed as oxidative stress. Besides these metals have high affinity for thiol groups containing enzymes and proteins, which are responsible for normal cellular defense mechanism. Long term exposure to these metals could lead to apoptosis. Signaling components affected by metals include growth factor receptors, G-proteins, MAP kinases and transcription factors. Chelation therapy with chelating agents like calcium disodium ethylenediamine tetra acetic acid (CaNa(2)EDTA), British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3-dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against metal poisoning. Despite many years of research we are still far away from effective treatment against toxicity caused due to exposure to heavy metals/metalloids. The treatment with these chelating agents is compromised with number of serious side-effects. Studies show that supplementation of antioxidants along-with a chelating agent prove to be a better treatment regimen than monotherapy with chelating agents. This review attempts a comprehensive account of recent developments in the research on heavy metal poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a

  9. Chelation Ion Exchange Properties of 2, 4-Dihydroxyacetophenone-Biuret-Formaldehyde Terpolymer Resin

    OpenAIRE

    Sanjiokumar S. Rahangdale; Anil B. Zade; Wasudeo B. Gurnule

    2009-01-01

    The terpolymer resin 2, 4-HABF has been synthesized by the condensation of 2, 4-dihydroxyacetophenone (2, 4-HA) and biuret (B) with formaldehyde (F) in 1:1:2 molar ratios in presence of 2 M hydrochloric acid as catalyst. UV-Visible, IR and proton NMR spectral studies have been carried out to elucidate the structure of the resin. A terpolymer (2, 4-HABF) proved to be a selective chelating ion exchange polymer for certain metals. Chelating ion-exchange properties of this polymer were studied fo...

  10. Arsenic induced blood and brain oxidative stress and its response to some thiol chelators in rats.

    Science.gov (United States)

    Flora, Swaran J S; Bhadauria, Smrati; Pant, Satish C; Dhaked, Ram K

    2005-09-16

    Chronic arsenic toxicity is a widespread problem, not only in India and Bangladesh but also in various other regions of the world. Exposure to arsenic may occur from natural or industrial sources. The treatment that is in use at present employs administration of thiol chelators, such as meso 2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), which facilitate its excretion from the body. However, these chelating agents are compromised with number of limitations due to their lipophobic nature, particularly for their use in cases of chronic poisoning. During chronic exposure, arsenic gains access into the cell and it becomes mandatory for a drug to cross cell membrane to chelate intracellular arsenic. To address this problem, analogs of DMSA having lipophilic character, were examined against chronic arsenic poisoning in experimental animals. In the present study, therapeutic efficacy of meso 2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), monoisoamyl DMSA (MiADMSA) were compared in terms of reducing arsenic burden, as well as recovery in the altered biochemical variables particularly suggestive of oxidative stress. Adult male Wistar rats were given 100-ppm arsenic for 10 weeks followed by chelation therapy with the above chelating agents at a dose of 50 mg/Kg (orally) once daily for 5 consecutive days. Arsenic exposure resulted in marked elevation in reactive oxygen species (ROS) in blood, inhibition of ALAD activity and depletion of GSH. These changes were accompanied by significant decline in blood hemoglobin level. MiADMSA was the most effective chelator in reducing ROS in red blood cells, and in restoring blood ALAD compared to two other chelators. Brain superoxide dismutase (SOD) and glutathione peroxidase (GPx) decreased, while ROS and TBARS increased significantly following arsenic exposure. There was a significant increase in the activity of glutathione-S-transferase (GST) with a

  11. New aryloxybenzylidene ruthenium chelates – synthesis, reactivity and catalytic performance in ROMP

    Directory of Open Access Journals (Sweden)

    Patrycja Żak

    2015-10-01

    Full Text Available New phenoxybenzylidene ruthenium chelates were synthesised from the second generation Grubbs catalysts bearing a triphenylphosphine ligand (or its para-substituted analogues by metathesis exchange with substituted 2-vinylphenols. The complexes behave like a latent catalyst and are characterized by an improved catalytic behaviour as compared to that of the known analogues, i.e., they exhibit high catalytic inactivity in their dormant forms and a profound increase in activity after activation with HCl. The strong electronic influence of substituents in the chelating ligand on the catalytic activity was demonstrated. The catalytic properties were tested in ROMP of cyclooctadien (COD and a single selected norbornene derivative.

  12. IRON CHELATING AND ANTIRADICAL ACTIVITY OF KAYU MANIK LEAVES (Trema orientalis

    Directory of Open Access Journals (Sweden)

    Salprima Yudha S.

    2011-11-01

    Full Text Available A methanol soluble fraction extracted from Kayu Manik leaves (Trema orientalis from Seluma, Bengkulu, exhibited an antiradical activity 69.73% (scavenging activity of the stable 1,1-diphenyl-2-picryl hydrazyl (DPPH free radical that was almost similar to that of 1 mM ascorbic acid. On the other hand, the iron chelating activity was 40.74%. We believe that it would be useful to take the results as an alternative for processing industries and can be observed as a good source of new agent for iron chelator.

  13. Synthesis and evaluation of novel bifunctional chelating agents based on 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid for radiolabeling proteins

    Energy Technology Data Exchange (ETDEWEB)

    Chappell, L.L.; Ma, D.; Milenic, D.E.; Garmestani, K.; Venditto, V.; Beitzel, M.P.; Brechbiel, M.W. E-mail: martinwb@mail.nih.gov

    2003-08-01

    Detailed synthesis of the bifunctional chelating agents 2-methyl-6-(p-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10 -tetraacetic acid (1B4M-DOTA) and 2-(p-isothiocyanatobenzyl)-5, 6-cyclohexano-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetate (CHX-DOTA) are reported. These chelating agents were compared to 2-(p-isothiocyanatobenzyl)-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (C-DOTA) and 1, 4, 7, 10-Tetraaza-N-(1-carboxy-3-(4-nitrophenyl)propyl)-N', N'', N'''-tris(acetic acid) cyclododecane (PA-DOTA) as their {sup 177}Lu radiolabeled conjugates with Herceptin{sup TM}. In vitro stability of the immunoconjugates radiolabeled with {sup 177}Lu was assessed by serum stability studies. The in vivo stability of the radiolabeled immunoconjugates and their targeting characteristics were determined by biodistribution studies in LS-174T xenograft tumor-bearing mice. Relative radiolabeling rates and efficiencies were determined for all four immunoconjugates. Insertion of the 1B4M moiety into the DOTA backbone increases radiometal chelation rate and provides complex stability comparable to C-DOTA and PA-DOTA while the CHX-DOTA appears to not form as stable a {sup 177}Lu complex while exhibiting a substantial increase in formation rate. The 1B4M-DOTAmay have potential for radioimmunotherapy applications. Published by Elsevier Inc. All rights reserved.

  14. Solution thermodynamic evaluation of hydroxypyridinonate chelators 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO) for UO{sub 2}(VI) and Th(IV) decorporation

    Energy Technology Data Exchange (ETDEWEB)

    Sturzbecher-Hoehne, M.; Deblonde, G.J.P.; Abergel, R.J. [Lawrence Berkeley National Laboratory, CA (United States). Chemical Sciences Div.

    2013-08-01

    Solution thermodynamic studies were performed to characterize the coordination of U(VI) and Th(IV) by the multidentate hydroxypyridinonate chelating agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO). Species distribution and conditional stability pM profiles were calculated based on the determined formation constants, showing that both ligands form extremely stable uranyl and thorium complexes in solution. At physiological pH, the formation of 1:1 ligand:uranyl complexes is favored for both ligands, while a 2:1 ligand:thorium complex is predominant with the tetradentate 5-LIO(Me-3,2-HOPO). Comparisons with functionally similar bidentate ligands as well as with the common actinide chelator diethylenetriamine pentaacetic acid emphasized the superior affinity for U(VI) and Th(IV) of both experimental compounds over a wide pH range. These analytical results corroborate the in vivo chelation efficacy of 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO) and validate their selection for further development as therapeutic actinide decorporation agents. (orig.)

  15. Improvement of Oxidative and Metabolic Parameters by Cellfood Administration in Patients Affected by Neurodegenerative Diseases on Chelation Treatment

    Directory of Open Access Journals (Sweden)

    Alessandro Fulgenzi

    2014-01-01

    Full Text Available Objective. This prospective pilot study aimed at evaluating the effects of therapy with antioxidant compounds (Cellfood, and other antioxidants on patients affected by neurodegenerative diseases (ND, who displayed toxic metal burden and were subjected to chelation treatment with the chelating agent calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA or EDTA. Methods. Two groups of subjects were studied: (a 39 patients affected by ND and (b 11 subjects unaffected by ND (controls. The following blood parameters were analyzed before and after three months’ treatment with chelation + Cellfood or chelation + other antioxidants: oxidative status (reactive oxygen species, ROS; total antioxidant capacity, TAC; oxidized LDL, oxLDL; glutathione, homocysteine, vitamin B12, and folate. Results. After 3-months’ chelation + Cellfood administration oxLDL decreased, ROS levels were significantly lower, and TAC and glutathione levels were significantly higher than after chelation + other antioxidants treatment, both in ND patients and in controls. Moreover, homocysteine metabolism had also improved in both groups. Conclusions. Chelation + Cellfood treatment was more efficient than chelation + other antioxidants improving oxidative status and homocysteine metabolism significantly in ND patients and controls. Although limited to a small number of cases, this study showed how helpful antioxidant treatment with Cellfood was in improving the subjects’ metabolic conditions.

  16. Effects of nutrient trace metal speciation on algal growth in the presence of the chelator [S,S]-EDDS

    NARCIS (Netherlands)

    Schowanek, D.; McAvoy, D.; Versteeg, D.; Hanstveit, A.

    1996-01-01

    This study tests the hypothesis that the apparent toxicity of strong chelators in standard algal growth inhibition tests (e.g. method OECD 201, EC C.3., ISO 8692) is related to essential trace metal bioavailability. This hypothesis was investigated for the chelator [S,S]-ethylene diamine disuccinate

  17. Ascorbate status modulates reticuloendothelial iron stores and response to deferasirox iron chelation in ascorbate-deficient rats

    DEFF Research Database (Denmark)

    Brewer, Casey; Otto-Duessel, Maya; Lykkesfeldt, Jens

    2012-01-01

    Iron chelation is essential to patients on chronic blood transfusions to prevent toxicity from iron overload and remove excess iron. Deferasirox (DFX) is the most commonly used iron chelator in the United States; however, some patients are relatively refractory to DFX therapy. We postulated that ...

  18. A chelating tetrapeptide rhodium complex comprised of a histidylidene residue: biochemical tailoring of an NHC-Rh hydrosilylation catalyst.

    Science.gov (United States)

    Monney, Angèle; Albrecht, Martin

    2012-11-18

    Coupling of a histidinium salt with a MetAlaAla amino acid sequence followed by metallation with [RhCl(cod)](2) yields a rhodium(I) NHC complex with a pending peptide residue. Methionine chelation, induced by chloride abstraction from the metal coordination sphere, affords an efficient hydrosilylation catalyst precursor comprised of a peptidic macrocyclic chelate backbone.

  19. Iron(III) chelating resins. VI. Stability constants of iron(III)-ligand complexes on insoluble polymeric matrices

    NARCIS (Netherlands)

    Feng, M.H.; Feng, Minhua; van der Does, L.; Bantjes, A.; Bantjes, Adriaan

    1995-01-01

    A method is presented for the determination of stability constants of iron(III)-ligand complexes on insoluble polymeric matrices based on a competition chelation reaction for iron(III) of the resin with a soluble chelator. Stability constants (K') were calculated for iron(III)-ligand complexes on

  20. Characterization of radionuclide-chelating agent complexes found in low-level radioactive decontamination waste. Literature review

    Energy Technology Data Exchange (ETDEWEB)

    Serne, R.J.; Felmy, A.R.; Cantrell, K.J.; Krupka, K.M.; Campbell, J.A.; Bolton, H. Jr.; Fredrickson, J.K. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-03-01

    The US Nuclear Regulatory Commission is responsible for regulating the safe land disposal of low-level radioactive wastes that may contain organic chelating agents. Such agents include ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), picolinic acid, oxalic acid, and citric acid, and can form radionuclide-chelate complexes that may enhance the migration of radionuclides from disposal sites. Data from the available literature indicate that chelates can leach from solidified decontamination wastes in moderate concentration (1--100 ppm) and can potentially complex certain radionuclides in the leachates. In general it appears that both EDTA and DTPA have the potential to mobilize radionuclides from waste disposal sites because such chelates can leach in moderate concentration, form strong radionuclide-chelate complexes, and can be recalcitrant to biodegradation. It also appears that oxalic acid and citric acid will not greatly enhance the mobility of radionuclides from waste disposal sites because these chelates do not appear to leach in high concentration, tend to form relatively weak radionuclide-chelate complexes, and can be readily biodegraded. In the case of picolinic acid, insufficient data are available on adsorption, complexation of key radionuclides (such as the actinides), and biodegradation to make definitive predictions, although the available data indicate that picolinic acid can chelate certain radionuclides in the leachates.

  1. Iron chelators do not reduce cold-induced cell injury in the isolated perfused rat kidney model.

    NARCIS (Netherlands)

    Bartels-Stringer, M.; Wetzels, J.F.M.; Wouterse, A.C.; Steenbergen, E.; Russel, F.G.M.; Kramers, C.

    2005-01-01

    BACKGROUND: In vitro, cold-induced injury is an important contributor to renal tubular cell damage. It is mediated by iron-dependent formation of reactive oxygen species and can be prevented by iron chelation. We studied whether iron chelators can prevent cold-induced damage in the isolated perfused

  2. Synergistic Activities of an Efflux Pump Inhibitor and Iron Chelators against Pseudomonas aeruginosa Growth and Biofilm Formation

    DEFF Research Database (Denmark)

    Liu, Yang; Yang, Liang; Molin, Søren

    2010-01-01

    The efflux pump inhibitor phenyl-arginine-beta-naphthylamide (PA beta N) was paired with iron chelators 2,2'-dipyridyl, acetohydroxamic acid, and EDTA to assess synergistic activities against Pseudomonas aeruginosa growth and biofilm formation. All of the tested iron chelators synergistically...

  3. Iron Oxide Decorated MoS2 Nanosheets with Double PEGylation for Chelator-Free Radiolabeling and Multimodal Imaging Guided Photothermal Therapy

    Science.gov (United States)

    Liu, Teng; Shi, Sixiang; Liang, Chao; Shen, Sida; Cheng, Liang; Wang, Chao; Song, Xuejiao; Goel, Shreya; Barnhart, Todd E.; Cai, Weibo; Liu, Zhuang

    2015-01-01

    Theranostics for in vivo cancer diagnosis and treatment generally requires well-designed nanoscale platforms with multiple integrated functionalities. In this study, we uncover that functionalized iron oxide nanoparticles (IONPs) could be self-assembled on the surface of two-dimensional MoS2 nanosheets via sulfur chemistry, forming MoS2-IO nanocomposites, which are then modified with two types of polyethylene glycol (PEG) to acquire enhanced stability in physiological environments. Interestingly, 64Cu, a commonly used positron-emitting radioisotope, could be firmly adsorbed on the surface of MoS2 without the need of chelating molecules, to enable in vivo positron emission tomography (PET) imaging. On the other hand, the strong near-infrared (NIR) and superparamagnetism of MoS2-IO-PEG could also be utilized for photoacoustic tomography (PAT) and magnetic resonance (MR) imaging, respectively. Under the guidance by such triple-modal imaging, which uncovers efficient tumor retention of MoS2-IO-(d)PEG upon intravenous injection, in vivo photothermal therapy is finally conducted, achieving effective tumor ablation in an animal tumor model. Our study highlights the promise of constructing multifunctional theranostic nanocomposites based on 2D transitional metal dichalcogenides for multimodal imaging-guided cancer therapy. PMID:25562533

  4. Iron oxide decorated MoS2 nanosheets with double PEGylation for chelator-free radiolabeling and multimodal imaging guided photothermal therapy.

    Science.gov (United States)

    Liu, Teng; Shi, Sixiang; Liang, Chao; Shen, Sida; Cheng, Liang; Wang, Chao; Song, Xuejiao; Goel, Shreya; Barnhart, Todd E; Cai, Weibo; Liu, Zhuang

    2015-01-27

    Theranostics for in vivo cancer diagnosis and treatment generally requires well-designed nanoscale platforms with multiple integrated functionalities. In this study, we uncover that functionalized iron oxide nanoparticles (IONPs) could be self-assembled on the surface of two-dimensional MoS2 nanosheets via sulfur chemistry, forming MoS2-IO nanocomposites, which are then modified with two types of polyethylene glycol (PEG) to acquire enhanced stability in physiological environments. Interestingly, (64)Cu, a commonly used positron-emitting radioisotope, could be firmly adsorbed on the surface of MoS2 without the need of chelating molecules, to enable in vivo positron emission tomography (PET) imaging. On the other hand, the strong near-infrared (NIR) and superparamagnetism of MoS2-IO-PEG could also be utilized for photoacoustic tomography (PAT) and magnetic resonance (MR) imaging, respectively. Under the guidance by such triple-modal imaging, which uncovers efficient tumor retention of MoS2-IO-(d)PEG upon intravenous injection, in vivo photothermal therapy is finally conducted, achieving effective tumor ablation in an animal tumor model. Our study highlights the promise of constructing multifunctional theranostic nanocomposites based on 2D transitional metal dichalcogenides for multimodal imaging-guided cancer therapy.

  5. TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo.

    Science.gov (United States)

    Kalanaky, Somayeh; Hafizi, Maryam; Safari, Sepideh; Mousavizadeh, Kazem; Kabiri, Mahboubeh; Farsinejad, Alireza; Fakharzadeh, Saideh; Nazaran, Mohammad Hassan

    2016-03-01

    Iron chelation therapy is an effective approach to the treatment of iron overload conditions, in which iron builds up to toxic levels in the body and may cause organ damage. Treatments using deferoxamine, deferasirox and deferiprone have been introduced and despite their disadvantages, they remain the first-line therapeutics in iron chelation therapy. Our study aimed to compare the effectiveness of the iron chelation agent TLc-A, a nano chelator synthetized based on the novel nanochelating technology, with deferoxamine. We found that TLc-A reduced iron overload in Caco2 cell line more efficiently than deferoxamine. In rats with iron overload, very low concentrations of TLc-A lowered serum iron level after only three injections of the nanochelator, while deferoxamine was unable to reduce iron level after the same number of injections. Compared with deferoxamine, TLc-A significantly increased urinary iron excretion and reduced hepatic iron content. The toxicity study showed that the intraperitoneal median lethal dose for TLc-A was at least two times higher than that for deferoxamine. In conclusion, our in vitro and in vivo studies indicate that the novel nano chelator compound, TLc-A, offers superior performance in iron reduction than the commercially available and widely used deferoxamine.

  6. Modelling chelate-Induced phytoextraction: functional models predicting bioavailability of metals in soil, metal uptake and shoot biomass

    Directory of Open Access Journals (Sweden)

    Pasqualina Sacco

    Full Text Available Chelate-induced phytoextraction of heavy metals from contaminated soils requires special care to determine, a priori, the best method of chelate application, in terms of both dose and timing. In fact, the chelate dose must assure the bioavailability of the metal to the plant without increasing leaching risk and giving toxic effects. Three mathematical models are here proposed for usefully interpreting the processes taking place: a increased soil bioavailability of metals by chelants; b metal uptake by plants; c variation in plant biomass. The models are implemented and validated using data from pot and lysimeter trials. Both the chelate dose and the time elapsed since its application affected metal bioavailability and plant response. Contrariwise, the distribution strategy (single vs. split application seems to produce significant differences both in plant growth and metal uptake, but not in soil metal bioavailability. The proposed models may help to understand and predict the chelate dose – effect relationship with less experimental work.

  7. p-NO2-Bn-H4neunpa and H4neunpa-Trastuzumab: Bifunctional Chelator for Radiometalpharmaceuticals and (111)In Immuno-Single Photon Emission Computed Tomography Imaging.

    Science.gov (United States)

    Spreckelmeyer, Sarah; Ramogida, Caterina F; Rousseau, Julie; Arane, Karen; Bratanovic, Ivica; Colpo, Nadine; Jermilova, Una; Dias, Gemma M; Dude, Iulia; Jaraquemada-Peláez, Maria de Guadalupe; Bénard, François; Schaffer, Paul; Orvig, Chris

    2017-08-16

    Potentially nonadentate (N5O4) bifunctional chelator p-SCN-Bn-H4neunpa and its immunoconjugate H4neunpa-trastuzumab for (111)In radiolabeling are synthesized. The ability of p-SCN-Bn-H4neunpa and H4neunpa-trastuzumab to quantitatively radiolabel (111)InCl3 at an ambient temperature within 15 or 30 min, respectively, is presented. Thermodynamic stability determination with In(3+), Bi(3+), and La(3+) resulted in high conditional stability constant (pM) values. In vitro human serum stability assays have demonstrated both (111)In complexes to have high stability over 5 days. Mouse biodistribution of [(111)In][In(p-NO2-Bn-neunpa)](-), compared to that of [(111)In][In(p-NH2-Bn-CHX-A″-diethylenetriamine pentaacetic acid (DTPA))](2-), at 1, 4, and 24 h shows fast clearance of both complexes from the mice within 24 h. In a second mouse biodistribution study, the immunoconjugates (111)In-neunpa-trastuzumab and (111)In-CHX-A″-DTPA-trastuzumab demonstrate a similar distribution profile but with slightly lower tumor uptake of (111)In-neunpa-trastuzumab compared to that of (111)In-CHX-A″-DTPA-trastuzumab. These results were also confirmed by immuno-single photon emission computed tomography (immuno-SPECT) imaging in vivo. These initial investigations reveal the acyclic bifunctional chelator p-SCN-Bn-H4neunpa to be a promising chelator for (111)In (and other radiometals) with high in vitro stability and also show H4neunpa-trastuzumab to be an excellent (111)In chelator with promising biodistribution in mice.

  8. Isolation and gene expression profiling of intestinal epithelial cells: crypt isolation by calcium chelation from in vivo samples.

    LENUS (Irish Health Repository)

    Balfe, Aine

    2018-01-01

    The epithelial layer within the colon represents a physical barrier between the luminal contents and its underlying mucosa. It plays a pivotal role in mucosal homeostasis, and both tolerance and anti-pathogenic immune responses. Identifying signals of inflammation initiation and responses to stimuli from within the epithelial layer is critical to understanding the molecular pathways underlying disease pathology. This study validated a method to isolate and analyze epithelial populations, enabling investigations of epithelial function and response in a variety of disease setting.

  9. Exploiting the Metal-Chelating Properties of the Drug Cargo for In Vivo Positron Emission Tomography Imaging of Liposomal Nanomedicines

    DEFF Research Database (Denmark)

    Edmonds, Scott; Volpe, Alessia; Shmeeda, Hilary

    2016-01-01

    The clinical value of current and future nanomedicines can be improved by introducing patient selection strategies based on noninvasive sensitive whole-body imaging techniques such as positron emission tomography (PET). Thus, a broad method to radiolabel and track preformed nanomedicines such as ...

  10. Modern Chemistry Techniques Applied to Metal Behavior and Chelation in Medical and Environmental Systems ? Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Sutton, M; Andresen, B; Burastero, S R; Chiarappa-Zucca, M L; Chinn, S C; Coronado, P R; Gash, A E; Perkins, J; Sawvel, A M; Szechenyi, S C

    2005-02-03

    This report details the research and findings generated over the course of a 3-year research project funded by Lawrence Livermore National Laboratory (LLNL) Laboratory Directed Research and Development (LDRD). Originally tasked with studying beryllium chemistry and chelation for the treatment of Chronic Beryllium Disease and environmental remediation of beryllium-contaminated environments, this work has yielded results in beryllium and uranium solubility and speciation associated with toxicology; specific and effective chelation agents for beryllium, capable of lowering beryllium tissue burden and increasing urinary excretion in mice, and dissolution of beryllium contamination at LLNL Site 300; {sup 9}Be NMR studies previously unstudied at LLNL; secondary ionization mass spec (SIMS) imaging of beryllium in spleen and lung tissue; beryllium interactions with aerogel/GAC material for environmental cleanup. The results show that chelator development using modern chemical techniques such as chemical thermodynamic modeling, was successful in identifying and utilizing tried and tested beryllium chelators for use in medical and environmental scenarios. Additionally, a study of uranium speciation in simulated biological fluids identified uranium species present in urine, gastric juice, pancreatic fluid, airway surface fluid, simulated lung fluid, bile, saliva, plasma, interstitial fluid and intracellular fluid.

  11. Theoretical study, and infrared and Raman spectra of copper(II) chelated complex with dibenzoylmethane

    DEFF Research Database (Denmark)

    Nekoei, A.-R.; Vakili, M.; Hakimi-Tabar, M.

    2014-01-01

    There are some discrepancies in both the vibrational assignments and in the metal-ligand (M-L) bond strengths predicted in the previous studies on the copper (II) chelated complex of dibenzoylmethane, Cu(dbm)2. Also, there is a lack of theoretical structure, Raman spectrum and full vibrational as...

  12. Aluminum and other metals in Alzheimer's disease: a review of potential therapy with chelating agents.

    Science.gov (United States)

    Domingo, Jose L

    2006-11-01

    Alzheimer's disease (AD) is characterized by the presence of neuritic plaques and neurofibrillary tangles in the brain. Although the causes of AD remain still unknown, it seems that certain environmental factors may be involved in the etiology and pathogenesis of the disease. While AD is associated with the abnormal aggregation of beta-amyloid protein in the brain, evidence shows that certain metals play a role in the precipitation and cytotoxicity of this protein. Among these metals, the potential role of aluminum as a possible ethiopathogenic factor in AD has been especially controversial. This review is mainly focused on the role of aluminum and metals such as copper and zinc in AD, as well as on metal chelator therapy as a potential treatment for AD. The effects of desferrioxamine and other Al chelating agents have been reviewed. The role of the metal chelator clioquinol in AD, which has been reported to reduce beta-amyloid plaques, presumably by chelation associated with copper and zinc, is also revised. Finally, the potential role of silicon in AD is also discussed.

  13. Flavonoids function as antioxidants: By scavenging reactive oxygen species or by chelating iron?

    Science.gov (United States)

    Wuguo, Deng; Xingwang, Fang; Jilan, Wu

    1997-09-01

    Flavonoids have been reported to exhibit strong antioxidative activity. In the present work, a systematic mechanistic study has been performed on five flavonoids (baicalin, hesperidin, naringin, quercetin and rutin) selected according to their structural characteristics. The experimental results reveal that flavonoids function as antioxidant mainly by chelating iron ions and by scavenging peroxyl radicals whereas their OH radical scavenging effect is much less important.

  14. Determination of proteins by a reverse biuret method combined with the copper-bathocuproine chelate reaction.

    Science.gov (United States)

    Matsushita, M; Irino, T; Komoda, T; Sakagishi, Y

    1993-07-16

    A method of protein determination has been developed which combines the biuret reaction and the copper(I)-bathocuproine chelate reaction. Protein in the specimen forms a Cu(2+)-protein chelate complex (biuret reaction) during the first step. Excess Cu2+ is reduced to Cu+ by ascrobic acid, allowing the Cu+ to form a Cu(+)-bathocuproine chelate complex during the second step. The amount of Cu(+)-bathocuproine chelate complex formed is inversely proportional to the protein concentration. The sensitivity (epsilon = 1.4 x 10(6) 1.mol-1.cm-1 against human albumin) of this method was higher than that of the original Lowry (9.8 x 10(5)), pyrogallol red (1.0 x 10(6)) and commercially available Coomassie Brilliant Blue G.250 methods (6.7 x 10(5)). The color intensities of human gamma-globulin, human globulin (fractions IV-1 and IV-4), bovine albumin, egg albumin and horse gamma-globulin against human albumin (100%) ranged from 92 to 101%. The results obtained with the present method (y) correlated well with those determined by the biuret method (r = 0.998, y = 0.98 chi - 0.002, x = 1.31, y = 1.29 g/l) in 30 diluted sera. These results confirm that this assay is similar in sensitivity to the original Lowry method, is rapid and has similar reactivity to each of the various proteins in biological fluids.

  15. Spectroscopy, modeling and computation of metal chelate solubility in supercritical CO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    J. F. Brennecke; M. A. Stadtherr

    1999-12-10

    The overall objectives of this project were to gain a fundamental understanding of the solubility and phase behavior of metal chelates in supercritical CO{sub 2}. Extraction with CO{sub 2} is an excellent way to remove organic compounds from soils, sludges and aqueous solutions, and recent research has demonstrated that, together with chelating agents, it is a viable way to remove metals, as well. In this project the authors sought to gain fundamental knowledge that is vital to computing phase behavior, and modeling and designing processes using CO{sub 2} to separate organics and metal compounds from DOE mixed wastes. The overall program was a comprehensive one to measure, model and compute the solubility of metal chelate complexes in supercritical CO{sub 2} and CO{sub 2}/cosolvent mixtures. Through a combination of phase behavior measurements, spectroscopy and the development of a new computational technique, the authors have achieved a completely reliable way to model metal chelate solubility in supercritical CO{sub 2} and CO{sub 2}/co-contaminant mixtures. Thus, they can now design and optimize processes to extract metals from solid matrices using supercritical CO{sub 2}, as an alternative to hazardous organic solvents that create their own environmental problems, even while helping in metals decontamination.

  16. Luminescent solutions and films of new europium complexes with chelating ligands

    Science.gov (United States)

    Kharcheva, Anastasia V.; Ivanov, Alexey V.; Borisova, Nataliya E.; Kaminskaya, Tatiana P.; Patsaeva, Svetlana V.; Popov, Vladimir V.; Yuzhakov, Viktor I.

    2015-03-01

    The development of new complexes of rare earth elements (REE) with chelating organic ligands opens up the possibility of purposeful alteration in the composition and structure of the complexes, and therefore tuning their optical properties. New ligands possessing two pyridine rings in their structure were synthesized to improve coordination properties and photophysical characteristics of REE compounds. Complexes of trivalent europium with novel chelating ligands were investigated using luminescence and absorption spectroscopy, as well as atomic force microscopy. Luminescence properties of new compounds were studied both for solutions and films deposited on the solid support. All complexes exhibit the characteristic red luminescence of Eu (III) ion with the absolute lumenescence quantum yield in polar acetonitrile solution varying from 0.21 to 1.45 % and emission lifetime ranged from 0.1 to 1 ms. Excitation spectra of Eu coordination complexes correspond with absorption bands of chelating ligand. The energy levels of the triplet state of the new ligands were determined from the phosphorescence at 77 K of the corresponding Gd (III) complexes. The morphology of films of europium complexes with different substituents in the organic ligands was investigated by atomic force microscopy (AFM). It strongly depends both on the type of substituent in the organic ligand, and the rotation speed of the spin-coater. New europium complexes with chelating ligands containing additional pyridine fragments represent outstanding candidates for phosphors with improved luminescence properties.

  17. Design and Application of Latent Olefin Metathesis Catalysts Featuring S-Chelating Alkylidene Ligands

    Science.gov (United States)

    Szadkowska, Anna; Grela, Karol

    This review article is devoted to recent advances in the design and application of so-called “dormant” or “latent” ruthenium olefin metathesis catalysts bearing S-chelating alkylidene ligands. Selected ruthenium complexes containing S-donor ligands, which possess controllable initiation behaviour are presented. Applications of these complexes in olefin metathesis are described.

  18. Comparison of the antibacterial activity of chelating agents using the agar diffusion method

    Science.gov (United States)

    The agar diffusion assay was used to examine antibacterial activity of 2 metal chelators. Concentrations of 0 to 40 mM of ethylenediaminetetraacetic acid (EDTA) and ethylenediamine-N,N’-disuccinic acid (EDDS) were prepared in 1.0 M potassium hydroxide (KOH). The pH of the solutions was adjusted to 1...

  19. Anti-Proliferative, Antioxidant and Iron-Chelating Properties of the ...

    African Journals Online (AJOL)

    Anti-Proliferative, Antioxidant and Iron-Chelating Properties of the Tropical Highland Fern, Phymatopteris triloba (Houtt) Pichi Serm (Family Polypodiaceae). TT Chai, Y Quah, KF Ooh, NIM Ismail, YV Ang, S Elamparuthi, LY Yeoh, HC Ong, FC Wong ...

  20. Synthesis and characterization of functional multicomponent nanosized gallium chelated gold crystals.

    Science.gov (United States)

    Zambre, Ajit; Silva, Francisco; Upendran, Anandhi; Afrasiabi, Zahra; Xin, Yan; Paulo, António; Kannan, Raghuraman

    2014-03-28

    In this communication, we describe a novel synthetic method for fabricating multicomponent gold nanoparticles containing both gallium ions and biomolecules on the surface. Detailed compositional analysis, using STEM-HAADF and EELS spectroscopy, confirmed the crystalline nature of gold and chelation of gallium ions. The presence of the biomolecule was validated using conventional ELISA.

  1. Modeling the effect of succimer (DMSA; dimercaptosuccinic acid) chelation therapy in patients poisoned by lead

    NARCIS (Netherlands)

    van Eijkeren, Jan C H; Olie, J. Daniël N; Bradberry, Sally M; Vale, J Allister; de Vries, Irma|info:eu-repo/dai/nl/41398625X; Clewell, Harvey J.; Meulenbelt, Jan; Hunault, Claudine C|info:eu-repo/dai/nl/297757849

    CONTEXT: Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer

  2. Modeling the effect of succimer (DMSA; dimercaptosuccinic acid) chelation therapy in patients poisoned by lead.

    Science.gov (United States)

    van Eijkeren, Jan C H; Olie, J Daniël N; Bradberry, Sally M; Vale, J Allister; de Vries, Irma; Clewell, Harvey J; Meulenbelt, Jan; Hunault, Claudine C

    2017-02-01

    Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer (dimercaptosuccinic acid; DMSA) chelation therapy on blood lead concentrations. We integrated a two-compartment kinetic succimer model into an existing PBPK lead model and produced a Chelation Lead Therapy (CLT) model. The accuracy of the model's predictions was assessed by simulating clinical observations in patients poisoned by lead and treated with succimer. The CLT model calculates blood lead concentrations as the sum of the background exposure and the acute or chronic lead poisoning. The latter was due either to ingestion of traditional remedies or occupational exposure to lead-polluted ambient air. The exposure duration was known. The blood lead concentrations predicted by the CLT model were compared to the measured blood lead concentrations. Pre-chelation blood lead concentrations ranged between 99 and 150 μg/dL. The model was able to simulate accurately the blood lead concentrations during and after succimer treatment. The pattern of urine lead excretion was successfully predicted in some patients, while poorly predicted in others. Our model is able to predict blood lead concentrations after succimer therapy, at least, in situations where the duration of lead exposure is known.

  3. Iron-chelating agents never suppress Fenton reaction but participate in quenching spin-trapped radicals.

    Science.gov (United States)

    Li, Linxiang; Abe, Yoshihiro; Kanagawa, Kiyotada; Shoji, Tomoko; Mashino, Tadahiko; Mochizuki, Masataka; Tanaka, Miho; Miyata, Naoki

    2007-09-19

    Hydroxyl radical formation by Fenton reaction in the presence of an iron-chelating agent such as EDTA was traced by two different assay methods; an electron spin resonance (ESR) spin-trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and high Performance liquid chromatography (HPLC)-fluorescence detection with terephthalic acid (TPA), a fluorescent probe for hydroxyl radicals. From the ESR spin-trapping measurement, it was observed that EDTA seemed to suppress hydroxyl radical formation with the increase of its concentration. On the other hand, hydroxyl radical formation by Fenton reaction was not affected by EDTA monitored by HPLC assay. Similar inconsistent effects of other iron-chelating agents such as nitrylotriacetic acid (NTA), diethylenetriamine penta acetic acid (DTPA), oxalate and citrate were also observed. On the addition of EDTA solution to the reaction mixture 10 min after the Fenton reaction started, when hydroxyl radical formation should have almost ceased but the ESR signal of DMPO-OH radicals could be detected, it was observed that the DMPO-OH* signal disappeared rapidly. With the simultaneous addition of Fe(II) solution and EDTA after the Fenton reaction ceased, the DMPO-OH* signal disappeared more rapidly. The results indicated that these chelating agents should enhance the quenching of [DMPO-OH]* radicals by Fe(II), but they did not suppress Fenton reaction by forming chelates with iron ions.

  4. The effects of Fe-chelate type and PH on substrate grown roses

    NARCIS (Netherlands)

    Voogt, W.; Sonneveld, C.

    2009-01-01

    Substrate grown roses appear to be susceptible to chlorosis, which indicates problems with Fe or Mn uptake and hence yield reduction. In common practice this problem is often treated by the addition of extra Fe-chelate, or the use of Fe-EDDHA instead of Fe-DTPA. In previous tests, it was shown that

  5. The preparation and characterization of novel human-like collagen metal chelates.

    Science.gov (United States)

    Zhu, Chenhui; Sun, Yan; Wang, Yaoyu; Luo, Yane; Fan, Daidi

    2013-07-01

    In order to develop the nutritional trace elements which could be absorbed and utilized effectively, protein chelates were adopted. Calcium, copper and manganese were considered based on their physiological functions, and the new chelates of HLC-Ca, HLC-Cu and HLC-Mn were formed in MOPS or MES buffer and purified by gel chromatography, and then freeze-dried. And they were detected and analyzed by atomic absorption spectrophotometry, ultraviolet-visible absorption (UV-vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, fluorescence quenching method, circular dichroism (CD) and differential scanning calorimetry (DSC). The results showed that some chemical reactions happened between HLC and the three metal ions to form new chemical compounds. The thermodynamic parameters, ∆H, ∆G and ∆S, showed that the chelation process between HLC and metal ions was performed spontaneously. Fluorescence quenching spectra of HLC indicated that the quenching mechanism was static in nature. According to the data of DSC, the new chelates were more stable than the free HLC. And HLC-metal complex was non-toxic to the BHK21 cell through MTT assay. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Isolation and characterization of iron chelators from turmeric (Curcuma longa): selective metal binding by curcuminoids.

    Science.gov (United States)

    Messner, Donald J; Surrago, Christine; Fiordalisi, Celia; Chung, Wing Yin; Kowdley, Kris V

    2017-10-01

    Iron overload disorders may be treated by chelation therapy. This study describes a novel method for isolating iron chelators from complex mixtures including plant extracts. We demonstrate the one-step isolation of curcuminoids from turmeric, the medicinal food spice derived from Curcuma longa. The method uses iron-nitrilotriacetic acid (NTA)-agarose, to which curcumin binds rapidly, specifically, and reversibly. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin each bound iron-NTA-agarose with comparable affinities and a stoichiometry near 1. Analyses of binding efficiencies and purity demonstrated that curcuminoids comprise the primary iron binding compounds recovered from a crude turmeric extract. Competition of curcuminoid binding to the iron resin was used to characterize the metal binding site on curcumin and to detect iron binding by added chelators. Curcumin-Iron-NTA-agarose binding was inhibited by other metals with relative potency: (>90% inhibition) Cu2+ ~ Al3+ > Zn2+ ≥ Ca2+ ~ Mg2+ ~ Mn2+ (80% by addition of iron to the media; uptake was completely restored by desferoxamine. Ranking of metals by relative potencies for blocking curcumin uptake agreed with their relative potencies in blocking curcumin binding to iron-NTA-agarose. We conclude that curcumin can selectively bind toxic metals including iron in a physiological setting, and propose inhibition of curcumin binding to iron-NTA-agarose for iron chelator screening.

  7. Functionalized dithiocarbamate chelating resin for the removal of Co2+ from simulated wastewater

    Science.gov (United States)

    Shi, Xuewei; Fu, Linwei; Wu, Yanyang; Zhao, Huiling; Zhao, Shuangliang; Xu, Shouhong

    2017-12-01

    Industrial wastewater that contains trace amounts of heavy metal ions is often seen in petrochemical industry. While this wastewater can not be directly discharged, it is difficult to treat due to the low concentration of metal ions. Introducing chelating reagents into this wastewater for selective ion adsorption, followed by a mechanical separation process, provides an appealing solution. Toward the success of this technology, the development of effective chelating resins is of key importance. In the present work, a chelating resin containing amino and dithiocarbamate groups was reported for the removal of Co(II) metal ions in trace concentrations from simulated wastewater. By investigating the adsorption performance of the chelating resin at different solution pH values, adsorbent dosages, contact time, initial ion concentrations, and adsorption temperatures, the maximum adsorption capacity of the resin for Co(II) was identified to be 24.89 mg g-1 for a 2 g L-1 adsorbent dosage and a pH value of 5. After four adsorption-desorption cycles, 97% of the adsorption capacity of the resin was maintained. The adsorption kinetics and thermodynamics were analyzed and discussed as well.

  8. The performance of 2-nitroso-1-naphthol chelating pigment in paint ...

    African Journals Online (AJOL)

    The performance of 2-nitroso-1-naphthol chelating pigment in paint formulation with gum Arabic and polyvinyl acetate as binders, Paper I: UV- visible spectroscopy, viscosity and breaking stress of the paints. ... This effect was more pronounced with the Gum Arabic than with PVAc. The Gum Arabic binder recorded the ...

  9. Lanthanide Chelates as Bilayer Alignment Tools in NMR Studies of Membrane-Associated Peptides

    Science.gov (United States)

    Prosser, R. S.; Bryant, H.; Bryant, R. G.; Vold, Regitze R.

    1999-12-01

    Theequimolar complex, consisting of the lipid-like, amphiphilic chelating agent 1,11-bis[distearylamino]-diethylenetriamine pentaacetic acid (DTPA-18) and Tm3+, is shown by deuterium (2H) NMR to be useful in aligning bicelle-like model membranes, consisting of dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC). As shown previously (1996, R. S. Prosser et al., J. Am. Chem. Soc. 118, 269-270), in the absence of chelate, the lanthanide ions bind loosely with the lipid phosphate groups and confer the membrane with a sufficient positive magnetic anisotropy to result in parallel alignment (i.e., average bilayer normal along the field). Apparently, DTPA-18 sequesters the lanthanide ions and inserts into the phospholipid bilayer in such a manner that bilayer morphology is preserved over a wide temperature range (35-70°C). The inherent paramagnetic shifts and line broadening effects are illustrated by 2H NMR spectra of the membrane binding peptide, Leu-enkephalin (Lenk-d2, Tyr-(Gly-d2)-Gly-Phe-Leu-OH), in the presence of varying concentrations of Tm3+, and upon addition of DTPA-18. Two conclusions could be drawn from this study: (1) The addition of Tm3+ to the bicelle system is consistent with a conformational change in the surface associated peptide, and this effect is shown to be reversed by addition of the chelate, and (2) The paramagnetic shifts are shown to be significantly reduced by addition of chelate.

  10. Heavy metals in the spinal cord of normal rats and of animals treated with chelating agents

    DEFF Research Database (Denmark)

    Schrøder, H D; Fjerdingstad, E; Danscher, G

    1978-01-01

    , the effects of six chelating agents (DEDTC, dithizone, oxine, EDTA, dipyridyl, and phenantroline) on the Timm pattern were tested. EDTA left the pattern unchanged, while the other compounds showed individual differences in their influence on the Timm pattern, suggesting that the heavy metal pattern...

  11. Lead toxicosis of captive vultures: case description and responses to chelation therapy

    Directory of Open Access Journals (Sweden)

    Pikula Jiri

    2013-01-01

    Full Text Available Abstract Background Lead, a serious threat for raptors, can hamper the success of their conservation. This study reports on experience with accidental lead intoxication and responses to chelation therapy in captive Cinereous (Aegypius monachus and Egyptian (Neophron percnopterus Vultures. Results Soil contamination by lead-based paint sanded off the steel aviary resulted in poisoning of eight Cinereous and two Egyptian Vultures. A male Egyptian Vulture developed signs of apathy, polydipsia, polyuria, regurgitation, and stupor, and died on the next day. Liver, kidney and blood lead concentrations were 12.2, 8.16 and 2.66 μg/g, respectively. Laboratory analyses confirmed severe liver and kidney damage and anaemia. Blood Pb levels of Pb-exposed Cinereous Vultures were 1.571 ± 0.510 μg/g shortly after intoxication, decreased to 0.530 ± 0.165 μg/g without any therapy in a month and to 0.254 ± 0.097 μg/g one month after CaNa2EDTA administration. Eight months later, blood lead levels decreased to close to the background of the control group. Blood parameters of healthy Pb-non-exposed Cinereous Vultures were compared with those of the exposed group prior to and after chelation therapy. Iron levels in the lead-exposed pre-treatment birds significantly decreased after chelation. Haematocrit levels in Pb-exposed birds were significantly lower than those of the controls and improved one month after chelation. Creatine kinase was higher in pre-treatment birds than in the controls but normalised after therapy. Alkaline phosphatase increased after chelation. A marked increase in the level of lipid peroxidation measured as thiobarbituric acid reactive species was demonstrated in birds both prior to and after chelation. The ferric reducing antioxidant power was significantly lower in pre-treatment vultures and returned to normal following chelation therapy. Blood metallothionein levels in lead-exposed birds were higher than in controls

  12. Lead toxicosis of captive vultures: case description and responses to chelation therapy.

    Science.gov (United States)

    Pikula, Jiri; Hajkova, Pavlina; Bandouchova, Hana; Bednarova, Ivana; Adam, Vojtech; Beklova, Miroslava; Kral, Jiri; Ondracek, Karel; Osickova, Jitka; Pohanka, Miroslav; Sedlackova, Jana; Skochova, Hana; Sobotka, Jakub; Treml, Frantisek; Kizek, Rene

    2013-01-16

    Lead, a serious threat for raptors, can hamper the success of their conservation. This study reports on experience with accidental lead intoxication and responses to chelation therapy in captive Cinereous (Aegypius monachus) and Egyptian (Neophron percnopterus) Vultures. Soil contamination by lead-based paint sanded off the steel aviary resulted in poisoning of eight Cinereous and two Egyptian Vultures. A male Egyptian Vulture developed signs of apathy, polydipsia, polyuria, regurgitation, and stupor, and died on the next day. Liver, kidney and blood lead concentrations were 12.2, 8.16 and 2.66 μg/g, respectively. Laboratory analyses confirmed severe liver and kidney damage and anaemia. Blood Pb levels of Pb-exposed Cinereous Vultures were 1.571 ± 0.510 μg/g shortly after intoxication, decreased to 0.530 ± 0.165 μg/g without any therapy in a month and to 0.254 ± 0.097 μg/g one month after CaNa(2)EDTA administration. Eight months later, blood lead levels decreased to close to the background of the control group. Blood parameters of healthy Pb-non-exposed Cinereous Vultures were compared with those of the exposed group prior to and after chelation therapy. Iron levels in the lead-exposed pre-treatment birds significantly decreased after chelation. Haematocrit levels in Pb-exposed birds were significantly lower than those of the controls and improved one month after chelation. Creatine kinase was higher in pre-treatment birds than in the controls but normalised after therapy. Alkaline phosphatase increased after chelation. A marked increase in the level of lipid peroxidation measured as thiobarbituric acid reactive species was demonstrated in birds both prior to and after chelation. The ferric reducing antioxidant power was significantly lower in pre-treatment vultures and returned to normal following chelation therapy. Blood metallothionein levels in lead-exposed birds were higher than in controls. Reduced glutathione dropped after CaNa(2)EDTA therapy, while

  13. f-Element Ion Chelation in Highly Basic Media - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Paine, R.T.

    2000-12-12

    A large body of data has been collected over the last fifty years on the chemical behavior of f-element ions. The ions undergo rapid hydrolysis reactions in neutral or basic aqueous solutions that produce poorly understood oxide-hydroxide species; therefore, most of the fundamental f-element solution chemistry has allowed synthetic and separations chemists to rationally design advanced organic chelating ligands useful for highly selective partitioning and separation of f-element ions from complex acidic solution matrices. These ligands and new examples under development allow for the safe use and treatment of solutions containing highly radioactive species. This DOE/EMSP project was undertaken to address the following fundamental objectives: (1) study the chemical speciation of Sr and lanthanide (Ln) ions in basic aqueous media containing classical counter anions found in waste matrices; (2) prepare pyridine N-oxide phosphonates and phosphonic acids that might act as selective chelator s for Ln ions in model basic pH waste streams; (3) study the binding of the new chelators toward Ln ions and (4) examine the utility of the chelators as decontamination and dissolution agents under basic solution conditions. The project has been successful in attacking selected aspects of the very difficult problems associated with basic pH solution f-element waste chemistry. In particular, the project has (1) shed additional light on the initial stages of Ln ion sol-gel-precipitate formulation under basic solution conditions; (2) generated new families of pyridine phosphonic acid chelators; (3) characterized the function of the chelators and (4) examined their utility as oxide-hydroxide dissolution agents. These findings have contributed significantly to an improved understanding of the behavior of Ln ions in basic media containing anions found in typical waste sludges as well as to the development of sludge dissolution agents. The new chelating reagents are easily made and could be

  14. High performance ion chromatography of transition metal chelate complexes and aminopolycarboxylate ligands.

    Science.gov (United States)

    Tófalvi, Renáta; Horváth, Krisztián; Hajós, Péter

    2013-01-11

    A simple ion chromatographic method was developed for the separation of transition metal chelates (CuEDTA, CuDCTA, ZnEDTA, ZnDCTA) and free anionic complexing ligands (EDTA, DCTA) using alkaline carbonate eluents and conductivity detection. The complex equilibria and kinetic process of separations were studied in order to understand major factors in the control of selectivity and retention order of complex anions. A systematic study was applied to identify the additional peaks of the system as NaEDTA(3-), NaHEDTA(2-), Na(2)EDTA(2-), EDTA(4-)/HEDTA(3-), DCTA(4-)/HDCTA(-3). On the basis of microequilibrium considerations of chelating ligand, it was shown that one should expect the peaks of sodium chelates when the ligand is in excess in the sample solution. The probability density function was introduced for calculation of complex chromatograms, because complexing ligands can exist in at least two different interconvertible forms in the presence of metal ion. The chromatogram of interconverting chelate species can be given as the sum of probability density functions (P) weighed by the molar fractions of complexed (Φ(ML)) and dissociated (Φ(L)) forms. The influences of kinetic rate of complex formation and dissociation on the distribution of components between eluents and ion exchange stationary phases were quantitatively described and demonstrated by elution profiles. The applicability of the developed method is represented by the simultaneous analysis of transition metal chelates and inorganic anions. ICP-AES analysis and FTIR-ATR technique were used for confirmation of IC results for metals and ligands, respectively. Collection protocols for the heart-cutting procedure of chromatograms were applied in the analysis of target components. The limit of detection and linearity of the method in the range of 0.01-0.25 mM sample concentration were also presented. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Photophysical investigation of energy transfer luminescence of lanthanide chelates with aromatic polyaminocarboxylate ligands in aqueous solutions

    Energy Technology Data Exchange (ETDEWEB)

    Hoshino, Hitoshi; Saitoh, Takashi; Yotsuyanagi, Takao [Tohoku Univ., Sendai (Japan). Faculty of Engineering

    1995-02-01

    Some photophysical data including emission lifetimes ({tau}), total emission quantum yields ({Phi}), and ligand phosphorescence data are reported for the energy-transfer luminescence of the Eu(III) chelate of Quin 2 and the Tb(III) chelate of BAPTA: Quin 2 means 2-[(2-amino-5-methylphenoxy)methyl]-6-methoxy-8-aminoquinoline-N,N,N`,N`-tetraacetic acid; BAPTA means 1,2-bis(2-aminophenoxy)ethane-N,N,N`,N`-tetraacetic acid. The energy diagrams for the ligand T{sub 1} and the metal-center f-f levels are proposed. The {tau} values of Tb(III)-BAPTA chelates are 1.73 ms in H{sub 2}O and 3.44 ms in D{sub 2}O. The Eu(III)-Quin 2 chelate system shows a bi-exponential decay of emission; {tau}=0.048 and 0.20 ms in H{sub 2}O and 0.066 and 1.44 ms in D{sub 2}O. The Quin 2 chelate is kinetically inert, so that the interchange of these two conformer structures are very slow at room temperature. The number of water molecules in the primary coordination sphere is calculated from the lifetime data to be 1.9-2.4 for Eu-Quin 2 and 0.5 for Tb-BAPTA. The {Phi} values in aqueous solutions are rather small in these systems; 0.009 for Tb-BAPTA and 0.0023 for Eu-Quin 2, but these are enough counterbalanced by the large molar absorptivities giving the great sensitization factors for the ions; the sensitization factors against each aqua ion are 1380 for Eu-Quin 2 and 1600 for Tb-BAPTA. (author).

  16. Chelation technology: a promising green approach for resource management and waste minimization.

    Science.gov (United States)

    Chauhan, Garima; Pant, K K; Nigam, K D P

    2015-01-01

    Green chemical engineering recognises the concept of developing innovative environmentally benign technologies to protect human health and ecosystems. In order to explore this concept for minimizing industrial waste and for reducing the environmental impact of hazardous chemicals, new greener approaches need to be adopted for the extraction of heavy metals from industrial waste. In this review, a range of conventional processes and new green approaches employed for metal extraction are discussed in brief. Chelation technology, a modern research trend, has shown its potential to develop sustainable technology for metal extraction from various metal-contaminated sites. However, the interaction mechanism of ligands with metals and the ecotoxicological risk associated with the increased bioavailability of heavy metals due to the formation of metal-chelant complexes is still not sufficiently explicated in the literature. Therefore, a need was felt to provide a comprehensive state-of-the-art review of all aspects associated with chelation technology to promote this process as a green chemical engineering approach. This article elucidates the mechanism and thermodynamics associated with metal-ligand complexation in order to have a better understanding of the metal extraction process. The effects of various process parameters on the formation and stability of complexes have been elaborately discussed with respect to optimizing the chelation efficiency. The non-biodegradable attribute of ligands is another important aspect which is currently of concern. Therefore, biotechnological approaches and computational tools have been assessed in this review to illustrate the possibility of ligand degradation, which will help the readers to look for new environmentally safe mobilizing agents. In addition, emerging trends and opportunities in the field of chelation technology have been summarized and the diverse applicability of chelation technology in metal extraction from

  17. Regulation of the catalytic behavior of pullulanases chelated onto nickel (II)-modified magnetic nanoparticles.

    Science.gov (United States)

    Wang, Jianfeng; Liu, Zhongmei; Zhou, Zhemin

    2017-06-01

    Chelating of pullulanases onto nickel (II)-modified magnetic nanoparticles results in one-step purification and immobilization of pullulanase, and facilitates the commercial application of pullulanase in industrial scale. To improve the catalytic behavior, especially the operational stability, of the nanocatalyst in consecutive batch reactions, we prepared various iminodiacetic acid-modified magnetic nanoparticles differed in surface polarity and spacer length, on which the His6-tagged pullulanases were chelated via nickel ions, and then studied the correlation between the MNPs surface property and the corresponding catalyst behavior. When pullulanases were chelated onto the surface-modified MNPs, the thermostability of all pullulanase derivatives were lower than that of free counterpart, being not relevant to the protein orientation guided by the locality of the His6-tag, but related to the MNPs basal surface polarity and the grafted spacer length. After chelating of pullulanases onto MNPs, there were changes observed in the pH-activity profile and the apparent Michaelis constant toward pullulan. The changing tendencies were mainly dependent on the His6-tagged pullulanase orientation, and the changing extents were tuned by the spacer length. The reusability of pullulanase immobilized by N-terminal His6-tag was higher than that of pullulanase immobilized by C-terminal His6-tag. Moreover, the reusability of the immobilized pullulanase tested increased till grafting polyether amine-400 as spacer-arm, therefore the N-terminal His6-tagged pullulanase chelating MNPs grafted polyether amine-400 gave the best reusability, which retained 60% of initial activity after 18 consecutive cycles with a total reaction time of 9h. Additionally, the correlation analysis of the catalyst behaviors indicated that the reusability was independent from other catalytic properties such as thermostability and substrate affinity. All the results revealed that the catalyst behavior can be

  18. Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis.

    Directory of Open Access Journals (Sweden)

    José A G Pertusa

    Full Text Available β-cells release hexameric Zn2+-insulin into the extracellular space, but monomeric Zn2+-free insulin appears to be the only biologically active form. The mechanisms implicated in dissociation of the hexamer remain unclear, but they seem to be Zn2+ concentration-dependent. In this study, we investigate the influence of albumin binding to Zn2+ on Zn2+-insulin dissociation into Zn2+-free insulin and its physiological, methodological and therapeutic relevance. Glucose and K+-induced insulin release were analyzed in isolated mouse islets by static incubation and perifusion experiments in the presence and absence of albumin and Zn2+ chelators. Insulin tolerance tests were performed in rats using different insulin solutions with and without Zn2+ and/or albumin. Albumin-free buffer does not alter quantification by RIA of Zn2+-free insulin but strongly affects RIA measurements of Zn2+-insulin. In contrast, accurate determination of Zn2+-insulin was obtained only when bovine serum albumin or Zn2+ chelators were present in the assay buffer solution. Albumin and Zn2+ chelators do not modify insulin release but do affect insulin determination. Preincubation with albumin or Zn2+ chelators promotes the conversion of "slow" Zn2+-insulin into "fast" insulin. Consequently, insulin diffusion from large islets is ameliorated in the presence of Zn2+ chelators. These observations support the notion that the Zn2+-binding properties of albumin improve the dissociation of Zn2+-insulin into subunits after exocytosis, which may be useful in insulin determination, insulin pharmacokinetic assays and islet transplantation.

  19. Zn availability in nutrient solutions for cucumber (Cucumis sativus L) in hydroponics as affected by Fe-chelates and pH

    NARCIS (Netherlands)

    Voogt, W.; Sonneveld, C.

    2017-01-01

    In soil-less culture systems Fe is usually supplied as chelate to ensure an adequate availability of this element. As chelates have affinity for many metal ions these chelates will interact with other cation nutrients in nutrient solutions. This affects the availability of Fe and other nutrients.

  20. Studies of inclusion complexes between cyclodextrins and polyazamacrocyclic chelates of lanthanide (III) ions[Binding equilibria; Titration calorimetry; Molecular dynamics; Lanthanide (III) chelates of polyazamacrocycles; {gamma}-Cyclodextrin

    Energy Technology Data Exchange (ETDEWEB)

    Henriques, Elsa S.; Bastos, Margarida E-mail: mbastos@fc.up.pt; Geraldes, Carlos F.G.C.; Ramos, Maria Joao

    2003-10-01

    The complexes between {gamma}-cyclodextrin and lanthanide (III) chelates of the polyazamacrocycles DOTA (DOTA {identical_to} 1,4,7,10-tertraazacyclododecane-1,4,7,10-tetraacetate) and DOTP (DOTP {identical_to} 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonate) have been thought out to enhance the potential of such chelates as contrast agents for MRI. Given the actual demand for the design of new contrast agents, we thought it worthwhile to confirm previous results for the equilibrium constant K obtained by one of us by NMR on the DOTP complex, as well as to determine K for a new one with DOTA. Further, we wanted to study and quantify the interactions present in these complexes, with a view to improve them in newly designed complexes. The interactions between {gamma}-cyclodextrin and the lanthanide (III)-polyazamacrocyclic chelates, [Tm(DOTP)]{sup 5-}, and [Gd(DOTA)]{sup -} were then studied by isothermal calorimetry (ITC) and molecular dynamics. The calorimetric experiments can be interpreted by considering that in both cases there is a weak association, characterized by low values for the equilibrium constant as well as for the molar enthalpy change for complex formation, at T=298.15 K. The K value for the complex with DOTP obtained now by ITC is of the same order of magnitude of the one determined previously by NMR. Further, the complex formation seems rather insensitive to the macrocycle, as the values now obtained by ITC for the DOTA complex are very similar to the ones obtained for the DOTP complex. We have also carried out molecular dynamics simulations on these very same inclusion complexes, which provided quantitative data on the interactions present, as well as a plausible explanation for the data obtained, leading to the proposal of possible solutions to improve the modelling of new contrast agents on a host-guest basis.

  1. Enhancement effects of chelating agents on the degradation of tetrachloroethene in Fe(III) catalyzed percarbonate system.

    Science.gov (United States)

    Miao, Zhouwei; Gu, Xiaogang; Lu, Shuguang; Brusseau, Mark L; Zhang, Xiang; Fu, Xiaori; Danish, Muhammad; Qiu, Zhaofu; Sui, Qian

    2015-12-01

    The performance of Fe(III)-based catalyzed sodium percarbonate (SPC) for stimulating the oxidation of tetrachloroethene (PCE) for groundwater remediation applications was investigated. The chelating agents citric acid monohydrate (CIT), oxalic acid (OA), and Glutamic acid (Glu) significantly enhanced the degradation of PCE. Conversely, ethylenediaminetetraacetic acid (EDTA) had a negative impact on PCE degradation, which may due to its strong Fe chelation and HO• scavenging abilities. However, excessive SPC or chelating agent will retard PCE degradation. In addition, investigations using free radical probe compounds and radical scavengers revealed that PCE was primarily degraded by HO• radical oxidation in both the chelated and non-chelated systems, while O2•- also participated in the non-chelated system and the OA and Glu modified systems. According to the electron paramagnetic resonance (EPR) studies, the presence of HO• in the Fe(III)/SPC system was maintained much longer than that in the Fe(II)/SPC system. The results indicated that the addition of CIT, OA or Glu indeed enhanced the generation of HO• in the first 10 min and promoted degradation efficiency by increasing the amount of Fe(III) and maintaining the concentration of HO• radicals in solution. In conclusion, chelated Fe(III)-based catalyzed SPC oxidation is a promising method for the remediation of PCE-contaminated groundwater.

  2. Antimicrobial Properties of Copper Nanoparticles and Amino Acid Chelated Copper Nanoparticles Produced by Using a Soya Extract

    Science.gov (United States)

    DeAlba-Montero, I.; Morales-Sánchez, Elpidio; Araujo-Martínez, Rene

    2017-01-01

    This paper reports a comparison of the antibacterial properties of copper-amino acids chelates and copper nanoparticles against Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis. These copper-amino acids chelates were synthesized by using a soybean aqueous extract and copper nanoparticles were produced using as a starting material the copper-amino acids chelates species. The antibacterial activity of the samples was evaluated by using the standard microdilution method (CLSI M100-S25 January 2015). In the antibacterial activity assays copper ions and copper-EDTA chelates were included as references, so that copper-amino acids chelates can be particularly suitable for acting as an antibacterial agent, so they are excellent candidates for specific applications. Additionally, to confirm the antimicrobial mechanism on bacterial cells, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was carried out. A significant enhanced antimicrobial activity and a specific strain were found for copper chelates over E. faecalis. Its results would eventually lead to better utilization of copper-amino acids chelate for specific application where copper nanoparticles can be not used. PMID:28286459

  3. Chelating Properties of Peptides from Red Seaweed Pyropia columbina and Its Effect on Iron Bio-Accessibility.

    Science.gov (United States)

    Cian, Raúl E; Garzón, Antonela G; Ancona, David Betancur; Guerrero, Luis Chel; Drago, Silvina R

    2016-03-01

    The aim of this work was to evaluate copper-chelating, iron-chelating and anticariogenic activity of peptides obtained by enzymatic hydrolysis of P. columbina protein concentrate and to study the effects of chelating peptides on iron bio-accessibility. Two hydrolyzates were obtained from P. columbina protein concentrate (PC) using two hydrolysis systems: alkaline protease (A) and alkaline protease + Flavourzyme (AF). FPLC gel filtration profile of PC shows a peak having molecular weight (MW) higher than 7000 Da (proteins). A and AF hydrolyzates had peptides with medium and low MW (1013 and 270 Da), respectively. Additionally, AF presented free amino acids with MW around 82 Da and higher content of His and Ser. Peptides from AF showed the highest chelating properties measured as copper-chelating activity (the lowest β-carotene oxidation rate: Ro; 0.7 min(-1)), iron-chelating activity (33%), and phosphorous and Ca(2+) release inhibition (87 and 81%, respectively). These properties could indicate antioxidant properties, promotion of iron absorption and anticariogenic activity, respectively. In fact, hydrolyzates promoted iron dialyzability (≈ 16%), values being higher than that found for P. columbina seaweed. Chelating peptides from both hydrolyzates can maintain the iron in a soluble and bio-accessible form after gastrointestinal digestion.

  4. Assessment of the efficacy of chelate-assisted phytoextraction of lead by coffeeweed (Sesbania exaltata Raf.).

    Science.gov (United States)

    Miller, Gloria; Begonia, Gregorio; Begonia, Maria; Ntoni, Jennifer; Hundley, Oscar

    2008-12-01

    Lead (Pb), depending upon the reactant surface, pH, redox potential and other factors can bind tightly to the soil with a retention time of many centuries. Soil-metal interactions by sorption, precipitation and complexation processes, and differences between plant species in metal uptake efficiency, transport, and susceptibility make a general prediction of soil metal bioavailability and risks of plant metal toxicity difficult. Moreover, the tight binding characteristic of Pb to soils and plant materials make a significant portion of Pb unavailable for uptake by plants. This experiment was conducted to determine whether the addition of ethylenediaminetetraacetic acid (EDTA), ethylene glycol tetraacetic acid (EGTA), or acetic acid (HAc) can enhance the phytoextraction of Pb by making the Pb soluble and more bioavailable for uptake by coffeeweed (Sesbania exaltata Raf.). Also we wanted to assess the efficacy of chelates in facilitating translocation of the metal into the above-ground biomass of this plant. To test the effect of chelates on Pb solubility, 2 g of Pb-spiked soil (1000 mg Pb/kg dry soil) were added to each 15 mL centrifuge tube. Chelates (EDTA, EGTA, HAc) in a 1:1 ratio with the metal, or distilled deionized water were then added. Samples were shaken on a platform shaker then centrifuged at the end of several time periods. Supernatants were filtered with a 0.45 mum filter and quantified by inductively coupled plasma-optical emission spectrometry (ICP-OES) to determine soluble Pb concentrations. Results revealed that EDTA was the most effective in bringing Pb into solution, and that maximum solubility was reached 6 days after chelate amendment. Additionally, a greenhouse experiment was conducted by planting Sesbania seeds in plastic tubes containing top soil and peat (2:1, v:v) spiked with various levels (0, 1000, 2000 mg Pb/kg dry soil) of lead nitrate. At six weeks after emergence, aqueous solutions of EDTA and/or HAc (in a 1:1 ratio with the metal) or

  5. Assessment of the Efficacy of Chelate-Assisted Phytoextraction of Lead by Coffeeweed (Sesbania exaltata Raf.

    Directory of Open Access Journals (Sweden)

    Gloria Miller

    2008-12-01

    Full Text Available Lead (Pb, depending upon the reactant surface, pH, redox potential and other factors can bind tightly to the soil with a retention time of many centuries. Soil-metal interactions by sorption, precipitation and complexation processes, and differences between plant species in metal uptake efficiency, transport, and susceptibility make a general prediction of soil metal bioavailability and risks of plant metal toxicity difficult. Moreover, the tight binding characteristic of Pb to soils and plant materials make a significant portion of Pb unavailable for uptake by plants. This experiment was conducted to determine whether the addition of ethylenediaminetetraacetic acid (EDTA, ethylene glycol tetraacetic acid (EGTA, or acetic acid (HAc can enhance the phytoextraction of Pb by making the Pb soluble and more bioavailable for uptake by coffeeweed (Sesbania exaltata Raf.. Also we wanted to assess the efficacy of chelates in facilitating translocation of the metal into the above-ground biomass of this plant. To test the effect of chelates on Pb solubility, 2 g of Pb-spiked soil (1000 mg Pb/kg dry soil were added to each 15 mL centrifuge tube. Chelates (EDTA, EGTA, HAc in a 1:1 ratio with the metal, or distilled deionized water were then added. Samples were shaken on a platform shaker then centrifuged at the end of several time periods. Supernatants were filtered with a 0.45 μm filter and quantified by inductively coupled plasma-optical emission spectrometry (ICP-OES to determine soluble Pb concentrations. Results revealed that EDTA was the most effective in bringing Pb into solution, and that maximum solubility was reached 6 days after chelate amendment. Additionally, a greenhouse experiment was conducted by planting Sesbania seeds in plastic tubes containing top soil and peat (2:1, v:v spiked with various levels (0, 1000, 2000 mg Pb/kg dry soil of lead nitrate. At six weeks after emergence, aqueous solutions of EDTA and/or HAc (in a 1:1 ratio

  6. CaNa2EDTA chelation attenuates cell damage in workers exposed to lead--a pilot study.

    Science.gov (United States)

    Čabarkapa, A; Borozan, S; Živković, L; Stojanović, S; Milanović-Čabarkapa, M; Bajić, V; Spremo-Potparević, B

    2015-12-05

    Lead induced oxidative cellular damage and long-term persistence of associated adverse effects increases risk of late-onset diseases. CaNa2EDTA chelation is known to remove contaminating metals and to reduce free radical production. The objective was to investigate the impact of chelation therapy on modulation of lead induced cellular damage, restoration of altered enzyme activities and lipid homeostasis in peripheral blood of workers exposed to lead, by comparing the selected biomarkers obtained prior and after five-day CaNa2EDTA chelation intervention. The group of smelting factory workers diagnosed with lead intoxication and current lead exposure 5.8 ± 1.2 years were administered five-day CaNa2EDTA chelation. Elevated baseline activity of antioxidant enzymes Cu, Zn-SOD and CAT as well as depleted thiols and increased protein degradation products-carbonyl groups and nitrites, pointing to Pb induced oxidative damage, were restored toward normal values following the treatment. Lead showed inhibitor potency on both RBC AChE and BChE in exposed workers, and chelation re-established the activity of BChE, while RBC AChE remained unaffected. Also, genotoxic effect of lead detected in peripheral blood lymphocytes was significantly decreased after therapy, exhibiting 18.9% DNA damage reduction. Administration of chelation reversed the depressed activity of serum PON 1 and significantly decreased lipid peroxidation detected by the post-chelation reduction of MDA levels. Lactate dehydrogenase LDH1-5 isoenzymes levels showed evident but no significant trend of restoring toward normal control values following chelation. CaNa2EDTA chelation ameliorates the alterations linked with Pb mediated oxidative stress, indicating possible benefits in reducing health risks associated with increased oxidative damage in lead exposed populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Influence of macrocyclic chelators on the targeting properties of (68Ga-labeled synthetic affibody molecules: comparison with (111In-labeled counterparts.

    Directory of Open Access Journals (Sweden)

    Joanna Strand

    Full Text Available Affibody molecules are a class of small (7 kDa non-immunoglobulin scaffold-based affinity proteins, which have demonstrated substantial potential as probes for radionuclide molecular imaging. The use of positron emission tomography (PET would further increase the resolution and quantification accuracy of Affibody-based imaging. The rapid in vivo kinetics of Affibody molecules permit the use of the generator-produced radionuclide (68Ga (T1/2=67.6 min. Earlier studies have demonstrated that the chemical nature of chelators has a substantial influence on the biodistribution properties of Affibody molecules. To determine an optimal labeling approach, the macrocyclic chelators 1,4,7,10-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA, 1,4,7-triazacyclononane-N,N,N-triacetic acid (NOTA and 1-(1,3-carboxypropyl-1,4,7- triazacyclononane-4,7-diacetic acid (NODAGA were conjugated to the N-terminus of the synthetic Affibody molecule ZHER2:S1 targeting HER2. Affibody molecules were labeled with (68Ga, and their binding specificity and cellular processing were evaluated. The biodistribution of (68Ga-DOTA-ZHER2:S1, (68Ga-NOTA-ZHER2:S1 and (68Ga-NODAGA-ZHER2:S1, as well as that of their (111In-labeled counterparts, was evaluated in BALB/C nu/nu mice bearing HER2-expressing SKOV3 xenografts. The tumor uptake for (68Ga-DOTA-ZHER2:S1 (17.9 ± 0.7%IA/g was significantly higher than for both (68Ga-NODAGA-ZHER2:S1 (16.13 ± 0.67%IA/g and (68Ga-NOTA-ZHER2:S1 (13 ± 3%IA/g at 2 h after injection. (68Ga-NODAGA-ZHER2:S1 had the highest tumor-to-blood ratio (60 ± 10 in comparison with both (68Ga-DOTA-ZHER2:S1 (28 ± 4 and (68Ga-NOTA-ZHER2:S1 (42 ± 11. The tumor-to-liver ratio was also higher for (68Ga-NODAGA-ZHER2:S1 (7 ± 2 than the DOTA and NOTA conjugates (5.5 ± 0.6 vs.3.3 ± 0.6. The influence of chelator on the biodistribution and targeting properties was less pronounced for (68Ga than for (111In. The results of this study demonstrate that macrocyclic

  8. Regulation of copper and iron homeostasis by metal chelators: a possible chemotherapy for Alzheimer's disease.

    Science.gov (United States)

    Robert, Anne; Liu, Yan; Nguyen, Michel; Meunier, Bernard

    2015-05-19

    With the increase of life expectancy of humans in more than two-thirds of the countries in the World, aging diseases are becoming the frontline health problems. Alzheimer's disease (AD) is now one of the major challenges in drug discovery, since, with the exception of memantine in 2003, all clinical trials with drug candidates failed over the past decade. If we consider that the loss of neurons is due to a high level of oxidative stress produced by nonregulated redox active metal ions like copper linked to amyloids of different sizes, regulation of metal homeostasis is a key target. The difficulty for large copper-carrier proteins to directly extract copper ions from metalated amyloids might be considered as being at the origin of the rupture of the copper homeostasis regulation in AD brains. So, there is an urgent need for new specific metal chelators that should be able to regulate the homeostasis of metal ions, specially copper and iron, in AD brains. As a consequence of that concept, chelators promoting metal excretion from brain are not desired. One should favor ligands able to extract copper ions from sinks (amyloids being the major one) and to transfer these redox-active metal ions to copper-carrier proteins or copper-containing enzymes. Obviously, the affinity of these chelators for the metal ion should not be a sufficient criterion, but the metal specificity and the ability of the chelators to release the metal under specific biological conditions should be considered. Such an approach is still largely unexplored. The requirements for the chelators are very high (ability to cross the brain-blood barrier, lack of toxicity, etc.), few chemical series were proposed, and, among them, biochemical or biological data are scarce. As a matter of fact, the bioinorganic pharmacology of AD represents less than 1% of all articles dedicated to AD drug research. The major part of these articles deals with an old and rather toxic drug, clioquinol and related analogs, that

  9. Determining lead, cadmium and mercury in cosmetics using sweeping via dynamic chelation by capillary electrophoresis.

    Science.gov (United States)

    Chen, Kuan-Ling; Jiang, Shiuh-Jen; Chen, Yen-Ling

    2017-03-01

    International limits have been established for metal impurities in cosmetics to prevent overexposure to heavy metal ions. Sweeping via dynamic chelation was developed using capillary electrophoresis to analyze lead (Pb), cadmium (Cd) and mercury (Hg) impurities in cosmetics. The sweeping via dynamic chelation mechanism involves a large volume of metal ions being swept by a small quantity of chelating agents that were electrokinetically injected into the capillary to chelate metal ions and increase the detection sensitivity. The optimized conditions were as follows: Firstly, the capillary was rinsed by a 0.6 mM TTAB solution to reverse the EOF. The sample solution, which was diluted using 25 mM ammonium acetate (pH 6.0), was injected into the capillary using a pressure of 3.5 psi for 99.9 s. Then, EDTA was injected at -25 kV for 1 min from the EDTA buffer (25 mM ammonium acetate containing 0.6 mM TTAB and 5 mM EDTA), and the metal ions were swept and stacked simultaneously. Finally, the separation was performed at -20 kV using a separation buffer (100 mM ammonium acetate (pH 6.0)). A small quantity of chelating agents introduced into the capillary could yield 33-, 50- and 100-fold detection improvements for Pb, Cd and Hg, respectively, more sensitive than conventional capillary zone electrophoresis. Correlation coefficients greater than 0.998 indicated that this method exhibited good linearity. The relative standard deviation and relative error were less than 8.7%, indicating high precision and accuracy. The recovery value of the homemade lotion, which was employed to simulate the real sample matrix, was 93-104%, which indicated that the sample matrix does not affect the quantitative results. Finally, commercial cosmetics were employed to demonstrate the feasibility of the method to determine Pb, Cd and Hg without complicated sample pretreatment. Graphical Abstract The procedure of analyzing metal ions in cosmetics by sweeping via dynamic chelation.

  10. Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Singh Rakesh K

    2010-02-01

    Full Text Available Abstract Background Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC, including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19. Methods Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS Results HNTMB displayed high cytotoxicity (IC50 200-400 nM compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM. In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM. In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels. Conclusions The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other

  11. Cost-utility of chelators in transfusion-dependent β-thalassemia major patients: a review of the pharmacoeconomic literature.

    Science.gov (United States)

    Lee, Todd A; von Riedemann, Sarah; Tricta, Fernando

    2014-10-01

    In the inherited hematologic disorder β-thalassemia major, patients receive regular, lifelong blood transfusions, which carry excess iron that the body is unable to eliminate. Chelation therapy (deferoxamine, deferiprone, deferasirox or deferoxamine-deferiprone combination) is required to reduce iron accumulation in target organs and the associated morbidity and mortality. Each chelation regimen has a distinct safety/efficacy profile and particular costs associated with its use. This review aims to provide an overview of published cost-utility analyses of currently used chelation regimens, and to comment on the potential relevance of their findings in the USA market, where deferiprone has recently been introduced.

  12. Effects of zinc supplementation and zinc chelation on in vitro β-cell function in INS-1E cells

    DEFF Research Database (Denmark)

    Nygaard, Sanne Bjørn; Larsen, Agnete; Knuhtsen, Astrid

    2014-01-01

    cells, we found that zinc supplementation and zinc chelation had significant effects on insulin content and insulin secretion. Supplemental zinc within the physiological concentration range induced insulin secretion. Insulin content was reduced by zinc chelation with N,N,N',N-tektrakis(2-pyridylmethyl......)-ethylenediamine. The changes in intracellular insulin content following exposure to various concentrations of zinc were reflected by changes in the expression patterns of MT-1A, ZnT-8, ZnT-5, and ZnT-3. Furthermore, high zinc concentrations induced cell necrosis while zinc chelation induced apoptosis. Finally, cell...

  13. Synthesis and Analytical Study of New Chelating Resin Containing Sulfadiazine Drug

    Directory of Open Access Journals (Sweden)

    Madher N. Abdulla

    2010-01-01

    Full Text Available A new chelating resin was prepared by mixing sulfadiazine drug and TMP (trimethylolphenol. It was polymerized by heating to 90 °C then it was post cured to 100 °C after that it was grinded. The chelating behavior was examined against Cu2+, Ni2+ using patch method in deferent conditions like treatment time and pH at room temperature. The resin show a good loading capacity toward Cu2+ (in treatment time = 3 h & pH=4 = 0.2174 mg ion / 100 mg resin and it show good loading capacity toward Ni2+ (in treatment time = 24 h & pH=4 = 0.14 mg ion / 100 mg resin.

  14. Design of intrahepatocyte copper(I) chelators as drug candidates for Wilson's disease.

    Science.gov (United States)

    Gateau, Christelle; Delangle, Pascale

    2014-05-01

    Wilson's disease is an autosomal recessive disease caused by mutations on the ATP7B gene found on chromosome 13. Since the corresponding ATPase is in charge of copper (Cu) distribution and excretion in the liver, its malfunctioning leads to Cu overload. This short review deals with treatments of this rare disease, which aim at decreasing Cu toxicity and are, therefore, based on chelation therapy. The drugs used since the 1950s are described first, then a novel approach developed in our laboratory is presented. Since the liver is the main organ of Cu distribution in the body, we targeted the pool of intracellular Cu in hepatocytes. This Cu pool is in the +1 oxidation state, and therefore soft sulfur ligands inspired from binding sites found in metallothioneins were developed. Their targeting to the hepatocytes by functionalization with ligands of the asialoglycoprotein receptor led to their cellular incorporation and intracellular Cu chelation. © 2014 New York Academy of Sciences.

  15. Mass-dependent and -independent fractionation of isotopes in Ni and Pb chelate complex formation reactions

    Science.gov (United States)

    Nomura, Masao; Kudo, Takashi; Adachi, Atsuhiko; Aida, Masao; Fujii, Yasuhiko

    2013-11-01

    Mass independent fractionation (MIF) has been a very interesting topic in the field of inorganic isotope chemistry, in particular, geo- and cosmo- chemistry. In the present work, we studied the isotope fractionation of Ni(II) and Pb(II) ions in complex formation with chelating reagent EDTA. To obtain clear results on the mass dependence of the isotope fractionation, we have conducted long-distance ion exchange chromatography of Ni(II) and Pb(II), using chelate complex reagent EDTA. The results apparently show that the isotope fractionation in Ni complex formation system is governed by the mass dependent rule. On the other hand the isotope fractionation in the Pb complex system is governed by the mass independent rule or the nuclear volume effect.

  16. UNDERSTANDING THE CHEMISTRY IN CHELATE SMEAR LAYER REMOVAL: REVIEW OF LITERATURA

    Directory of Open Access Journals (Sweden)

    Fabiano Luiz Heggendorn

    2015-06-01

    Full Text Available The friction caused by endodontic instruments on mineralized matrix of the root canal begets dentin shavings. These shavings associated with organic debris take the appearance of smear layer, which can difficult the penetration of the root canal sealer. Thus, the root canal needs to be clean and free of smear layer in order to achieving the success of the endodontic therapy. In this way, the current study performed a bibliographic review in order to define and discuss about smear layer. It was discussed the desirable properties and chemical kinetics of two different chelating utilized to removing smear layer: EDTA e citric acid. Different mechanism of action of these chelating can provide difference in removing smear layer. Discussion of these results needs to be deepened and assessed regarding clinical utilization. In addition, the association with other irrigates can result in the decrease or enhancement of effectiveness.

  17. UNDERSTANDING THE CHEMISTRY IN CHELATE SMEAR LAYER REMOVAL: REVIEW OF LITERATURA

    Directory of Open Access Journals (Sweden)

    Fabiano Luiz Heggendorn

    2015-01-01

    Full Text Available The friction caused by endodontic instruments on mineralized matrix of the root canal begets dentin shavings. These shavings associated with organic debris take the appearance of smear layer, which can difficult the penetration of the root canal sealer. Thus, the root canal needs to be clean and free of smear layer in order to achieving the success of the endodontic therapy. In this way, the current study performed a bibliographic review in order to define and discuss about smear layer. It was discussed the desirable properties and chemical kinetics of two different chelating utilized to removing smear layer: EDTA e citric acid. Different mechanism of action of these chelating can provide difference in removing smear layer. Discussion of these results needs to be deepened and assessed regarding clinical utilization. In addition, the association with other irrigates can result in the decrease or enhancement of effectiveness.

  18. Aerosol-OT micelles in Sephadex gels for concentrating metal-dithizone chelates from water

    Energy Technology Data Exchange (ETDEWEB)

    Saitoh, Tohru [Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan)]. E-mail: saitoh@numse.nagoya-u.ac.jp; Hattori, Kazuki [Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan); Hiraide, Masataka [Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan)

    2005-07-06

    Anionic surfactants, sodium dodecyl sulfate (SDS), and di-2-ethylhexyl sodium sulfosuccinate (Aerosol-OT, AOT), were incorporated into a hydrated macroreticular anion-exchanger such as a DEAE- or QAE-Sephadex A-25 gel. The observation of fluorescence spectra of N-phenyl-1-naphthlamine indicated the formation of the surfactant micelles in gels. The hydrophobicity of the micelles corresponded to octanol, tetrahydrofuran, or ethyl acetate. A hydrophobic chelating agent, dithizone (1,5-diphenylthiocarbazone), and its metal chelates were incorporated into the Sephadex gels. The complex formation with dithizone and the subsequent adsorption on Sephadex gels required 10 min. The metals collected in gels were desorbed with 8 M nitric acid. As a result of 300-fold concentrations, traces of heavy metal ions at ng l{sup -1} levels in river water were successfully determined by graphite-furnace atomic absorption spectrometry.

  19. Aerosolization of a chelating agent, Ca-DTPA, for emergent inhalation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Yuji; Koizumi, Akira; Fukuda, Satoshi [National Inst. of Radiological Sciences, Chiba (Japan)

    1997-06-01

    Aerosolization of the chelating agent, Ca-DTPA (diethylenetriaminepentaacetic acid), was studied for removal of inhaled radioactive particles. Four methods of generating aerosols from the powder and from the solution were examined. The particle size and concentration of the Ca-DTPA aerosols were measured by the API Aero-Sizer. The aerosol particles generated by the dry powder inhaler were over 40 {mu}m in MMAD (Mass Median Aerodynamic Diameter) and might be too large for administration to the deep lung. The sizes of aerosol particles generated by other three methods (dispersion dust generator, compressed air nebulizer and ultrasonic nebulizer) ranged from 2 to 15 {mu}m in MMAD, and those concentrations were over 10 mg/m{sup 3} at maximum. The generated chelate aerosols were evaluated as inhalable and applicable for inhalation therapy. (author)

  20. Studies and syntheses of siderophores, microbial iron chelators, and analogs as potential drug delivery agents.

    Science.gov (United States)

    Roosenberg, J M; Lin, Y M; Lu, Y; Miller, M J

    2000-02-01

    Siderophores (microbial iron chelators) play an extremely important role in microbial pathogenicity. Microbial uptake of siderophore-iron complexes through active transport systems allow microbes to survive and proliferate even under iron deficient environments during invasion of a host. Due to their structural complexity, unique iron (III) chelation, acquisition properties, and their therapeutic potential, siderophores have attracted much attention in a broad range of disciplines. Tremendous progress has been made in siderophore syntheses, in determination of the structures and functions of outer membrane receptors (e.g. FhuA and FepA), and in the mechanistic insight into siderophore-iron-mediated active transport processes. One of the important practical applications of this active transport system is development of species-selective active drug transport (the Trojan Horse approach) to potentially treat infections due to drug resistant strains of microbes. Siderophore-drug conjugates have shown great potential in active drug delivery to target pathogenic microbes.

  1. Spectral and colorimetric characteristics of metal chelates of acylated cyanidin derivatives.

    Science.gov (United States)

    Sigurdson, G T; Robbins, R J; Collins, T M; Giusti, M M

    2017-04-15

    Colorants derived from nature are increasingly popular due to consumer demand. Anthocyanins are a class of naturally occurring pigments that produce red-purple-blue hues in nature, especially when interacting with metal ions and co-pigments. The role of various acylations of cyanidin (Cy) derivatives on color expression and stability of Al(3+) and Fe(3+) chelates in pH 6-7 were evaluated by spectrophotometry (380-700nm) and colorimetry (CIE-L(∗)a(∗)b(∗)) during dark, ambient storage (48h). Increased substitution generally increased λmax of Cy chelates: malonic acid monoacylationimproved with increasing proportions of metal ions and acylation. Stability followed that diacylated cyanidin (p-coumaric-sinapic>ferulic-sinapic>sinapic-sinapic)>monoacylated (malonic≈sinapic>ferulic>p-coumaric). Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Sorbent extraction of rubeanic acid-metal chelates on a new adsorbent: Sepabeads SP70.

    Science.gov (United States)

    Soylak, Mustafa; Tuzen, Mustafa

    2006-11-02

    A sorbent extraction procedure for lead, iron, cadmium and manganese ions on Sepabeads SP70 adsorption resin has been presented prior to their flame atomic absorption spectrometric determinations. By the passage of aqueous samples including analyte ions-rubeanic acid chelates through Sepabeads SP70 column, metal chelates adsorb quantitatively and almost all matrix elements will pass through the column to drain. The influence of potential interfering ions was also studied. The validation of the method was made though the analysis of LGC 6010 Hard drinking water, SRM 1577b Bovine liver and GBW 07603 Bush branches and leaves standard reference materials (SRM). The method was applied to the determination of analyte ions from various water, wastewater, cow meat and milk, red wine, and tobacco samples with successfully results.

  3. A Simple and Sensitive Method to Quantify Biodegradable Nanoparticle Biodistribution using Europium Chelates.

    Science.gov (United States)

    Crawford, Lindsey; Higgins, Jaclyn; Putnam, David

    2015-09-08

    The biodistribution of biodegradable nanoparticles can be difficult to quantify. We report a method using time resolved fluorescence (TRF) from a lanthanide chelate to minimize background autofluorescence and maximize the signal to noise ratio to detect biodegradable nanoparticle distribution in mice. Specifically, antenna chelates containing europium were entrapped within nanoparticles composed of polylactic acid-polyethylene glycol diblock copolymers. Tissue accumulation of nanoparticles following intravenous injection was quantified in mice. The TRF of the nanoparticles was found to diminish as a second order function in the presence of serum and tissue compositions interfered with the europium signal. Both phenomena were corrected by linearization of the signal function and calculation of tissue-specific interference, respectively. Overall, the method is simple and robust with a detection limit five times greater than standard fluorescent probes.

  4. Reversible immobilization of invertase on Cu-chelated polyvinylimidazole-grafted iron oxide nanoparticles.

    Science.gov (United States)

    Uzun, Kerem; Çevik, Emre; Şenel, Mehmet; Baykal, Abdülhadi

    2013-12-01

    Polyvinylimidazole (PVI)-grafted iron oxide nanoparticles (PVIgMNP) were prepared by grafting of telomere of PVI on the iron oxide nanoparticles. Different metal ions (Cu(2+), Zn(2+), Cr(2+), Ni(2+)) ions were chelated on polyvinylimidazole-grafted iron oxide nanoparticles, and then the metal-chelated magnetic particles were used in the adsorption of invertase. The maximum invertase immobilization capacity of the PVIgMNP-Cu(2+) beads was observed to be 142.856 mg/g (invertase/PVIgMNP) at pH 5.0. The values of the maximum reaction rate (V max) and Michaelis-Menten constant (Km) were determined for the free and immobilized enzymes. The enzyme adsorption-desorption studies, pH effect on the adsorption efficiency, affinity of different metal ions, the kinetic parameters and storage stability of free and immobilized enzymes were evaluated.

  5. The use of iron chelators in biocidal compositions: evaluation of patent, WO2014059417A1.

    Science.gov (United States)

    Sahni, Sumit; Krishan, Sukriti; Palanimuthu, Duraippandi; Richardson, Des R

    2015-03-01

    Anti-microbial-potentiating compositions, containing one or more anti-microbial agents and an iron chelator, are claimed in the patent application. Different combinations of anti-microbial agents with various classes of iron chelators are claimed. The use of such formulations enhances the biocidal activity of the anti-microbial agents. The compositions can be used for a number of applications, such as preservatives, personal care formulations, water-based paints, household cleaning products, and so on. These compositions have therapeutic use in the treatment of acne where they have been shown to markedly potentiate the effect of anti-microbial agents. They also have possible use in wound-healing products.

  6. Solution mining dawsonite from hydrocarbon containing formations with a chelating agent

    Science.gov (United States)

    Vinegar, Harold J [Bellaire, TX

    2009-07-07

    A method for treating an oil shale formation comprising dawsonite includes providing heat from one or more heaters to the formation to heat the formation. Hydrocarbon fluids are produced from the formation. At least some dawsonite in the formation is decomposed with the provided heat. A chelating agent is provided to the formation to dissolve at least some dawsonite decomposition products. The dissolved dawsonite decomposition products are produced from the formation.

  7. Csp(3) -H Activation without Chelation Assistance in an Iridium Pincer Complex Forming Cyclometallated Products.

    Science.gov (United States)

    Ahlstrand, David A; Polukeev, Alexey V; Marcos, Rocío; Ahlquist, Mårten S G; Wendt, Ola F

    2017-02-03

    Cyclometallation of 8-methylquinoline and 2-(dimethylamino)-pyridine in an iridium-based pincer complex is described. The C-H activation of 2-(dimethylamino)pyridine is not chelation assisted, which has not been described before for Csp(3) -H bonds in cyclometallation reactions. The mechanism of the cyclometallation of 2-(dimethylamino)pyridine was studied by DFT calculations and kinetic measurements. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. DFT study of the interaction between DOTA chelator and competitive alkali metal ions.

    Science.gov (United States)

    Frimpong, E; Skelton, A A; Honarparvar, B

    2017-09-01

    1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetracetic acid (DOTA) is an important chelator for radiolabeling of pharmaceuticals. The ability of alkali metals found in the body to complex with DOTA and compete with radio metal ions can alter the radiolabeling process. Non-covalent interactions between DOTA complexed with alkali metals Li + , Na + , K + and Rb + , are investigated with density functional theory using B3LYP and ωB97XD functionals. Conformational possibilities of DOTA were explored with a varying number of carboxylic pendant arms of DOTA in close proximity to the ions. It is found that the case in which four arms of DOTA are interacting with ions is more stable than other conformations. The objective of this study is to explore the electronic structure properties upon complexation of alkali metals Li + Na + , K + and Rb + with a DOTA chelator. Interaction energies, relaxation energies, entropies, Gibbs free energies and enthalpies show that the stability of DOTA, complexed with alkali metals decreases down the group of the periodic table. Implicit water solvation affects the complexation of DOTA-ions leading to decreases in the stability of the complexes. NBO analysis through the natural population charges and the second order perturbation theory, revealed a charge transfer between DOTA and alkali metals. Conceptual DFT-based properties such as HOMO/LUMO energies, ΔE HOMO-LUMO and chemical hardness and softness indicated a decrease in the chemical stability of DOTA-alkali metal complexes down the alkali metal series. This study serves as a guide to researchers in the field of organometallic chelators, particularly, radiopharmaceuticals in finding the efficient optimal match between chelators and various metal ions. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Salivary proline-rich protein may reduce tannin-iron chelation: a systematic narrative review

    OpenAIRE

    Delimont, Nicole M.; Rosenkranz, Sara K.; Haub, Mark D.; Lindshield, Brian L.

    2017-01-01

    Background Tannins are often cited for antinutritional effects, including chelation of non-heme iron. Despite this, studies exploring non-heme iron bioavailability inhibition with long-term consumption have reported mixed results. Salivary proline-rich proteins (PRPs) may mediate tannin-antinutritional effects on non-heme iron bioavailability. Aim To review evidence regarding biochemical binding mechanisms and affinity states between PRPs and tannins, as well as effects of PRPs on non-heme ir...

  10. Flavonoids function as antioxidants: by scavenging reactive oxygen species or by chelating iron?

    Energy Technology Data Exchange (ETDEWEB)

    Wuguo Deng; Xingwang Fang; Jilan Wu [Peking Univ., Technical Physics Dept., Beijing (China)

    1997-09-01

    Flavonoids have been reported to exhibit strong antioxidative activity. In the present work, a systematic mechanistic study has been performed on five flavonoids (baicalin, hesperidin, naringin, quercetin and rutin) selected according to their structural characteristics. The experimental results reveal that flavonoids function as antioxidant mainly by chelating iron ions and by scavenging peroxyl radicals whereas their OH radical scavenging effect is much less important. (author).

  11. Novel Rhodate and Iridate Complexes containing C,N Chelating Arylamine Ligand Systems

    NARCIS (Netherlands)

    Koten, G. van; Wehman-Ooyevaar, I.C.M.; Vedral, J.A.; Jastrzebski, J.T.B.H.; Grove, D.M.

    1993-01-01

    The synthesis is described of a series of new iridate and rhodate complexes Li(L-C, N){2}M(cod) (M = Rh, Ir; cod = cycloocta-1,5-diene) containing the ortho-chelating, mono-anionic, arylamine ligands L = C{6}H{4}CH{2}NR{2}-2 (R = Me, Et), C{6}H{3}CH{2}NMe{2}- 2-Me-5, C{6}H{4}CH(Me)NMe{2}-(R)-2 or

  12. Recoil and conversion electron considerations of the {sup 166}Dy/{sup 166}Ho in vivo generator

    Energy Technology Data Exchange (ETDEWEB)

    Zeevaart, J.R. [North-West Univ., Mmabatho (South Africa). CARST; Szuecs, Z. [Nesca (South African Nuclear Energy Corporation Ltd.), Pretoria (South Africa). Radiochemistry; Hungarian Academy of Sciences, Debrecen (Hungary). Inst. of Nuclear Research; Takacs, S.; Jarvis, N. [Hungarian Academy of Sciences, Debrecen (Hungary). Inst. of Nuclear Research; Jansen, D. [Nesca (South African Nuclear Energy Corporation Ltd.), Pretoria (South Africa). Radiochemistry

    2012-07-01

    The use of radionuclides as potential therapeutic radiopharmaceuticals is increasingly investigated. An important aspect is the delivery of the radionuclide to the target, i.e. the radionuclide is not lost from the chelating agent. For in vivo generators, it is not only the log K of complexation between the metal ion and the chelator that is important, but also whether the daughter radionuclide stays inside the chelator after decay of the parent radionuclide. In our previous work, we showed that the classical recoil effect is only applicable for decays with a Q value higher than 0.6 MeV (in the atomic mass range around 100). However, Zhernosekov et al. published a result for {sup 140}Nd/{sup 140}Pr (Q = 0.222 MeV) which indicated that > 95% of the daughter ({sup 140}Pr) was lost by a DOTA chelator upon decay of {sup 140}Nd. The authors ascribed this to the ''post-effect''. Their experiment was repeated with the {sup 166}Dy/{sup 166}Ho generator to ascertain whether our calculations were correct. It was found that 72% of the daughter ({sup 166}Ho) was liberated from the DOTA chelator, indicating that the 'post effect' does exist in contrast to our recoil calculations. Upon further investigation, we determined that one should not only consider recoil energy levels but also the mode of decay which was able to explain the partial recoil found for {sup 166}Dy/{sup 166}Ho. It is concluded for the {sup 166}Dy/{sup 166}Ho system that the low recoil energy of the daughter nucleus {sup 166}Ho is not a sufficient reason to rule out release of the nuclide from chelators. On the other hand, we found that the ratio of the {sup 166}Ho that gets released corresponds to the ratio of relaxation of Ho atoms via the Auger process. (orig.)

  13. Advantages of gadolinium based ultrasmall nanoparticles vs molecular gadolinium chelates for radiotherapy guided by MRI for glioma treatment

    OpenAIRE

    Le Duc, G.; ROUX, S; Paruta-Tuarez, A.; Dufort, S.; Bräuer, E; Marais, A.; Truillet, C.; Sancey, L.; Perriat, P.; Lux, F.; Tillement, O

    2014-01-01

    AGuIX nanoparticles are formed of a polysiloxane network surrounded by gadolinium chelates. They present several characteristics. They are easy to produce, they present very small hydrodynamic diameters (

  14. Characterization of new specific copper chelators as potential drugs for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Nguyen, Michel; Robert, Anne; Sournia-Saquet, Alix; Vendier, Laure; Meunier, Bernard

    2014-05-26

    The non-controlled redox-active metal ions, especially copper, in the brain of patients with Alzheimer disease (AD) should be considered at the origin of the intense oxidative damage in the AD brain. Several bis(8-aminoquinoline) ligands, such as 1 and PA1637, are able to chelate Cu(2+) with high affinity, and are specific chelators of copper with respect to iron and zinc. They are able to efficiently extract Cu(2+) from a metal-loaded amyloid. In addition, these tetradentate ligands are specific for the chelation of Cu(2+) compared with Cu(+). Consequently, the copper ion is easily released from the bis(8-aminoquinoline) ligand under reductive conditions, and can be trapped again by a protein having some affinity for copper such as human serum albumin (HSA) proteins. In addition, the copper is not efficiently released from [Cu(CQ)2] in reductive conditions. The catalytic production of H2O2 by [Cu(2+)-Aβ(1-28)]/ascorbate is inhibited in vitro by the bis(8-aminoquinoline) 1, suggesting that 1 should be able to play a protective role against oxidative damages induced by copper-loaded amyloids. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. The iron chelating agent, deferoxamine detoxifies Fe(Salen)-induced cytotoxicity.

    Science.gov (United States)

    Umemura, Masanari; Kim, Jeong-Hwan; Aoyama, Haruki; Hoshino, Yujiro; Fukumura, Hidenobu; Nakakaji, Rina; Sato, Itaru; Ohtake, Makoto; Akimoto, Taisuke; Narikawa, Masatoshi; Tanaka, Ryo; Fujita, Takayuki; Yokoyama, Utako; Taguri, Masataka; Okumura, Satoshi; Sato, Motohiko; Eguchi, Haruki; Ishikawa, Yoshihiro

    2017-08-01

    Iron-salen, i.e., μ-oxo-N,N'-bis(salicylidene)ethylenediamine iron (Fe(Salen)) was a recently identified as a new anti-cancer compound with intrinsic magnetic properties. Chelation therapy has been widely used in management of metallic poisoning, because an administration of agents that bind metals can prevent potential lethal effects of particular metal. In this study, we confirmed the therapeutic effect of deferoxamine mesylate (DFO) chelation against Fe(Salen) as part of the chelator antidote efficacy. DFO administration resulted in reduced cytotoxicity and ROS generation by Fe(Salen) in cancer cells. DFO (25 mg/kg) reduced the onset of Fe(Salen) (25 mg/kg)-induced acute liver and renal dysfunction. DFO (300 mg/kg) improves survival rate after systematic injection of a fatal dose of Fe(Salen) (200 mg/kg) in mice. DFO enables the use of higher Fe(Salen) doses to treat progressive states of cancer, and it also appears to decrease the acute side effects of Fe(Salen). This makes DFO a potential antidote candidate for Fe(Salen)-based cancer treatments, and this novel strategy could be widely used in minimally-invasive clinical settings. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  16. Potassium fulvate-modified graft copolymer of acrylic acid onto cellulose as efficient chelating polymeric sorbent.

    Science.gov (United States)

    Mohamed, Magdy F; Essawy, Hisham A; Ammar, Nabila S; Ibrahim, Hanan S

    2017-01-01

    Acrylic acid (AA) was graft copolymerized from cellulose (Cell) in presence of potassium fulvate (KF) in order to enhance the chemical activity of the resulting chelating polymer and the handling as well. Fourier transform infrared (FTIR) proved that KF was efficiently inserted and became a permanent part of the network structure of the sorbent in parallel during the grafting copolymerization. Scanning electron microscopy (SEM) revealed intact homogeneous structure with uniform surface. This indicates improvement of the handling, however, it was not the case for the graft copolymer of acrylic acid onto cellulose in absence of KF, which is known to be brittle and lacks mechanical integrity. Effective insertion of this co-interpenetrating agent provided more functional groups, such as OH and COOH, which improved the chelating power of the produced sorbent as found for the removal of Cu(2+) ions from its aqueous solutions (the removal efficiency reached ∼98.9%). Different models were used to express the experimental data. The results corroborated conformity of the pseudo-second order kinetic model and Langmuir isotherm model to the sorption process, which translates into dominance of the chemisorption. Regeneration of the chelating polymers under harsh conditions did not affect the efficiency of copper ions uptake up to three successive cycles. A thermodynamic investigation ensured exothermic nature of the adsorption process that became less favourable at higher temperatures. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Lateral flow immunoassay using europium chelate-loaded silica nanoparticles as labels.

    Science.gov (United States)

    Xia, Xiaohu; Xu, Ye; Zhao, Xilin; Li, Qingge

    2009-01-01

    Despite their ease of use, lateral flow immunoassays (LFIAs) often suffer from poor quantitative discrimination and low analytical sensitivity. We explored the use of a novel class of europium chelate-loaded silica nanoparticles as labels to overcome these limitations. Antibodies were covalently conjugated onto europium chelate-loaded silica nanoparticles with dextran as a linker. The resulting conjugates were used as labels in LFIA for detection of hepatitis B surface antigen (HBsAg). We performed quantification with a digital camera and Adobe Photoshop software. We also used 286 clinical samples to compare the proposed method with a quantitative ELISA. A detection limit of 0.03 microg/L was achieved, which was 100 times lower than the colloidal gold-based LFIAs and lower than ELISA. A precise quantitative dose-response curve was obtained, and the linear measurement range was 0.05-3.13 microg/L, within which the CVs were 2.3%-10.4%. Regression analysis of LFIA on ELISA results gave: log (LFIA) = -0.14 log (ELISA) + 1.03 microg/L with r = 0.99 for the quantification of HBsAg in 35 positive serum samples. Complete agreement was observed for the qualitative comparison of 286 clinical samples assayed with LFIA and ELISA. Europium chelate-loaded silica nanoparticle labels have great potential to improve LFIAs, making them useful not only for simple screening applications but also for more sensitive and quantitative immunoassays.

  18. Effect of a novel chelating agent on defect removal during post-CMP cleaning

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jiao, E-mail: hongjiao072095@163.com [School of Electronic Information Engineering, Hebei University of Technology, Tianjin 300130 (China); Tianjin Key Laboratory of Electronic Materials and Devices, Tianjin 300130 (China); Niu, Xinhuan, E-mail: xhniu@hebut.edu.cn [School of Electronic Information Engineering, Hebei University of Technology, Tianjin 300130 (China); Tianjin Key Laboratory of Electronic Materials and Devices, Tianjin 300130 (China); Liu, Yuling; He, Yangang; Zhang, Baoguo; Wang, Juan; Han, Liying; Yan, Chenqi; Zhang, Jin [School of Electronic Information Engineering, Hebei University of Technology, Tianjin 300130 (China); Tianjin Key Laboratory of Electronic Materials and Devices, Tianjin 300130 (China)

    2016-08-15

    Highlights: • The post-CMP cleaning of wafers has become a key step in successful CMP processing. • The polyvinyl alcohol (PVA) brush is the most effective method for post-CMP in situ cleaning. • The chemicals used in this chapter are alkaline. • Emphasis on the effect of the different concentration of the chelating agent on defect removal is provided. • The mechanisms under the post-CMP cleaning process to realize optimum manufacturing conditions were studied. - Abstract: Chemical mechanical polishing (CMP) has become widely accepted for the planarization of device interconnect structures in deep submicron semiconductor manufacturing. However, during CMP process the foreign particles, metal contaminants, and other chemical components are introduced onto the wafer surface, so CMP process is considered as one of the dirtiest process to wafer surface defects which may damage the GLSI patterns and the metallic impurities can induce many crystal defects in wafers during the following furnace processing. Therefore, the post-CMP cleaning of wafers has become a key step in successful CMP process and the polyvinyl alcohol (PVA) brush cleaning is the most effective method for post-CMP in situ cleaning. In this study, the effect of the chelating agent with different concentrations on defect removal by using PVA brush cleaning was discussed emphatically. It can be seen from the surface images obtained by scanning electron microscopy and KLA digital comparison system analysis confirmed that the chelating agent can effectively act on the defect removal.

  19. Luminescent solutions and powders of new samarium complexes with N,N',O,O'-chelating ligands

    Science.gov (United States)

    Kharcheva, Anastasia V.; Nikolskiy, Kirill S.; Borisova, Nataliya E.; Ivanov, Alexey V.; Reshetova, Marina D.; Yuzhakov, Viktor I.; Patsaeva, Svetlana V.

    2016-04-01

    Imaging techniques in biology and medicine are crucial tools to obtain information on structural and functional properties of living cells and organisms. To fulfill the requirements associated with application of these techniques it appears necessary to design markers with specific characteristics. Luminescent complexes of trivalent lanthanide ions with chelating ligands are of increasing importance in biomedical applications because of their millisecond luminescence lifetime, narrow emission band, high signal-to-noise ratio and minimal photodamage to biological samples. In order to extend the available emission wavelength range the luminescent samarium chelates are highly desirable. In this study the ligands with diamides of 2,2'-bipyridin-6,6'-dicarboxylic acid were used to improve photophysical characteristics of samarium complexes. We report the luminescence characteristics of samarium complexes with novel ligands. All complexes exhibited the characteristic emission of Sm (III) ion with the lines at 565, 597, 605, 645 and 654 nm, the intensity strongly depended on the ligand. Absorption and luminescence excitation spectra of Sm (III) complexes showed main peaks in the UV range demonstrating lanthanide coordination to the ligand. The absolute lumenescence quantum yield was measured for solutions in acetonitrile with excitation at 350 nm. The largest luminescence quantum yield was found for the samarium complex Bipy 6MePy Sm (3%) being much higher that for samarium complexes reported in the literature earlier. These results prove as well that samarium chelates are potential markers for multiparametric imaging techniques.

  20. A Powerful Mitochondria-Targeted Iron Chelator Affords High Photoprotection against Solar Ultraviolet A Radiation.

    Science.gov (United States)

    Reelfs, Olivier; Abbate, Vincenzo; Hider, Robert C; Pourzand, Charareh

    2016-08-01

    Mitochondria are the principal destination for labile iron, making these organelles particularly susceptible to oxidative damage on exposure to ultraviolet A (UVA, 320-400 nm), the oxidizing component of sunlight. The labile iron-mediated oxidative damage caused by UVA to mitochondria leads to necrotic cell death via adenosine triphosphate depletion. Therefore, targeted removal of mitochondrial labile iron via highly specific tools from these organelles may be an effective approach to protect the skin cells against the harmful effects of UVA. In this work, we designed a mitochondria-targeted hexadentate (tricatechol-based) iron chelator linked to mitochondria-homing SS-like peptides. The photoprotective potential of this compound against UVA-induced oxidative damage and cell death was evaluated in cultured primary skin fibroblasts. Our results show that this compound provides unprecedented protection against UVA-induced mitochondrial damage, adenosine triphosphate depletion, and the ensuing necrotic cell death in skin fibroblasts, and this effect is fully related to its potent iron-chelating property in the organelle. This mitochondria-targeted iron chelator has therefore promising potential for skin photoprotection against the deleterious effects of the UVA component of sunlight. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Conjugates of magnetic nanoparticle-actinide specific chelator for radioactive waste separation.

    Science.gov (United States)

    Kaur, Maninder; Zhang, Huijin; Martin, Leigh; Todd, Terry; Qiang, You

    2013-01-01

    A novel nanotechnology for the separation of radioactive waste that uses magnetic nanoparticles (MNPs) conjugated with actinide specific chelators (MNP-Che) is reviewed with a focus on design and process development. The MNP-Che separation process is an effective way of separating heat generating minor actinides (Np, Am, Cm) from spent nuclear fuel solution to reduce the radiological hazard. It utilizes coated MNPs to selectively adsorb the contaminants onto their surfaces, after which the loaded particles are collected using a magnetic field. The MNP-Che conjugates can be recycled by stripping contaminates into a separate, smaller volume of solution, and then become the final waste form for disposal after reusing number of times. Due to the highly selective chelators, this remediation method could be both simple and versatile while allowing the valuable actinides to be recovered and recycled. Key issues standing in the way of large-scale application are stability of the conjugates and their dispersion in solution to maintain their unique properties, especially large surface area, of MNPs. With substantial research progress made on MNPs and their surface functionalization, as well as development of environmentally benign chelators, this method could become very flexible and cost-effective for recycling used fuel. Finally, the development of this nanotechnology is summarized and its future direction is discussed.

  2. The evaluation of chelating agents on cat’s periradicular tissues

    Directory of Open Access Journals (Sweden)

    Razmi H.

    2001-09-01

    Full Text Available "nAbstract: The cleaning and shaping of root canals is one of the most important proccesses in endodontics. In many cases, the physiologic or pathologic proccedures can affect the canals. So, using the instruments and materials, which could be applied in cleaning and shaping of narrow canals is necessary. The aim of this study was the evaluation of Iranian and foreign chelating agents on periradicular tissue of cats. After cleaning and shaping of canals in 18 lower canines of cats, the original RC-Prep and an Iranian chelating agents were placed equally in two groups with 9 teeth in each one. The patency of canals preserved for materials leakage. In 3 lower canines of cats, phosphoric acid was placed as positive controls.3 canine teeth as negative controls had nothing in them. The crowns were sealed and the cats were sacrificed in 1/21/42 days periods after conducting vital perfussions. The teeth samples with their surrounding osseous tissues were gathered and placed in three groups each contained 6 samples. Histologic preparations were done and the tissue reactions to these materials were evaluated by counting the proliferative inflammatory cells. Also the morphometric analysis for these samples was done. The inflammatory reactions of these materials (the original RC-Prep. & the Iranian chelating agent were not statistically different. Both of these materials were different in inducing tissue reactions in comparison with those of positive and negative controls, and these differences were statistically important.

  3. Molecular Docking Assessment of Efficacy of Different Clinically Used Arsenic Chelator Drugs

    Directory of Open Access Journals (Sweden)

    Durjoy Majumder

    2013-01-01

    Full Text Available Arsenic contamination of ground water has become a global problem affecting specially, south-east Asian countries like Bangladesh and eastern parts of India. It also affects South America and some parts of the US. Different organs of the physiological system are affected due to contamination of inorganic arsenic in water. Animal studies with different chelators are not very conclusive as far as the multi/differential organ effect(s of arsenic is concerned. Our docking study establishes the molecular rationale of blood test for early detection of arsenic toxicity; as arsenic has a high affinity to albumin, a plasma protein and actin, a structural protein of all cells including Red Blood Cells. This study also shows that there is a little possibility of male reproductive organs toxicity by different forms of inorganic arsenic; however, female reproductive system is very much susceptible to sodium-arsenite. Through comparative analysis regarding the chelating effectiveness among the available arsenic chelator drugs, meso-2,3 dimercaptosuccinic acid (DMSA and in some cases lipoic acid is the most preferred choice of drug for removing of arsenic deposits. This computational method actually reinforces the clinical finding regarding DMSA as the most preferred drug in removal of arsenic deposits from majority of the human tissues.

  4. A New Synthesis of TE2A-a Potential Bifunctional Chelator for {sup 64}Cu

    Energy Technology Data Exchange (ETDEWEB)

    Pandya, Darpan N.; Kwak, Won Jung; Park, Jeong Chan; Gawande, Manoj B.; Yoo, Jeong Soo [Kyungpook National University, Daegu (Korea, Republic of); Kim, Jung Young; An, Gwang Il [Molecular Imaging Research Center, Seoul (Korea, Republic of); Ryu, Eun Kyoung [Korea Basic Science Institute, Chungbuk (Korea, Republic of)

    2010-09-15

    The development of a new bifunctional chelator, which holds radio metals strongly in living systems, is a prerequisite for the successful application of disease-specific biomolecules to medical diagnosis and therapy. Recently, TE2A was reported to make kinetically more stable Cu({Pi}) complexes than TETA. Herein, we report a new synthetic route to TE2A and explore its potential as a bifunctional chelator. TE2A was synthesized using the regioselective alkylation of benzyl bromoacetate and successive de protection of the methylene bridge and benzyl group. Salt-free TE2A was radiolabeled with {sup 64}Cu and micro PET imaging was performed to follow the clearance pattern of the {sup 64}Cu-TE2A complex. TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was radiolabeled with {sup 64}Cu. TE2A was prepared in salt-free form cyclam in an overall yield of 74%. The micro PET images showed that {sup 64}Cu-TE2A is excreted rapidly from the body by the kidney and liver. TE2A was successfully conjugated with c(RGDyK) peptide through on carboxylate group and the TE2A-c(RGDyK) conjugate was radiolabeled with {sup 64}Cu in 94% yield within 30 min. TE2A can be used by itself as a bifunctional chelator without any further structural modification.

  5. Enhancing radium solubilization in soils by citrate, EDTA, and EDDS chelating amendments.

    Science.gov (United States)

    Prieto, C; Lozano, J C; Blanco Rodríguez, P; Tomé, F Vera

    2013-04-15

    The effect of three chelating agents (citrate, EDTA, and EDDS) on the solubilization of radium from a granitic soil was studied systematically, considering different soil pH values, chelating agent concentrations, and leaching times. For all the chelating agents tested, the amount of radium leached proved to be strongly dependent on the pH of the substrate: only for acidic conditions did the amount of radium released increase significantly relative to the controls. Under the best conditions, the radium released from the amended soil was greater by factors of 20 in the case of citrate, 18 for EDTA, and 14 for EDDS. The greatest improvement in the release of radium was obtained for the citrate amendment at the highest concentration tested (50 mmol kg(-1)). A slightly lower amount of radium was leached with EDTA at 5 mmol kg(-1) soil, but the solubilization over time was very different from that observed with citrate or EDDS. With EDTA, a maximum in radium leaching was reached on the first day after amendment, while with citrate, the maximum was attained on the fourth day. With EDDS, radium leaching increased slightly but steadily with time (until the sixth day), but the net effect for the period tested was the lowest of the three reagents. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. The interactive effects of chelator, fertilizer, and rhizobacteria for enhancing phytoremediation of heavy metal contaminated soil

    Energy Technology Data Exchange (ETDEWEB)

    Chen, H.; Cutright, T.J. [Dept. of Civil Engineering, Univ. of Akron, Akron, OH (United States)

    2002-07-01

    The role of chelator, fertilizer, and enriched rhizobacteria in facilitating Cd, Cr, and Ni accumulation by Helianthus annuus was studied. It was found that by adding a synthetic chelator, EDTA, the shoot concentrations of Cd and Ni were significantly increased from 34.2 mg kg{sup -1} and 14.5 mg kg{sup -1} to 115 mg kg{sup -1} and 117 mg kg{sup -1}, respectively. However, the total biomass of plants was drastically decreased by 50 to 60%. Compared with this treatment, inoculating enriched rhizobacteria to plants grown under similar conditions maintained the surged shoot concentrations of Cd and Ni while increasing the plants biomass by more than 1.6-fold. It was also found that introducing a commercial fertilizer, Hydro-Gro trademark, to plants significantly increased the Ni accumulation by 3-fold and the plant biomass by 1.43-fold. These results suggest that combing fertilizers, chelators and/or rhizobacteria might provide a more effective approach for enhancing phytoremediation. (orig.)

  7. XAS studies of the effectiveness of iron chelating treatments of Mary Rose timbers

    Energy Technology Data Exchange (ETDEWEB)

    Berko, A; Schofield, E J; Chadwick, A V [School of Physical Sciences, University of Kent, CT2 7NR (United Kingdom); Smith, A D [STFC Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Jones, A M [The Mary Rose Trust, HM Naval Base, Portsmouth, PO1 3LX (United Kingdom); Mosselmans, J F W, E-mail: a.berko@kent.ac.u [Diamond Light Source, Didcot, OX11 0DE (United Kingdom)

    2009-11-15

    The oxidation of sulfur in marine archaeological timbers under museum storage conditions is a recently identified problem, particularly for major artefacts such as historic ships excavated from the seabed. Recent work on the Vasa has stressed the role of iron in catalysing the oxidative degradation of the wood cellulose and the polyethylene glycols used to restore mechanical integrity to the timbers. In developing new treatment protocols for the long term preservation of Henry VIII of England's flagship, the Mary Rose, we are investigating the potential of chelating agents to neutralise and remove the iron products from the ships timbers. We have explored the use of aqueous solutions of chelating agents of calcium phytate, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ammonium citrate to extract the iron compounds. All of these solutions exhibit some level of iron removal; however the key is to find the most effective concentration at pH of around 7 of the reagent solution, to minimise the treatment time and find the most cost-effective treatment for the whole of the Mary Rose hull. Fe K-edge XAFS data from samples of Mary Rose timbers, before and after treatment by the chelating agents mentioned has been collected. The data collected provide valuable insights into the effectiveness of the treatment solutions.

  8. In search of a viable reaction pathway in the chelation of a metallo-protein

    Science.gov (United States)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2010-03-01

    Misfolded metallo-proteins are potential causal agents in the onset of neuro-degenerative diseases, such as Alzheimer's and Parkinson's Diseases (PD). Experimental results involving metal chelation have shown significant promise in symptom reduction and misfolding reversal. We explore, through atomistic simulations, potential reaction pathways for the chelation of Cu^2+ from the metal binding site in our representation of a partially misfolded α-synuclein, the protein implicated in PD. Our ab initio simulations use Density Functional Theory (DFT) and nudged elastic band to obtain the minimized energy coordinates of this reaction. Our simulations include ab initio water at the interaction site and in its first solvation shells, while the remainder is fully solvated with orbital-free DFT water representation [1]. Our ongoing studies of viable chelation agents include nicotine, caffeine and other potential reagents, we will review the best case agents in this presentation. [4pt] [1] Hodak M, Lu W, Bernholc J. Hybrid ab initio Kohn-Sham density functional theory/frozen-density orbital-free density functional theory simulation method suitable for biological systems. J. Chem. Phys. 2008 Jan;128(1):014101-9.

  9. Conjugates of Magnetic Nanoparticle -- Actinide Specific Chelator for Radioactive Waste Separation

    Energy Technology Data Exchange (ETDEWEB)

    Maninder Kaur; Huijin Zhang; Leigh Martin; Terry Todd; You Qiang

    2013-11-01

    A novel nanotechnology for the separation of radioactive waste that uses magnetic nanoparticles (MNPs) conjugated with actinide specific chelators (MNP-Che) is reviewed with a focus on design and process development. The MNP-Che separation process is an effective way of separating heat generating minor actinides (Np, Am, Cm) from spent nuclear fuel solution to reduce the radiological hazard. It utilizes coated MNPs to selectively adsorb the contaminants onto their surfaces, after which the loaded particles are collected using a magnetic field. The MNP-Che conjugates can be recycled by stripping contaminates into a separate, smaller volume of solution, and then become the final waste form for disposal after reusing number of times. Due to the highly selective chelators, this remediation method could be both simple and versatile while allowing the valuable actinides to be recovered and recycled. Key issues standing in the way of large-scale application are stability of the conjugates and their dispersion in solution to maintain their unique properties, especially large surface area, of MNPs. With substantial research progress made on MNPs and their surface functionalization, as well as development of environmentally benign chelators, this method could become very flexible and cost-effective for recycling used fuel. Finally, the development of this nanotechnology is summarized and its future direction is discussed.

  10. Disaggregation ability of different chelating molecules on copper ion-triggered amyloid fibers.

    Science.gov (United States)

    Zhu, Linyi; Han, Yuchun; He, Chengqian; Huang, Xu; Wang, Yilin

    2014-08-07

    Dysfunctional interaction of amyloid-β (Aβ) with excess metal ions is proved to be related to the etiology of Alzheimer's disease (AD). Using metal-binding compounds to reverse metal-triggered Aβ aggregation has become one of the potential therapies for AD. In this study, the ability of a carboxylic acid gemini surfactant (SDUC), a widely used metal chelator (EDTA), and an antifungal drug clioquinol (CQ) in reversing the Cu(2+)-triggered Aβ(1-40) fibers have been systematically studied by using turbidity essay, BCA essay, atomic force microscopy, transmission electron microscopy, and isothermal titration microcalorimetry. The results show that the binding affinity of Cu(2+) with CQ, SDUC, and EDTA is in the order of CQ > EDTA > SDUC, while the disaggregation ability to Cu(2+)-triggered Aβ(1-40) fibers is in the order of CQ > SDUC > EDTA. Therefore, the disaggregation ability of chelators to the Aβ(1-40) fibers does not only depend on the binding affinity of the chelators with Cu(2+). Strong self-assembly ability of SDUC and π-π interaction of the conjugate group of CQ also contributes toward the disaggregation of the Cu(2+)-triggered Aβ(1-40) fibers and result in the formation of mixed small aggregates.

  11. Effect of chelators and nisin produced in situ on inhibition and inactivation of gram negatives.

    Science.gov (United States)

    Boziaris, I S; Adams, M R

    1999-12-15

    The ability of chelators and nisin generated in situ to inhibit and inactivate E. coli and other gram negatives in a model substrate was investigated. The effect of various chelators and different concentrations of exogenous nisin on inhibition of E. coli in broth medium showed that only EDTA and pyrophosphates were able to cause appreciable inhibition of E. coli by nisin. In a broth where L. lactis NCFB 497 produced nisin in a concentration of 250-300 IU/ml, pyrophosphates were unable to inactivate E. coli. Under the same conditions, addition of EDTA led to inactivation of E. coli at neutral and slightly acidic pH only. A cocktail of strains of E. coli was less sensitive than E. coli ATCC 25922 alone. Pseudomonas aeruginosa was more sensitive and salmonellae more resistant. EDTA also caused a slight reduction in the L. lactis population and its biochemical activity as regards pH drop and acid production. Some of the inhibition of E. coli could be ascribed to the physical presence of Lactococcus cells rather than their metabolites excreted into the medium. Failure to observe any inhibition in fermented broths at their natural pH (4.0) was ascribed to the poor chelating power of EDTA under acid conditions.

  12. Effect of diphenylthiocarbazone (dithizone) on glutamate level in hippocampus preparation in vitro and in vivo.

    Science.gov (United States)

    Kihara, T; Ishihara, T; Baba, A; Iwata, H

    1990-04-01

    To assess the functional interaction between Zn2+ and glutamate in hippocampus, diphenylthiocarbazone (dithizone), a Zn2+ chelator, was used to alter the glutamate level in hippocampus in vitro and in vivo. Dithizone at the concentration of 1 microM stimulated high K(+)- and veratrine-induced release of [3H]glutamate both in the presence and absence of Ca2+ from rat hippocampal slices preloaded with [3H]glutamate without affecting the release of [3H]gamma-aminobutyric acid and [3H]acetylcholine. Metal chelators other than dithizone did not evoke the [3H]glutamate release at the concentration of 10 microM. Two weeks after the intrahippocampal injection of 20 micrograms of dithizone, both Zn2+ and glutamate levels of the hippocampus significantly decreased with no change in the levels of other metals, amino acids, monoamines and acetylcholine.

  13. A mouse model for studying the interaction of bisdioxopiperazines with topoisomerase IIα in vivo

    DEFF Research Database (Denmark)

    Grauslund, Morten; Vinding, Annemette; Füchtbauer, Annette C.

    2007-01-01

    their intracellular iron chelating activity. In an attempt to distinguish between these possibilities, we here present a transgenic mouse model aimed at identifying the contribution of topoisomerase IIα to the effects of bisdioxopiperazines. A tyrosine 165 to serine mutation (Y165S) in topoisomerase IIα, demonstrated......-opened hydrolysis products are strong iron chelator. The clinically approved analog ICRF-187 is a pharmacological modulator of topoisomerase II poisons such as etoposide in preclinical animal models. ICRF-187 is also used to protect against anthracycline-induced cardiomyopathy and has recently been approved...... as an antidote for alleviating tissue damage and necrosis after accidental anthracycline extravasation. This dual modality of bisdioxopiperazines, including ICRF-187, raises the question of whether their pharmacological in vivo effects are mediated through interaction with topoisomerase II or via...

  14. Photo-Curable Metal-Chelating Coatings Offer a Scalable Approach to Production of Antioxidant Active Packaging.

    Science.gov (United States)

    Lin, Zhuangsheng; Goddard, Julie

    2018-02-01

    Synthetic metal chelators (for example, ethylenediaminetetraacetic acid, EDTA) are widely used as additives to control trace transition metal induced oxidation in consumer products. To enable removal of synthetic chelators in response to increasing consumer demand for clean label products, metal-chelating active food packaging technologies have been developed with demonstrated antioxidant efficacy in simulated food systems. However, prior work in fabrication of metal-chelating materials leveraged batch chemical reactions to tether metal-chelating ligands, a process with limited industrial translatability for large-scale fabrication. To improve the industrial translatability, we have designed a 2-step laminated photo-grafting process to introduce metal chelating functionality onto common polymeric packaging materials. Iminodiacetic acid (IDA) functionalized materials were fabricated by photo-grafting poly(acrylic acid) onto polypropylene (PP) films, followed by a second photo-grafting process to graft-polymerize an IDA functionalized vinyl monomer (GMA-IDA). The photo-grafting was conducted under atmospheric conditions and was completed in 2 min. The resulting IDA functionalized metal-chelating material was able to chelate iron and copper, and showed antioxidant efficacy against ascorbic acid degradation, supporting its potential to be used synergistically with natural antioxidants for preservation of food and beverage products. The 2-step photo-grafting process improves the throughput of active packaging coatings, enabling potential roll-to-roll fabrication of metal-chelating active packaging materials for antioxidant food packaging applications. To address consumer and retail demands for "clean label" foods and beverages without a corresponding loss in product quality and shelf life, producers are seeking next generation technologies such as active packaging. In this work, we will report the synthesis of metal-chelating active packaging films, which enable removal

  15. Synergistic Activities of an Efflux Pump Inhibitor and Iron Chelators against Pseudomonas aeruginosa Growth and Biofilm Formation ▿

    OpenAIRE

    Liu, Yang; Yang, Liang; Molin, Søren

    2010-01-01

    The efflux pump inhibitor phenyl-arginine-β-naphthylamide (PAβN) was paired with iron chelators 2,2′-dipyridyl, acetohydroxamic acid, and EDTA to assess synergistic activities against Pseudomonas aeruginosa growth and biofilm formation. All of the tested iron chelators synergistically inhibited P. aeruginosa growth and biofilm formation with PAβN. PAβN-EDTA showed the most promising activity against P. aeruginosa growth and biofilm formation.

  16. Investigation of metal–flavonoid chelates and the determination of flavonoids via metal–flavonoid complexing reactions

    OpenAIRE

    DUSAN MALESEV; VESNA KUNTIC

    2007-01-01

    Flavonoids constitute a large group of polyphenolic phytochemicals with antioxidant properties which are overwhelmingly exerted through direct free radical scavenging. Flavonoids also exhibit antioxidant properties through chelating with transition metals, primarily Fe(II), Fe(III) and Cu(II), which participate in reactions generating free radicals. Metal–flavonoid chelates are considerably more potent free radical scavengers than the parent flavonoids and play a prominent role in protecting ...

  17. Development of Iron-Chelating Poly(ethylene terephthalate) Packaging for Inhibiting Lipid Oxidation in Oil-in-Water Emulsions.

    Science.gov (United States)

    Johnson, David R; Tian, Fang; Roman, Maxine J; Decker, Eric A; Goddard, Julie M

    2015-05-27

    Foods such as bulk oils, salad dressings, and nutritionally fortified beverages that are susceptible to oxidative degradation are often packaged in poly(ethylene terephthalate) (PET) bottles with metal chelators added to the food to maintain product quality. In the present work, a metal-chelating active packaging material is designed and characterized, in which poly(hydroxamic acid) (PHA) metal-chelating moieties were grafted from the surface of PET. Biomimetic PHA groups were grafted in a two-step UV-initiated process without the use of a photoinitiator. Surface characterization of the films by attenuated total reflective Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM) suggested successful grafting and conversion of poly(hydroxyethyl acrylate) (PHEA) to PHA chelating moieties from the surface of PET. Colorimetric (ferrozine) and inductively coupled plasma mass spectroscopy (ICP-MS) assays demonstrated the ability of PET-g-PHA to chelate iron in a low-pH (3.0) environment containing a competitive metal chelator (citric acid). Lipid oxidation studies demonstrated the antioxidant activity of PET-g-PHA films in inhibiting iron-promoted oxidation in an acidified oil-in-water (O/W) emulsion model system (pH 3.0). Particle size and ζ-potential analysis indicated that the addition of PET-g-PHA films did not affect the physical stability of the emulsion system. This work suggests that biomimetic chelating moieties can be grafted from PET and effectively inhibit iron-promoted degradation reactions, enabling removal of metal-chelating additives from product formulations.

  18. Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

    Energy Technology Data Exchange (ETDEWEB)

    Nagai, Rhoji; Murray, David B.; Metz, Thomas O.; Baynes, John

    2012-03-01

    Advanced glycation or glycoxidation end-products (AGE) increase in tissue proteins with age, and their rate of accumulation is increased in diabetes, nephropathy and inflammatory diseases. AGE inhibitors include a range of compounds that are proposed to act by trapping carbonyl and dicarbonyl intermediates in AGE formation. However, some among the newer generation of AGE inhibitors lack reactive functional groups that would trap reaction intermediates, indicating an alternative mechanism of action. We propose that AGE inhibitors function primarily as chelators, inhibiting metal-catalyzed oxidation reactions. The AGE-inhibitory activity of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is also consistent with their chelating activity. Finally, compounds described as AGE breakers, or their hydrolysis products, also have strong chelating activity, suggesting that these compounds also act through their chelating activity. We conclude that chelation is the common, and perhaps the primary, mechanism of action of AGE inhibitors and breakers, and that chronic, mild chelation therapy should prove useful in treatment of diabetes and age-related diseases characterized by oxidative stress, inflammation and increased chemical modification of tissue proteins by advanced glycoxidation and lipoxidation end-products.

  19. Characterization of the effect of serum and chelating agents on Staphylococcus aureus biofilm formation; chelating agents augment biofilm formation through clumping factor B

    Science.gov (United States)

    Abraham, Nabil Mathew

    Staphylococcus aureus is the causative agent of a diverse array of acute and chronic infections, and some these infections, including infective endocarditis, joint infections, and medical device-associated bloodstream infections, depend upon its capacity to form tenacious biofilms on surfaces. Inserted medical devices such as intravenous catheters, pacemakers, and artificial heart valves save lives, but unfortunately, they can also serve as a substrate on which S. aureus can form a biofilm, attributing S. aureus as a leading cause of medical device-related infections. The major aim of this work was take compounds to which S. aureus would be exposed during infection and to investigate their effects on its capacity to form a biofilm. More specifically, the project investigated the effects of serum, and thereafter of catheter lock solutions on biofilm formation by S. aureus. Pre-coating polystyrene with serum is frequently used as a method to augment biofilm formation. The effect of pre-coating with serum is due to the deposition of extracellular matrix components onto the polystyrene, which are then recognized by MSCRAMMs. We therefore hypothesized that the major component of blood, serum, would induce biofilm formation. Surprisingly, serum actually inhibited biofilm formation. The inhibitory activity was due to a small molecular weight, heat-stable, non-proteinaceous component/s of serum. Serum-mediated inhibition of biofilm formation may represent a previously uncharacterized aspect of host innate immunity that targets the expression of a key bacterial virulence factor: the ability to establish a resistant biofilm. Metal ion chelators like sodium citrate are frequently chosen to lock intravenous catheters because they are regarded as potent inhibitors of bacterial biofilm formation and viability. We found that, while chelating compounds abolished biofilm formation in most strains of S. aureus, they actually augmented the phenotype in a subset of strains. We

  20. Complexation of uranium(VI) with peptidoglycan.

    Science.gov (United States)

    Barkleit, Astrid; Moll, Henry; Bernhard, Gert

    2009-07-21

    We investigated the interaction of UO(2)(2+) with peptidoglycan (PG), the main part of the outer membrane of Gram-positive bacteria, by potentiometric titration and time-resolved laser-induced fluorescence spectroscopy (TRLFS) over a wide pH (2.0 to 9.0) and concentration range (10(-5) to 10(-4) M U(vi), 0.01 to 0.2 g L(-1) PG). With potentiometry two different dissociation constants for the carboxyl sites of glutamic acid and diaminopimelic acid (pK(a) = 4.55 +/- 0.02 and 6.31 +/- 0.01), and one averaged pK(a) for hydroxyl and amino groups (which are not distinguishable) (9.56 +/- 0.03) and the site densities could be identified. With potentiometry three different uranyl PG complexes were ascertained: two 1 : 1 uranyl carboxyl complexes R-COO-UO(2)(+), one with the glutamic acid carboxyl group (log beta(110) = 4.02 +/- 0.03), which has a very small formation ratio, and one with the diaminopimelic acid carboxyl group (log beta(110) = 7.28 +/- 0.03), and a mixed 1 : 1 : 1 complex with additional hydroxyl or amino coordination, R-COO-UO(2)((+))-A(i)-R (A(i) = NH(2) or O(-)) (log beta(1110) = 14.95 +/- 0.02). With TRLFS, also three, but different, species could be identified: a 1 : 1 uranyl carboxyl complex R-COO-UO(2)(+) (log beta(110) = 6.9 +/- 0.2), additionally a 1 : 2 uranyl carboxyl complex (R-COO)(2)-UO(2) (log beta(120) = 12.1 +/- 0.2), both with diaminopimelic acid carboxyl groups, and the mixed species R-COO-UO(2)((+))-A(i)-R (A(i) = NH(2) or O(-)) (log beta(1110) = 14.5 +/- 0.1). The results are in accordance within the errors of determination.

  1. DOTA-functionalized polylysine: a high number of DOTA chelates positively influences the biodistribution of enzymatic conjugated anti-tumor antibody chCE7agl.

    Directory of Open Access Journals (Sweden)

    Jürgen Grünberg

    Full Text Available Site-specific enzymatic reactions with microbial transglutaminase (mTGase lead to a homogenous species of immunoconjugates with a defined ligand/antibody ratio. In the present study, we have investigated the influence of different numbers of 1,4,7,10-tetraazacyclododecane-N-N'-N''-N'''-tetraacetic acid (DOTA chelats coupled to a decalysine backbone on the in vivo behavior of the chimeric monoclonal anti-L1CAM antibody chCE7agl. The enzymatic conjugation of (DOTA1-decalysine, (DOTA3-decalysine or (DOTA5-decalysine to the antibody heavy chain (via Gln295/297 gave rise to immunoconjugates containing two, six or ten DOTA moieties respectively. Radiolabeling of the immunoconjugates with (177Lu yielded specific activities of approximately 70 MBq/mg, 400 MBq/mg and 700 MBq/mg with increasing numbers of DOTA chelates. Biodistribution experiments in SKOV3ip human ovarian cancer cell xenografts demonstrated a high and specific accumulation of radioactivity at the tumor site for all antibody derivatives with a maximal tumor accumulation of 43.6±4.3% ID/g at 24 h for chCE7agl-[(DOTA-decalysine]2, 30.6±12.0% ID/g at 24 h for chCE7agl-[(DOTA3-decalysine]2 and 49.9±3.1% ID/g at 48 h for chCE7agl-[(DOTA5-decalysine]2. The rapid elimination from the blood of chCE7agl-[(DOTA-decalysine]2 (1.0±0.1% ID/g at 24 h is associated with a high liver accumulation (23.2±4.6% ID/g at 24 h. This behavior changed depending on the numbers of DOTA moieties coupled to the decalysine peptide with a slower blood clearance (5.1±1.0 (DOTA3 versus 11.7±1.4% ID/g (DOTA5, p<0.005 at 24 h and lower radioactivity levels in the liver (21.4±3.4 (DOTA3 versus 5.8±0.7 (DOTA5, p<0.005 at 24 h. We conclude that the site-specific and stoichiometric uniform conjugation of the highly DOTA-substituted decalysine ((DOTA5-decalysine to an anti-tumor antibody leads to the formation of immunoconjugates with high specific activity and excellent in vivo behavior and is a valuable option for

  2. Investigation into Iron Chelating and Antioxidant Potential of Melilotus officinalis in Iron Dextran Induced Iron Overloaded Sprague Dawley Rat Model.

    Science.gov (United States)

    Sheikh, N A; Desai, T R; Tirgar, P R

    2016-12-01

    Excess of iron leads to generates free radicals, causes organ damage. Melilotus officinalis (Fabaceae) reported to have various pharmacological activities. It contains flavonoids and phenolic compounds which have iron chelating and antioxidant property. Hence, present study was designed to investigate the beneficial effects of different fractions of M. officinalis for the management of iron overload disease and its complications. Iron overload was induced by 6 IP injections of iron dextran (12.5 mg/100 g) uniformly distributed over the period of 30 days. The different fractions of M. officinalis were given orally and Deferoxamine (DFO) subcutaneously for 30 days. The iron chelating and various biochemical parameters were estimated on 15th and 30th day. The different fractions of M. officinalis demonstrated dose dependant in-vitro iron chelating ability. There were significant (Piron chelating potential shows in rats treated with methanolic fraction of methanolic extract (MFME) and methanolic fraction of aqueous extract (MFAE) of M. officinalis as compared to disease control (DC) rats. The rats treated with MFME and MFAE of M. officinalis shows significant (Piron chelation was observed on 30th day and at higher dose (300 mg/kg) as compared to 15th day and at lower dose (150 mg/kg). The present study concludes that MFME and MFAE of M. officinalis have reversible iron chelating and antioxidant potential in rats. The study also proves the possible mechanism of action, as an iron chelator by increasing the excretion of iron in urine and feces. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Synthesis and biological evaluation of 2-benzoylpyridine thiosemicarbazones in a dimeric system: structure-activity relationship studies on their anti-proliferative and iron chelation efficacy.

    Science.gov (United States)

    Lukmantara, Adeline Y; Kalinowski, Danuta S; Kumar, Naresh; Richardson, Des R

    2014-12-01

    Thiosemicarbazone chelators represent an exciting class of biologically active compounds that show great potential as anti-tumor agents. Our previous studies demonstrated the potent anti-tumor activity of the 2'-benzoylpyridine thiosemicarbazone series. While extensive studies have been performed on monomeric thiosemicarbazone compounds, dimeric thiosemicarbazone chelators have received comparatively less attention. Thus, it was of interest to investigate the anti-proliferative activity and iron chelation efficacy of dimeric thiosemicarbazones. Two classes of dimeric thiosemicarbazones were designed and synthesized. The first class consisted of two benzoylpyridine-based thiosemicarbazone units connected via a hexane or dodecane alkyl bridge, while the second class of dimer consisted of two thiosemicarbazones attached to a 2,6-dibenzoylpyridine core. These dimeric ligands demonstrated greater anti-proliferative activity than the clinically used iron chelator, desferrioxamine. This study highlights the importance of optimal lipophilicity as a factor influencing the cytotoxicity and iron chelation efficacy of these chelators. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Adsorption characteristics of Ni(II) onto MA-DTPA/PVDF chelating membrane

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xiaodan [Department of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao 066004 (China); Song, Laizhou, E-mail: songlz@ysu.edu.cn [Department of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao 066004 (China); Fu, Jie; Tang, Pei; Liu, Feng [Department of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao 066004 (China)

    2011-05-30

    The melamine-diethylenetriaminepentaacetic acid/polyvinylidene fluoride (MA-DTPA/PVDF) chelating membrane bearing polyaminecarboxylate groups was prepared for the removal of Ni(II) from wastewater effluents. The membrane was characterized by SEM, {sup 13}C NMR and FTIR techniques. Quantitative adsorption experiments were performed in view of pH, contact time, temperature, the presence of Ca(II) and lactic acid as the controlling parameters. Adsorption kinetics and equilibrium were examined regarding the single Ni(II) system, binary Ni(II) and Ca(II) system and nickel-lactic acid complexes system. The desorption efficiency was also evaluated, and the adsorption mechanism was suggested based on experimental data. The results show that the sorption kinetics fit well to Lagergren second-order equation and the isotherms can be well described by Langmuir model. At 298 K, the second-order rate constant is calculated to be 4.171, 11.39, 6.203 cm{sup 2}/(mg min) and the equilibrium uptake is 0.0264, 0.0211 and 0.0216 mg/cm{sup 2} in the aforementioned three systems. The distribution coefficient of Ni(II) slowly decreases from 4.27 to 2.72, and the separation factor (f{sub Ni(II)/Ca(II)}) increases from 3.10 to 8.46 when the initial Ca(II) concentration varies from 20 to 200 mg/L. This reveals the chelating membrane shows more affinity for Ni(II) than Ca(II) ions. In the studied range of lactic acid concentration, Ni(II) uptake decreases with the maximum ratio of 10%. Chemical bonding (chelation) dominates in the adsorption process, and the negative {Delta}G{sup o} and {Delta}H{sup o} indicate the spontaneous and exothermic nature of adsorption.

  5. Chelating agents in combination with rosmarinic acid for boar sperm freeze-drying.

    Science.gov (United States)

    Olaciregui, Maite; Luño, Victoria; González, Noelia; Domingo, Paula; de Blas, Ignacio; Gil, Lydia

    2017-09-01

    The presence of DNA protective agents in the medium is necessary to maintain sperm functionality after freeze-drying procedure. The objective of this study was to investigate the effect of chelating agents, ethylene diaminetetraacetic acid (EDTA) and ethylene glycoltetraacetic acid (EGTA), in combination with rosmarinic acid (RA) on DNA integrity of freeze-dried boar sperm. We also examined the effect of these agents on the in vitro developmental ability of porcine oocytes following sperm injection (ICSI). Heterospermic mix, obtained from ejaculated sperm of three boars, was freeze-dried in two different chelating agents' media: 50mM EDTA or 50mM EGTA, and in these media supplemented with 105μM of rosmarinic acid. Frozen-thawed sperm was used as control. After rehydration, samples were subjected to DNA damage detection using Sperm Chromatin Dispersion test. ICSI was performed to verify the ability of freeze-dried sperm to participate in embryonic development. Five replicated trials were carried out for each group. In the presence of rosmarinic acid, the percentage of spermatozoa with DNA damage decreased significantly (p=0.010), without differences between the two chelating agents combination. EDTA solution preserves more efficiently DNA integrity of boar sperm than EGTA solution (p=0.002). There were no significant differences among the studied groups related to the blastocyst formation rate. Results suggested that the addition of rosmarinic acid to the medium improves sperm DNA integrity after freeze-drying, but does not promote fertilization and blastocyst development. We also observed a similar percentage of embryos production with freeze-dried and with frozen-thawed sperm. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  6. Effects of synthetic Zn chelates on flax response and soil Zn status

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, D.; Almendros, P.; Alvarez, J.M.

    2016-11-01

    Throughout the world, flax (Linum usitatissimum L.) is often grown in Zn-deficient soils, but appropriate fertilizer management can optimize both crop yield and micronutrient content. A greenhouse experiment was conducted on Typic Haploxeralf (pH 6.1) and Typic Calcixerept (pH 8.1) soils to study the relative efficiency of chelated Zn using two application rates of three different Zn sources [Zn-EDDHSA, ethylenediamine-di-(2-hydroxy-5-sulfophenylacetate of Zn); Zn-HEDTA, N-2-hydroxyethyl-ethylenediaminetriacetate of Zn; and Zn-EDTA, ethylenediaminetetraacetate of Zn]. Dry matter /DM) yield, Zn concentration, chlorophyll content, crude fiber and tensile properties were monitored and the soil-Zn status (available-Zn, Zn-fractions and total-Zn) was assessed. Zinc chelate applications increased the most labile forms of Zn in soils and Zn concentrations in plants. The low rate of Zn generally had a beneficial effect on DM yield and tensile properties. The exception was Zn-EDTA in the weakly acidic soil, where the highest Zn concentrations were observed in leaves and whole shoots; this coincided with the largest concentrations of labile Zn in soil. The most efficient fertilizers were Zn-EDDHSA (in both soils) and Zn-EDTA (in the calcareous soil). The relatively large amounts of labile and available Zn present in both of the soils fertilized with Zn-EDTA points to the applying this chelate at lower rate than 5 mg Zn/kg; this should, in turn, reduce the cost of Zn fertilization and minimize environmental pollution risk. (Author)

  7. Iron-Chelating Drugs Enhance Cone Photoreceptor Survival in a Mouse Model of Retinitis Pigmentosa.

    Science.gov (United States)

    Wang, Ke; Peng, Bo; Xiao, Jia; Weinreb, Orly; Youdim, Moussa B H; Lin, Bin

    2017-10-01

    Retinitis pigmentosa (RP) is a group of hereditary retinal degeneration in which mutations commonly result in the initial phase of rod cell death followed by gradual cone cell death. The mechanisms by which the mutations lead to photoreceptor cell death in RP have not been clearly elucidated. There is currently no effective treatment for RP. The purpose of this work was to explore iron chelation therapy for improving cone survival and function in the rd10 mouse model of RP. Two iron-chelating drugs, 5-(4-(2-hydroxyethyl) piperazin-1-yl (methyl)-8-hydroxyquinoline (VK28) and its chimeric derivative 5-(N-methyl-N-propargyaminomethyl)-quinoline-8-oldihydrochloride (VAR10303), were injected intraperitoneally to rd10 mice every other day starting from postnatal day 14. We investigate the effects of the two compounds on cone rescue at three time points, using a combination of immunocytochemistry, RT-PCR, Western blot analysis, and a series of visual function tests. VK28 and VAR10303 treatments partially rescued cones, and significantly improved visual function in rd10 mice. Moreover, we showed that the neuroprotective effects of VK28 and VAR10303 were correlated to inhibition of neuroinflammation, oxidative stress, and apoptosis. Furthermore, we demonstrated that downregulation of NF-kB and p53 is likely to be the mechanisms by which proinflammatory mediators and apoptosis are reduced in the rd10 retina, respectively. VK28 and VAR10303 provided partial histologic and functional rescue of cones in RD10 mice. Our study demonstrated that iron chelation therapy might represent an effective therapeutic strategy for RP patients.

  8. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

    Science.gov (United States)

    Polvi, Elizabeth J; Averette, Anna F; Lee, Soo Chan; Kim, Taeyup; Bahn, Yong-Sun; Veri, Amanda O; Robbins, Nicole; Heitman, Joseph; Cowen, Leah E

    2016-10-01

    Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which metal chelation

  9. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Polvi

    2016-10-01

    Full Text Available Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which

  10. Effects of synthetic Zn chelates on flax response and soil Zn status

    Directory of Open Access Journals (Sweden)

    Demetrio Gonzalez

    2016-08-01

    Full Text Available Throughout the world, flax (Linum usitatissimum L. is often grown in Zn-deficient soils, but appropriate fertilizer management can optimize both crop yield and micronutrient content. A greenhouse experiment was conducted on Typic Haploxeralf (pH 6.1 and Typic Calcixerept (pH 8.1 soils to study the relative efficiency of chelated Zn using two application rates of three different Zn sources [Zn-EDDHSA, ethylenediamine-di-(2-hydroxy-5-sulfophenylacetate of Zn; Zn-HEDTA, N-2-hydroxyethyl-ethylenediaminetriacetate of Zn; and Zn-EDTA, ethylenediaminetetraacetate of Zn]. Dry matter /DM yield, Zn concentration, chlorophyll content, crude fiber and tensile properties were monitored and the soil-Zn status (available-Zn, Zn-fractions and total-Zn was assessed. Zinc chelate applications increased the most labile forms of Zn in soils and Zn concentrations in plants. The low rate of Zn generally had a beneficial effect on DM yield and tensile properties. The exception was Zn-EDTA in the weakly acidic soil, where the highest Zn concentrations were observed in leaves and whole shoots; this coincided with the largest concentrations of labile Zn in soil. The most efficient fertilizers were Zn-EDDHSA (in both soils and Zn-EDTA (in the calcareous soil. The relatively large amounts of labile and available Zn present in both of the soils fertilized with Zn-EDTA points to the applying this chelate at lower rate than 5 mg Zn/kg; this should, in turn, reduce the cost of Zn fertilization and minimize environmental pollution risk.

  11. Water-soluble chelating polymers for removal of actinides from wastewater

    Energy Technology Data Exchange (ETDEWEB)

    Jarvinen, G.D. [Los Alamos National Lab., NM (United States)

    1997-10-01

    Polymer filtration is a technology under development to selectively recover valuable or regulated metal ions from process or wastewaters. The technology uses water-soluble chelating polymers that are designed to selectively bind with metal ions in aqueous solutions. The polymers have a sufficiently large molecular weight that they can be separated and concentrated using available ultrafiltration (UF) technology. The UF range is generally considered to include molecular weights from about 3000 to several million daltons and particles sizes of about 2 to 1000 nm. Water and smaller unbound components of the solution pass freely through the UF membrane. The polymers can then be reused by changing the solution conditions to release the metal ions that are recovered in concentrated form for recycle or disposal. Some of the advantages of polymer filtration relative to technology now in use are rapid binding kinetics, high selectivity, low energy and capital costs, and a small equipment footprint. Some potential commercial applications include electroplating rinse waters, photographic processing, nuclear power plant cooling water; remediation of contaminated soils and groundwater; removal of mercury contamination; and textile, paint and dye production. The purpose of this project is to evaluate this technology to remove plutonium, americium, and other regulated metal ions from various process and waste streams found in nuclear facilities. The work involves preparation of the water-soluble chelating polymers; small-scale testing of the chelating polymer systems for the required solubility, UF properties, selectivity and binding constants; followed by an engineering assessment at a larger scale to allow comparison to competing separation technologies. This project focuses on metal-ion contaminants in waste streams at the Plutonium Facility and the Waste Treatment Facility at LANL. Potential applications at other DOE facilities are also apparent.

  12. Investigation of Changing Pore Topology and Porosity During Matrix Acidizing using Different Chelating Agents

    Science.gov (United States)

    Umer Shafiq, Mian; Khaled Ben Mahmud, Hisham; Rezaee, Reza; Testamanti, Nadia

    2017-07-01

    Core flooding acidizing experiments on sandstone/carbonate formation are usually performed in the laboratory to observe different physical phenomena and to design acidizing stimulation jobs for the field. During the tests, some key parameters are analyzed such as pore volume required for breakthrough as well as pressure. Hydrochloric acid (HCl) is commonly used in the carbonate matrix acidizing while Mud acid (HF: HCl) is usually applied during the sandstone acidizing to remove damage around the well bore. However, many problems are associated with the application of these acids, such as fast reaction, corrosion and incompatibility of HCl with some minerals (illite). To overcome these problems, chelating agents (HEDTA, EDTA and GLDA) were used in this research. Colton tight sandstone and Guelph Dolomite core samples were used in this study. The experiments usually are defined in terms of porosity, permeability, dissolution and pore topology. Effluent samples were analyzed to determine dissolved iron, sodium, potassium, calcium and other positive ions using Inductively Coupled Plasma (ICP). Meanwhile Nuclear Magnetic Resonance (NMR) was employed to determine porosity and pore structure of the core sample. Core flood experiments on Berea sandstone cores and dolomite samples with dimensions of 1.5 in × 3 in were conducted at a flow rate of 1 cc/min under 150oF temperature. NMR and porosity analysis concluded that applied chemicals are effective in creating fresh pore spaces. ICP analysis concluded that HEDTA showed good ability to chelate calcium, sodium, magnesium, potassium and iron. It can be established from the analysis that HEDTA can increase more amount of permeability as compared to other chelates.

  13. SYNTHESIS OF N- ACETONITRIL AND N- ETHYLAMINE- 3- HYDROXYPYRIDINONES AS IRON (III CHELATORS

    Directory of Open Access Journals (Sweden)

    L.A. SAGHAEI

    2000-12-01

    Full Text Available Background. The need of iron-chelating agents as orally active alternatives to desferal for the treatment of iron overload in thalassaemic patients, has stimulated considerable research efforts in the synthesis of new metal chelators. One of the member of hydroxypyridinones (2,3- dimethyl-3- hydroxypyridinones has so far received the most attention. This compound is rapidly glucuronidated into a non-chelating metabolite, which partly explains why high doses of the compound has to be used in order to achieve negative balance. This metabolic behavior has led the medicinal chemists to design compounds such as N-hydroxyalkyl derivatives which do not undergo extensive metabolism. The objective of the present work was to further synthesis and design new derivatives of hydroxypyridinones (N- acetonitril and N-ethylamine derivatives Methods. The synthesis route involves the benzylation of hydroxyl group of maltol (ethyl maltol using benzyl chloride conversion of the benazylated maltol (ethyl maltol to the N-acetonitril bezylated pyridinone derivatives by introducing the aminoacetonitril in pyridine solvent and cleavage of benzyl group by hydrogenation method or using the bromodimethyl borane to form the N-acetonitril or N- ethylamine- 3- hydroxypyridinones respectively.
    Results. In this work three final compounds such as 1- (2- aminoethyl- 2- methyl- 3-hydroxypyridin- 4- one, 1- (2- aminoethyl- 2- ethyl- 3- hydroxypyridin-4- one and 1- cyanomethyl -2- methyl- 3- hydroxypyridin- 4- one were synthesized.
    Discussion. Identification and structural elucidation of compounds were achieved by IH NMR and Mass spectra, elemental analysis and through physical constants. The biological effects of compounds will be studied in the near future.

  14. Crystal Structures, Properties and Reactivity of Selected Macrocyclic and Chelate Complexes of Ni(II)

    OpenAIRE

    Churchard, Andrew James

    2012-01-01

    In this dissertation we describe the structure, properties and decomposition reactions of a series of Ni(II) coordination complexes formed from reaction of the appropriate macrocyclic or chelating ligand with a simple nickel salt. The ligands used were 12aneS4 (1,4,7,10-tetrathiacyclododecane), 14aneS4 (1,4,8,11-tetrathiacyclotetradecane), cyclam (1,4,8,11-tetraazacyclotetradecane), dppe (1,2- (diphenylphosphino)ethane), and PP3 (tris-(2-(diphenylphosphino)ethyl)phosphine). The wo...

  15. Water-soluble chelating polymers for removal of actinides from watewater

    Energy Technology Data Exchange (ETDEWEB)

    Jarvinen, G. [Los Alamos National Lab., NM (United States)

    1996-10-01

    Polymer filtration is a technology being developed to recover valuable or regulated metal ions selectively from process or wastewaters. Water-soluble chelating polymers are specially designed to bind selectively with metal ions in aqueous solutions. The polymers molecular weight is large enough so they can be separated and concentrated using available ultrafiltration technology. Water and smaller unbound components of the solution pass freely through the ultrafiltration membrane. The polymers can then be reused by changing the solution conditions to release the metal ions, which are recovered in concentrated form, for recycle or disposal.

  16. Synthesis, structural characterization, and electrochemical studies of nickel porphyrins bearing two peripheral conjugated chelating groups.

    Science.gov (United States)

    Richeter, Sébastien; Jeandon, Christophe; Gisselbrecht, Jean-Paul; Ruppert, Romain; Callot, Henry J

    2007-11-26

    This article describes the synthesis of several new nickel porphyrins bearing peripheral chelating groups conjugated with the macrocyclic pi system. These monomeric nickel porphyrins display quite unusual chromophoric properties, some of them absorbing in the near-infrared region. Extension of the aromatic core of the porphyrin was realized by connecting meso-aryl groups with pyrroles by ketone functionalities. Further functionalizations led to bisenaminoketones or bisenaminothioketones, which are useful building blocks for the elaboration of oligomeric porphyrins linked by metal ions. All new compounds were studied by electrochemistry, some of them showing up to six electron transfers and/or splitting of the first oxidation wave.

  17. Fabrication of chelating diethylenetriaminated pan micro and nano fibers for heavy metal removal

    Directory of Open Access Journals (Sweden)

    Abdouss Majid

    2012-01-01

    Full Text Available In this study, commercial acrylic fibers were modified with diethylenetriamine to prepare metal chelating fibers. The effects of process parameters on the efficiency of the reaction were investigated. FTIR spectroscopy and TGA analysis were used to confirm the chemical changes made to the fibers during the reaction. The ability of the modified fibers for removal of Pb (II, Cu (II and Ce (IV ions from aqueous media was determined. The modified fibers showed a slight decrease in mechanical properties compared to raw ones. Furthermore, the acrylic micro fibers were electrospun to nanofibers and the ability of modified nanofibers for the adsorption of the metal ions was studied.

  18. Bis-ligated Ti and Zr complexes of chelating N-heterocyclic carbenes

    KAUST Repository

    El-Batta, Amer

    2011-07-01

    In this communication we report the synthesis of novel titanium and zirconium complexes ligated by bidentate "salicylaldimine-like" N-heterocyclic carbenes (NHC). Double addition of the NHC chelate to either TiCl4(thf)2 or ZrCl4 forms bis-ligated organometallic fragments with a distorted octahedral geometry. These complexes are rare examples of group IV transition-metal NHC adducts. Preliminary catalytic tests demonstrate that in the presence of methylaluminoxane (MAO) these complexes are useful initiators for the polymerization of ethylene and the copolymerization of ethylene with norbornene and 1-octene. © 2011 Elsevier B.V. All rights reserved.

  19. Conjugates of Actinide Chelator-Magnetic Nanoparticles for Used Fuel Separation Technology

    Energy Technology Data Exchange (ETDEWEB)

    Qiang, You; Paszczynski, Andrzej; Rao, Linfeng

    2011-10-30

    The actinide separation method using magnetic nanoparticles (MNPs) functionalized with actinide specific chelators utilizes the separation capability of ligand and the ease of magnetic separation. This separation method eliminated the need of large quantity organic solutions used in the liquid-liquid extraction process. The MNPs could also be recycled for repeated separation, thus this separation method greatly reduces the generation of secondary waste compared to traditional liquid extraction technology. The high diffusivity of MNPs and the large surface area also facilitate high efficiency of actinide sorption by the ligands. This method could help in solving the nuclear waste remediation problem.

  20. Thermodynamic stability and relaxation studies of small, triaza-macrocylic Mn(II) chelates

    OpenAIRE

    Sá, Arsénio Vasconcelos; Bonnet, Célia S.; Geraldes, Carlos F. G. C.; Tóth, Éva; Ferreira, Paula M.T.; André, João P.

    2013-01-01

    Due to its favorable relaxometric properties, Mn2+ is an appealing metal ion for magnetic resonance imaging (MRI) contrast agents. This paper reports the synthesis and characterization of three new triazadicarboxylate-type ligands and their Mn2+ chelates (NODAHep, 1,4,7-triazacyclononane-1,4-diacetate-7-heptanil; NODABA, 1,4,7-triazacyclononane-1,4-diacetate-7-benzoic acid; and NODAHA (1,4,7-triazacyclononane-1,4-diacetate-7-hexanoic acid). The protonation constants of the ligands and the sta...

  1. Synthesis of Two New Group 13 Benzoato-Chloro Complexes: A Structural Study of Gallium and Indium Chelating Carboxylates

    Science.gov (United States)

    Duraj, Stan A.; Hepp, Aloysius F.; Woloszynek, Robert; Protasiewicz, John D.; Dequeant, Michael; Ren, Tong

    2010-01-01

    Two new heteroleptic chelated-benzoato gallium (III) and indium (III) complexes have been prepared and structurally characterized. The molecular structures of [GaCl2(4-Mepy)2(O2CPh)]4-Mepy (1) and [InCl(4-Mepy)2(O2CPh)2]4-Mepy (2) have been determined by single-crystal x-ray diffraction. The gallium compound (1) is a distorted octahedron with cis-chloride ligands co-planar with the chelating benzoate and the 4-methylpyridines trans to each other. This is the first example of a Ga(III) structure with a chelating benzoate. The indium compound (2) is a distorted pentagonal bipyramid with two chelating benzoates, one 4-methylpyridine in the plane and a chloride trans to the other 4-methylpyridine. The indium bis-benzoate is an unusual example of a seven-coordinate structure with classical ligands. Both complexes, which due to the chelates, could also be described as pseudo-trigonal bipyramidal, include a three-bladed motif with three roughly parallel aromatic rings that along with a solvent of crystallization and electron-withdrawing chloride ligand(s) stabilize the solid-state structures.

  2. Antioxidant and Chelating Activity of Nontoxic Jatropha curcas L. Protein Hydrolysates Produced by In Vitro Digestion Using Pepsin and Pancreatin

    Directory of Open Access Journals (Sweden)

    Santiago Gallegos Tintoré

    2015-01-01

    Full Text Available The antioxidant and metal chelating activities in J. curcas protein hydrolysates have been determined. The hydrolysates were produced by treatment of a nontoxic genotype with the digestive enzymes pepsin and pancreatin and then were characterized by fast protein liquid chromatography and reverse phase chromatography. Peptidic fractions with higher radical scavenging activity were analysed by matrix-assisted laser desorption/ionization mass spectrometry. The antioxidant activity was determined by measuring inhibition of the oxidative degradation of β-carotene and by measuring the reactive oxygen species (ROS in Caco-2 cell cultures. Cu2+ and Fe2+ chelating activities were also determined. The hydrolysates inhibited the degradation of β-carotene and the formation of ROS in Caco-2 cells. The lower molecular weight peptidic fractions from FPLC had stronger antioxidant activity in cell cultures compared with the hydrolysates, which correlated with a higher content in antioxidant and chelating amino acids. These fractions were characterized by a large presence of peptides with different molecular masses. The hydrolysates exhibited both Cu2+ and Fe2+ chelating activity. It was concluded that J. curcas is a good source of antioxidant and metal chelating peptides, which may have a positive impact on the economic value of this crop, as a potential source of food functional components.

  3. Positron Emission Tomography Based Analysis of Long-Circulating Cross-Linked Triblock Polymeric Micelles in a U87MG Mouse Xenograft Model and Comparison of DOTA and CB-TE2A as Chelators of Copper-64

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann; Binderup, Tina; Ek, Pramod Kumar

    2014-01-01

    Copolymers of ABC-type (PEG-PHEMA-PCMA) architecture were prepared by atom transfer radical polymerization and formulated as micelles with functionalizable primary alcohols in the shell-region (PHEMA-block) to which the metal-ion chelators DOTA or CB-TE2A were conjugated. Using this micelle system...... we compared the in vivo stabilities of DOTA and CB-TE2A as chelators of 64Cu in micelle nanoparticles. The coumarin polymer (PCMA-block) micelle core was cross-linked by UV irradiation at 2 W/cm2 for 30 min. The cross-linked micelles were labeled with 64Cu at room temperature for 2 h (DOTA) or 80 °C...... for 3 h (CB-TE2A), giving labeling efficiencies of 60–76% (DOTA) and 40–47% (CB-TE2A). 64Cu-micelles were injected into tumor-bearing mice (8 mg/kg) and PET/CT scans were carried out at 1, 22, and 46 h postinjection. The micelles showed good blood stability (T1/2: 20–26 h) and tumor uptake...

  4. Tailored Gallium(III) chelator NOPO: synthesis, characterization, bioconjugation, and application in preclinical Ga-68-PET imaging.

    Science.gov (United States)

    Simeček, Jakub; Zemek, Ondřej; Hermann, Petr; Notni, Johannes; Wester, Hans-Jürgen

    2014-11-03

    The bifunctional chelator NOPO (1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid]) shows remarkably high Ga(III) complexation efficiency and comprises one carboxylic acid moiety which is not involved into metal ion coordination. An improved synthetic protocol affords NOPO with 45% overall yield. Stepwise protonation constants (log Ka), determined by potentiometry, are 11.96, 5.22, 3.77, and 1.54; the stability constant of the Ga(III) complex is log KGaL = 25.0. Within 5 min, (68)Ga(III) incorporation by NOPO is virtually quantitative at room temperature between pH 3 and 4, and at 95 °C at pH ranging from 0.5 to 7, at NOPO concentrations of 30 μM and 10 μM, respectively. During amide bond formation at the distant carboxylate using the HATU coupling reagent, an intramolecular phosphinic acid ester (phosphilactone) is formed, which is cleaved during (68)Ga complexation or in acidic media, such as trifluoroacetic acid (TFA). Phosphilactone formation can also be suppressed by complexation of Zn(2+) prior to conjugation, the resulting zinc-containing conjugates nevertheless being suitable for direct (68)Ga-labeling. In AR42J (rat pancreatic carcinoma) xenografted CD-1 nude mice, (68)Ga-labeled NOPO-NaI(3)-octreotide conjugate ((68)Ga-NOPO-NOC) showed high and fully blockable tumor uptake (13.9 ± 5% ID/g, 120 min p.i., compared to 0.9 ± 0.4% ID/g with 5 mg/kg of nonlabeled peptide). Uptake in other tissues was generally below 3% ID/g, except appearance of excretion-related activity accumulation in kidneys. NOPO-functionalized compounds tend to be more hydrophilic than the corresponding DOTA- and NODAGA-conjugates, thus promoting fast and extensive renal excretion of (68)Ga-NOPO-radiopharmaceuticals. NOPO-functionalized peptides provide suitable pharmacokinetics in vivo and meet all requirements for efficient (68)Ga-labeling even at room temperature in a kit-like manner.

  5. PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice

    DEFF Research Database (Denmark)

    Huda, Pie; Binderup, Tina; Pedersen, Martin Cramer

    2015-01-01

    64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model...... radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold....

  6. Biomimetic Taste Receptors with Chiral Recognition by Photoluminescent Metal-Organic Frameworks Chelated with Polyaniline Helices.

    Science.gov (United States)

    Lee, Tu; Lin, Tsung Yan; Lee, Hung Lin; Chang, Yun Hsuan; Tsai, Yee Chen

    2016-01-22

    The adsorption of phenylaniline (Phe) enantiomers on (+)-polyaniline (PAN)-chelated [In(OH)(bdc)]n microcrystals was carefully designed and studied by using the Job titration, circular dichroism, X-ray photoelectron spectroscopy, and photoluminescence to mimic heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors in selective, but not specific, ligand binding with chiral recognition and signal transduction. Six essential working principles across different length scales are unraveled: 1) a chiral (+)-PAN (host), 2) specific sites for Phe-(+)/PAN (guest-host) binding, 3) a conformational change of (+)-PAN after binding with Phe enantiomers, 4) different degrees of packing for (+)-PAN, 5) interactions between (+)-PAN and the underlying signal-generating framework (i.e., [In(OH)(bdc)]n microcrystals), and 6) a systematic photoluminescent signal combination by using principal-component analysis from the other three polymer-chelated metal-organic frameworkds (MOFs), such as poly(acrylic acid) (PAA), sodium alginate (SA), and polyvinylpyrrolidone (PVP) to enhance the selectivity and discrimination capabilities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Trace Minerals in Poultry Nutrition and the Efficiency of Chelating Forms

    Directory of Open Access Journals (Sweden)

    Kasım Özek

    2016-11-01

    Full Text Available The efficiency of chelated forms of trace minerals in poultry nutrition and the trace minerals requirements of poultry were discussed in this review. Trace minerals are essential for all farm animals, and these minerals, individually or together with other mineral, take part in many events such as metabolic activities, development and repair of different tissues, growth, immune and reproductive systems. In the last years, lots of studies related to different organic forms of trace minerals on the effects of broiler and laying hens were carried out. The results of these studies have showed that organic trace minerals added to poultry diets at lower levels than inorganic trace minerals are more efficient than inorganic trace minerals and they provide some advantages in poultry nutrition. One of the most important advantages is the reduction of mineral amount excreted in faces. In addition, the results of researches conducted especially in the last few years have shown that the chelated forms of trace minerals strengthen the poultry immune system, and increase the use of other nutrients. However, there are inconsistent between the effects of different forms of trace minerals used in poultry diets on the performance.

  8. Effects of copper glycine chelate on liver and faecal mineral concentrations, and blood parameters in broilers

    Directory of Open Access Journals (Sweden)

    Małgorzata Kwiecień

    2015-06-01

    Full Text Available The aim of the study was to determine the influence of Cu-glycine chelate on the chemical composition of the liver and blood parameters of broiler chickens. A total of 250 one-day-old Ross 308 male chicks were allotted into 5 groups with 5 replicates of 10 birds each. Rearing of birds lasted 42 days. In the experiment Cu was added to the premix in the form of CuSO4 (16 mg, 8 mg Cu, and in the form of Cu glycine chelate (16 mg, 8 mg, 4 mg Cu. The parameters in the chickens’ blood remained within the range of physiological norms when lower levels of the analyzed elements were added. Adding lower levels of Cu (8 or 4 mg·kg-1 in comparison with the recommended doses (16 mg·kg-1 for broilers, in the form of highly assimilable organic sources, did not reduce the content of minerals Cu, Fe, and Zn in the chickens’ liver, but reduced the faecal Fe, Cu and Zn concentrations compared to CuSO4.

  9. Mechanisms for chelator stimulation of microbial Fe(III) -oxide reduction

    Science.gov (United States)

    Lovley, D.R.; Woodward, J.C.

    1996-01-01

    The mechanisms by which nitrilotriacetic acid (NTA) stimulated Fe(III) reduction in sediments from a petroleum-contaminated aquifer were investigated in order to gain insight into how added Fe(III) chelators stimulate the activity of hydrocarbon-degrading, Fe(III)-reducing microorganisms in these sediments, and how naturally occurring Fe(III) chelators might promote Fe(III) reduction in aquatic sediments. NTA solubilized Fe(III) from the aquifer sediments. NTA stimulation of microbial Fe(III) reduction did not appear to be the result of making calcium, magnesium, potassium, or trace metals more available to the microorganisms. Stimulation of Fe(III) reduction could not be attributed to NTA serving as a source of carbon or fixed nitrogen for Fe(III)-reducing bacteria as NTA was not degraded in the sediments. Studies with the Fe(III)-reducing microorganism, Geobacter metallireducens, and pure Fe(III)-oxide forms, demonstrated that NTA stimulated the reduction of a variety of Fe(III) forms, including highly crystalline Fe(III)-oxides such as goethite and hematite. The results suggest that NTA solubilization of insoluble Fe(III)-oxide is an important mechanism for the stimulation of Fe(III) reduction by NTA in aquifer sediments.

  10. Thermal Decomposition and Phase Formation of Cerate-Zirconate Ceramics Prepared with Different Chelating Agents

    Science.gov (United States)

    Osman, Nafisah; Abdullah, Nur Athirah; Hasan, Sharizal

    2013-07-01

    Chelating agents of citric acid, lactic acid, glycine and ethylenediaminetetra acetic acid (EDTA) were used to synthesize a ceramic compound of Ba(Ce0.6Zr0.4)0.9Y0.1O2.95 (BCZY10) by a sol-gel method. Thermal decomposition and phase formation of the samples were analyzed by thermogravimetric analysis (TGA), Fourier transform infra-red (FTIR) spectroscopy and X-ray diffractometer (XRD). At heating rate of 10 °C min-1, all the samples exhibited almost similar pattern of TG-DTG profiles. A complete thermal decomposition process of the samples took place by three stages. The powders prepared using EDTA exhibited the lowest temperature for thermal decomposition since there was no significant weight loss above than 770 °C. Even after calcined at 1100 °C, the carbonate residue still remains in the samples as proven by FTIR result. The presence of this intermediate phase was also detected in XRD spectra as a small peak at 2θ≈23.9 ° corresponds to BaCO3 appeared for S1, S2 S3 and S4 samples. It was found that the chelating agents used had a decisive influence on the thermal decomposition of samples but no significant effect in reducing calcination temperature to produce a pure perovskite-like phase.

  11. Zinc chelation and Klf9 knockdown cooperatively promote axon regeneration after optic nerve injury.

    Science.gov (United States)

    Trakhtenberg, Ephraim F; Li, Yiqing; Feng, Qian; Tso, Janice; Rosenberg, Paul A; Goldberg, Jeffrey L; Benowitz, Larry I

    2017-10-27

    The inability of axons to regenerate over long-distances in the central nervous system (CNS) limits the recovery of sensory, motor, and cognitive functions after various CNS injuries and diseases. Although pre-clinical studies have identified a number of manipulations that stimulate some degree of axon growth after CNS damage, the extent of recovery remains quite limited, emphasizing the need for improved therapies. Here, we used traumatic injury to the mouse optic nerve as a model system to test the effects of combining several treatments that have recently been found to promote axon regeneration without the risks associated with manipulating known tumor suppressors or oncogenes. The treatments tested here include TPEN, a chelator of mobile (free) zinc (Zn(2+)); shRNA against the axon growth-suppressing transcription factor Klf9; and the atypical growth factor oncomodulin combined with a cAMP analog. Whereas some combinatorial treatments produced only marginally stronger effects than the individual treatments alone, co-treatment with TPEN and Klf9 knockdown had a substantially stronger effect on axon regeneration than either one alone. This combination also promoted a high level of cell survival at longer time points. Thus, Zn(2+) chelation in combination with Klf9 suppression holds therapeutic potential for promoting axon regeneration after optic nerve injury, and may also be effective for treating other CNS injuries and diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Chelation Ion Exchange Properties of 2, 4-Dihydroxyacetophenone-Biuret-Formaldehyde Terpolymer Resin

    Directory of Open Access Journals (Sweden)

    Sanjiokumar S. Rahangdale

    2009-01-01

    Full Text Available The terpolymer resin 2, 4-HABF has been synthesized by the condensation of 2, 4-dihydroxyacetophenone (2, 4-HA and biuret (B with formaldehyde (F in 1:1:2 molar ratios in presence of 2 M hydrochloric acid as catalyst. UV-Visible, IR and proton NMR spectral studies have been carried out to elucidate the structure of the resin. A terpolymer (2, 4-HABF proved to be a selective chelating ion exchange polymer for certain metals. Chelating ion-exchange properties of this polymer were studied for Fe3+, Cu2+, Ni2+, Co2+, Zn2+, Cd2+ and Pb2+ ions. A batch equilibrium method was employed in the study of the selectivity of metal ion uptake involving the measurement of the distribution of a given metal ion between the polymer sample and a solution containing the metal ion. The study was carried out over a wide pH range and in media of various ionic strengths. The polymer showed highest selectivity for Fe3+, Cu2+ ions than for Ni2+, Co2+, Zn2+, Cd2+, and Pb2+ ions. Study of distribution ratio as a formation of pH indicates that the amount of metal ion taken by resin is increases with the increasing pH of the medium.

  13. Metal chelate affinity precipitation of RNA and purification of plasmid DNA

    Science.gov (United States)

    Balan, Sindhu; Murphy, Jason; Galaev, Igor; Kumar, Ashok; Fox, George E.; Mattiasson, Bo; Willson, Richard C.

    2003-01-01

    The affinity of metal chelates for amino acids, such as histidine, is widely used in purifying proteins, most notably through six-histidine 'tails'. We have found that metal affinity interactions can also be applied to separation of single-stranded nucleic acids through interactions involving exposed purines. Here we describe a metal affinity precipitation method to resolve RNA from linear and plasmid DNA. A copper-charged copolymer of N-isopropyl acrylamide (NIPAM) and vinyl imidazole (VI) is used to purify plasmid from an alkaline lysate of E. coli. The NIPAM units confer reversible solubility on the copolymer while the imidazole chelates metal ions in a manner accessible to interaction with soluble ligands. RNA was separated from the plasmid by precipitation along with the polymer in the presence of 800 mM NaCl. Bound RNA could be recovered by elution with imidazole and separated from copolymer by a second precipitation step. RNA binding showed a strong dependence on temperature and on the type of buffer used.

  14. Crochelins: Siderophores with an Iron-Chelating Moiety from the Nitrogen-Fixing Bacterium Azotobacter chroococcum.

    Science.gov (United States)

    Baars, Oliver; Zhang, Xinning; Gibson, Marcus I; Stone, Alan T; Morel, François M M; Seyedsayamdost, Mohammad R

    2017-11-14

    Microbes use siderophores to access essential iron resources in the environment. Over 500 siderophores are known, but they utilize a small set of common moieties to bind iron. Azotobacter chroococcum expresses iron-rich nitrogenases, with which it reduces N2 . Though an important agricultural inoculant, the structures of its iron-binding molecules remain unknown. Here, the "chelome" of A. chroococcum is examined using small molecule discovery and bioinformatics. The bacterium produces vibrioferrin and amphibactins as well as a novel family of siderophores, the crochelins. Detailed characterization shows that the most abundant member, crochelin A, binds iron in a hexadentate fashion using a new iron-chelating γ-amino acid. Insights into the biosynthesis of crochelins and the mechanism by which iron may be removed upon import of the holo-siderophore are presented. This work expands the repertoire of iron-chelating moieties in microbial siderophores. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Peptide-tethered monodentate and chelating histidylidene metal complexes: synthesis and application in catalytic hydrosilylation.

    Science.gov (United States)

    Monney, Angèle; Nastri, Flavia; Albrecht, Martin

    2013-04-28

    The Nδ,Nε-dimethylated histidinium salt (His*) was tethered to oligopeptides and metallated to form Ir(III) and Rh(I) NHC complexes. Peptide-based histidylidene complexes containing only alanine, Ala-Ala-His*-[M] and Ala-Ala-Ala-His*-[M] were synthesised ([M] = Rh(cod)Cl, Ir(Cp*)Cl2), as well as oligopeptide complexes featuring a potentially chelating methionine and tyrosine residue, Met-Ala-Ala-His*-Rh(cod)Cl and Tyr-Ala-Ala-His*-Rh(cod)Cl. Chelation of the methionine-containing histidylidene ligand was induced by halide abstraction from the rhodium centre, while tyrosine remained non-coordinating under identical conditions. High catalytic activities in hydrosilylation were achieved with all peptide-based rhodium complexes. The cationic S(Met),C(His*)-bidentate peptide rhodium catalyst outperformed the monodentate neutral peptide complexes and constitutes one of the most efficient rhodium carbene catalysts for hydrosilylation, providing new opportunities for the use of peptides as N-heterocyclic carbene ligands in catalysis.

  16. Determination of trace indium in urine after preconcentration with a chelating-resin-packed minicolumn.

    Science.gov (United States)

    Liu, Hui-Ming; Chang, Ching-Yao; Wu, Chia-Chan; Wei, Jian-Ming; Chen, Wei-Yu; Yeh, Cheng-Tsung

    2012-04-01

    A simple and rapid chelating-resin-packed column has been developed for preconcentration of trace indium in biological samples. A large-sized urine sample was pumped through a minicolumn at a flow rate of 1.0 mL/min by using a peristaltic pump, and the eluents were analyzed using graphite furnace atomic absorption spectrometry (GFAAS). Four commercially available chelating resins including Chelex-100, Amberlite IRC-50, Duolite GT-73, and Celite 545-AW were studied for evaluating the indium sorption performance. Several parameters, such as pH, resin amount, eluent volume, eluent flow rate, and the volume of sample, were investigated and optimized. A 100-200 mL of the sample was loaded into a column containing 1.2 g of wet Chelex-100 and subjected to the ion-exchange procedure. The retained analytes were eluted with 5.0 mL of 0.1 M HNO(3) and quantified by GFAAS. The correlation coefficient in the range 10-250 ng/mL was of 0.9994. The limit of detection of the proposed method was 2.75 ng/mL. The method developed was successfully applied to analysis of spiked urine samples with good recoveries of 93-103% (n = 6) and reproducibility (relative standard deviation indium determination in spiked certified reference materials. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. OligoG CF-5/20 normalizes cystic fibrosis mucus by chelating calcium.

    Science.gov (United States)

    Ermund, Anna; Recktenwald, Christian V; Skjåk-Braek, Gudmund; Meiss, Lauren N; Onsøyen, Edvar; Rye, Philip D; Dessen, Arne; Myrset, Astrid Hilde; Hansson, Gunnar C

    2017-06-01

    The goal of this study was to determine whether the guluronate (G) rich alginate OligoG CF-5/20 (OligoG) could detach cystic fibrosis (CF) mucus by calcium chelation, which is also required for normal mucin unfolding. Since bicarbonate secretion is impaired in CF, leading to insufficient mucin unfolding and thereby attached mucus, and since bicarbonate has the ability to bind calcium, we hypothesized that the calcium chelating property of OligoG would lead to detachment of CF mucus. Indeed, OligoG could compete with the N-terminus of the MUC2 mucin for calcium binding as shown by microscale thermophoresis. Further, effects on mucus thickness and attachment induced by OligoG and other alginate fractions of different length and composition were evaluated in explants of CF mouse ileum mounted in horizontal Ussing-type chambers. OligoG at 1.5% caused effective detachment of CF mucus and the most potent alginate fraction tested, the poly-G fraction of about 12 residues, had similar potency compared to OligoG whereas mannuronate-rich (M) polymers had minimal effect. In conclusion, OligoG binds calcium with appropriate affinity without any overt harmful effect on the tissue and can be exploited for treating mucus stagnation. © 2017 John Wiley & Sons Australia, Ltd.

  18. Effect of endodontic chelating solutions on the bond strength of endodontic sealers

    Directory of Open Access Journals (Sweden)

    Behram TUNCEL

    2015-01-01

    Full Text Available The purpose of this in vitro study was to evaluate the effect of various chelating solutions on the radicular push-out bond strength of calcium silicate-based and resin-based root canal sealers. Root canals of freshly-extracted single-rooted teeth (n = 80 were instrumented by using rotary instruments. The specimens were randomly divided into 4 groups according to the chelating solutions being tested: (1 17% ethylenediaminetetraacetic acid (EDTA; (2 9% etidronic acid; (3 1% peracetic acid (PAA; and (4 distilled water (control. In each group, the roots were further assigned into 2 subgroups according to the sealer used: (1 an epoxy resin-based sealer (AH Plus and (2 a calcium silicate-based sealer (iRoot SP. Four 1 mm-thick sections were obtained from the coronal aspect of each root (n = 40 slices/group. Push-out bond strength test was performed at a crosshead speed of 1 mm/min., and the bond strength data were analyzed statistically with two-way analysis of variance (ANOVA with Bonferroni’s post hoc test (p 0.05. iRoot SP showed higher resistance to dislocation than AH Plus. Final irrigation with 17% EDTA, 9% Etidronic acid, and 1% PAA did not improve the bond strength of AH Plus and iRoot SP to radicular dentin.

  19. Zinc chelates as new activators for sulphur vulcanization of acrylonitrile-butadiene elastomer

    Directory of Open Access Journals (Sweden)

    2009-04-01

    Full Text Available The goal of this work was to apply several zinc chelates as activators for sulphur vulcanization of acrylonitrilebutadiene elastomer (NBR, in order to find alternatives for the conventionally used zinc oxide. In this article, we discuss the effects of different zinc complexes on the cure characteristics, crosslinks distribution in the elastomer network and mechanical properties of acrylonitrile-butadiene rubber. Zinc chelates seem to be good substitutes for zinc oxide as activators for sulphur vulcanization of NBR rubber, without detrimental effects on the crosslinking process and physical properties of the obtained vulcanizates. Moreover, application of zinc complexes allows to reduce the amount of zinc ions in rubber compounds by 40% compared to conventionally crosslinked vulcanizates with zinc oxide. It is a very important ecological goal since zinc oxide is classified as toxic to aquatic species and its amount in rubber products must be reduced below 2.5% at least. From a technological point of view it is a very important challenge.

  20. Silver Recovery and Power Generation from Ammonia Chelated Silver Solution in a Bio-Electrochemical Reactor

    Science.gov (United States)

    Ho, N. A. D.; Babel, S.

    2017-06-01

    Silver has valuable features and limited availability, and thus recovery from wastewater or aqueous solutions plays an important role in environmental protection and economic profits. In this study, silver recovery along with power generation and COD removal were investigated in a bio-electrochemical system (BES). The BES comprised of an anode and a cathode chamber which were separated by a cation exchange membrane to prevent the cross-over of electrolytes. During the biological oxidation of acetate as an electron donor in the anode chamber, the reduction of ammonia chelated silver ions as electron acceptors in the cathode side occurred spontaneously. Results showed that a silver recovery of 99% and COD removal efficiency of 60% were achieved at the initial silver concentration of 1,000 mg/L after 48 hours of operation. The power generation improved 4.66%, from 3,618 to 3,795 mW/m3, by adding NaNO3 of 850 mg/L to the catholyte containing 2,000 mg/L of silver ions. Deposits on the cathode surface were characterized using scanning electron microscope (SEM) and energy dispersive X-ray (EDX). Metallic silver with dendritic structures and high purity were detected. This study demonstrated that BES technology can be employed to recover silver from complex chelating solution, produce electricity, and treat wastewater.

  1. Effect of enhanced iron chelation therapy on glucose metabolism in patients with beta-thalassaemia major.

    Science.gov (United States)

    Farmaki, Kalistheni; Angelopoulos, Nicholas; Anagnostopoulos, George; Gotsis, Efstathios; Rombopoulos, Grigorios; Tolis, George

    2006-08-01

    Recently introduced chelation regimens that combine deferoxamine (DFO) and deferiprone have been shown to have greater efficacy in promoting iron excretion than either chelator alone and have been associated with rapid reduction of the iron load in the heart and liver, and with reversal of cardiac dysfunction. It is unclear whether this combined therapy could be associated with a reduction in iron load or decline in the severity of iron-induced endocrinopathies. Starting in January 2001, 42 patients with beta-thalassaemia major, previously maintained on subcutaneous DFO only, were switched to combined treatment with DFO and deferiprone. The primary endpoint was to investigate the effects of this therapy on the glucose metabolism characteristics of this population. Combination therapy markedly decreased ferritin levels (638 +/- 1345 vs. 2991 +/- 2093 microg/l, P < 0.001). Glucose responses were improved at all times during an oral glucose tolerance test, particularly in patients in early stages of glucose intolerance. Glucose quantitative secretion also decreased significantly with combined therapy, while no significant change occurred in insulin levels in any group. Insulin secretion, according to the homeostasis assessment model, markedly increased in all groups, while overall reduction in insulin sensitivity did not reach statistical significance. This study showed that the combination of DFO and deferiprone was associated with an improvement in liver iron deposition and glucose intolerance.

  2. Chelate-assisted phytoextraction: effect of EDTA and EDDS on copper uptake by Brassica napus L.

    Directory of Open Access Journals (Sweden)

    TIJANA M. ZEREMSKI-ŠKORIĆ

    2010-09-01

    Full Text Available Chelate-assisted phytoextraction is proposed as an effective approach for the removal of heavy metals from contaminated soil through the use of high biomass plants. The aim of the present study was to compare the efficiency of the two chelators: EDTA and biodegradable EDDS in enhancing Cu uptake and translocation by Brassica napus L. grown on moderately contaminated soil and treated with increasing concentrations of EDTA or EDDS. Increasing amounts of EDDS caused serious growth suppression of B. napus and an increase in shoot metal concentrations. Growth suppression limited the actual amount of phytoextracted Cu at high concentrations of EDDS. The maximum amount of extracted Cu was achieved by the application of 8.0 and 4.0+4.0 mmol kg-1 EDDS. The shoot Cu concentrations after EDTA application were much lower than with EDDS at the same doses. According to these experiments, EDTA does not appear to be an efficient amendment if Cu phytoextraction with B. napus is considered but EDDS is.

  3. Ruthenium and osmium complexes that bear functional azolate chelates for dye-sensitized solar cells.

    Science.gov (United States)

    Chi, Yun; Wu, Kuan-Lin; Wei, Tzu-Chien

    2015-05-01

    The preparation of sensitizers for dye-sensitized solar cells (DSSCs) represents an active area of research for both sustainability and renewable energy. Both Ru(II) and Os(II) metal sensitizers offer unique photophysical and electrochemical properties that arise from the intrinsic electronic properties, that is, the higher propensity to form the lower-energy metal-to-ligand charge-transfer (MLCT) transition, and their capability to support chelates with multiple carboxy groups, which serve as a bridge to the metal oxide and enable efficient injection of the photoelectron. Here we present an overview of the synthesis and testing of these metal sensitizers that bear functional azolate chelates (both pyrazolate and triazolate), which are capable of modifying the metal sensitizers in a systematic and beneficial manner. Basic principles of the molecular designs, the structural relationship to the photophysical and electrochemical properties, and performances of the as-fabricated DSSCs are highlighted. The success in the breakthrough of the synthetic protocols and potential applications might provide strong stimulus for the future development of technologies such as DSSCs, organic light-emitting diodes, solar water splitting, and so forth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction.

    Directory of Open Access Journals (Sweden)

    Yasumasa Ikeda

    Full Text Available Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases (CKD. Although several mechanisms underlying renal fibrosis and candidate drugs for its treatment have been identified, the effect of iron chelator on renal fibrosis remains unclear. In the present study, we examined the effect of an iron chelator, deferoxamine (DFO, on renal fibrosis in mice with surgically induced unilateral ureter obstruction (UUO. Mice were divided into 4 groups: UUO with vehicle, UUO with DFO, sham with vehicle, and sham with DFO. One week after surgery, augmented renal tubulointerstitial fibrosis and the expression of collagen I, III, and IV increased in mice with UUO; these changes were suppressed by DFO treatment. Similarly, UUO-induced macrophage infiltration of renal interstitial tubules was reduced in UUO mice treated with DFO. UUO-induced expression of inflammatory cytokines and extracellular matrix proteins was abrogated by DFO treatment. DFO inhibited the activation of the transforming growth factor-β1 (TGF-β1-Smad3 pathway in UUO mice. UUO-induced NADPH oxidase activity and p22(phox expression were attenuated by DFO. In the kidneys of UUO mice, divalent metal transporter 1, ferroportin, and ferritin expression was higher and transferrin receptor expression was lower than in sham-operated mice. Increased renal iron content was observed in UUO mice, which was reduced by DFO treatment. These results suggest that iron reduction by DFO prevents renal tubulointerstitial fibrosis by regulating TGF-β-Smad signaling, oxidative stress, and inflammatory responses.

  5. Aggregation of a Cationic Gemini Surfactant with a Chelating Molecule and Effects from Calcium Ions.

    Science.gov (United States)

    Zhao, Weiwei; Song, Kai; Chen, Yao; Wang, Hua; Liu, Zhang; Shi, Qiang; Huang, Jianbin; Wang, Yilin

    2017-11-07

    The aggregation behavior of cationic ammonium gemini surfactant hexamethylene-1,6-bis(dodecyldimethylammonium bromide) (12-6-12) with chelating molecule ethylenediaminetetraacetic acid (EDTA) and the effects of calcium bromide (CaBr2) on the structure and morphology of the aggregates in the mixture have been investigated by surface tension, isothermal titration microcalorimetry, electrical conductivity, ζ potential, dynamic light scattering, cryogenic transmission electron microscopy, freeze-fracture transmission electron microscopy, and 1H NMR techniques. It was found that the electrostatic attraction between the carboxyl groups of EDTA and the headgroups of 12-6-12 leads to the formation of oligomeric-like surfactant EDTA(12-6-12)2 at an EDTA/12-6-12 molar ratio of 0.50. The critical aggregation concentration of the EDTA(12-6-12)2 complexes is much lower than that of 12-6-12, and the complexes form loose, large network-like premicellar aggregates and then transfer into small micelles with an increase in concentration. Moreover, the addition of CaBr2 induces the transition from the loose aggregates and micelles to vesicles owing to the coordination interaction between the calcium ion and EDTA and the electrostatic interaction between EDTA and 12-6-12. The work reveals that as a bridging molecule between the calcium ion and the gemini surfactant, the chelating molecule greatly promotes the assembly of the gemini surfactant and strengthens the molecular packing in the presence of calcium ions.

  6. Rates of nickel(II) capture from complexes with NTA, EDDA, and related tetradentate chelating agents by the hexadentate chelating agents EDTA and CDTA: Evidence of a "semijunctive" ligand exchange pathway

    Science.gov (United States)

    Boland, Nathan E.; Stone, Alan T.

    2017-09-01

    Many siderophores and metallophores produced by soil organisms, as well as anthropogenic chelating agent soil amendments, rely upon amine and carboxylate Lewis base groups for metal ion binding. UV-visible spectra of metal ion-chelating agent complexes are often similar and, as a consequence, whole-sample absorbance measurements are an unreliable means of monitoring the progress of exchange reactions. In the present work, we employ capillary electrophoresis to physically separate Ni(II)-tetradentate chelating agent complexes (NiL) from Ni(II)-hexadentate chelating agent complexes (NiY) prior to UV detection, such that progress of the reaction NiL + Y → NiY + L can be conveniently monitored. Rates of ligand exchange for Ni(II) are lower than for other +II transition metal ions. Ni(II) speciation in environmental media is often under kinetic rather than equilibrium control. Nitrilotriacetic acid (NTA), with three carboxylate groups all tethered to a central amine Lewis base group, ethylenediamine-N,N‧-diacetic acid (EDDA), with carboxylate-amine-amine-carboxylate groups arranged linearly, plus four structurally related compounds, are used as tetradentate chelating agents. Ethylenediaminetetraacetic acid (EDTA) and the structurally more rigid analog trans-cyclohexaneethylenediaminetetraacetic acid (CDTA) are used as hexadentate chelating agents. Effects of pH and reactant concentration are explored. Ni(II) capture by EDTA was consistently more than an order of magnitude faster than capture by CDTA, and too fast to quantify using our capillary electrophoresis-based technique. Using NiNTA as a reactant, Ni(II) capture by CDTA is independent of CDTA concentration and greatly enhanced by a proton-catalyzed pathway at low pH. Using NiEDDA as reactant, Ni(II) capture by CDTA is first order with respect to CDTA concentration, and the contribution from the proton-catalyzed pathway diminished by CDTA protonation. While the convention is to assign either a disjunctive

  7. Reversible immobilization of laccase to poly(4-vinylpyridine) grafted and Cu(II) chelated magnetic beads: biodegradation of reactive dyes.

    Science.gov (United States)

    Bayramoğlu, Gülay; Yilmaz, Meltem; Arica, M Yakup

    2010-09-01

    Poly(4-vinyl pyridine), poly(VP), as a novel metal-chelating fibrous polymer was grafted on the magnetic beads. Poly(4-VP) grafted and/or Cu(II) ions chelated magnetic beads were used for reversible immobilization of Trametes versicolor laccase, and the amounts of immobilized laccase on the beads were determined as 36.8 and 56.4 mg/g beads, respectively. The adsorption of laccase on both modified magnetic beads appeared to follow the Langmuir isotherm model. The degradation of textile dyes with immobilized laccase on the metal chelated magnetic beads was evaluated in a batch system. Three different reactive textile dyes (i.e., Reactive Green 19, Reactive Red 2 and Reactive Brown 10) were successfully degraded in the enzyme reactor. It was observed that the decolorization rate varied widely with chemical structure and types of the substitute group of the reactive dye molecules. (c) 2010 Elsevier Ltd. All rights reserved.

  8. Effect of zinc chelate and valnemulin for the treatment of swine dysentery in an experimental challenge study.

    Science.gov (United States)

    Šperling, Daniel; Čížek, Alois; Smola, Jiří

    2014-02-01

    The aim of study was to determine the influence of zinc chelate, valnemulin and it's combination on Brachyspira hyodysenteriae shedding and morphological changes of colonic mucosa in an experimental model of swine dysentery (SD). The study was performed on pigs coming from a dysentery-free herd. Animals were inoculated by B. hyodysenteriae strain B204. When the clinical signs of SD and B. hyodysenteriae shedding developed, the pigs were divided into four treatment groups. The first group was treated with zinc chelate (250 ml/1000 L in water), second group was given valnemulin in feed at 75 ppm; the third group was given a combination of both and the fourth group was control. The results demonstrated therapeutic effect of valnemulin in pigs with serious SD and did not show therapeutic effect of chelated zinc. Copyright © 2013. Published by Elsevier Ltd.

  9. Glucose metabolism disorders improvement in patients with thalassaemia major after 24-36 months of intensive chelation therapy.

    Science.gov (United States)

    Platis, Odysseas; Anagnostopoulos, Georgios; Farmaki, Kallisteni; Posantzis, Markos; Gotsis, Efstathios; Tolis, Georgios

    2004-12-01

    Thalassaemic patients with haemocromatosis often present with metabolic disturbances such as diabetes mellitus. A group of adult thalassaemic patients who received intensive oral and subcutaneous chelation therapy (Defferiprone/Ferriprox and Desferioxamine/Desferal) for a period of 24-36 months was studied for the presence of glucose metabolism disturbances (GMD). Investigation of the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) was carried out by yearly oral glucose tolerance tests (OGTT). Results showed that GMD (DM and IGT) improved in 1/3 of the patients after the intensive combined chelation treatment, a finding that we attributed to a reduction in liver iron deposits. Although this study is still in progress we believe that intensive combined chelation therapy may have a positive effect on glucose metabolism.

  10. On the Anticataractogenic Effects of L-Carnosine: Is It Best Described as an Antioxidant, Metal-Chelating Agent or Glycation Inhibitor?

    Directory of Open Access Journals (Sweden)

    Hamdy Abdelkader

    2016-01-01

    Full Text Available Purpose. L-Carnosine is a naturally occurring dipeptide which recently gained popularity as an anticataractogenic agent due to its purported antioxidant activities. There is a paucity of research and conclusive evidence to support such claims. This work offers compelling data that help clarify the mechanism(s behind the anticataract properties of L-carnosine. Methods. Direct in vitro antioxidant free radical scavenging properties were assayed using three different antioxidant (TEAC, CUPRAC, and DPPH assays. Indirect in vitro and ex vivo antioxidant assays were studied by measuring glutathione bleaching capacity and total sulfhydryl (SH capacity of bovine lens homogenates as well as hydrogen-peroxide-stress assay using human lens epithelial cells. Whole porcine lenses were incubated in high galactose media to study the anticataract effects of L-carnosine. MTT cytotoxicity assays were conducted on human lens epithelial cells. Results. The results showed that L-carnosine is a highly potent antiglycating agent but with weak metal chelating and antioxidant properties. There were no significant decreases in lens epithelial cell viability compared to negative controls. Whole porcine lenses incubated in high galactose media and treated with 20 mM L-carnosine showed a dramatic inhibition of advanced glycation end product formation as evidenced by NBT and boronate affinity chromatography assays. Conclusion. L-Carnosine offers prospects for investigating new methods of treatment for diabetic cataract and any diseases that are caused by glycation.

  11. The Zinc Ion Chelating Agent TPEN Attenuates Neuronal Death/apoptosis Caused by Hypoxia/ischemia Via Mediating the Pathophysiological Cascade Including Excitotoxicity, Oxidative Stress, and Inflammation.

    Science.gov (United States)

    Wang, Wei-Ming; Liu, Zhao; Liu, Ai-Jun; Wang, Yu-Xiang; Wang, Hong-Gang; An, Di; Heng, Bin; Xie, Lai-Hua; Duan, Jun-Li; Liu, Yan-Qiang

    2015-09-01

    We aim to determine the significant effect of TPEN, a Zn(2+) chelator, in mediating the pathophysiological cascade in neuron death/apoptosis induced by hypoxia/ischemia. We conducted both in vivo and in vitro experiments in this study. PC12 cells were used to establish hypoxia/ischemia model by applying oxygen-glucose deprivation (OGD). SHR-SP rats were used to establish an acute ischemic model by electrocoagulating middle cerebral artery occlusion. The effect of TPEN on neuron death/apoptosis was evaluated. In addition, the relative biomarks of excitotoxicity, oxidative stress, and inflammation reactions in hypoxia/ischemia PC12 cell model as well as in SHR-SP rat hypoxia/ischemia model were also assessed. TPEN significantly attenuates the neurological deficit, reduced the cerebral infarction area and the ratio of apoptotic neurons, and increased the expression of GluR2 in the rat hypoxia/ischemia brain. TPEN also increased blood SOD activity, decreased blood NOS activity and blood MDA and IL-6 contents in rats under hypoxia/ischemia. In addition, TPEN significantly inhibited the death and apoptosis of cells and attenuated the alteration of GluR2 and NR2 expression caused by OGD or OGD plus high Zn(2+) treatments. Zn(2+) is involved in neural cell apoptosis and/or death caused by hypoxia/ischemia via mediating excitotoxicity, oxidative stress, and inflammation. © 2015 John Wiley & Sons Ltd.

  12. Chelate-Modified Fenton Reaction for the Degradation of Trichloroethylene in Aqueous and Two-Phase Systems

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Scott [Univ of KY, dept of chemical and materials engineering; lynch, Andrew [Univ of KY, dept of chemical and materials engineering; Bachas, Leonidas [Univ of KY, Dept of Chemistry; hampson, Steve [Univ of KY Center for Applied Energy Research - KY Research Consortium of Energy and Environment; Ormsbee, Lindelle [Univ of KY Center for Applied Energy Research - KY Research Consortium of Energy and Environment; Bhattacharyya, Dibakar [Univ of KY, dept of chemical and materials engineering

    2008-06-01

    The Standard Fenton reaction has been used for In-Situ Chemical Oxidation (ISCO) of toxic organics in groundwater. However, it requires low pH operating conditions, and thus has limitations for in situ applications. In addition, hydroxyl radicals are rapidly consumed by hydroxyl scavengers found in the subsurface. These problems are alleviated through the chelate-modified Fenton (hydroxyl radical) reaction, which includes the addition of nontoxic chelate (L) such as citrate or gluconic acid. This chelate allows the reaction to take place at bear neutral pH and control hydrogen peroxide consumption by binding to Fe(II), forming an FeL complex. The chelate also binds to Fe(III), preventing its precipitation as ferric hydroxide and thus prevents problems associated with injection well plugging. The rate of TCE dechlorination in chelate-modified Fenton systems is a function of pH, H2O2 concentration, and FE:L ratio. The primary objective of this research is to model and apply this process to the destruction of trichloroethylene (TCE) present in both the aqueous and organic (in the form of droplets) phases. Experimentation proved the chelate-modified Fenton reaction effectively dechlorinates TCE in both the aqueous and organic phases at near-neutral pH. Other focuses of this work include determining the effect of [L]:[Fe] ratios on H2O2 and TCE degradation as well as reusability of the FE citrate solution under repeated H2O2 injections. Generalized models were developed to predict the concentration of TCE in the aqueous phase and TCE droplet radius as a function of time using established hydroxyl radial kinetics and mass transfer relationships.

  13. The effect of regioisomerism on the coordination chemistry and CEST properties of lanthanide(III) NB-DOTA-tetraamide chelates

    Science.gov (United States)

    Slack, Jacqueline R.; Woods, Mark

    2014-01-01

    Chemical exchange saturation transfer (CEST) offers many advantages as a method of generating contrast in magnetic resonance images. However, many of the exogenous agents currently under investigation suffer from detection limits that are still somewhat short of what can be achieved with more traditional Gd3+ agents. To remedy this limitation we have undertaken an investigation of Ln3+ DOTA-tetraamide chelates (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) that have unusually rigid ligand structures: the nitrobenzyl derivatives of DOTA-tetraamides with (2-phenylethyl)amide substituents. In this report we examine the effect of incorporating hydrophobic amide substituents on water exchange and CEST. The ligand systems chosen afforded a total of three CEST-active isomeric square antiprismatic chelates; each of these chelates was found to have different water exchange and CEST characteristics. The position of a nitrobenzyl substituent on the macrocyclic ring strongly influenced the way in which the chelate and Ln3+ coordination cage distorted. These differential distortions were found to affect the rate of water proton exchange in the chelates. But, by far the greatest effect arose from altering the position of the hydrophobic amide substituent, which, when forced upwards around the water binding site, caused a substantial reduction in the rate of water proton exchange. Such slow water proton exchange afforded a chelate that was 4.5 times more effective as a CEST agent than its isomeric counterparts in dry acetonitrile and at low temperatures and very low presaturation powers. PMID:24287873

  14. Zn and Mn o,p-EDDHA chelates for soybean nutrition in hydroponics in high pH conditions

    OpenAIRE

    López-Rayo, Sandra; Lucena, Juan J

    2009-01-01

    The low solubility of the iron, manganese and zinc oxides in the pH range of calcareous soils contributes, among other factors, to the low availability of these nutrients to plants. The aim of this work was study the efficacy of the application of Fe, Mn, Zn and Cu chelates to correct the deficiencies in soybean in hydroponic solution in the presence of CaCO3. Fe was applied as o,oEDDHA/Fe3+ in all the cases while Mn, Zn and Cu were applied as o,pEDDHA, EDDS, EDTA, HEDTA or DTPA chelates, wit...

  15. Chemical and biological properties of toxic metals and use of chelating agents for the pharmacological treatment of metal poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Sinicropi, Maria Stefania; Caruso, Anna [University of Calabria, Department of Pharmaceutical Sciences, Rende (Italy); Amantea, Diana [University of Calabria, Department of Pharmacobiology, Rende (Italy); Saturnino, Carmela [University of Salerno, Department of Pharmaceutical Sciences, Fisciano (Italy)

    2010-07-15

    Exposure to toxic metals is a well-known problem in industrialized countries. Metals interfere with a number of physiological processes, including central nervous system (CNS), haematopoietic, hepatic and renal functions. In the evaluation of the toxicity of a particular metal it is crucial to consider many parameters: chemical forms (elemental, organic or inorganic), binding capability, presence of specific proteins that selectively bind metals, etc. Medical treatment of acute and chronic metal toxicity is provided by chelating agents, namely organic compounds capable of interacting with metal ions to form structures called chelates. The present review attempts to provide updated information about the mechanisms, the cellular targets and the effects of toxic metals. (orig.)

  16. Synthesis, Characterization and Antimicrobial Activity of 5-(4-Methyl piperazinyl methylene-8-hydroxy quinoline and its Various Metal Chelates

    Directory of Open Access Journals (Sweden)

    I. J. Patel

    2006-01-01

    Full Text Available 5-Chloromethyl-8-quinolinol was condensed with 4-methyl piperazine in presence of sodium bicarbonate. The resulting 5-(4-methyl piper-azinylmethylene-8-quinolinol (MPQ was characterized by elemental analysis and spectral studies. The transition metal chelates viz Cu+2, Ni+2, Co+2, Mn+2, Zn+2, Cd+2, and Fe+3 of MPQ were prepared and characterized by metal-ligand (M:L ratio, IR and reflectance spectroscopies and magnetic properties. The antifungal activity of MPQ and its metal chelates was screened against various fungi. The results show that all these samples are good antifungal agents.

  17. The in vivo biofilm

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Alhede, Maria; Alhede, Morten

    2013-01-01

    Bacteria can grow and proliferate either as single, independent cells or organized in aggregates commonly referred to as biofilms. When bacteria succeed in forming a biofilm within the human host, the infection often becomes very resistant to treatment and can develop into a chronic state. Biofilms...... have been studied for decades using various in vitro models, but it remains debatable whether such in vitro biofilms actually resemble in vivo biofilms in chronic infections. In vivo biofilms share several structural characteristics that differ from most in vitro biofilms. Additionally, the in vivo...... experimental time span and presence of host defenses differ from chronic infections and the chemical microenvironment of both in vivo and in vitro biofilms is seldom taken into account. In this review, we discuss why the current in vitro models of biofilms might be limited for describing infectious biofilms...

  18. Effect of calcium chelators on heat coagulation and heat-induced changes of concentrated micellar casein solutions: The role of calcium-ion activity and micellar integrity

    NARCIS (Netherlands)

    Kort, de E.J.P.; Minor, M.; Snoeren, T.A.L.; Hooijdonk, van A.C.M.; Linden, van der E.

    2012-01-01

    There is general consensus that calcium chelators enhance heat stability in milk. However, they increase the heat stability to considerably different extents. For this reason, the effect of various calcium chelators on heat coagulation and heat-induced changes of concentrated micellar casein

  19. Iron(III) chelating resins. V. Cross-linked copolymers of 1-(B-acrylamidoethyl)-3-hydroxy-2-methyl-4(1H) pyridinone (AHMP) and N,N-dimethylacrylamide (DMAA) for iron(III) chelation studies

    NARCIS (Netherlands)

    Feng, Minhua; Feng, M.H.; van der Does, L.; Bantjes, A.; Bantjes, Adriaan

    1994-01-01

    Iron (III) chelating resins containing 3-hydroxy-2-methyl-4(1H)pyridinone (HMP) groups were prepared from 1-(β-acrylamidoethyl)-3-hydroxy-2-methyl-4(1H)pyridinone (AHMP) and N,N-dimethylacrylamide (DMAA), using N,N-ethylene-bis-acrylamide (EBAA) as a cross-linking agent. The cross-linked AHMP-DMAA

  20. Simultaneous Determination of Chelating Agents by Ion-Suppression and Ion-Pair Chromatography in Wastewater

    Energy Technology Data Exchange (ETDEWEB)

    Dodi, Alain; Bouscarel, Maelle [Commissariat a l' energie atomique - C.E.A, Centre d' Etude de Cadarache, Laboratoire d' Analyses Radiochimiques et Chimiques, St Paul lez Durance (France)

    2008-07-01

    This article describes two methods for analysing chelating agents found in nuclear waste. First, ion-suppression chromatography using an anion exchange stationary phase and mobile phase consisting of a nitric acid solution and pure water gradient. UV detection was performed at 330 nm after the reaction with a post-column reagent composed of iron nitrate in perchloric acid. Secondly, ion-pair chromatography with a mobile phase consisting of a mixture of nitric acid, tetra-butyl-ammonium hydrogeno-sulphate, tetra-butyl-ammonium hydroxide and iron chloride. A reversed-phase material was used as a stationary phase and detection was performed by direct measurement of the UV absorption at 260 nm. The quantification limits were lower for ion-pair chromatography than for ion-suppression chromatography. Both methods were easy to implement and allow a multi-element separation in less than 30 min with low detection limits. (authors)

  1. Therapeutic potential of copper chelation with triethylenetetramine in managing diabetes mellitus and Alzheimer's disease.

    Science.gov (United States)

    Cooper, Garth J S

    2011-07-09

    This article reviews recent evidence, much of which has been generated by my group's research programme, which has identified for the first time a previously unknown copper-overload state that is central to the pathogenesis of diabetic organ damage. This state causes tissue damage in the blood vessels, heart, kidneys, retina and nerves through copper-mediated oxidative stress. This author now considers this copper-overload state to provide an important new target for therapeutic intervention, the objective of which is to prevent or reverse the diabetic complications. Triethylenetetramine (TETA) has recently been identified as the first in a new class of anti-diabetic molecules through the original work reviewed here, thus providing a new use for this molecule, which was previously approved by the US FDA in 1985 as a second-line treatment for Wilson's disease. TETA acts as a highly selective divalent copper (Cu(II)) chelator that prevents or reverses diabetic copper overload, thereby suppressing oxidative stress. TETA treatment of diabetic animals and patients has identified and quantified the interlinked defects in copper metabolism that characterize this systemic copper overload state. Copper overload in diabetes mellitus differs from that in Wilson's disease through differences in their respective causative molecular mechanisms, and resulting differences in tissue localization and behaviour of the excess copper. Elevated pathogenetic tissue binding of copper occurs in diabetes. It may well be mediated by advanced-glycation endproduct (AGE) modification of susceptible amino-acid residues in long-lived fibrous proteins, for example, connective tissue collagens in locations such as blood vessel walls. These AGE modifications can act as localized, fixed endogenous chelators that increase the chelatable-copper content of organs such as the heart and kidneys by binding excessive amounts of catalytically active Cu(II) in specific vascular beds, thereby focusing the

  2. Improved Metathesis Lifetime: Chelating Pyridinyl-Alcoholato Ligands in the Second Generation Grubbs Precatalyst

    Directory of Open Access Journals (Sweden)

    Jean I. du Toit

    2014-04-01

    Full Text Available Hemilabile ligands can release a free coordination site “on demand” of an incoming nucleophilic substrate while occupying it otherwise. This is believed to increase the thermal stability and activity of catalytic systems and therefore prevent decomposition via free coordination sites. In this investigation chelating pyridinyl-alcoholato ligands were identified as possible hemilabile ligands for incorporation into the second generation Grubbs precatalyst. The O,N-alcoholato ligands with different steric bulk could be successfully incorporated into the precatalysts. The incorporation of the sterically hindered, hemilabile O,N-ligands improved the thermal stability, activity, selectivity and lifetime of these complexes towards the metathesis of 1-octene. A decrease in the activity of the second generation Grubbs precatalyst was additionally observed after incorporating a hemilabile O,N-ligand with two phenyl groups into the system, while increasing their lifetime.

  3. Self-assembly of supramolecualr metallogelator containing 2-(2'-hydroxyphenyl) benzoxazole/Zn(II) chelate.

    Science.gov (United States)

    Kim, Tae Hyeon; Kwon, Na Young; Son, Ji Hye; Yang, Changduk; Lee, Minjung; Lee, Taek Seung

    2010-10-01

    A low molar mass organogelator 1 containing 2-(2'-hydroxyphenyl)benzoxazole (HPB) unit with long alkyl chain was synthesized by the reaction with HPB and octyl isocyanate in THF at room temperature. A new chelate-based organogelator 1-Zn(II) was prepared with the reaction of 1 and zinc(II) acetate in methanol and dichloromethane at mild condition. The gelation ability of organogelator was tested by heating-cooling method in various organic solvents, and the opaque gel was formed from DMF. Well-developed self-assembled structure of organogel was confirmed with field emission-scanning electron microscope (FE-SEM) and transmission electron microscope (TEM), and the optical properties of organogel upon aggregation were monitored by UV-Vis and fluorescence spectroscopy, 1-Zn(II) was self-assembled to the sheet-like structure with the thickness of fully extended length of molecules.

  4. Emulsifier type, metal chelation and pH affect oxidative stability of n-3-enriched emulsions

    DEFF Research Database (Denmark)

    Haahr, Anne-Mette; Jacobsen, Charlotte

    2008-01-01

    -enriched oil-in-water emulsion. The selected food emulsifiers were Tween 80, Citrem, sodium caseinate and lecithin. Lipid oxidation was evaluated by determination of peroxide values and secondary volatile oxidation products. Moreover, the zeta potential and the droplet sizes were determined. Twen resulted......Recent research has shown that the oxidative stability of oil-in-water emulsions is affected by the type of surfactant used as emulsifier. The aim of this study was to evaluate the effect of real food emulsifiers as well as metal chelation by EDTA and pH on the oxidative stability of a 10% n-3...... in the least oxidatively stable emulsions, followed by Citrem. When iron was present, caseinate-stabilized emulsions oxidized slower than lecithin emulsions at pH 3, whereas the opposite was the case at pH 7. Oxidation generally progressed faster at pH 3 than at pH 7, irrespective of the addition of iron. EDTA...

  5. Determination of metal ions by high-performance liquid chromatographic separation of their hydroxamic acid chelates

    Energy Technology Data Exchange (ETDEWEB)

    Palmieri, M.D.; Fritz, J.S.

    1987-09-15

    Metal ions are determined by adding N-methylfurohydroxamic acid to an aqueous sample and then separating the metal chelates by direct injection onto a liquid chromatographic column. Separations on a C/sub 8/ silica column and a polystyrene-divinylbenzene column are compared, with better separations seen on the polymeric column. The complexes formed at low pH values are cationic and are separated by an ion pairing mechanism. Retention times and selectivity of the metal complexes can be varied by changing the pH. Several metal ions can be separated and quantified; separation conditions, linear calibration curve ranges, and detection limits are presented for Zr(IV), Hf(IV), Fe(III), Nb(V), Al(III), and Sb(III). Interferences due to the presence of other ions in solution are investigated. Finally, an antiperspirant sample is analyzed for zirconium by high-performance liquid chromatography.

  6. Chelator effects on bioconcentration and translocation of cadmium by hyperaccumulators, Tagetes patula and Impatiens walleriana.

    Science.gov (United States)

    Wei, Jhen-Lian; Lai, Hung-Yu; Chen, Zueng-Sang

    2012-10-01

    French marigold (Tagetes patula) and impatiens (Impatiens walleriana) can act as hyperaccumulator plants for removal of cadmium (Cd) from contaminated sites. In this study, an exponential decay model was used to predict the maximum removal of Cd from artificially spiked soils by impatiens. Application of a chelator, EDTA, was also assessed for effects on the bioconcentration (BCF) and translocation (TF) factors of the two species with four replicates. Exposure to Cd significantly decreased the biomass of two plant species. Impatiens and French marigold accumulated Cd at a rate of 200-1200 mg Cd kg(-1) in shoots, with BCFs and TFs of 8.5-15 and 1.7-2.6, respectively. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  7. Evaluation of extractants and chelating resins in polishing actinide-contaminated waste streams

    Energy Technology Data Exchange (ETDEWEB)

    Schreiber, S.B.; Dunn, S.L.; Yarbro, S.L.

    1991-06-01

    At the Los Alamos National Laboratory Plutonium Facility, anion exchange is used for recovering plutonium from nitric acid solutions. Although this approach recovers >99%, the trace amounts of plutonium and other actinides remaining in the effluent require additional processing. We are doing research to develop a secondary unit operation that can directly polish the effluent so that actinide levels are reduced to below the maximum allowed for facility discharge. We selected solvent extraction, the only unit operation that can meet the stringent process requirements imposed; several carbonyl and phosphoryl extractants were evaluated and their performance characterized. We also investigated various engineering approaches for solvent extraction; the most promising was a chelating resin loaded with extractant. Our research now focuses on the synthesis of malonamides, and our goal is to bond these extractants to a resin matrix. 7 refs., 12 figs., 1 tab.

  8. A chelating dendritic ligand capped quantum dot: preparation, surface passivation, bioconjugation and specific DNA detection

    Science.gov (United States)

    Zhou, Dejian; Li, Yang; Hall, Elizabeth A. H.; Abell, Chris; Klenerman, David

    2011-01-01

    Herein we report the synthesis of a new chelating dendritic ligand (CDL) and its use in the preparation a compact, stable and water-soluble quantum dot (QD), and further development of specific DNA sensor. The CDL, which contains a chelative dihydrolipoic acid moiety for strong QD surface anchoring and four dendritic carboxylic acidgroups, provides a stable, compact and entangled hydrophilic coating around the QD that significantly increases the stability of the resulting water-soluble QD. A CDL-capped CdSe/ZnS core/shell QD (CDL-QD) has stronger fluorescence than that capped by a monodendate single-chain thiol, 3-mercapto-propionic acid (MPA-QD). In addition, the fluorescence of the CDL-QD can be enhanced by 2.5-fold by treatments with Zn2+ or S2- ions, presumably due to effective passivation of the surface defects. This level of fluorescence enhancement obtained for the CDL-QD is much greater than that for the MPA-QD. Further, by coupling a short single-stranded DNA target to the QD via the CDL carboxylic acidgroup, a functional QD-DNA conjugate that can resist non-specific adsorption and hybridize quickly to its complementary DNAprobe has been obtained. This functional QD-DNA conjugate is suitable for specific quantification of short, labelled complementary probes at the low DNAprobe:QD copy numbers via a QD-sensitised dyefluorescence resonance energy transfer (FRET) response with 500 pM sensitivity on a conventional fluorimeter.Herein we report the synthesis of a new chelating dendritic ligand (CDL) and its use in the preparation a compact, stable and water-soluble quantum dot (QD), and further development of specific DNA sensor. The CDL, which contains a chelative dihydrolipoic acid moiety for strong QD surface anchoring and four dendritic carboxylic acidgroups, provides a stable, compact and entangled hydrophilic coating around the QD that significantly increases the stability of the resulting water-soluble QD. A CDL-capped CdSe/ZnS core/shell QD (CDL-QD) has

  9. The Utility of Iron Chelators in the Management of Inflammatory Disorders

    Directory of Open Access Journals (Sweden)

    C. Lehmann

    2015-01-01

    Full Text Available Since iron can contribute to detrimental radical generating processes through the Fenton and Haber-Weiss reactions, it seems to be a reasonable approach to modulate iron-related pathways in inflammation. In the human organism a counterregulatory reduction in iron availability is observed during inflammatory diseases. Under pathological conditions with reduced or increased baseline iron levels different consequences regarding protection or susceptibility to inflammation have to be considered. Given the role of iron in development of inflammatory diseases, pharmaceutical agents targeting this pathway promise to improve the clinical outcome. The objective of this review is to highlight the mechanisms of iron regulation and iron chelation, and to demonstrate the potential impact of this strategy in the management of several acute and chronic inflammatory diseases, including cancer.

  10. Cage-like bifunctional chelators, copper-64 radiopharmaceuticals and PET imaging using the same

    Energy Technology Data Exchange (ETDEWEB)

    Conti, Peter S.; Cai, Hancheng; Li, Zibo; Liu, Shuanglong

    2016-08-02

    Disclosed is a class of versatile Sarcophagine based bifunctional chelators (BFCs) containing a hexa-aza cage for labeling with metals having either imaging, therapeutic or contrast applications radiolabeling and one or more linkers (A) and (B). The compounds have the general formula ##STR00001## where A is a functional group selected from group consisting of an amine, a carboxylic acid, an ester, a carbonyl, a thiol, an azide and an alkene, and B is a functional group selected from the group consisting of hydrogen, an amine, a carboxylic acid, and ester, a carbonyl, a thiol, an azide and an alkene. Also disclosed are conjugate of the BFC and a targeting moiety, which may be a peptide or antibody. Also disclosed are metal complexes of the BFC/targeting moiety conjugates that are useful as radiopharmaceuticals, imaging agents or contrast agents.

  11. Characterization of 2,3-dihydroxyterephthalamides as M(IV) chelators.

    Science.gov (United States)

    Gramer, Christine J; Raymond, Kenneth N

    2004-10-04

    The ligand N,N'-diethyl-2,3-dihydroxyterephthalamide (ETAM) has been characterized as a chelator for Zr(IV), Ce(IV), and Th(IV). The K(+) salts of the complexes [Zr(ETAM)(4)](4)(-), [Ce(ETAM)(4)](4)(-), and [Th(ETAM)(4)](4)(-) were prepared in a MeOH solution containing H(2)ETAM, the corresponding M(acac)(4), and 4 equiv of KOH. Single-crystal X-ray diffraction analyses are reported for K(4)[Zr(ETAM)(4)] (C2/c, Z = 8, a = 27.576(3) A, b = 29.345(3) A, c = 15.266(2) A, alpha = 90 degrees, beta = 118.688(4) degrees, gamma = 90 degrees ), [Me(3)BnN](4)[Th(ETAM)(4)] (P, Z = 2, a = 13.7570(3) A, b = 13.9293(3) A, c = 26.9124(6) A, alpha = 99.941(1) degrees, beta = 94.972(1) degrees, gamma = 103.160(1) degrees ), and the dimeric (NMe(4))(4)[Th(ETAM)(3)MeOH](2) (P2(1)/c, Z = 4, a = 18.2603(9) A, b = 18.5002(9) A, c = 19.675(1) A, beta = 117.298(1) degrees ). Solution thermodynamic studies were used to determine formation constants (log K(f) and esd) for Th(IV)-ETAM log K(110) =17.47(1), log K(120) = 13.23(1), log K(130) = 8.28(3), log K(140) = 6.57(6), and log beta(140) = 45.54(5). These results support the hypothesis that the terephthalamides are high-affinity chelators for the actinide(IV) ions and thus promising ligands for use in nuclear waste remediation.

  12. [Surface characterization of urushiol-titanium chelate polymers by inverse gas chromatography].

    Science.gov (United States)

    Xu, Yanlian; Lin, Jinhuo; Xia, Jianrong; Hu, Binghuan

    2011-03-01

    Urushiol-titanium chelate polymer (UTP), the reaction product of urushiol with titanium compound, is a special eco-friendly polymer with excellent performances, such as strong acids-resistance, strong alkalis-resistance, salt solution-resistance and several organic solvent-resistance. Inverse gas chromatography (IGC) was used to measure the dispersive component of surface free energy (gamma(s)d) and the Lewis acid-base parameters of UTP in this work. The gamma(s)d and the acid/base characters of UTP' surfaces were estimated by the retention time with different non-polar and polar probes at infinite dilution region. n-Pentane (C5), n-hexane (C6), n-heptane (C7), n-octane (C8) and n-nonane (C9) were chosen as the non-polar probes to characterize the gamma(s)d. Trichloromethane (CHCl3), tetrahydrofuran (THF) and acetone were chosen as polar probes to detect the Lewis acid-base parameters. The specific free energy (deltaG(a)AB) and the enthalpy (deltaH(a)AB) of adsorption corresponding to acid-base surface interactions were determined. By correlating deltaH(a)AB with the donor and acceptor numbers of the probes, the acidic (K(a)) and the basic (K(b)) parameters of the samples were calculated. The results showed that the dispersive components of the free energy of UTP were 37.68, 33.53, 35.92, 24.01 and 31.32 mJ/m2 at 70, 80, 90, 100 and 110 degrees C, respectively. The Lewis acidic number K(a) of UTP was 0.185 3, and the Lewis basic number K(b) was 0.966 2. The results were of great importance to the study of the surface properties and the applications for urushiol-metal chelate polymers.

  13. Methods for Generating Highly Magnetically Responsive Lanthanide-Chelating Phospholipid Polymolecular Assemblies.

    Science.gov (United States)

    Isabettini, Stéphane; Baumgartner, Mirjam E; Reckey, Pernille Q; Kohlbrecher, Joachim; Ishikawa, Takashi; Fischer, Peter; Windhab, Erich J; Kuster, Simon

    2017-06-27

    Mixtures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and its lanthanide ion (Ln3+) chelating phospholipid conjugate, 1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylene triaminepentaacetate (DMPE-DTPA), assemble into highly magnetically responsive polymolecular assemblies such as DMPC/DMPE-DTPA/Ln3+ (molar ratio 4:1:1) bicelles. Their geometry and magnetic alignability is enhanced by introducing cholesterol into the bilayer in DMPC/Cholesterol/DMPE-DTPA/Ln3+ (molar ratio 16:4:5:5). However, the reported fabrication procedures remain tedious and limit the generation of highly magnetically alignable species. Herein, a simplified procedure where freeze thawing cycles and extrusion are replaced by gentle heating and cooling cycles for the hydration of the dry lipid film was developed. Heating above the phase transition temperature Tm of the lipids composing the bilayer before cooling back below the Tm was essential to guarantee successful formation of the polymolecular assemblies composed of DMPC/DMPE-DTPA/Ln3+ (molar ratio 4:1:1). Planar polymolecular assemblies in the size range of hundreds of nanometers are achieved and deliver unprecedented gains in magnetic response. The proposed heating and cooling procedure further allowed to regenerate the highly magnetically alignable DMPC/Cholesterol/DMPE-DTPA/Ln3+ (molar ratio 16:4:5:5) species after storage for one month frozen at -18 °C. The simplicity and viability of the proposed fabrication procedure offers a new set of highly magnetically responsive lanthanide ion chelating phospholipid polymolecular assemblies as building blocks for the smart soft materials of tomorrow.

  14. Actual clinical use of gadolinium-chelates for non-MRI applications

    Energy Technology Data Exchange (ETDEWEB)

    Strunk, Holger M.; Schild, H. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn (Germany)

    2004-06-01

    For many years, alternatives to iodinated X-ray contrast media have been sought. Of the contrast media investigated to date, only CO{sub 2} and the gadolinium-chelates have been shown to be viable alternatives for selected X-ray examinations. Therefore, we have reviewed the general literature and that specific for gadopentetate (Magnevist) in particular, since this agent has been studied the most. This review indicates that diagnostic CT examinations can be achieved following the intravenous administration of gadolinium-containing contrast media (CM) for evaluation of aortic abnormalities. Gadolinium-containing CM at the dose approved for MR imaging are not useful for CT evaluation of the abdominal parenchymal organs. Intravenous/intraarterial injections have also been used in a variety of angiographic and interventional procedures. Image quality, however, is generally inferior to iodinated contrast media. Gadolinium-containing CM require no special handling and can be administered by hand injection or via conventional angiographic automated injectors with the same flow rates and pressures as are used with iodinated contrast media. For CT, a peripheral bolus injection of a diluted gadolinium agent (1:1 with saline) of 60-90 ml at 3-5 ml/s is usually performed. Similar to all other gadolinium-chelates, the non-MRI use of gadopentetate (Magnevist) is not approved by regulatory agencies. However, the literature suggests that a dose of 0.3-0.4 mmol/kg b.w. has been safely administered for CT as well as for angiography and interventional procedures intravenously and intraarterially. Even at this dose, though, this results in a relatively small overall volume to be injected, which limits utility somewhat. (orig.)

  15. Aloin: a natural antitumor anthraquinone glycoside with iron chelating and non-atherogenic activities.

    Science.gov (United States)

    Esmat, Amr Y; Said, Mahmoud M; Khalil, Sally A

    2015-01-01

    The antitumor activity of aloin, the active anthraquinone of Aloe juice, against different murine and human tumors has been reported. In the present study, the impact of repeated aloin treatment at its maximum tolerated dose on serum levels of lipid profile, some elements, iron status and kidney function, compared with doxorubicin (a cardiotoxic anthracycline and inhibitor of erythropoiesis), was assessed. Rats were treated with a single dose of doxorubicin (30 mg/kg body weight, intraperitoneal) or aloin (50 mg/kg body weight, intramuscular) twice weekly over 2 weeks. Acute doxorubicin treatment elevated serum levels of triacylglycerols (59.90%), total cholesterol (42.29%), cholesteryl esters (54.75%), low density lipoprotein-cholesterol (230.16%), very low density lipoprotein-cholesterol (56.42%), urea (287.53%), and creatinine (85.38%), whereas serum high density lipoprotein-cholesterol, sodium, and calcium levels were reduced (44.61, 9.61, and 9.76%, respectively), as compared with controls. In contrast, aloin treatment showed insignificant changes in all the aforementioned parameters. Both doxorubicin and aloin induced erythropoiesis impairment demonstrated by a reduction in blood hemoglobin concentration. While aloin treatment elevated serum iron level (30.28%), doxorubicin treatment reduced serum levels of iron (51.47%) and percent transferrin saturation (55.21%), and in contrast, increased serum total iron binding capacity (34.85%). The chelating affinities of iron-aloin and -doxorubicin complexes, which contain bidentate iron-binding moieties, have been shown in the infrared spectra. The non-cardiotoxic effect of aloin treatment was due to its non-atherogenic and iron-chelating activities, which might also contribute in part to its anti-proliferative activity.

  16. Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

    Directory of Open Access Journals (Sweden)

    Murtadha Al-Khabori

    2013-03-01

    Full Text Available Objectives: Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX side effects in patients with thalassemia major or intermedia.Methods: A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period.Results: Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline, feeling unwell (2, severe diarrhea (1, pregnancy (1, death unrelated to chelator (2 and rise in serum transaminases (2. Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013.Conclusion: Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings.

  17. Factors affecting chelating extraction of Cr, Cu, and As from CCA-treated wood.

    Science.gov (United States)

    Chang, Fang-Chih; Wang, Ya-Nang; Chen, Pin-Jui; Ko, Chun-Han

    2013-06-15

    The disposal of chromated copper arsenate (CCA)-treated waste wood is becoming a serious problem in many countries due to potential leaching of hazardous elements from in-service use in the environment or disposal of solutions after remediation; therefore, it is necessary to develop proper remediation techniques. The effects of concentration, extraction period, temperature, and sequential extraction on the extraction of Cr, Cu, and As from CCA-treated wood using [S,S]-ethylenediaminedisuccinic acid (EDDS), ethylenediaminetetraacetic acid (EDTA), and nitrilotriacetic acid (NTA) were studied. Mobility of metal in the samples was evaluated by using a sequential extraction scheme that could give the information needed to explain different extraction efficiencies for different metals. Results of long-term leaching tests of CCA-treated wood before and after EDDS extraction were used to evaluate Cr, Cu, and As leachability. Kinetic experiments showed that 6 h was the optimum extraction time for all metals and CCA-treated wood. Experimental results showed that EDDS is a very effective chelating agent for the extraction of Cr, Cu, and As from CCA-treated wood. Increased temperature significantly enhanced the extraction efficiency of CCA metals, especially Cr and As. The much better extractability of Cu compared to Cr and As by chelating agents can be attributed to the presence of larger weakly bound fractions. The CCA-treated woods after EDDS extraction have met the EPA's TCLP regulatory limit and could be classified as a non-hazardous waste according to identification standard of hazardous wastes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Synthetic and Predictive Approach to Unsymmetrical Biphenols by Iron-Catalyzed Chelated Radical-Anion Oxidative Coupling.

    Science.gov (United States)

    Libman, Anna; Shalit, Hadas; Vainer, Yulia; Narute, Sachin; Kozuch, Sebastian; Pappo, Doron

    2015-09-09

    An iron-catalyzed oxidative unsymmetrical biphenol coupling in 1,1,1,3,3,3-hexafluoropropan-2-ol that proceeds via a chelated radical-anion coupling mechanism was developed. Based on mechanistic studies, electrochemical methods, and density functional theory calculations, we suggest a general model that enables prediction of the feasibility of cross-coupling for a given pair of phenols.

  19. Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial

    NARCIS (Netherlands)

    Kersten, M. J.; Lange, R.; Smeets, M. E.; Vreugdenhil, G.; Roozendaal, K. J.; Lameijer, W.; Goudsmit, R.

    1996-01-01

    We performed an open, nonrandomized, multicenter phase-II trial to evaluate the efficacy and toxicity of 1 year of treatment with the oral iron chelator deferiprone in 38 mainly nonthalassemic patients with transfusional iron overload. Initial serum ferritin varied between 996 and 11.644

  20. Thumbnail Sketches: EDTA-Type Chelating Agents in Everyday Consumer Products: Some Food, Cleaning, and Photographic Applications.

    Science.gov (United States)

    Hart, J. Roger

    1985-01-01

    Discusses the role of chelating agents in (1) mayonnaise and salad dressings; (2) canned legumes; (3) plant foods; (4) liquid dishwashing detergents; (5) toilet soaps; (6) floor wax removers; (7) hard surface cleaners; (8) carpet cleaning; (9) bathtub and tile cleaners; and (10) photography. (JN)

  1. Interaction of Aluminum with PHFτ in Alzheimer’s Disease Neurofibrillary Degeneration Evidenced by Desferrioxamine-Assisted Chelating Autoclave Method

    Science.gov (United States)

    Murayama, Harunobu; Shin, Ryong-Woon; Higuchi, Jun; Shibuya, Satoshi; Muramoto, Tamaki; Kitamoto, Tetsuyuki

    1999-01-01

    To demonstrate that aluminum III (Al) interacts with PHFτ in neurofibrillary degeneration (NFD) of Alzheimer’s disease (AD) brain, we developed a “chelating autoclave method” that allows Al chelation by using trivalent-cationic chelator desferrioxamine. Its application to AD brain sections before Morin histochemistry for Al attenuated the positive fluorescence of neurofibrillary tangles, indicating Al removal from them. This method, applied for immunostaining with phosphorylation-dependent anti-τ antibodies, significantly enhanced the PHFτ immunoreactivity of the NFD. These results suggest that each of the phosphorylated epitopes in PHFτ are partially masked by Al binding. Incubation of AD sections with AlCl3 before Morin staining revealed Al accumulation with association to neurofibrillary tangles. Such incubation before immunostaining with the phosphorylation-dependent anti-τ antibodies abolished the immunolabeling of the NFD and this abolition was reversed by the Al chelation. These findings indicate cumulative Al binding to and thereby antigenic masking of the phosphorylated epitopes of PHFτ. Al binding was further documented for electrophoretically-resolved PHFτ on immunoblots, indicating direct Al binding to PHFτ. In vitro aggregation by AlCl3 was observed for PHFτ but was lost on dephosphorylation of PHFτ. Taken together, phosphorylation-dependent and direct PHFτ-Al interaction occurs in the NFD of the AD brain. PMID:10487845

  2. Synthesis and luminescence properties of lanthanide(III) chelates with polyacid derivatives of thienyl-substituted terpyridine analogues

    Energy Technology Data Exchange (ETDEWEB)

    Yuan Jingli E-mail: jingliyuan@yahoo.com.cn; Tan Mingqian; Wang Guilan

    2004-03-01

    Two new polyacid derivative ligands of thienyl-substituted terpyridine analogues, N,N,N{sup 1},N{sup 1}-[4'-(2'''-thienyl)-2,2':6',2''-terpyridine-6,6''-diyl]bis (methylenenitrilo) tetrakis(acetic acid) (TTTA) and N,N,N{sup 1},N{sup 1}-[2,6-bis(3'-aminomethyl-1'-pyrazolyl)-4-(2''-thienyl)pyridine] tetrakis(acetic acid) (BTTA), were synthesized, and the luminescence properties of their Eu{sup 3+} and Tb{sup 3+} chelates were investigated. The Eu{sup 3+}chelates of the two ligands are strongly luminescent having luminescence quantum yields of 0.150 (TTTA-Eu{sup 3+}) and 0.114 (BTTA-Eu{sup 3+}), and lifetimes of 1.284 ms (TTTA-Eu{sup 3+}) and 1.352 ms (BTTA-Eu{sup 3+}), whereas their Tb{sup 3+} chelates are weakly luminescent. The TTTA-Eu{sup 3+} chelate was used for streptavidin (SA) labeling, and the labeled SA was used for time-resolved fluoroimmunoassay of insulin in human sera. The method gives the detection limits of 33 pg ml{sup -1}.

  3. Rapid iron loading in a pregnant woman with transfusion-dependent thalassemia after brief cessation of iron chelation therapy.

    Science.gov (United States)

    Farmaki, Kallistheni; Gotsis, Efstathios; Tzoumari, Ioanna; Berdoukas, Vasilios

    2008-08-01

    In general, in women with transfusion-dependent thalassemia, during pregnancy, iron chelation therapy is ceased. We report a splenectomized patient, who was an excellent complier with chelation therapy, who before embarking on a pregnancy showed no evidence of iron overload, with normal cardiac, thyroid function and glucose metabolism. Laboratory findings showed ferritin 67 microg/L, myocardial T(2)* of 34 ms and liver magnetic resonance imaging (MRI) liver iron concentration of 1 mg/g dry weight. She became pregnant by in vitro fertilization in October 2006, delivery occurred in June 2007. She breast fed for 2 months. After 12 months without iron chelation, ferritin was 1583 microg/L. Quantitative MRI showed myocardial T(2)* of 27 ms, that the liver iron concentration had increased to 11.3 mg/g dry weight, indicative of moderate to heavy iron load. This case demonstrates that iron overload can develop rapidly and that physicians caring for patients with transfusion-dependent thalassemia should be particularly alert to any discontinuation of chelation therapy over time.

  4. Synthesis and Properties of Chelating N-Heterocyclic Carbene Rhodium(I) Complexes: Synthetic Experiments in Current Organometallic Chemistry

    Science.gov (United States)

    Mata, Jose A.; Poyatos, Macarena; Mas-Marza, Elena

    2011-01-01

    The preparation and characterization of two air-stable Rh(I) complexes bearing a chelating N-heterocyclic carbene (NHC) ligand is described. The synthesis involves the preparation of a Ag(I)-NHC complex and its use as carbene transfer agent to a Rh(I) precursor. The so obtained complex can be further reacted with carbon monoxide to give the…

  5. Ferrous Ion Chelating, Superoxide Anion Radical Scavenging and Tyrosinase Inhibitory Properties of Pure and Commercial Essential Oils of Anetrhum Graveolens

    Directory of Open Access Journals (Sweden)

    Sh Darvish Alipour Astaneh

    2013-04-01

    Full Text Available Introduction: Despite slight toxicities of essential oils, they are not under strict control in many countries. Anethum graveolens is widely consumed and its essential oils are at public reach. This study was designed to study essential oils of Anethum graveolens. Methods: The biological properties of pure and commercial essential oils of Anethum graveolens were investigated. In fact, Ferrous ion chelating activity, superoxide anion radical scavenging property, tyrosinase inhibition and total flavonoids of the oils were determined. Results: Chelating activity of 7.8 µg of EDTA was equivalent to 2 µg of the pure oil. The oils had superoxide anion radical scavenging activities which may be related to their total phenol and flavonoid contents. IC50 of ferrous ion chelating, antityrosiase and superoxide anion radical scavenging activities of pure and commercial oils were 1.3, 1.4, 1 and (171.6, 589, 132 µg respectively. Antityrosiase activity of 6.4 µg pure oil was equal to 1000 µg of the commercial oil. Conclusion: Anethum possesses antioxidative and free radical scavenging properties. This oil chelates ferrous ions and superoxide radicals. It is effective in formation of reactive toxic products. Anethum has good potentials regarding its applications in food and drug industries.

  6. Effective removal of heavy metals from industrial sludge with the aid of a biodegradable chelating ligand GLDA

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Qing; Cui, Yanrui; Li, Qilu; Sun, Jianhui, E-mail: sunjh@htu.cn

    2015-02-11

    Highlights: • A novel readily biodegradable chelating ligand was employed to remove heavy metals. • The effects of different conditions on the extraction with GLDA were probed. • Species distribution of metals before and after extraction with GLDA was analyzed. • GLDA was effective for Cd extraction from sludge samples under various conditions. • GLDA offers special insights in the effective removal of heavy metals. - Abstract: Tetrasodium of N,N-bis(carboxymethyl) glutamic acid (GLDA), a novel readily biodegradable chelating ligand, was employed for the first time to remove heavy metals from industrial sludge generated from a local battery company. The extraction of cadmium, nickel, copper, and zinc from battery sludge with the presence of GLDA was studied under different experimental conditions such as contact times, pH values, as well as GLDA concentrations. Species distribution of metals in the sludge sample before and after extraction with GLDA was also analyzed. Current investigation showed that (i) GLDA was effective for Cd extraction from sludge samples under various conditions. (ii) About 89% cadmium, 82% nickel and 84% copper content could be effectively extracted at the molar ratio of GLDA:M(II) = 3:1 and at pH = 4, whereas the removal efficiency of zinc was quite low throughout the experiment. (iii) A variety of parameters, such as contact time, pH values, the concentration of chelating agent, stability constant, as well as species distribution of metals could affect the chelating properties of GLDA.

  7. Mild formation of cyclic carbonates using Zn(II) complexes based on N2S2-chelating ligands

    NARCIS (Netherlands)

    Anselmo, D.; Bocokic, V.; Decortes, A.; Escudero-Adan, E.C.; Benet-Buchholz, J.; Reek, J.N.H.; Kleij, A.W.

    2012-01-01

    We have prepared a series of Zn(II) complexes (1-3) based on a versatile N2S2-chelating ligand abbreviated as btsc [btsc = bis-(thiosemicarbazonato)] derived from simple and accessible building blocks. These complexes comprise a Lewis acidic Zn(II) center useful for substrate activation, and we have

  8. In silico strategies for the selection of chelating compounds with potential application in metal-promoted neurodegenerative diseases

    Science.gov (United States)

    Rodríguez-Rodríguez, Cristina; Rimola, Albert; Alí-Torres, Jorge; Sodupe, Mariona; González-Duarte, Pilar

    2011-01-01

    The development of new strategies to find commercial molecules with promising biochemical features is a main target in the field of biomedicine chemistry. In this work we present an in silico-based protocol that allows identifying commercial compounds with suitable metal coordinating and pharmacokinetic properties to act as metal-ion chelators in metal-promoted neurodegenerative diseases (MpND). Selection of the chelating ligands is done by combining quantum chemical calculations with the search of commercial compounds on different databases via virtual screening. Starting from different designed molecular frameworks, which mainly constitute the binding site, the virtual screening on databases facilitates the identification of different commercial molecules that enclose such scaffolds and, by imposing a set of chemical and pharmacokinetic filters, obey some drug-like requirements mandatory to deal with MpND. The quantum mechanical calculations are useful to gauge the chelating properties of the selected candidate molecules by determining the structure of metal complexes and evaluating their stability constants. With the proposed strategy, commercial compounds containing N and S donor atoms in the binding sites and capable to cross the BBB have been identified and their chelating properties analyzed.

  9. Influence of calcium chelators on concentrated micellar casein solutions : from micellar structure to viscosity and heat stability

    NARCIS (Netherlands)

    Kort, de E.J.P.

    2012-01-01

    In practice it is challenging to prepare a concentrated medical product with high heat stability
    and low viscosity. Calcium chelators are often added to dairy products to improve heat stability,
    but this may increase viscosity through interactions with the casein proteins. The aim of

  10. Chelated Nitrogen-Sulphur-Codoped TiO2: Synthesis, Characterization, Mechanistic, and UV/Visible Photocatalytic Studies

    Directory of Open Access Journals (Sweden)

    Hayat Khan

    2017-01-01

    Full Text Available This study presents in detail the physicochemical, photoluminescent, and photocatalytic properties of carboxylic acid chelated nitrogen-sulphur-codoped TiO2. From the Fourier transform infrared spectroscopic study, it was revealed that the formate group formed bidentate bridging linkage while the acetate group coordinated in a bidentate chelating mode with a titanium precursor. In compliance with X-ray diffraction data, the anatase to rutile transformation temperature was extended due to carboxylic acid chelation and NS codoping. Raman analysis indicated four Raman peaks at 146, 392, 512, and 632 cm−1 for the precalcined chelated TiO2; on incorporation with NS dopants, an increase in Raman intensity for these peaks was recorded, indicating the structure stability of the anatase phase. Furthermore, X-ray photoelectron spectroscopic study revealed the presence of anionic doping of nitrogen and cationic doping of sulphur in the lattice of TiO2. When evaluating the UV-visible photodegradation rate of 4-chlorophenol, the modified TiO2 (NS0.06-TFA showed the highest photocatalytic activity. In connection with the activity tests, several scavenger agents were employed to elucidate the significance of the different reactive oxidizing species during the photocatalytic process. Moreover, the transfer pathways of photogenerated carriers and the photocatalytic reaction mechanism of modified TiO2 were also explained in detail.

  11. Theoretical and experimental studies on isotachophoresis in multi-moving chelation boundary system formed with metal ions and EDTA.

    Science.gov (United States)

    Zhang, Wei; Guo, Chen-Gang; Fan, Liu-Yin; Cao, Cheng-Xi

    2013-09-07

    In this paper, a general mode and theory of moving chelation boundary based isotachophoresis (MCB-based ITP), together with the concept of decisive metal ion (DMI) having the maximum complexation constant (lg Kmax) with the chelator, were developed from a multi-MCB (mMCB) system. The theoretical deductions were: (i) the reaction boundary velocities in the mMCB system at steady state were equal to each other, resulting in a novel MCB-based ITP separation of metal ions; (ii) the boundary directions and velocities in the system were controlled by the fluxes of chelator and DMI, rather than other metal ions; and (iii) a controllable stacking of metal ions could be simultaneously achieved in the developed system. To demonstrate the deductions, a series of experiments were conducted by using model chelator of EDTA and metal ions of Cu(II) and Co(II) due to characteristic colors of blue [Cu-EDTA](2-) and pink [Co-EDTA](2-) complexes. The experiments demonstrated the correctness of theoretical deductions, indicating the validity of the developed model and theory of ITP. These findings provide guidance for the development of MRB-based ITP separation and stacking of metal ions in biological sample matrix and heavy metal ions in environmental samples.

  12. pi-Conjugated chelating polymers with charged iridium complexes in the backbones: synthesis, characterization, energy transfer, and electrochemical properties.

    Science.gov (United States)

    Liu, Shu-Juan; Zhao, Qiang; Chen, Run-Feng; Deng, Yun; Fan, Qu-Li; Li, Fu-You; Wang, Lian-Hui; Huang, Chun-Hui; Huang, Wei

    2006-05-24

    A series of pi-conjugated chelating polymers with charged iridium (Ir) complexes in the backbones were synthesized by a Suzuki polycondensation reaction, leading to homogeneous polymeric materials that phosphoresce red light. The fluorene and bipyridine (bpy) segments were used as polymer backbones. 5,5'-Dibromobipyridine served as a ligand to form a charged iridium complex monomer with 1-(9'9-dioctylfluorene-2-yl)isoquinoline (Fiq) as the cyclometalated ligand. Chemical and photophysical characterization confirmed that Ir complexes were incorporated into the backbones as one of the repeat units by means of the 5,5'-dibromobipyridine ligand. Chelating polymers showed almost complete energy transfer from the host fluorene segments to the guest Ir complexes in the solid state when the feed ratio was 2 mol %. In the films of the corresponding blend system, however, energy transfer was not complete even when the content of Ir complexes was as high as 16 mol %. Both intra- and intermolecular energy-transfer processes existed in this host-guest system, and the intramolecular energy transfer was a more efficient process. All chelating polymers displayed good thermal stability, redox reversibility, and film formation. These chelating polymers also showed more efficient energy transfer than the corresponding blended system and the mechanism of incorporation of the charged Ir complexes into the pi-conjugated polymer backbones efficiently avoided the intrinsic problems associated with the blend system, thus offering promise in optoelectronic applications.

  13. Spectrophotometric Determination and Removal of Unchelated Europium Ions from Solutions Containing Eu-Diethylenetriaminepentaacetic Acid Chelate-Peptide Conjugates1

    Science.gov (United States)

    Dayan Elshan, N. G. R.; Patek, Renata; Vagner, Josef; Mash, Eugene A.

    2014-01-01

    Europium chelates conjugated with peptide ligands are routinely used as probes for conducting in vitro binding experiments. The presence of unchelated Eu ions in these formulations gives high background luminescence and can lead to poor results in binding assays. In our experience, the reported methods for purification of these probes do not achieve adequate removal of unchelated metal ions in a reliable manner. In this work, a xylenol orange-based assay for the quantification of unchelated metal ions was streamlined and used to determine levels of metal ion contamination, as well as the success of metal ion removal upon attempted purification. We compared the use of Empore™ chelating disks and Chelex® 100 resin for the selective removal of unchelated Eu ions from several Eu-diethylenetriaminepentaacetic acid chelate-peptide conjugates. Both purification methods gave complete and selective removal of the contaminant metal ions. However, Empore™ chelating disks were found to give much higher recoveries of the probes under the conditions utilized. Related to the issue of probe recovery, we also describe a significantly more efficient method for the synthesis of one such probe using Rink amide AM resin in place of Tentagel S resin. PMID:25058927

  14. Spectrophotometric determination and removal of unchelated europium ions from solutions containing Eu-diethylenetriaminepentaacetic acid chelate-peptide conjugates.

    Science.gov (United States)

    Elshan, N G R Dayan; Patek, Renata; Vagner, Josef; Mash, Eugene A

    2014-11-01

    Europium chelates conjugated with peptide ligands are routinely used as probes for conducting in vitro binding experiments. The presence of unchelated Eu ions in these formulations gives high background luminescence and can lead to poor results in binding assays. In our experience, the reported methods for purification of these probes do not achieve adequate removal of unchelated metal ions in a reliable manner. In this work, a xylenol orange-based assay for the quantification of unchelated metal ions was streamlined and used to determine levels of metal ion contamination as well as the success of metal ion removal on attempted purification. We compared the use of Empore chelating disks and Chelex 100 resin for the selective removal of unchelated Eu ions from several Eu-diethylenetriaminepentaacetic acid chelate-peptide conjugates. Both purification methods gave complete and selective removal of the contaminant metal ions. However, Empore chelating disks were found to give much higher recoveries of the probes under the conditions used. Related to the issue of probe recovery, we also describe a significantly more efficient method for the synthesis of one such probe using Rink amide AM resin in place of Tentagel S resin. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Differential response of Arabidopsis leaves and roots to cadmium: Glutathione-related chelating capacity vs antioxidant capacity.

    NARCIS (Netherlands)

    Jozefczak, M.; Keunen, E.; Schat, H.; Bliek, M.; Hernandez, L.; Carleer, R.; Remans, T.; Bohler, S.; Vangronsveld, J.; Cuypers, A.

    2014-01-01

    This study aims to uncover the spatiotemporal involvement of glutathione (GSH) in two major mechanisms of cadmium (Cd)-induced detoxification (i.e. chelation and antioxidative defence). A kinetic study was conducted on hydroponically grown Arabidopsis thaliana (L. Heyhn) to gain insight into the

  16. Synthesis of novel chelating benzimidazole-based carbenes and their nickel(II) complexes: activity in the Kumada coupling reaction

    NARCIS (Netherlands)

    Berding, J.; Lutz, M.; Spek, A.L.; Bouwman, E.

    2009-01-01

    Nickel(II) halide complexes of novel chelating bidentate benzimidazole-based N-heterocyclic carbenes have been prepared from Ni(OAc)2 and bisbenzimidazolium salts. Single-crystal X-ray structure determination on four complexes revealed a cis-geometry on a square-planar nickel center. The complexes

  17. Enhancing the antitumor cell proliferation and Cu(2+)-chelating effects of black soybeans through fermentation with Aspergillus awamori.

    Science.gov (United States)

    Chen, Yu-Fei; Chiang, Ming-Lun; Chou, Cheng-Chun; Lo, Yi-Chen

    2013-04-01

    In the present study, black soybeans were fermented with Aspergillus awamori at 30°C for 3 days. The effect of fermentation on the antiproliferative effect against human colon cancer cells, Caco-2 and HT-29 as well as Cu(2+)-chelating effect of black soybeans was investigated. It was found that the water, 80% methanol or 80% ethanol extract of fermented black soybeans showed a significantly higher (P soybeans. Generally, the methanol extract and the ethanol extract of fermented black soybeans exerted higher antiproliferative effect on both Caco-2 and HT-29 cells. While water extract of fermented black soybeans showed the highest Cu(2+)-chelating effect among the various extracts examined. Taking into account of extraction yields further revealed that bioactive principles that exhibit Cu(2+)-chelating effect could be extracted to the largest extent with water as the extraction solvent. With same amount of sample, water extract obtained from fermented black soybeans possesses the highest Cu(2+)-chelating abilities. Copyright © 2012 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  18. The Metal Chelators, Trientine and Citrate, Inhibit the Development of Cardiac Pathology in the Zucker Diabetic Rat

    Directory of Open Access Journals (Sweden)

    John W. Baynes

    2009-01-01

    Full Text Available Purpose. The objective of this study was to determine the efficacy of dietary supplementation with the metal chelators, trientine or citric acid, in preventing the development of cardiomyopathy in the Zucker diabetic rat. Hypothesis. We hypothesized that dietary chelators would attenuate metal-catalyzed oxidative stress and damage in tissues and protect against pathological changes in ventricular structure and function in type II diabetes. Methods. Animals (10 weeks old included lean control (LC, fa/+, untreated Zucker diabetic fatty (ZDF, fa/fa, and ZDF rats treated with either trientine (triethylenetetramine or citrate at 20 mg/d in drinking water, starting when rats were frankly diabetic. Cardiac functional assessment was determined using a Millar pressure/volume catheter placed in the left ventricle at 32 weeks of age. Results. End diastolic volume for the ZDF animals increased by 36% indicating LV dilatation (P<.05 and was accompanied by a 30% increase in the end diastolic pressure (P≤.05. Both trientine and citric acid prevented the increases in EDV and EDP (P<.05. Ejection fraction and myocardial relaxation were also significantly improved with chelator treatment. Conclusion. Dietary supplementation with trientine and citric acid significantly prevented structural and functional changes in the diabetic heart, supporting the merits of mild chelators for prevention of cardiovascular disease in diabetes.

  19. On Hydrogen Bonding in the Intramolecularly Chelated Taitomers of Enolic Malondialdehyde and its Mono- and Dithio-Analogues

    DEFF Research Database (Denmark)

    Carlsen, Lars; Duus, Fritz

    1980-01-01

    The intramolecular hydrogen bondings in enolic malondialdehyde and it mono- and dithio-analogues have been evaluated by a semiempricial SCF–MO–CNDO method. The calculations predict that the hydrogen bonds play an important part in the stabilities of malondialdehyde and monothiomalondialdehyde, wh......, whereas dithiomalondialdehyde hardly exists as a hydrogen-chelated tautomeric form....

  20. Conjugation, immunoreactivity, and immunogenicity of calix[4]arenes; model study to potential calix[4]arene-based Ac3+ chelators

    NARCIS (Netherlands)

    Grote Gansey, Marcel H.B.; Grote gansey, M.H.B.; de Haan, Annemarie S.; Bos, Ebo S.; Verboom, Willem; Reinhoudt, David

    1999-01-01

    For the development of calix[4]arene-based radiotherapeutic agents, the conjugation to biomolecules and immunogenicity in mice of potential 225Ac3+-chelating calix[4]arenes were studied. A calix[4]arene triethyl ester isothiocyanate and a bis(calix[4]arene) hexacarboxylic acid, containing a masked

  1. The metal chelators, trientine and citrate, inhibit the development of cardiac pathology in the Zucker diabetic rat.

    Science.gov (United States)

    Baynes, John W; Murray, David B

    2009-01-01

    The objective of this study was to determine the efficacy of dietary supplementation with the metal chelators, trientine or citric acid, in preventing the development of cardiomyopathy in the Zucker diabetic rat. We hypothesized that dietary chelators would attenuate metal-catalyzed oxidative stress and damage in tissues and protect against pathological changes in ventricular structure and function in type II diabetes. Animals (10 weeks old) included lean control (LC, fa/+), untreated Zucker diabetic fatty (ZDF, fa/fa), and ZDF rats treated with either trientine (triethylenetetramine) or citrate at 20 mg/d in drinking water, starting when rats were frankly diabetic. Cardiac functional assessment was determined using a Millar pressure/volume catheter placed in the left ventricle at 32 weeks of age. End diastolic volume for the ZDF animals increased by 36% indicating LV dilatation (P < .05) and was accompanied by a 30% increase in the end diastolic pressure (P chelator treatment. Dietary supplementation with trientine and citric acid significantly prevented structural and functional changes in the diabetic heart, supporting the merits of mild chelators for prevention of cardiovascular disease in diabetes.

  2. Physiological Responses of Some Iranian Grape Cultivars to Iron Chelate Application in Calcareous Soil

    Directory of Open Access Journals (Sweden)

    H. Doulati Baneh

    2016-07-01

    Full Text Available Introduction: Iron chlorosis is considered to be one of the most important nutritional disorders in grapevines, particularly in calcareous soils that under these conditions fruit yield and quality is depressed in the current year and fruit buds poorly develop for following year. Symptoms of iron chlorosis in orchards and vineyards are usually more frequent in spring when shoot growth is rapid and bicarbonate concentration in the soil solution buffers soil pH in the rhizosphere and root apoplast. Several native grapevine (Vitis vinifera L. genotypes, highly appreciated for their organoleptic characteristics and commercial potential, are widely cultivated in Iran. Cultivated plants differ as to their susceptibility to Fe deficiency in calcareous soils, some being poorly affected while others showing severe leaf chlorotic symptoms. Selection and the use of Fe-efficient genotypes is one of the important approaches to prevent this nutritional problem. In this research the response of three local grapevine cultivars was evaluated to iron chelate consumption in a calcareous soil (26% T.N.V. Materials and Methods: Well rooted woody cuttings of three autochthonous varieties (Rasha, Qezel uzum, Keshmeshi Qermez were cultivated in pots filled with a calcareous soil with iron chelate consumption at three rates (0, 7.5 and 15 mg Fe/ Kg soil. The study was conducted with two factors (cultivar and iron chelate and 3 replicates in a factorial arrangement based on randomized complete block design. Plant parameters including vegetative growth, chlorophyll index and leaf area were monitored during the growth period. At the end of the treatment, fresh and dry weight of shoots and roots were determined. The concentrations of macro and micro elements in the leaves were assayed using an atomic absorption and spectrophotometer. One-way-ANOVA was applied comparing the behavior of the cultivars growing. Results and Discussion: Analysis of variance showed that chlorophyll

  3. Renal functions in pediatric patients with beta-thalassemia major: relation to chelation therapy: original prospective study

    Directory of Open Access Journals (Sweden)

    ElMelegy Nagla T

    2010-05-01

    Full Text Available Abstract Background In β-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies mainly in adult demonstrating renal involvement in β-thalassemia. This prospective study was aimed to investigate renal involvement in pediatric patients with transfusion dependant beta-thalassemia major (TD-βTM, using both conventional and early markers of glomerular and tubular dysfunctions, and to correlate findings to oxidative stress and iron chelation therapy. Methods Sixty-nine TD-βTM patients (aged 1-16 years and 15 healthy controls (aged 3-14 years were enrolled in this study. Based on receiving chelation therapy (deferoxamine, DFO, patients were divided into two groups: group [I] with chelation (n = 34 and group [II] without chelation (n = 35. Levels of creatinine (Cr, calcium (Ca, inorganic phosphorus (PO4, uric acid (UA and albumin were measured by spectrophotometer. Serum (S levels of cystatin-C (SCysC and total antioxidant capacity (STAC and urinary (U levels of β2-microglobulin (Uβ2MG were measured by immunosorbent assay (ELISA. Urinary N-acetyl-beta-D-glucosaminidase (UNAG activity and malondialdehyde (UMDA were measured by chemical methods. Estimated glomerular filtration rate (eGFR was determined from serum creatinine. Results In patient with and without chelation, glomerular [elevated SCysC, SCr, Ualbumin/Cr and diminished eGFR]; and tubular dysfunctions [elevated SUA, SPO4, UNAG/Cr, Uβ2MG/Cr] and oxidative stress marker disturbances [diminished STAC and elevated UMDA/Cr] were reported than controls. In patients with chelation, SCysC was significantly higher while, STAC was significantly lower than those without chelation. In all patients, SCysC showed significant positive correlation with SCr and negative correlation with eGFR; STAC showed significant positive correlation with eGFR and negative correlation with

  4. Progressing Toward a Cohesive Pediatric 18F-FDG PET/MR Protocol: Is Administration of Gadolinium Chelates Necessary?

    Science.gov (United States)

    Klenk, Christopher; Gawande, Rakhee; Tran, Vy Thao; Leung, Jennifer Trinh; Chi, Kevin; Owen, Daniel; Luna-Fineman, Sandra; Sakamoto, Kathleen M; McMillan, Alex; Quon, Andy; Daldrup-Link, Heike E

    2016-01-01

    With the increasing availability of integrated PET/MR scanners, the utility and need for MR contrast agents for combined scans is questioned. The purpose of our study was to evaluate whether administration of gadolinium chelates is necessary for evaluation of pediatric tumors on (18)F-FDG PET/MR images. First, in 119 pediatric patients with primary and secondary tumors, we used 14 diagnostic criteria to compare the accuracy of several MR sequences: unenhanced T2-weighted fast spin-echo imaging; unenhanced diffusion-weighted imaging; and-before and after gadolinium chelate contrast enhancement-T1-weighted 3-dimensional spoiled gradient echo LAVA (liver acquisition with volume acquisition) imaging. Next, in a subset of 36 patients who had undergone (18)F-FDG PET within 3 wk of MRI, we fused the PET images with the unenhanced T2-weighted MR images (unenhanced (18)F-FDG PET/MRI) and the enhanced T1-weighted MR images (enhanced (18)F-FDG PET/MRI). Using the McNemar test, we compared the accuracy of the two types of fused images using the 14 diagnostic criteria. We also evaluated the concordance between (18)F-FDG avidity and gadolinium chelate enhancement. The standard of reference was histopathologic results, surgical notes, and follow-up imaging. There was no significant difference in diagnostic accuracy between the unenhanced and enhanced MR images. Accordingly, there was no significant difference in diagnostic accuracy between the unenhanced and enhanced (18)F-FDG PET/MR images. (18)F-FDG avidity and gadolinium chelate enhancement were concordant in 30 of the 36 patients and 106 of their 123 tumors. Gadolinium chelate administration is not necessary for accurate diagnostic characterization of most solid pediatric malignancies on (18)F-FDG PET/MR images, with the possible exception of focal liver lesions. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  5. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Orcutt, Kelly Davis; Slusarczyk, Adrian L. [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cieslewicz, Maryelise [Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ruiz-Yi, Benjamin [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Bhushan, Kumar R. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Frangioni, John V. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Wittrup, K. Dane, E-mail: wittrup@mit.ed [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2011-02-15

    Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2{+-}1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a {sup 111}In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

  6. Mercury exposure: evaluation and intervention the inappropriate use of chelating agents in the diagnosis and treatment of putative mercury poisoning.

    Science.gov (United States)

    Risher, John F; Amler, Sherlita N

    2005-08-01

    Public awareness of the potential for mercury to cause health problems has increased dramatically in the last 15 years. It is now widely recognized that significant exposure to all forms of mercury (elemental/metallic and both inorganic and organic compounds) can result in a variety of adverse health effects, including neurological, renal, respiratory, immune, dermatologic, reproductive, and developmental sequellae. And while the various media have made the general population cognizant of the need to avoid unnecessary exposure to this naturally occurring element, there has also evolved a growing tendency to attribute unexplainable neurologic, as well as other, signs and symptoms to mercury, whether or not significant exposure to mercury has actually occurred. For the physician, making a diagnosis of mercury intoxication can be difficult, because many of the clinical signs and symptoms of mercury exposure can also be attributed to any number of causes, including undiagnosed neurological diseases, pharmacotherapy, vitamin or mineral deficiencies, and psychological stress. The physician must be able to recognize the clinical manifestations of mercury intoxication, and understand the importance of biological markers in making a definitive diagnosis of mercury poisoning. In a desire to treat the patient complaining of symptoms similar to some that can be caused by mercury, a growing number of physicians, particularly those in alternative medicine fields, result to chelation to "rid" the body of the mercury, believed to be the cause of the ailments. And although the use of chelation is increasing, controlled studies showing that this procedure actually improves outcome are lacking. If chelation therapy is considered to be indicated, the attending physician should communicate the risks of chelation to the patient before beginning treatment with metal-chelating drugs.

  7. Synthesis and initial in vitro biological evaluation of two new zinc-chelating compounds: comparison with TPEN and PAC-1.

    Science.gov (United States)

    Strand, O Alexander H; Aziz, Gulzeb; Ali, Sidra Farzand; Paulsen, Ragnhild E; Hansen, Trond Vidar; Rongved, Pål

    2013-09-01

    The lipophilic, cell-penetrating zinc chelator N,N,N',N',-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN, 1) and the zinc chelating procaspase-activating compound PAC-1 (2) both have been reported to induce apoptosis in various cell types. The relationship between apoptosis-inducing ability and zinc affinity (Kd), have been investigated with two new model compounds, ZnA-DPA (3) and ZnA-Pyr (4), and compared to that of TPEN and PAC-1. The zinc-chelating o-hydroxybenzylidene moiety in PAC-1 was replaced with a 2,2'-dipicoylamine (DPA) unit (ZnA-DPA, 3) and a 4-pyridoxyl unit (ZnA-Pyr, 4), rendering an order of zinc affinity TPEN>ZnA-Pyr>ZnA-DPA>PAC-1. The compounds were incubated with the rat pheochromocytoma cell line PC12 and cell death was measured in combination with ZnSO4, a caspase-3 inhibitor, or a ROS scavenger. The model compounds ZnA-DPA (3) and ZnA-Pyr (4) induced cell death at higher concentrations as compared to PAC-1 and TPEN, reflecting differences in lipophilicity and thereby cell-penetrating ability. Addition of ZnSO4 reduced cell death induced by ZnA-Pyr (4) more than for ZnA-DPA (3). The ability to induce cell death could be reversed for all compounds using a caspase-3-inhibitor, and most so for TPEN (1) and ZnA-Pyr (4). Reactive oxygen species (ROS), as monitored using dihydro-rhodamine (DHR), were involved in cell death induced by all compounds. These results indicate that the Zn-chelators ZnA-DPA (3) and ZnA-Pyr (4) exercise their apoptosis-inducing effect by mechanisms similar to TPEN (1) and PAC-1 (2), by chelation of zinc, caspase-3 activation, and ROS production. Copyright © 2013. Published by Elsevier Ltd.

  8. ex vivo DNA assembly

    Directory of Open Access Journals (Sweden)

    Adam B Fisher

    2013-10-01

    Full Text Available Even with decreasing DNA synthesis costs there remains a need for inexpensive, rapid and reliable methods for assembling synthetic DNA into larger constructs or combinatorial libraries. Advances in cloning techniques have resulted in powerful in vitro and in vivo assembly of DNA. However, monetary and time costs have limited these approaches. Here, we report an ex vivo DNA assembly method that uses cellular lysates derived from a commonly used laboratory strain of Escherichia coli for joining double-stranded DNA with short end homologies embedded within inexpensive primers. This method concurrently shortens the time and decreases costs associated with current DNA assembly methods.

  9. Scaphoid kinematics in vivo

    NARCIS (Netherlands)

    Moojen, Thybout M.; Snel, Jeroen G.; Ritt, Marco J. P. F.; Venema, Henk W.; Kauer, John M. G.; Bos, Kurt E.

    2002-01-01

    The purpose of this study was to quantify 3-dimensional (3-D) in vivo scaphoid kinematics during flexion-extension motion (FEM) and radial-ulnar deviation (RUD) of the hand. The right wrists of 11 healthy volunteers were imaged by spiral computed tomography during RUD and 5 of those wrists also

  10. Synthesis of Copper-Chelates Derived from Amino Acids and Evaluation of Their Efficacy as Copper Source and Growth Stimulator for Lactuca sativa in Nutrient Solution Culture.

    Science.gov (United States)

    Kaewchangwat, Narongpol; Dueansawang, Sattawat; Tumcharern, Gamolwan; Suttisintong, Khomson

    2017-11-15

    Five tetradentate ligands were synthesized from l-amino acids and utilized for the synthesis of Cu(II)-chelates 1-5. The efficacy of Cu(II)-chelates as copper (Cu) source and growth stimulator in hydroponic cultivation was evaluated with Lactuca sativa. Their stability test was performed at pH 4-10. The results suggested that Cu(II)-chelate 3 is the most pH tolerant complex. Levels of Cu, Zn, and Fe accumulated in plants supplied with Cu(II)-chelates were compared with those supplied with CuSO 4 at the same Cu concentration of 8.0 μM. The results showed that Cu(II)-chelate 3 significantly enhanced Cu, Zn, and Fe content in shoot by 35, 15, and 48%, respectively. Application of Cu(II)-chelate 3 also improved plant dry matter yield by 54%. According to the results, Cu(II)-chelate 3 demonstrated the highest stimulating effect on plant growth and plant mineral accumulation so that it can be used as an alternative to CuSO 4 for supplying Cu in nutrient solutions and enhancing the plant growth.

  11. Effective sulfur and energy recovery from hydrogen sulfide through incorporating an air-cathode fuel cell into chelated-iron process.

    Science.gov (United States)

    Sun, Min; Song, Wei; Zhai, Lin-Feng; Cui, Yu-Zhi

    2013-12-15

    The chelated-iron process is among the most promising techniques for the hydrogen sulfide (H2S) removal due to its double advantage of waste minimization and resource recovery. However, this technology has encountered the problem of chelate degradation which made it difficult to ensure reliable and economical operation. This work aims to develop a novel fuel-cell-assisted chelated-iron process which employs an air-cathode fuel cell for the catalyst regeneration. By using such a process, sulfur and electricity were effectively recovered from H2S and the problem of chelate degradation was well controlled. Experiment on a synthetic sulfide solution showed the fuel-cell-assisted chelated-iron process could maintain high sulfur recovery efficiencies generally above 90.0%. The EDTA was preferable to NTA as the chelating agent for electricity generation, given the Coulombic efficiencies (CEs) of 17.8 ± 0.5% to 75.1 ± 0.5% for the EDTA-chelated process versus 9.6 ± 0.8% to 51.1 ± 2.7% for the NTA-chelated process in the pH range of 4.0-10.0. The Fe (III)/S(2-) ratio exhibited notable influence on the electricity generation, with the CEs improved by more than 25% as the Fe (III)/S(2-) molar ratio increased from 2.5:1 to 3.5:1. Application of this novel process in treating a H2S-containing biogas stream achieved 99% of H2S removal efficiency, 78% of sulfur recovery efficiency, and 78.6% of energy recovery efficiency, suggesting the fuel-cell-assisted chelated-iron process was effective to remove the H2S from gas streams with favorable sulfur and energy recovery efficiencies. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. In vivo copper-mediated free radical production: an ESR spin-trapping study

    Science.gov (United States)

    Kadiiska, Maria B.; Mason, Ronald P.

    2002-04-01

    Copper has been suggested to facilitate oxidative tissue injury through a free radical-mediated pathway analogous to the Fenton reaction. By applying the electron spin resonance (ESR) spin-trapping technique, evidence for hydroxyl radical formation in vivo was obtained in rats treated simultaneously with copper and ascorbic acid or paraquat. A secondary radical spin-trapping technique was used in which the hydroxyl radical formed the methyl radical upon reaction with dimethylsulfoxide. The methyl radical was then detected by ESR spectroscopy as its adduct with the spin trap phenyl- N- t-butyl- nitrone (PBN). In contrast, lipid derived radical was detected in vivo in copper-challenged, vitamin E and selenium-deficient rats. These findings support the proposal that dietary selenium and vitamin E can protect against lipid peroxidation and copper toxicity. Since copper excreted into the bile from treated animals is expected to be maintained in the Cu(I) state (by ascorbic acid or glutathione), a chelating agent that would redox-stablilize it in the Cu(I) state was used to prevent ex vivo redox chemistry. Bile samples were collected directly into solutions of bathocuproinedisulfonic acid, a Cu(I)-stabilizing agent, and 2,2'-dipyridyl, a Fe(II)-stabilizing agent. If these precautions were not taken, radical adducts generated ex vivo could be mistaken for radical adducts produced in vivo and excreted into the bile.

  13. Mechanisms of Fe biofortification and mitigation of Cd accumulation in rice (Oryza sativa L.) grown hydroponically with Fe chelate fertilization.

    Science.gov (United States)

    Chen, Zhe; Tang, Ye-Tao; Zhou, Can; Xie, Shu-Ting; Xiao, Shi; Baker, Alan J M; Qiu, Rong-Liang

    2017-05-01

    Cadmium contaminated rice from China has become a global food safety issue. Some research has suggested that chelate addition to substrates can affect metal speciation and plant metal content. We investigated the mitigation of Cd accumulation in hydroponically-grown rice supplied with EDTANa2Fe(II) or EDDHAFe(III). A japonica rice variety (Nipponbare) was grown in modified Kimura B solution containing three concentrations (0, 10, 100 μΜ) of the iron chelates EDTANa2Fe(II) or EDDHAFe(III) and 1 μΜ Cd. Metal speciation in solution was simulated by Geochem-EZ; growth and photosynthetic efficiency of rice were evaluated, and accumulation of Cd and Fe in plant parts was determined. Net Cd fluxes in the meristematic zone, growth zone, and maturation zone of roots were monitored by a non-invasive micro-test technology. Expression of Fe- and Cd-related genes in Fe-sufficient or Fe-deficient roots and leaves were studied by QRT-PCR. Compared to Fe deficiency, a sufficient or excess supply of Fe chelates significantly enhanced rice growth by elevating photosynthetic efficiency. Both Fe chelates increased the Fe content and decreased the Cd content of rice organs, except for the Cd content of roots treated with excess EDDHAFe(III). Compared to EDDHAFe(III), EDTANa2Fe(II) exhibited better mitigation of Cd accumulation in rice by generating the EDTANa2Cd complex in solution, decreasing net Cd influx and increasing net Cd efflux in root micro-zones. Application of EDTANa2Fe(II) and EDDHAFe(III) also reduced Cd accumulation in rice by inhibiting expression of genes involved in transport of Fe and Cd in the xylem and phloem. The 'win-win' situation of Fe biofortification and Cd mitigation in rice was achieved by application of Fe chelates. Root-to-stem xylem transport of Cd and redistribution of Cd in leaves by phloem transport can be regulated in rice through the use of Fe chelates that influence Fe availability and Fe-related gene expression. Fe fertilization decreased Cd

  14. Effects of metal ion chelators on DNA strand breaks and inactivation produced by hydrogen peroxide in Escherichia coli: detection of iron-independent lesions.

    OpenAIRE

    Asad, N R; Leitão, A C

    1991-01-01

    In order to study the role of metallic ions in the H2O2 inactivation of Escherichia coli cells, H2O2-sensitive mutants were treated with metal ion chelators and then submitted to H2O2 treatment. o-Phenanthroline, dipyridyl, desferrioxamine, and neocuproine were used as metal chelators. Cell sensitivity to H2O2 treatment was not modified by neocuproine, suggesting that copper has a minor role in OH production in E. coli. On the other hand, prior treatment with iron chelators protected the cell...

  15. Determination of deferasirox plasma concentrations: do gender, physical and genetic differences affect chelation efficacy?

    Science.gov (United States)

    Mattioli, Francesca; Puntoni, Matteo; Marini, Valeria; Fucile, Carmen; Milano, Giulia; Robbiano, Luigi; Perrotta, Silverio; Pinto, Valeria; Martelli, Antonietta; Forni, Gian Luca

    2015-04-01

    Bioavailability of deferasirox (DFX) is significantly affected by the timing of administration relative to times and to composition of meals. Its elimination half-life is also highly variable - in some patients as a result of gene polymorphisms. Understanding whether deferasirox plasma levels are related to specific characteristics of patients could help physicians to devise a drug regimen tailored the individual patient. We analyzed deferasirox plasma concentrations (CDFX ) in 80 patients with transfusion-dependent anemias, such as thalassemia, by a high performance liquid chromatography (HPLC) assay. We used a multivariate linear regression model to find significant associations between CDFX and clinical/demographical characteristics of patients. All patients were genotyped for UGT1A1. Fifty-six patients were female, 24 were male, the great majority (88%) affected by β-thalassemia, and 15 were children and adolescents. No statistical correlation was detectable between CDFX and DFX dose (P = 0.6). Age, time from last drug intake to blood sampling, and ferritin levels in the 6 months before study initiation were significantly and inversely associated with CDFX in univariate analysis. In the multivariate analysis, the only two factors independently and inversely associated with CDFX levels were time from last drug intake to blood sampling and ferritin levels (P = 0.006). A significant inverse correlation (P = 0.03) was observed between CDFX and UGT1A1*28 gene polymorphism, but only in patients with levels of lean body mass (LBM) below the median (P for interaction = 0.05). The results could indicate that a higher plasma DFX concentration could be associated with greater chelation efficacy. As a correlation between dose and CDFX was not demonstrated, it seems useful to monitor the concentrations to optimize and determine the most appropriate dose for each patient. Interesting results emerged from the analysis of genetic and physical characteristics of

  16. Effect of chelate dynamics on water exchange reactions of paramagnetic aminopolycarboxylate complexes.

    Science.gov (United States)

    Maigut, Joachim; Meier, Roland; Zahl, Achim; van Eldik, Rudi

    2008-07-07

    Because of our interest in evaluating a possible relationship between complex dynamics and water exchange reactivity, we performed (1)H NMR studies on the paramagnetic aminopolycarboxylate complexes Fe (II)-TMDTA and Fe (II)-CyDTA and their diamagnetic analogues Zn (II)-TMDTA and Zn (II)-CyDTA. Whereas a fast Delta-Lambda isomerization was observed for the TMDTA species, no acetate scrambling between in-plane and out-of-plane positions is accessible for any of the CyDTA complexes because the rigid ligand backbone prevents any configurational changes in the chelate system. In variable-temperature (1)H NMR studies, no evidence of spectral coalescence due to nitrogen inversion was found for any of the complexes in the available temperature range. The TMDTA complexes exhibit the known solution behavior of EDTA, whereas the CyDTA complexes adopt static solution structures. Comparing the exchange kinetics of flexible EDTA-type complexes and static CyDTA complexes appears to be a suitable method for evaluating the effect of ligand dynamics on the overall reactivity. In order to assess information concerning the rates and mechanism of water exchange, we performed variable-temperature and -pressure (17)O NMR studies of Ni (II)-CyDTA, Fe (II)-CyDTA, and Mn (II)-CyDTA. For Ni (II)-CyDTA, no significant effects on line widths or chemical shifts were apparent, indicating either the absence of any chemical exchange or the existence of a very small amount of the water-coordinated complex in solution. For [Fe (II)(CyDTA)(H 2O)] (2-) and [Mn (II)(CyDTA)(H 2O)] (2-), exchange rate constant values of (1.1 +/- 0.3) x 10 (6) and (1.4 +/- 0.2) x 10 (8) s (-1), respectively, at 298 K were determined from fits to resonance-shift and line-broadening data. A relationship between chelate dynamics and reactivity seems to be operative, since the CyDTA complexes exhibited significantly slower reactions than their EDTA counterparts. The variable-pressure (17)O NMR measurements for [Mn (II

  17. Chelating effect of citric acid is negligible for development of enamel erosions.

    Science.gov (United States)

    Azadi-Schossig, Parastu; Becker, Klaus; Attin, Thomas

    2016-09-01

    Citric acid (CA) is a component in beverages responsible for dental erosion. The aim of this study was to examine the influence of CA with different pH, titratable acid and buffer capacity (ß), and the impact of the chelating effect of CA on development of enamel erosions. In a superfusion model, hydroxy apatite (HAp) dissolution of bovine enamel was measured in four experiments (EXP 1-4) with 27 experimental groups (n = 8 per group). The samples were superfused with different CA variations and respective controls. EXP-1: Dilution series of HCl (pH 2.15-3.02). EXP-2: Dilution series of natural CA (56-1.75 mmol l(-1); pH 2.15-3.02). EXP-3: CA solutions (56 and 14 mmol l(-1), ß: 39.7 and 10.2 mmol l(-1) pH(-1), respectively) with different titratable acidity at equal pH values. EXP-4: CA concentrations (56-1.75 mmol l(-1)) neutralized to pH 7. CA led to higher HAp-dissolution than HCl. With higher pH, the difference in HAp-dissolution rate between the two acids became increasingly smaller. At equal pH, HAp-dissolution was higher for the CA with the higher amount of titratable acid. However, no clear correlation between erosion and titratable acid or ß could be found. Only minimal amounts of HAp were dissolved by neutralized CA compared to CA with natural pH. Under the chosen conditions chelating effects of CA do not have a relevant influence of HAp-dissolution of enamel. Moreover, amount of HAp-dissolution by CA is not attributed to a single factor alone. The interplay between the different parameters of CA seems to be responsible for its erosive potential. The erosive potential of solutions containing citric acid with unknown concentrations could not be predicted using a single parameter alone, and should at best determined in experimental set-ups.

  18. Hexacoordinate Silicon Compounds with a Dianionic Tetradentate (N,N′,N′,N-Chelating Ligand

    Directory of Open Access Journals (Sweden)

    Daniela Gerlach

    2016-04-01

    Full Text Available In the context of our systematic investigations of penta- and hexacoordinate silicon compounds, which included dianionic tri- (O,N,O′; O,N,N′ and tetradentate (O,N,N,O; O,N,N′,O′ chelators, we have now explored silicon coordination chemistry with a dianionic tetradentate (N,N′,N′,N chelator. The ligand [o-phenylene-bis(pyrrole-2-carbaldimine, H2L] was obtained by condensation of o-phenylenediamine and pyrrole-2-carbaldehyde and subsequently silylated with chlorotrimethylsilane/triethylamine. Transsilylation of this ligand precursor (Me3Si2L with chlorosilanes SiCl4, PhSiCl3, Ph2SiCl2, (Anis2SiCl2 and (4-Me2N-C6H4PhSiCl2 afforded the hexacoordinate Si complexes LSiCl2, LSiPhCl, LSiPh2, LSi(Anis2 and LSiPh(4-Me2N-C6H4, respectively (Anis = anisyl = 4-methoxyphenyl. 29Si NMR spectroscopy and, for LSiPh2, LSi(Anis2 and LSiPh(4-Me2N-C6H4, single-crystal X-ray diffraction confirm hexacoordination of the Si atoms. The molecular structures of LSiCl2 and LSiPhCl were elucidated by computational methods. Despite the two different N donor sites (pyrrole N, X-type donor; imine N, L-type donor, charge delocalization within the ligand backbone results in compounds with four similar Si–N bonds. Charge distribution within the whole molecules was analyzed by calculating the Natural Charges (NCs. Although these five compounds carry electronically different monodentate substituents, their constituents reveal rather narrow ranges of their charges (Si atoms: +2.10–+2.22; monodentate substituents: −0.54–−0.56; L2−: −1.02–−1.11.

  19. Chitosan-Fe (III) Complex as a Phosphate Chelator in Uraemic Rats: A Novel Treatment Option.

    Science.gov (United States)

    do Carmo, Wander Barros; Castro, Bárbara Bruna Abreu; Rodrigues, Clóvis Antônio; Custódio, Melani Ribeiro; Sanders-Pinheiro, Helady

    2017-07-20

    Phosphate retention and hyperphosphataemia are associated with increased mortality in patients with chronic kidney disease (CKD). We tested the use of cross-linked iron chitosan III (CH-FeCl) as a potential phosphate chelator in rats with CKD. We evaluated 96 animals, divided equally into four groups (control, CKD, CH-FeCl and CKD/CH-FeCl), over 7 weeks. We induced CKD by feeding animals an adenine-enriched diet (0.75% in the first 4 weeks and 0.1% in the following 3 weeks). We administered 30 mg/kg daily of the test polymer, by gavage, from the third week until the end of the study. All animals received a diet supplemented with 1% phosphorus. Uraemia was confirmed by the increase in serum creatinine in week 4 (36.24 ± 18.56 versus 144.98 ± 22.1 μmol/L; p = 0.0001) and week 7 (41.55 ± 22.1 versus 83.98 ± 18.56 μmol/L; p = 0.001) in CKD animals. Rats from the CKD group treated with CH-FeCl had a 54.5% reduction in serum phosphate (6.10 ± 2.23 versus 2.78 ± 0.55 mmol/L) compared to a reduction of 25.6% in the untreated CKD group (4.75 ± 1.45 versus 3.52 ± 0.74 mmol/L, p = 0.021), between week 4 and week 7. At week 7, renal function in both CKD groups was similar (serum creatinine: 83.98 ± 18.56 versus 83.10 ± 23.87 μmol/L, p = 0.888); however, the CH-FeCl-treated rats had a reduction in phosphate overload measured by fractional phosphate excretion (FEPi) (0.71 ± 0.2 versus 0.4 ± 0.16, p = 0.006) compared to the untreated CKD group. Our study demonstrated that CH-FeCl had an efficient chelating action on phosphate. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  20. Action of a specific iron chelate for the metabolism of iron-59 in subjects affected with thalassemia major. [Desferal

    Energy Technology Data Exchange (ETDEWEB)

    Clemente, G.F.; Ingrao, G.; Bianco, I.; Lerone, M.

    1982-01-01

    Some subjects, ranging in age from 6 to 12 years, suffering with thalassemia major, which causes a continuous iron overload in most organs and tissues of the patients, were treated with Desferal, an iron-chelating agent. Supposing that iron accumulates both in the reticuloendothelial and parenchymatous cells, particularly in liver and myocardium, where its overload is very dangerous, we have tried to identify the exact site of action of Desferal. Therefore the patients were injected with a /sup 59/Fe solution and treated regularly with a chelating therapy with Desferal. Measurements of the /sup 59/Fe body burden were made during a period of about 6 months post injection and measurements of /sup 59/Fe and stable iron in blood, urine, and feces samples during a period of about 1 month post injection.

  1. Crosslinking photosensitized by a ruthenium chelate as a tool for labeling and topographical studies of G-protein-coupled receptors.

    Science.gov (United States)

    Duroux-Richard, Isabelle; Vassault, Philippe; Subra, Guy; Guichou, Jean-François; Richard, Eric; Mouillac, Bernard; Barberis, Claude; Marie, Jacky; Bonnafous, Jean-Claude

    2005-01-01

    The purpose was to apply oxidative crosslinking reactions to the study of recognition and signaling mechanisms associated to G-protein-coupled receptors. Using a ruthenium chelate, Ru(bipy)(3)(2+), as photosensitizer and visible light irradiation, in the presence of ammonium persulfate, we performed fast and efficient covalent labeling of the B(2) bradykinin receptor by agonist or antagonist ligands possessing a radio-iodinated phenol moiety. The chemical and topographical specificities of these crosslinking experiments were investigated. The strategy could also be applied to the covalent labeling of the B(1) bradykinin receptor, the AT(1) angiotensin II receptor, the V(1a) vasopressin receptor and the oxytocin receptor. Interestingly, we demonstrated the possibility to covalently label the AT(1) and B(2) receptors with functionalized ligands. The potential applications of metal-chelate chemistry to receptor structural and signaling studies through intramolecular or intermolecular crosslinking are presented.

  2. Role of chelation in the treatment of lead poisoning: discussion of the Treatment of Lead-Exposed Children Trial (TLC).

    Science.gov (United States)

    McKay, Charles A

    2013-12-01

    Lead exposure in children is one component leading to cognitive impairment. The Treatment of Lead-Exposed Children Trial (1994-2004) studied the effect of succimer in treating low levels of lead exposure (20-44 mcg/dL) in children 12 to 33 months old. While succimer was effective in reducing blood lead concentrations in the short term, treatment of blood lead levels did not result in any detectable improvement in a wide variety of measurements of cognitive or behavioral function. Furthermore, blood lead concentrations were not distinguishable between chelated and non-chelated individuals at 1 year. The most important treatment strategy is identification and termination of major sources of lead exposure.

  3. Efficacy Study of Metho-Chelated Organic Minerals preparation Feeding on Milk Production and Fat Percentage in dairy cows

    Directory of Open Access Journals (Sweden)

    Somkuwar A.P.1

    2011-02-01

    Full Text Available The objective of the study was to compare the effect of feeding different mineral based formulation on dairy cow production performance, namely milk yield and fat percentage. The trial was conducted with dairy cows across various stages of lactation (Early, Mid and Late stage with 30 cows per stage. The experimental treatments included: Bestmin Gold (Metho-chelated organic minerals, given 30 gms per day, Inorganic mineral preparation (Inorg. Mineral, @ 50 gms/day/ cow and control. The study lasted from 0 to 40 days. Milk yield and fat percentage of cows were measured individually on Days 0, 5, 10, 15, 20, 25, 30 and 40. The Bestmin Gold treated group (Metho-chelated organic minerals improved the milk yield, net gain in milk and the milk fat percentage of animals across the various stages of lactation as compared to in control and inorganic mineral treated group of animals. [Veterinary World 2011; 4(1.000: 19-21

  4. Metallic Element Chelated Tag Labeling (MeCTL) for Quantitation of N-Glycans in MALDI-MS.

    Science.gov (United States)

    Yang, Lijun; Peng, Ye; Jiao, Jing; Tao, Tao; Yao, Jun; Zhang, Ying; Lu, Haojie

    2017-07-18

    N-glycosylation plays an important role in chief biological and pathological processes. Quantifying the N-glycan is important since glycan alterations are related to many diseases. In this study, we developed a novel N-glycan quantitation approach using metallic element chelated tag labeling (MeCTL) through reductive amination. The MeCTL strategy is of high labeling efficiency and accurate in quantitation with high reproducibility (CV 0.99) within 2 orders of magnitude of dynamic range. Additionally, it provides significant cross-ring fragmentation to distinguish N-glycan isomers. Furthermore, multiplex quantitation by chelation with several different rare earth elements can be achieved. At last, this strategy has been successfully used for evaluation of N-glycan changes in human serum associated with CRC, indicating its potential in clinical applications including disease N-glycome profiling and relative quantitation.

  5. A new chelating reagent and application for coprecipitation of some metals in food samples by FAAS.

    Science.gov (United States)

    Yıldız, Esra; Saçmacı, Şerife; Kartal, Şenol; Saçmacı, Mustafa

    2016-03-01

    A new, simple and rapid coprecipitation method has been developed to separate and preconcentrate traces of Co(II), Cu(II), Fe(III), Pb(II) and Mn(II) in different samples prior to their determinations by flame atomic absorption spectrometry (FAAS). 2-[(E)-(8-hydroxy-2-methylquinolin-5-yl) diazenyl] benzoic acid (QAN) was firstly synthesized and characterized as a new chelating reagent for determination of some metals. IR spectra, (1)H-NMR spectrum and elemental analysis were evaluated for the characterization of the reagent. These metals were quantitatively recovered with Ni(II)/QAN precipitate in pH range of 8-10. Different factors such as sample volume, amount of QAN, and Ni(II) as carrier element, sample volume, and matrix effects for improving the quality of the preconcentration procedure were optimized. Under optimized experimentally established conditions, analytical detection limits were in the range of 0.03-0.83μgL(-1), while precision (RSD) was coprecipitation method was verified by the analysis of certified reference materials. The method was applied to the determination of the analytes in real samples such as food samples and make up products, and accuracy was found high (recoveries >95%). Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Cytotoxicity of superoxide dismutase 1 in cultured cells is linked to Zn2+ chelation.

    Directory of Open Access Journals (Sweden)

    Ann-Sofi Johansson

    Full Text Available Neurodegeneration in protein-misfolding disease is generally assigned to toxic function of small, soluble protein aggregates. Largely, these assignments are based on observations of cultured neural cells where the suspect protein material is titrated directly into the growth medium. In the present study, we use this approach to shed light on the cytotoxic action of the metalloenzyme Cu/Zn superoxide dismutase 1 (SOD1, associated with misfolding and aggregation in amyotrophic lateral sclerosis (ALS. The results show, somewhat unexpectedly, that the toxic species of SOD1 in this type of experimental setting is not an aggregate, as typically observed for proteins implicated in other neuro-degenerative diseases, but the folded and fully soluble apo protein. Moreover, we demonstrate that the toxic action of apoSOD1 relies on the protein's ability to chelate Zn(2+ ions from the growth medium. The decreased cell viability that accompanies this extraction is presumably based on disturbed Zn(2+ homeostasis. Consistently, mutations that cause global unfolding of the apoSOD1 molecule or otherwise reduce its Zn(2+ affinity abolish completely the cytotoxic response. So does the addition of surplus Zn(2+. Taken together, these observations point at a case where the toxic response of cultured cells might not be related to human pathology but stems from the intrinsic limitations of a simplified cell model. There are several ways proteins can kill cultured neural cells but all of these need not to be relevant for neurodegenerative disease.

  7. Investigation of DOTA-Metal Chelation Effects on the Chemical Shift of 129 Xe

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, K; Slack, CC; Vassiliou, CC; Dao, P; Gomes, MD; Kennedy, DJ; Truxal, AE; Sperling, LJ; Francis, MB; Wemmer, DE; Pines, A

    2015-09-17

    Recent work has shown that xenon chemical shifts in cryptophane-cage sensors are affected when tethered chelators bind to metals. Here in this paper, we explore the xenon shifts in response to a wide range of metal ions binding to diastereomeric forms of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) linked to cryptophane-A. The shifts induced by the binding of Ca2+, Cu2+, Ce3+, Zn2+, Cd2+, Ni2+, Co2+, Cr2+, Fe3+, and Hg2+ are distinct. In addition, the different responses of the diastereomers for the same metal ion indicate that shifts are affected by partial folding with a correlation between the expected coordination number of the metal in the DOTA complex and the chemical shift of 129Xe. Lastly, these sensors may be used to detect and quantify many important metal ions, and a better understanding of the basis for the induced shifts could enhance future designs.

  8. 8-Hydroxyquinolines: a review of their metal chelating properties and medicinal applications

    Directory of Open Access Journals (Sweden)

    Prachayasittikul V

    2013-10-01

    Full Text Available Veda Prachayasittikul,1 Supaluk Prachayasittikul,2 Somsak Ruchirawat,3 Virapong Prachayasittikul11Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, 2Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand; 3Laboratory of Medicinal Chemistry, Chulabhorn Research Institute and Chulabhorn Graduate Institute, Bangkok, ThailandAbstract: Metal ions play an important role in biological processes and in metal homeostasis. Metal imbalance is the leading cause for many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. 8-Hydroxyquinoline (8HQ is a small planar molecule with a lipophilic effect and a metal chelating ability. As a result, 8HQ and its derivatives hold medicinal properties such as antineurodegenerative, anticancer, antioxidant, antimicrobial, anti-inflammatory, and antidiabetic activities. Herein, diverse bioactivities of 8HQ and newly synthesized 8HQ-based compounds are discussed together with their mechanisms of actions and structure–activity relationships.Keywords: metal binding compound, antineurodegenerative, anticancer, antidiabetic, multifunctional actions, structure–activity relationships

  9. Antimicrobial Effect and Surface Tension of Some Chelating Solutions with Added Surfactants.

    Science.gov (United States)

    Giardino, Luciano; Andrade, Flaviana Bombarda de; Beltrami, Riccardo

    2016-01-01

    This study assessed the antimicrobial efficacy and surface tension of established irrigating solutions with a new experimental chelating solution in infected dentin tubes. Twenty-five specimens were randomly assigned to each of the irrigating solutions. Twenty specimens were used as negative and positive controls. After 21 days of contamination with E. faecalis, the irrigating solutions MTAD, QMiX and Tetraclean NA were delivered into each infected root canal. The solutions were removed and dentin samples were withdrawn from the root canals with sterile low-speed round burs with increasing ISO diameters. The dentin powder samples obtained with each bur were immediately collected in separate test tubes containing 3 mL of BHI broth. After that, 100 μL from each test tube was cultured on blood agar. The grown colonies were counted and recorded as colony-forming units (CFU). The surface tension of the irrigants was measured using a Cahn DCA-322 Dynamic Contact Angle Analyzer. A Kruskal Wallis nonparametric ANOVA and a Friedman test were used (psurface tension and CFU values than MTAD and QMiX. Better antibacterial action and low surface tension were observed for Tetraclean NA, probably due to the improved penetration into the root canal and dentinal tubes.

  10. The role of chelating agents on the corrosion mechanisms of aluminium in alkaline aqueous solutions

    Energy Technology Data Exchange (ETDEWEB)

    Mercier, D. [Centre d' Etudes de Chimie Metallurgique, CNRS, 15 rue Georges Urbain, 94407 Vitry Cedex (France); Barthes-Labrousse, M.-G. [Centre d' Etudes de Chimie Metallurgique, CNRS, 15 rue Georges Urbain, 94407 Vitry Cedex (France)], E-mail: marie-genevieve.barthes@u-psud.fr

    2009-02-15

    The influence of 1,2-diaminoethane (DAE) on the mechanism of aluminium corrosion in KOH solutions at pH 13 was investigated by combining time-resolved inductively coupled plasma optical emission spectrocopy, open-circuit potential measurements and X-ray photoelectron spectroscopy. In pure KOH solutions, a very slow corrosion rate is initially observed, corresponding to the dissolution of the native oxide layer. Following this incubation stage, the corrosion rate is increasing due to the formation and oxidation of Al hydride, until a steady state is reached. DAE behaves as a strong initial corrosion accelerator, due to synergistic effects with hydroxyl ions and a dissolution mechanism in three successive steps has been proposed: (i) a rapid initial dissolution induced by the formation and detachment from the surface of bidentate (chelate) Al-DAE metal bound surface complexes; (ii) a slower step ascribed to the formation and release of monodentate Al-DAE metal bound surface complexes and (iii) a final step dominated by direct oxidation of surface aluminium hydride by hydroxyl species as in pure KOH.

  11. Preparation of Amidoxime Polyacrylonitrile Chelating Nanofibers and Their Application for Adsorption of Metal Ions

    Directory of Open Access Journals (Sweden)

    You-Lo Hsieh

    2013-03-01

    Full Text Available Polyacrylonitrile (PAN nanofibers were prepared by electrospinning and they were modified with hydroxylamine to synthesize amidoxime polyacrylonitrile (AOPAN chelating nanofibers, which were applied to adsorb copper and iron ions. The conversion of the nitrile group in PAN was calculated by the gravimetric method. The structure and surface morphology of the AOPAN nanofiber were characterized by a Fourier transform infrared spectrometer (FT-IR and a scanning electron microscope (SEM, respectively. The adsorption abilities of Cu2+ and Fe3+ ions onto the AOPAN nanofiber mats were evaluated. FT-IR spectra showed nitrile groups in the PAN were partly converted into amidoxime groups. SEM examination demonstrated that there were no serious cracks or sign of degradation on the surface of the PAN nanofibers after chemical modification. The adsorption capacities of both copper and iron ions onto the AOPAN nanofiber mats were higher than those into the raw PAN nanofiber mats. The adsorption data of Cu2+ and Fe3+ ions fitted particularly well with the Langmuir isotherm. The maximal adsorption capacities of Cu2+ and Fe3+ ions were 215.18 and 221.37 mg/g, respectively.

  12. Removal of PCR error products and unincorporated primers by metal-chelate affinity chromatography.

    Directory of Open Access Journals (Sweden)

    Indhu Kanakaraj

    Full Text Available Immobilized Metal Affinity Chromatography (IMAC has been used for decades to purify proteins on the basis of amino acid content, especially surface-exposed histidines and "histidine tags" genetically added to recombinant proteins. We and others have extended the use of IMAC to purification of nucleic acids via interactions with the nucleotide bases, especially purines, of single-stranded RNA and DNA. We also have demonstrated the purification of plasmid DNA from contaminating genomic DNA by IMAC capture of selectively-denatured genomic DNA. Here we describe an efficient method of purifying PCR products by specifically removing error products, excess primers, and unincorporated dNTPs from PCR product mixtures using flow-through metal-chelate affinity adsorption. By flowing a PCR product mixture through a Cu(2+-iminodiacetic acid (IDA agarose spin column, 94-99% of the dNTPs and nearly all the primers can be removed. Many of the error products commonly formed by Taq polymerase also are removed. Sequencing of the IMAC-processed PCR product gave base-calling accuracy comparable to that obtained with a commercial PCR product purification method. The results show that IMAC matrices (specifically Cu(2+-IDA agarose can be used for the purification of PCR products. Due to the generality of the base-specific mechanism of adsorption, IMAC matrices may also be used in the purification of oligonucleotides, cDNA, mRNA and micro RNAs.

  13. Dinuclear metal complexes derived from a bis-chelating heterocyclic ligand

    Directory of Open Access Journals (Sweden)

    Worku Assefa

    2009-08-01

    Full Text Available 4,6-bis-{1-[(4,6-dichloro-[1,3,5]triazine-2-yl-hydrazone]-ethyl-benzene-1,3-diol, C16H12N10O2Cl4 (H2-BDTD, and Co(II, Ni(II, Cu(II and Zn(II complexes derived from its dibasic bis-chelating form (BDTD2- or L2- were prepared in methanol-triethylamine and characterized by MS, NMR, IR, UV-VIS and AA spectroscopic studies. Conductivities, magnetic susceptibility measurements and thermal analyses showed bis-N,N,O donor behavior of L2-. The analytical data indicate that the metal to ligand ratio is 2:1 in all the complexes. The coordination of triethylamine, water and chloride ion are observed in the Co(II, Zn(II and Ni(II complexes. The absence of ionizable or coordinated chloride in Cu(II complex is a notable feature. Octahedral geometry for Co(II, Zn(II and Ni(II and square planar geometry for Cu(II complexes are proposed. The paramagnetic complexes exhibit subnormal magnetic moments at room temperature (RT.

  14. Chelation Therapy with Oral Solution of Deferiprone in Transfusional Iron-Overloaded Children with Hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Alexandros Makis

    2013-01-01

    Full Text Available Iron overload in hemoglobinopathies is secondary to blood transfusions, chronic hemolysis, and increased iron absorption and leads to tissue injury requiring the early use of chelating agents. The available agents are parenteral deferoxamine and oral deferiprone and deferasirox. There are limited data on the safety and efficacy of deferiprone at a very young age. The aim of our study was the presentation of data regarding the use of oral solution of deferiprone in 9 children (mean age 6.5, range 2–10 with transfusion dependent hemoglobinopathies (6 beta thalassemia major, 1 thalassemia intermedia, and 2 sickle cell beta thalassemia. The mean duration of treatment was 21.5 months (range 15–31. All children received the oral solution without any problems of compliance. Adverse reactions were temporary abdominal discomfort and diarrhea (1 child, mild neutropenia (1 child that resolved with no need of discontinuation of treatment, and transient arthralgia (1 child that resolved spontaneously. The mean ferritin levels were significantly reduced at the end of 12 months (initial 2440 versus final 1420 μg/L, . This small study shows that oral solution of deferiprone was well tolerated by young children and its use was not associated with major safety concerns. Furthermore, it was effective in decreasing serum ferritin.

  15. Optimization of isolation of cellulose from orange peel using sodium hydroxide and chelating agents.

    Science.gov (United States)

    Bicu, Ioan; Mustata, Fanica

    2013-10-15

    Response surface methodology was used to optimize cellulose recovery from orange peel using sodium hydroxide (NaOH) as isolation reagent, and to minimize its ash content using ethylenediaminetetraacetic acid (EDTA) as chelating agent. The independent variables were NaOH charge, EDTA charge and cooking time. Other two constant parameters were cooking temperature (98 °C) and liquid-to-solid ratio (7.5). The dependent variables were cellulose yield and ash content. A second-order polynomial model was used for plotting response surfaces and for determining optimum cooking conditions. The analysis of coefficient values for independent variables in the regression equation showed that NaOH and EDTA charges were major factors influencing the cellulose yield and ash content, respectively. Optimum conditions were defined by: NaOH charge 38.2%, EDTA charge 9.56%, and cooking time 317 min. The predicted cellulose yield was 24.06% and ash content 0.69%. A good agreement between the experimental values and the predicted was observed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Polyhydroxamic microcapsules prepared from proteins: a novel type of chelating microcapsules.

    Science.gov (United States)

    Hettler, D; Andry, M C; Levy, M C

    1994-01-01

    Microcapsules were prepared from three proteins, namely human serum albumin (HSA), bovine fibrinogen and ovalbumin, by an interfacial crosslinking process using terephthaloylchloride. They were further treated with alkaline hydroxylamine in order to disrupt ester and anhydride bonds in the walls. All microcapsules survived the treatment. They exhibited a significant increase in size and became sensitive to trypsin. The hydroxylamine treatment also resulted in attachment of hydroxamic groups to the membrane, making the microcapsules capable of iron binding. These properties were evaluated after soaking microcapsules in a 140 mumol/l ferric solution and determination of iron in the supernantant. Lower amounts of iron were found to be complexed by HSA microcapsules (mean value: 29.3 mumol iron/g microcapsule dry weight) as compared with fibrinogen and ovalbumin microcapsules (43.7 and 44.9 mumol/g, respectively). Microcapsule chelating properties were further improved by esterification of the free carboxyl groups of the membrane with benzyl alcohol or ethanol using a carbodiimide, prior to the hydroxylamine treatment. Comparable values of iron binding were obtained from esterified and hydroxylamine-treated batches prepared from the three proteins (about 50 mumol iron/g).

  17. Calcium-Mediated Control of Polydopamine Film Oxidation and Iron Chelation

    Directory of Open Access Journals (Sweden)

    Luke Klosterman

    2016-12-01

    Full Text Available The facile preparation of conformal polydopamine (PDA films on broad classes of materials has prompted extensive research into a wide variety of potential applications for PDA. The constituent molecular species in PDA exhibit diverse chemical moieties, and therefore highly variable properties of PDA-based devices may evolve with post-processing conditions. Here we report the use of redox-inactive cations for oxidative post-processing of deposited PDA films. PDA films incubated in alkaline CaCl2 solutions exhibit accelerated oxidative evolution in a dose-dependent manner. PDA films incubated in CaCl2 solutions exhibit 53% of the oxidative charge transfer compared to pristine PDA films. Carboxylic acid groups generated from the oxidation process lower the isoelectric point of PDA films from pH = 4.0 ± 0.2 to pH = 3.1 ± 0.3. PDA films exposed to CaCl2 solutions during post-processing also enhance Fe2+/Fe3+ chelation compared to pristine PDA films. These data illustrate that the molecular heterogeneity and non-equilibrium character of as-deposited PDA films afford control over the final composition by choosing post-processing conditions, but also demands forethought into how the performance of PDA-incorporated devices may change over time in salt solutions.

  18. Chelating, antioxidant and hypoglycaemic potential of Muscari comosum (L.) Mill. bulb extracts.

    Science.gov (United States)

    Loizzo, Monica R; Tundis, Rosa; Menichini, Federica; Pugliese, Alessandro; Bonesi, Marco; Solimene, Umberto; Menichini, Francesco

    2010-12-01

    The metal chelating activity, antioxidant properties and the effect on carbohydrate-hydrolysing enzyme inhibition of Muscari comosum extracts have been investigated. M. comosum bulbs contain a total amount of the phenols with a value of 56.6 mg chlorogenic acid equivalent per gram of extract and a flavonoid content of 23.4 mg quercetin equivalent per gram of extract. In order to evaluate the non-polar constituents, n-hexane extract was obtained. Gas chromatography-mass spectrometry analysis revealed the presence of fatty acids and ethyl esters as major constituents, with different aldehydes and alkanes as minor components. Ethanolic extract had the highest ferric-reducing ability power (66.7 μM Fe(II)/g) and DPPH scavenging activity with a concentration giving 50% inhibition (IC₅₀) value of 40.9 μg/ml. Moreover, this extract exhibited a good hypoglycaemic activity with IC₅₀ values of 81.3 and 112.8 μg/ml for α-amylase and α-glucosidase, respectively. In conclusion, M. comosum bulbs show promising antioxidant and hypoglycaemic activity via the inhibition of carbohydrate digestive enzymes. These activities may be of interest from a functional point of view and for the revalorization of this ancient non-cultivated vegetable of Mediterranean traditional gastronomy.

  19. Origins of initiation rate differences in ruthenium olefin metathesis catalysts containing chelating benzylidenes.

    Science.gov (United States)

    Engle, Keary M; Lu, Gang; Luo, Shao-Xiong; Henling, Lawrence M; Takase, Michael K; Liu, Peng; Houk, K N; Grubbs, Robert H

    2015-05-06

    A series of second-generation ruthenium olefin metathesis catalysts was investigated using a combination of reaction kinetics, X-ray crystallography, NMR spectroscopy, and DFT calculations in order to determine the relationship between the structure of the chelating o-alkoxybenzylidene and the observed initiation rate. Included in this series were previously reported catalysts containing a variety of benzylidene modifications as well as four new catalysts containing cyclopropoxy, neopentyloxy, 1-adamantyloxy, and 2-adamantyloxy groups. The initiation rates of this series of catalysts were determined using a UV/vis assay. All four new catalysts were observed to be faster-initiating than the corresponding isopropoxy control, and the 2-adamantyloxy catalyst was found to be among the fastest-initiating Hoveyda-type catalysts reported to date. Analysis of the X-ray crystal structures and computed energy-minimized structures of these catalysts revealed no correlation between the Ru-O bond length and Ru-O bond strength. On the other hand, the initiation rate was found to correlate strongly with the computed Ru-O bond strength. This latter finding enables both the rationalization and prediction of catalyst initiation through the calculation of a single thermodynamic parameter in which no assumptions about the mechanism of the initiation step are made.

  20. Calcium-Mediated Control of Polydopamine Film Oxidation and Iron Chelation.

    Science.gov (United States)

    Klosterman, Luke; Bettinger, Christopher J

    2016-12-22

    The facile preparation of conformal polydopamine (PDA) films on broad classes of materials has prompted extensive research into a wide variety of potential applications for PDA. The constituent molecular species in PDA exhibit diverse chemical moieties, and therefore highly variable properties of PDA-based devices may evolve with post-processing conditions. Here we report the use of redox-inactive cations for oxidative post-processing of deposited PDA films. PDA films incubated in alkaline CaCl₂ solutions exhibit accelerated oxidative evolution in a dose-dependent manner. PDA films incubated in CaCl₂ solutions exhibit 53% of the oxidative charge transfer compared to pristine PDA films. Carboxylic acid groups generated from the oxidation process lower the isoelectric point of PDA films from pH = 4.0 ± 0.2 to pH = 3.1 ± 0.3. PDA films exposed to CaCl₂ solutions during post-processing also enhance Fe2+/Fe3+ chelation compared to pristine PDA films. These data illustrate that the molecular heterogeneity and non-equilibrium character of as-deposited PDA films afford control over the final composition by choosing post-processing conditions, but also demands forethought into how the performance of PDA-incorporated devices may change over time in salt solutions.

  1. A square-planar tellurium(II) complex with Te,Te'-chelating ligands.

    Science.gov (United States)

    Chivers, Tristram; Ritch, Jamie S

    2015-05-01

    While exploring the chemistry of tellurium-containing dichalcogenidoimidodiphosphinate ligands, the first all-tellurium member of a series of related square-planar E(II)(E')4 complexes (E and E' are group 16 elements), namely bis(P,P,P',P'-tetraphenylditelluridoimidodiphosphinato-κ(2)Te,Te')tellurium(II) (systematic name: 2,2,4,4,8,8,10,10-octaphenyl-1λ(3),5,6λ(4),7λ(3),11-pentatellura-3,9-diaza-2λ(5),4λ(5),8λ(5),10λ(5)-tetraphosphaspiro[5.5]undeca-1,3,7,9-tetraene), C48H40N2P4Te5, was obtained unexpectedly. The formally Te(II) centre is situated on a crystallographic inversion centre and is Te,Te'-chelated to two anionic [(TePPh2)2N](-) ligands in an anti conformation. The central Te(II)(Te)4 unit is approximately square planar [Te-Te-Te = 93.51 (3) and 86.49 (3)°], with Te-Te bond lengths of 2.9806 (6) and 2.9978 (9) Å.

  2. Field-Portable Immunoassay Instruments and Reagents to Measure Chelators and Mobile Forms of Uranium

    Energy Technology Data Exchange (ETDEWEB)

    Blake, Diane A.

    2006-01-23

    Progress Report Date: 01/23/06 (report delayed due to Hurricane Katrina) Report of results to date: The goals of this 3-year project are to: (1) update and successfully deploy our present immunosensors at DOE sites; (2) devise immunosensor-based assays for Pb(II), Hg(II), chelators, and/or Cr(III) in surface and groundwater; and (3) develop new technologies in antibody engineering that will enhance this immunosensor program. Note: Work on this project was temporarily disrupted when Hurricane Katrina shut down the University on August 29, 2005. While most of the reagents stored in our refrigerators and freezers were destroyed, all of our hybridoma cell lines were saved because they had been stored in liquid nitrogen. We set up new tissue culture reactors with the hybridomas that synthesize the anti-uranium antibodies, and are purifying new monoclonal antibodies from these culture supernatants. Both the in-line and the field-portable sensor were rescued from our labs in New Orleans in early October, and we continued experiments with these sensors in the temporary laboratory we set up in Hammond, LA at Southeastern Louisiana University.

  3. Bright electroluminescence from a chelate phosphine oxide Eu{sup III} complex with high thermal performance

    Energy Technology Data Exchange (ETDEWEB)

    Xu Hui [School of Chemistry and Materials, Heilongjiang University, 74 Xuefu Road, Nangang District, Harbin 150080, Heilongjiang Province (China); Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, 66 Xinmofan Road, Nanjing 21003, Jiangsu Province (China); Yin Kun; Wang Lianhui [Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, 66 Xinmofan Road, Nanjing 21003, Jiangsu Province (China); Huang Wei [Institute of Advanced Materials (IAM), Fudan University, 220 Handan Road, Shanghai 200433 (China)], E-mail: wei-huang@njupt.edu.cn

    2008-10-01

    The chelate phosphine oxide ligand 1,8-bis(diphenylphosphino)naphthalene oxide (NaPO) was used to prepare complex 1 tris(2-thenoyltrifluoroacetonate)(1,8-bis(diphenylphosphino)naphthalene oxide)europium(III). The rigid structure of NaPO makes 1 have more compact structure resulting in a temperature of glass transition as high as 147 deg. C, which is the highest in luminescent Eu{sup III} complexes, and a higher decomposition temperature of 349 deg. C. The improvement of carrier transfer ability of NaPO was proved by Gaussian simulation. The multi-layered electroluminescent device based on 1 had a low turn-on voltage of 6.0 V, the maximum brightness of 601 cd m{sup -2} at 21.5 V and 481.4 mA cm{sup -2}, and the excellent voltage-independent spectral stability. These properties demonstrated NaPO cannot only be favorable to form the rigid and compact complex structure, and increase the thermal and morphological stability of the complex, but also reduce the formation of the exciplex.

  4. Antioxidant and Metal Chelation-Based Therapies in the Treatment of Prion Disease

    Directory of Open Access Journals (Sweden)

    Marcus W. Brazier

    2014-04-01

    Full Text Available Many neurodegenerative disorders involve the accumulation of multimeric assemblies and amyloid derived from misfolded conformers of constitutively expressed proteins. In addition, the brains of patients and experimental animals afflicted with prion disease display evidence of heightened oxidative stress and damage, as well as disturbances to transition metal homeostasis. Utilising a variety of disease model paradigms, many laboratories have demonstrated that copper can act as a cofactor in the antioxidant activity displayed by the prion protein while manganese has been implicated in the generation and stabilisation of disease-associated conformers. This and other evidence has led several groups to test dietary and chelation therapy-based regimens to manipulate brain metal concentrations in attempts to influence the progression of prion disease in experimental mice. Results have been inconsistent. This review examines published data on transition metal dyshomeostasis, free radical generation and subsequent oxidative damage in the pathogenesis of prion disease. It also comments on the efficacy of trialed therapeutics chosen to combat such deleterious changes.

  5. Preparation and bioavailability of calcium-chelating peptide complex from tilapia skin hydrolysates.

    Science.gov (United States)

    Chen, Jun; Qiu, Xujian; Hao, Gengxin; Zhang, Meng; Weng, Wuyin

    2017-11-01

    With the continuous improvement in material life, the generation of fish by-products and the market demand for calcium supplements have been increasing in China. Therefore a calcium-chelating peptide complex (CPC) from tilapia skins was prepared and its effect on calcium (Ca)-deficient mice was investigated. The molecular weight distribution of CPC mainly ranged from 2000 to 180 Da, and its contents of complete amino acids and free amino acids were 85.30 and 8.67% (w/w) respectively. Scanning electron microscopy images and Fourier transform infrared data revealed that Ca crystals were bound with gelatin hydrolysates via interaction between Ca ions and NH/CN groups. When Ca-deficient mice were fed CPC and CaCO 3 respectively for 4 weeks, no significant differences in serum biochemistry or bone mineral density were found. However, the length, weight, Ca content and hydroxyproline content of the femur, Ca absorption and body weight gain of mice fed CPC were significantly higher than those of mice fed CaCO 3 . It is concluded that the prepared CPC could promote bone formation via better bioavailability of Ca and an increase in bone collagen. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  6. Chelator-enhanced lead accumulation in Agropyron elongatum cv Szarvasi-1 in hydroponic culture.

    Science.gov (United States)

    Vashegyi, Ildikó; Cseh, Edit; Lévai, László; Fodor, Ferenc

    2011-03-01

    Hydroponic culture was applied to compare the efficiency of K2EDTA and citrate in mobilizing Pb for accumulation in Agropyron elongatum cv. Szarvasi-1 and their effects on some physiological characteristics of the plants. The plants were grown in nutrient solutions containing 0, 10, and 100 microM Pb(NO3)2 combined with chelating agents added to the nutrient solutions after 21 days of growth, in 3 concentrations (0, 100, and 500 microM). The effects were measured after eight days. The energy grass proved to be greatly resistant to the treatments, as was reflected in the slight inhibition of growth, the resistance of the photosynthetic electron transport chain and the chlorophyll composition and the lack of change in the malone-dialdehyde content. Fundamental differences can be identified between the effects of EDTA and citrate. Citrate had only a little effect on the physiological parameters, which may be due to the strongly increasing lead accumulation with increasing concentration of Pb in the nutrient solution. Additionally, citrate ensured a higher biomass yield with higher shoot Pb accumulation compared to EDTA in almost all treatments. Concerning biomass reduction, 10 microM Pb applied together with K2EDTA has the most deleterious effects on energy grass. The effects correlated with the concentration of EDTA.

  7. High-resolution Thermal Micro-imaging Using Europium Chelate Luminescent Coatings.

    Science.gov (United States)

    Benseman, Timothy M; Hao, Yang; Vlasko-Vlasov, Vitalii K; Welp, Ulrich; Koshelev, Alexei E; Kwok, Wai-Kwong; Divan, Ralu; Keiser, Courtney; Watanabe, Chiharu; Kadowaki, Kazuo

    2017-04-16

    Micro-electronic devices often undergo significant self-heating when biased to their typical operating conditions. This paper describes a convenient optical micro-imaging technique which can be used to map and quantify such behavior. Europium thenoyltrifluoroacetonate (EuTFC) has a 612 nm luminescence line whose activation efficiency drops strongly with increasing temperature, due to T-dependent interactions between the Eu3+ ion and the organic chelating compound. This material may be readily coated on to a sample surface by thermal sublimation in vacuum. When the coating is excited with ultraviolet light (337 nm) an optical micro-image of the 612 nm luminescent response can be converted directly into a map of the sample surface temperature. This technique offers spatial resolution limited only by the microscope optics (about 1 micron) and time resolution limited by the speed of the camera employed. It offers the additional advantages of only requiring comparatively simple and non-specialized equipment, and giving a quantitative probe of sample temperature.

  8. Metal chelate affinity precipitation: purification of BSA using poly(N-vinylcaprolactam-co-methacrylic acid) copolymers.

    Science.gov (United States)

    Ling, Yuan-Qing; Nie, Hua-Li; Brandford-White, Christopher; Williams, Gareth R; Zhu, Li-Min

    2012-06-01

    This investigation involves the metal chelate affinity precipitation of bovine serum albumin (BSA) using a copper ion loaded thermo-sensitive copolymer. The copolymer of N-vinylcaprolactam with methacrylic acid PNVCL-co-MAA was synthesized by free radical polymerization in aqueous solution, and Cu(II) ions were attached to provide affinity properties for BSA. A maximum loading of 48.1mg Cu(2+) per gram of polymer was attained. The influence of pH, temperature, BSA and NaCl concentrations on BSA precipitation and of pH, ethylenediaminetetraacetic acid (EDTA) and NaCl concentrations on elution were systematically probed. The optimum conditions for BSA precipitation occurred when pH, temperature and BSA concentration were 6.0, 10°C and 1.0 mg/ml, respectively and the most favorable elution conditions were at pH 4.0, with 0.2M NaCl and 0.06 M EDTA. The maximum amounts of BSA precipitation and elution were 37.5 and 33.7 mg BSA/g polymer, respectively. It proved possible to perform multiple precipitation/elution cycles with a minimal loss of polymer efficacy. The results show that PNVCL-co-MAA is a suitable matrix for the purification of target proteins from unfractionated materials. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. In vitro growth inhibition of mastitis causing bacteria by phenolics and metal chelators

    Energy Technology Data Exchange (ETDEWEB)

    Chew, B.P.; Tjoelker, L.W.; Tanaka, T.S.

    1985-11-01

    Antimicrobial activities of three phenolic compounds and four metal chelators were tested at 0, 250, 500, and 1000 ppm in vitro against four major mastitis-causing bacteria, Streptococcus agalactiae, Staphylococcus aureus, Klebsiella pnuemoniae, and Escherichia coli. Overall, butylated hydroxyanisole and tert-butylhydroquinone showed the greatest antimicrobial activity. These phenolics were bactericidal at 250 to 500 ppm against all four bacteria tested. The butylated hydroxytoluene was bactericidal against the gram-positive bacteria but was ineffective against the coliforms. At 250 ppm, disodium ethylenediaminetetraacetic acid was bactericidal against the gram-positive bacteria but much less effective against the gram-negatives. However, diethylene-triaminepentaacetic acid was more growth inhibitory than ethylenediaminetetraacetic acid against the gram-negative bacteria and especially against Escherichia coli. All other compounds were generally much less effective or ineffective against all four microorganisms. Therefore, butylated hydroxyanisole, butylated hydroxytoluene, tert-butylhydroquinone, ethylenediaminetetraacetic acid, and diethylenetriaminepentaacetic acid may have practical implications in the prevention or treatment of bovine mastitis.

  10. The fate of Gd and chelate following intravenous injection of gadodiamide in rats.

    Science.gov (United States)

    Kindberg, Grete Mørk; Uran, Steinar; Friisk, Grete; Martinsen, Ivar; Skotland, Tore

    2010-07-01

    The biodistribution of gadolinium (Gd) and chelate was studied in rats injected intravenously with a commercially available gadodiamide magnetic resonance contrast agent spiked with trace amounts of (14)C-labelled GdDTPA-BMA. Biodistribution of the (14)C-labelled ligand in whole animals was visualised using quantitative whole-body autoradiography, and quantified in individual tissue samples by analysing for radioactivity using beta-counting. Biodistribution of Gd was measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES) and inductively coupled plasma sector field mass spectrometry (ICP-SF-MS). The injected dose was rapidly excreted, with only 1.0% remaining in the body at 24 h. The radioactivity thereafter was mainly associated with kidney cortex, liver, lung, muscle and skin, with a similar rate of clearance for both ligand and Gd from these tissues. The ratio between (14)C-labelled substance and Gd was not significantly different from that of the injected substance in most tissue samples up to 24 h after injection; the ratio then slowly decreased. The data clearly show that measurements of Gd concentration alone in tissue samples from animals injected with Gd-based contrast agents (GBCAs) cannot be used as a measure of Gd released from the ligand. To our knowledge, such measurements comparing Gd and ligand concentrations and distribution in tissue samples have not been published previously for any of the commercial GBCAs.

  11. Efficient removal of heavy metal ions from aqueous solution using salicylic acid type chelate adsorbent.

    Science.gov (United States)

    An, Fuqiang; Gao, Baojiao; Dai, Xin; Wang, Min; Wang, Xiaohua

    2011-09-15

    In this study, 5-aminosalicylic acid was successfully grafted onto the poly(glycidyl methacrylate) (PGMA) macromolecular chains of PGMA/SiO(2) to obtain a novel adsorbent designated as ASA-PGMA/SiO(2). The adsorption properties of ASA-PGMA/SiO(2) for heavy metal ions were studied through batch and column methods. The experimental results showed that ASA-PGMA/SiO(2) possesses strong chelating adsorption ability for heavy metal ions, and its adsorption capacity for Cu(2+), Cd(2+), Zn(2+), and Pb(2+) reaches 0.42, 0.40, 0.35, and 0.31 mmol g(-1), respectively. In addition, pH has a great influence on the adsorption capacity in the studied pH range. The adsorption isotherm data greatly obey the Langmuir and Freundlich model. The desorption of metal ions from ASA-PGMA/SiO(2) is effective using 0.1 mol l(-1) of hydrochloric acid solution as eluent. Consecutive adsorption-desorption experiments showed that ASA-PGMA/SiO(2) could be reused almost without any loss in the adsorption capacity. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Synthesis of palladium(0) and -(II) complexes with chelating bis(N-heterocyclic carbene) ligands and their application in semihydrogenation

    OpenAIRE

    Sluijter, S.N.; Warsink, S.; Lutz, M.; Elsevier, C.J.

    2013-01-01

    A transmetallation route, using silver(I) precursors, to several zero-and di-valent palladium complexes with chelating bis(N-heterocyclic carbene) ligands bearing various N-substituents has been established. The resulting complexes have been characterized by NMR and mass spectroscopy. In addition, the structure of a representative compound, [Pd-0(bis-(Mes)NHC)(eta(2)-ma)] (3a), was confirmed by X-ray crystal structure determination. In contrast to the transfer semihydrogenation, in which only...

  13. Synthesis and characterization of ferrocene-chelating heteroscorpionate complexes of nickel(II) and zinc(II)

    OpenAIRE

    Abubekerov, M; Diaconescu, PL

    2015-01-01

    © 2015 American Chemical Society. The first example of a ferrocene-chelating heteroscorpionate, [Li(THF) 2 ][fc(PPh 2 )(BH[(3,5-Me) 2 pz] 2 )] ((fc P,B )Li(THF) 2 , fc = 1,1′-ferrocenediyl) is described. Starting from a previously reported compound, fcBr(PPh 2 ), a series of ferrocene derivatives, fc(PPh 2 )(B[OMe] 2 ), [Li(OEt 2 < /i...

  14. On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure

    Directory of Open Access Journals (Sweden)

    Carpenter JP

    2011-09-01

    Full Text Available Abstract Background Trials of iron chelator regimens have increased the treatment options for cardiac siderosis in beta-thalassemia major (TM patients. Treatment effects with improved left ventricular (LV ejection fraction (EF have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful. Methods This retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR to the relative risk (RR of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM and 63-70% (lower half of the normal range for TM. Results A total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p Conclusion These data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.

  15. Inhibition of microsomal oxidation of alcohols and of hydroxyl-radical-scavenging agents by the iron-chelating agent desferrioxamine.

    OpenAIRE

    Cederbaum, A I; Dicker, E

    1983-01-01

    Rat liver microsomes (microsomal fractions) catalyse the oxidation of straight-chain aliphatic alcohols and of hydroxyl-radical-scavenging agents during NADPH-dependent electron transfer. The iron-chelating agent desferrioxamine, which blocks the generation of hydroxyl radicals in other systems, was found to inhibit the following microsomal reactions: production of formaldehyde from either dimethyl sulphoxide or 2-methylpropan-2-ol (t-butylalcohol); generation of ethylene from 4-oxothiomethyl...

  16. Structure-activity relationships of novel salicylaldehyde isonicotinoyl hydrazone (SIH analogs: iron chelation, anti-oxidant and cytotoxic properties.

    Directory of Open Access Journals (Sweden)

    Eliška Potůčková

    Full Text Available Salicylaldehyde isonicotinoyl hydrazone (SIH is a lipophilic, tridentate iron chelator with marked anti-oxidant and modest cytotoxic activity against neoplastic cells. However, it has poor stability in an aqueous environment due to the rapid hydrolysis of its hydrazone bond. In this study, we synthesized a series of new SIH analogs (based on previously described aromatic ketones with improved hydrolytic stability. Their structure-activity relationships were assessed with respect to their stability in plasma, iron chelation efficacy, redox effects and cytotoxic activity against MCF-7 breast adenocarcinoma cells. Furthermore, studies assessed the cytotoxicity of these chelators and their ability to afford protection against hydrogen peroxide-induced oxidative injury in H9c2 cardiomyoblasts. The ligands with a reduced hydrazone bond, or the presence of bulky alkyl substituents near the hydrazone bond, showed severely limited biological activity. The introduction of a bromine substituent increased ligand-induced cytotoxicity to both cancer cells and H9c2 cardiomyoblasts. A similar effect was observed when the phenolic ring was exchanged with pyridine (i.e., changing the ligating site from O, N, O to N, N, O, which led to pro-oxidative effects. In contrast, compounds with long, flexible alkyl chains adjacent to the hydrazone bond exhibited specific cytotoxic effects against MCF-7 breast adenocarcinoma cells and low toxicity against H9c2 cardiomyoblasts. Hence, this study highlights important structure-activity relationships and provides insight into the further development of aroylhydrazone iron chelators with more potent and selective anti-neoplastic effects.

  17. Effect of foliar application of amino acid and calcium chelate on some quality and quantity of Golden Delicious and Granny Smith apples

    Directory of Open Access Journals (Sweden)

    M. Arabloo

    2017-03-01

    Full Text Available In order to investigate the effects of foliar application of amino acid and calcium chelate on „Golden Delicious‟ and „Granny smith‟ apple trees, a randomized complete block design with four repetitions was conducted. Apple trees were sprayed with (0, 2, 4 mg L-1 of amino acid and (0, 2, 4 mg L-1 calcium chelate and their combination. Fruit weight, fruit firmness, total soluble solids, titretable acidity and calcium content of fruits were determined. All the applied treatments significantly increased quality and quantity traits compared to the control trees in both cultivars. The combination of amino acid and calcium chelate increased weight of both cultivars. Thus, in this study combination of amino acid and calcium chelate foliar spray treatment could be recommended from results as they significantly increased quality and quantity traits of „Golden delicious‟ and „Granny smith‟ apple trees.

  18. General method for selective labelling of double-chain cysteine-rich peptides with a lanthanide chelate via solid-phase synthesis.

    Science.gov (United States)

    Shabanpoor, Fazel; Separovic, Frances; Wade, John D

    2011-03-01

    The use of lanthanides in preference to radioisotopes as probes for various biological assays has gained enormous popularity. The introduction of lanthanide chelates to peptides/proteins can be carried out either in solution using a commercially available labelling kit or by solid-phase peptide synthesis using an appropriate lanthanide chelate. Herein, a detailed protocol for the latter is provided for the labelling of peptides or small proteins with diethylenetriamine-N, N, N″, N″-tetra-tert-butyl acetate-N'-acetic acid (DTPA) chelate or other similar chelates on a solid support using a chimeric insulin-like peptide composed of human insulin-like peptide 5 (INSL5) A-chain and relaxin-3 B-chain as a model peptide. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.

  19. Structure-Activity Relationships and Identification of Optmized CC-Chemokine Receptor CCR1, 5, and 8 Metal-Ion Chelators

    DEFF Research Database (Denmark)

    Chalikiopoulos, Alexander; Thiele, Stefanie; Malmgaard-Clausen, Mikkel

    2013-01-01

    Chemokine receptors are involved in trafficking of leukocytes and represent targets for autoimmune conditions, inflammatory diseases, viral infections, and cancer. We recently published CCR1, CCR8, and CCR5 agonists and positive modulators based on a three metal-ion chelator series: 2,2'-bipyridine......, 1,10-phenanthroline, and 2,2';6',2″-terpyridine. Here, we have performed an in-depth structure-activity relationship study and tested eight new optimized analogs. Using density functional theory calculations we demonstrate that the chelator zinc affinities depend on how electron......-donating and -withdrawing substituents modulate the partial charges of chelating nitrogens. The zinc affinity was found to constitute the major factor for receptor potency, although the activity of some chelators deviate suggesting favorable or unfavorable interactions. Hydrophobic and halogen substituents are generally...

  20. In-vivo

    Science.gov (United States)

    Zhu, Timothy C; Kim, Michele M; Liang, Xing; Finlay, Jarod C; Busch, Theresa M

    2015-02-01

    Dosimetry of singlet oxygen ( 1 O 2 ) is of particular interest because it is the major cytotoxic agent causing biological effects for type-II photosensitizers during photodynamic therapy (PDT). An in-vivo model to determine the singlet oxygen threshold dose, [ 1 O 2 ] rx,sh , for PDT was developed. An in-vivo radiation-induced fibrosarcoma (RIF) tumor mouse model was used to correlate the radius of necrosis to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include five photosensitizer-specific photochemical parameters along with [ 1 O 2 ] rx,sh . Photosensitizer-specific model parameters were determined for benzoporphyrin derivative monoacid ring A (BPD) and compared with two other type-II photosensitizers, Photofrin ® and m-tetrahydroxyphenylchlorin (mTHPC) from the literature. The mean values (standard deviation) of the in-vivo [ 1 O 2 ] rx,sh are approximately 0.56 (0.26) and 0.72 (0.21) mM (or 3.6×10 7 and 4.6×10 7 singlet oxygen per cell to reduce the cell survival to 1/e) for Photofrin ® and BPD, respectively, assuming that the fraction of generated singlet oxygen that interacts with the cell is 1. While the values for the photochemical parameters (ξ, σ, g , β) used for BPD were preliminary and may need further refinement, there is reasonable confidence for the values of the singlet oxygen threshold doses. In comparison, the [ 1 O 2 ] rx,sh value derived from in-vivo mouse study was reported to be 0.4 mM for mTHPC-PDT. However, the singlet oxygen required per cell is reported to be 9×10 8 per cell per 1/ e fractional kill in an in-vitro mTHPC-PDT study on a rat prostate cancer cell line (MLL cells) and is reported to be 7.9 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC-PDT. A theoretical analysis is provided to relate the number of in-vitro singlet oxygen required per cell to reach cell killing of 1/ e to in-vivo singlet