Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers.

Science.gov (United States)

Otto, Nicola; Opatz, Till

2012-01-01

In the search for new ligands for the Ullmann diaryl ether synthesis, permitting the coupling of electron-rich aryl bromides at relatively low temperatures, 56 structurally diverse multidentate ligands were screened in a model system that uses copper iodide in acetonitrile with potassium phosphate as the base. The ligands differed largely in their performance, but no privileged structural class could be identified.

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

Directory of Open Access Journals (Sweden)

Nicola Otto

2012-07-01

Full Text Available In the search for new ligands for the Ullmann diaryl ether synthesis, permitting the coupling of electron-rich aryl bromides at relatively low temperatures, 56 structurally diverse multidentate ligands were screened in a model system that uses copper iodide in acetonitrile with potassium phosphate as the base. The ligands differed largely in their performance, but no privileged structural class could be identified.

Synthesis and Doping of Ligand-Protected Atomically-Precise Metal Nanoclusters

KAUST Repository

Aljuhani, Maha A.

2016-05-01

Rapidly expanding research in nanotechnology has led to exciting progress in a versatile array of applications from medical diagnostics to catalysis. This success resulted from the manipulation of the desired properties of nanomaterials by controlling their size, shape, and composition. Among the most thriving areas of research about nanoparticle is the synthesis and doping of the ligand-protected atomically-precise metal nanoclusters. In this thesis, we developed three different novel metal nanoclusters, such as doped Ag29 with five gold (Au) atoms leading to enhance its quantum yield with remarkable stability. We also developed half-doped (alloyed) cluster of Ni6 nanocluster with molybdenum (Mo). This enabled enhanced stability and better catalytic activity. The third metal nanocluster that we synthesized was Au28 nanocluster by using di-thiolate as the ligand stabilizer instead of mono-thiolate. The new metal clusters obtained have been characterized by spectroscopic, electrochemical and crystallographic methods.

Synthesis of symmetrical and non-symmetrical bivalent neurotransmitter ligands

DEFF Research Database (Denmark)

Stuhr-Hansen, Nicolai; Andersen, Jacob; Thygesen, Mikkel Boas

2016-01-01

A novel procedure for synthesis of bivalent neurotransmitter ligands was developed by reacting O-benzyl protected N-nosylated dopamine and serotonin with alkyl- or PEG-linked diols under Fukuyama-Mitsunobu conditions in the presence of DIAD/PPh3 generating three different bivalent neurotransmitte...

Design and synthesis of a tetradentate '3-amine-1-carboxylate' ligand to mimic the metal binding environment at the non-heme iron(II) oxidase active site.

Science.gov (United States)

Dungan, Victoria J; Ortin, Yannick; Mueller-Bunz, Helge; Rutledge, Peter J

2010-04-07

Non-heme iron(II) oxidases (NHIOs) catalyse a diverse array of oxidative chemistry in Nature. As part of ongoing efforts to realize biomimetic, iron-mediated C-H activation, we report the synthesis of a new 'three-amine-one-carboxylate' ligand designed to complex with iron(II) and mimic the NHIO active site. The tetradentate ligand has been prepared as a single enantiomer in nine synthetic steps from N-Cbz-L-alanine, pyridine-2,6-dimethanol and diphenylamine, using Seebach oxazolidinone chemistry to control the stereochemistry. X-Ray crystal structures are reported for two important intermediates, along with variable temperature NMR experiments to probe the hindered interconversion of conformational isomers of several key intermediates, 2,6-disubstituted pyridine derivatives. The target ligand and an N-Cbz-protected precursor were each then complexed with iron(II) and tested for their ability to promote alkene dihydroxylation, using hydrogen peroxide as the oxidant.

Synthesis of novel '4+1' Tc(III)/Re(III) mixed-ligand complexes with dendritically modified ligands

International Nuclear Information System (INIS)

Gniazdowska, E.; Kuenstler, J.U.; Stephan, H.; Pietzsch, H.J.

2006-01-01

Coordination chemistry of technetium and rhenium attracts a considerable interest due to the nuclear medicine applications of their radionuclides. Inert, so-called '3+1' or '4+1' technetium/rhenium mixed-ligand complexes open a new way to application of 99 mTc/ 188 Re labeled compounds in tumor diagnosis and therapy. In the presented paper, authors describe the synthesis and study of novel 99 mTc/ 188 Re complexes with dendritically functionalized tetradentate (tripodal chelator 2,2',2''-nitrilotris(ethanethiol), NS 3 and carboxyl group-bearing ligand, NS 3 (COOH) 3 ) and monodentate (dendritically modified isocyanide, CN-R(COOMe) 3 and isocyanide-modified peptide, CN-GGY) ligands. To verify the identity of the prepared n.c.a. complexes, non-radioactive analogous '4+1' Re compounds were synthesized. The experimental data show that a dendritic modification of the tetradentate/monodentate ligands changes the complex lipophilicity and does not influence its stability

Synthesis of n.c.a. 18F-fluorinated NMDA- and D4-receptor ligands via [18F]fluorobenzenes

International Nuclear Information System (INIS)

Ludwig, T.

2005-11-01

In this thesis new strategies were developed and evaluated for the no-carrier-added (n.c.a.) 18 F-labelling of receptor ligands as radiodiagnostics for characterization of brain receptors using positron-emission-tomography (PET). Special emphasis was placed on the synthesis of n.c.a. (±)-3-(4-hydroxy-4-(4-[ 18 F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol, a ligand with high affinity for the NR2B subtype of NMDA receptors and n.c.a. (3-(4-[ 18 F]fluorphenoxy)propyl)-(2-(4-tolylphenoxy)ethyl)amine ([ 18 F]FPTEA) a dopamine D 4 receptor ligand. In order to synthesize n.c.a. (±)-3-(4-hydroxy-4-(4-[ 18 F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol the 18 F-fluoroarylation method via metallorganic intermediates was modified and improved. The suitability of the organometallic 18 F-fluoroarylation agents was proven with several model compounds. High radiochemical yields of 20-30% were obtained also with piperidinone-derivatives. The preparation of a suitable precursor for the synthesis of the NMDA receptor ligand, however, could not be achieved by synthesis of appropriate 1,3-dioxolane protected piperidinone derivatives. Further, the synthesis of n.c.a. ([ 18 F]fluoroaryloxy)alkylamines via n.c.a. 4-[ 18 F]fluorophenol was developed and evaluated. The synthesis of n.c.a. [ 18 F]fluoroarylethers with corresponding model compounds was optimized and led to a radiochemical yield of 25-60%, depending on the alkylhalide used. The preparation of n.c.a. 1-(3-bromopropoxy)-4-[ 18 F]fluorobenzene proved advantageous in comparison to direct use of 4-[ 18 ]fluorophenol for coupling with a corresponding N-protected precursor for the synthesis of n.c.a. [ 18 F]FPTEA. With regard to the radiochemical yields and the loss of activity during the synthesis and isolation of n.c.a. 4-[ 18 F]fluorophenol and n.c.a. 1-(3-bromopropoxy)-4-[ 18 F]fluorobenzene, [ 18 F]FPTEA was obtained by reaction with 2-(4-tolyloxy)ethylamine in radiochemical yields of about 25-30% in ethanol or 2-butanone

A modular approach to neutral P,N-ligands: synthesis and coordination chemistry

Directory of Open Access Journals (Sweden)

Vladislav Vasilenko

2016-04-01

Full Text Available We report the modular synthesis of three different types of neutral κ2-P,N-ligands comprising an imine and a phosphine binding site. These ligands were reacted with rhodium, iridium and palladium metal precursors and the structures of the resulting complexes were elucidated by means of X-ray crystallography. We observed that subtle changes of the ligand backbone have a significant influence on the binding geometry und coordination properties of these bidentate P,N-donors.

Synthesis and Doping of Ligand-Protected Atomically-Precise Metal Nanoclusters

KAUST Repository

Aljuhani, Maha A.

2016-01-01

by controlling their size, shape, and composition. Among the most thriving areas of research about nanoparticle is the synthesis and doping of the ligand-protected atomically-precise metal nanoclusters. In this thesis, we developed three different novel metal

Cell-free H-cluster synthesis and [FeFe] hydrogenase activation: all five CO and CN⁻ ligands derive from tyrosine.

Directory of Open Access Journals (Sweden)

Jon M Kuchenreuther

Full Text Available [FeFe] hydrogenases are promising catalysts for producing hydrogen as a sustainable fuel and chemical feedstock, and they also serve as paradigms for biomimetic hydrogen-evolving compounds. Hydrogen formation is catalyzed by the H-cluster, a unique iron-based cofactor requiring three carbon monoxide (CO and two cyanide (CN⁻ ligands as well as a dithiolate bridge. Three accessory proteins (HydE, HydF, and HydG are presumably responsible for assembling and installing the H-cluster, yet their precise roles and the biosynthetic pathway have yet to be fully defined. In this report, we describe effective cell-free methods for investigating H-cluster synthesis and [FeFe] hydrogenase activation. Combining isotopic labeling with FTIR spectroscopy, we conclusively show that each of the CO and CN⁻ ligands derive respectively from the carboxylate and amino substituents of tyrosine. Such in vitro systems with reconstituted pathways comprise a versatile approach for studying biosynthetic mechanisms, and this work marks a significant step towards an understanding of both the protein-protein interactions and complex reactions required for H-cluster assembly and hydrogenase maturation.

Room-temperature sol–gel synthesis of organic ligand-capped ZnO nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Zobel, Mirijam, E-mail: mirijam.zobel@fau.de; Chatterjee, Haimantee [Friedrich-Alexander University Erlangen-Nürnberg (FAU), Department of Physics, Lehrstuhl für Kristallographie und Strukturphysik (Germany); Matveeva, Galina; Kolb, Ute [Johannes Gutenberg-Universität, Institut für Physikalische Chemie (Germany); Neder, Reinhard B., E-mail: reinhard.neder@fau.de [Friedrich-Alexander University Erlangen-Nürnberg (FAU), Department of Physics, Lehrstuhl für Kristallographie und Strukturphysik (Germany)

2015-05-15

Powders of zinc oxide nanoparticles with individual particle sizes below 10 nm in diameter are readily produced in base-induced sol–gel processes from ethanolic solutions of zinc acetate dihydrate. These particles are covered with acetate molecules and without further stabilization, they grow when stored as a powder. Here, we present three organic ligands, which reproducibly stabilize individual particle sizes <5 nm within the agglomerated powders for extended periods of time, up to months. Citric acid and 1,5-diphenyl-1,3,5-pentanetrione result in average diameters of 3 nm, whereas dimethyl-L-tartrate stabilizes 2.1 nm. X-ray diffraction and pair distribution function analysis were used to investigate the structural properties of the particles. TEM data confirm the individual particle size and crystallinity and show that the particles are agglomerated without structural coherence. Besides the introduction of these novel ligands for ZnO nanoparticles, we investigated, in particular, the influence of each synthesis step onto the final nanoparticle size in the powder. Previous studies often reported the employed synthesis parameters, but did not motivate the reasoning for their choice based on detailed experimental observations. Herein, we regard separately the steps of (i) the synthesis of the colloids, (ii) their precipitation, and (iii) the drying of the resulting gel to understand the role of the ligands therein. ZnO particles only covered with acetate grow to 5 nm during the drying process, whereas particles with any of the additional ligands retain their colloidal size of 2–3 nm. This clearly shows the efficient binding and effect of the presented ligands.

Role of Carboxylate ligands in the Synthesis of AuNPs: Size Control, Molecular Interaction and Catalytic Activity

KAUST Repository

Aljohani, Hind Abdullah

2016-05-22

low temperature. The structure of the citrate layer on the AuNP surface may be a key factor in gaining a more detailed understanding of nanoparticle formation and stabilization. This can be affecting the catalytic activity. These thoughts invited us to systematically examine the role of sodium citrate as a stabilizer of gold nanoparticles, which is the main theme of this thesis. This research is focused on three main objectives, controlling the size of the gold nanoparticles based on citrate (and other carboxylate ligands Trisodium citrate dihydrate, Isocitric Acid, Citric acid, Trimesic acid, Succinic Acid, Phthalic acid, Disodium glutarate, Tartaric Acid, Sodium acetate, Acetic Acid and Formic Acid by varying the concentration of Gold/sodium citrate, investigating the interaction of the citrate layer on the AuNP surface, and testing the activity of the Au/TiO2 catalysts for the oxidation of carbon monoxide. This thesis will be divided into five chapters. In Chapter 1, a general literature study on the various applications and methods of synthesis of Au nanoparticles is described. Then we present the main synthetic pathways of Au nanoparticles we selected. A part of the bibliographic study was given to the use of Au nanoparticles in catalysis. In Chapter 2, we give a brief description of the different experimental procedures and characterization techniques utilized over the course of the present work. The study of the size control and the interaction between gold nanoparticles and the stabilizer (carboxylate groups) was achieved by using various characterization techniques such as UV-visible spectroscopy, Transmission Electron Microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Nuclear Magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FTIR). In Chapter 3, we discuss the synthesis and size control of Au nanoparticles by following the growth of these nanoparticles by UV-Visible spectroscopy and TEM. We

Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-α

International Nuclear Information System (INIS)

Lee, Ji Hae; Jun, Hee-jin; Hoang, Minh-Hien; Jia, Yaoyao; Han, Xiang Hua; Lee, Dong-Ho; Lee, Hak-Ju; Hwang, Bang Yeon; Lee, Sung-Joon

2012-01-01

Highlights: ► Catalposide is a novel ligand for PPARα. ► Cell stimulated with catalposide improved fatty acid uptake, regulated target genes in fatty acid β-oxidation and synthesis. ► Catalposdie reduces hepatic triacylglycerides. ► Theses demonstrate catalposide could ameliorate hyperlipidemia and hepatic steatosis. -- Abstract: Peroxisome proliferator-activated receptor-alpha (PPARα) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPARα agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPARα agonist, identified from reporter gene assay-based activity screening with approximately 900 natural plant and seaweed extracts. Results of time-resolved fluorescence resonance energy transfer analyses suggested that the compound interacted directly with the ligand-binding domain of PPARα. Cultured hepatocytes stimulated with catalposide exhibited significantly reduced cellular triglyceride concentrations, by 21%, while cellular uptake of fatty acids was increased, by 70% (P < 0.05). Quantitative PCR analysis revealed that the increase in cellular fatty acid uptake was due to upregulation of fatty acid transporter protein-4 (+19% vs. the control) in cells stimulated with catalposide. Additionally, expression of genes related to fatty acid oxidation and high-density lipoprotein metabolism were upregulated, while that of genes related to fatty acid synthesis were suppressed. In conclusion, catalposide is hypolipidemic by activation of PPARα via a ligand-mediated mechanism that modulates the expression of in lipid metabolism genes in hepatocytes.

Template synthesis, characterization and antimicrobial activity of some new complexes with isonicotinoyl hydrazone ligands

Directory of Open Access Journals (Sweden)

LIVIU MITU

2009-09-01

Full Text Available Complexes of Cu(II, Ni(II, Co(II with the 9-anthraldehyde iso-nicotinoyl hydrazone ligand (HL1 and the 3,5-di-tert-butyl-4-hydroxy-benzaldehyde isonicotinoyl hydrazone ligand (H2L2 were synthesized by the template method. The complexes were characterized by analytical analysis, IR, UV-Vis and ESR spectroscopy, magnetic measurements, conductometry and thermal analysis and the two ligands by 1H-NMR spectroscopy. From the elemental analysis, 1:2 (metal:ligand stoichiometry for the complexes of Cu(II, Ni(II with the ligands HL1 and H2L2 and 1:1 (metal:ligand stoichiometry for the complex of Co(II with the ligand HL1 are proposed. The molar conductance data showed that the complexes are non-electrolytes. The magnetic susceptibility results coupled with the electronic and ESR spectra suggested a distorted octahedral geometry for the complexes Ni(II/HL1, Ni(II/H2L2 and Cu(II/H2L2, a tetrahedral stereochemistry for the complex Cu/HL1 and a square-planar geometry for the complex Co/HL1. The IR spectra demonstrated the bidentate coordination of the ligands HL1 and H2L2 by the O=C amide oxygen and the azomethine nitrogen, as well as monodentate coordination of the ligand HL1 by the azomethine nitrogen in the Cu(IIcomplex. The antibacterial activity of the ligands and their metallic complexes were tested against Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae.

Synthesis and evaluation of potential ligands for nuclear waste processing

NARCIS (Netherlands)

Iqbal, M.

2012-01-01

The research presented in this thesis deals with the synthesis and evaluation of new potential ligands for the complexation of actinide and lanthanide ions either for their extraction from bulk radioactive waste or their stripping from an extracted organic phase for final processing of the waste. In

Synthesis and Crystal Structures of Two Metal Complexes Incorporating Malonate and Organodiamine Ligands

International Nuclear Information System (INIS)

Zhang, Quan Zheng; Yang, Wen Bin; Chen, Shu Mei; Lu, Can Zhong

2005-01-01

In the present work we report the synthesis and X-ray crystal structures of two new malonato complexes incorporating organodiamine ligands: [Ni(phen)(mal)(H_2O)_2]·3H_2O (H_2mal = malonic acid, phen = 1,10-phenanthroline) and [Zn(bpy)(H_2O)]_2[Zn(bpy)(mal)(H_2O)_2]_2(NO_3)_4·4H_2O (bpy = 2,2'-bipyridine). Investigation on novel organic-inorganic hybrid framework assemblies represents one of the most active areas of material science and chemical research. Major advances have been made in these materials due to their interesting properties and potential in various applications, e. g., electrical conductivity, magnetism, host-guest chemistry, ion exchange, catalysis, nonlinear optics, etc. Moreover, discovery and design of such new materials with specific networks remain of a particularly important and active subject in the field of supramolecuar chemistry and crystal engineering. A variety of complexes with interesting compositions and topologies have been prepared through taking certain factors into account, such as the coordination nature of the metal ion and the shape, functionality, flexibility, and symmetry of organic ligand. Recently, some dicarboxylate ligands, such as oxalate, malonate, and terephthalate, have been widely used in the construction of these interesting structures

The synthesis, structures and characterisation of new mixed-ligand manganese and iron complexes with tripodal, tetradentate ligands

NARCIS (Netherlands)

van Gorkum, R.; Berding, J.; Mills, A.M.; Kooijman, H.; Tooke, D.M.; Spek, A.L.; Mutikainen, I.; Turpeinen, U.; Reedijk, J.; Bouwman, E.

2008-01-01

The preparation of new manganese and iron complexes with the general formula [M(tripod)(anion)] is described, where M = FeIII or MnIII, “tripod” is a dianionic tetradentate tripodal ligand and the anion is a chelating β-diketonate, 8-oxyquinoline or acetate. The synthesis of this type of complexes

Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-{alpha}

Energy Technology Data Exchange (ETDEWEB)

Lee, Ji Hae; Jun, Hee-jin; Hoang, Minh-Hien; Jia, Yaoyao [Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Han, Xiang Hua [College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Lee, Dong-Ho [Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Lee, Hak-Ju [Division of Green Business Management, Department of Forest Resources Utilization, Korean Forest Research Institute, Seoul 130-712 (Korea, Republic of); Hwang, Bang Yeon, E-mail: byhwang@chungbuk.ac.kr [College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Lee, Sung-Joon, E-mail: junelee@korea.ac.kr [Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

2012-06-15

Highlights: Black-Right-Pointing-Pointer Catalposide is a novel ligand for PPAR{alpha}. Black-Right-Pointing-Pointer Cell stimulated with catalposide improved fatty acid uptake, regulated target genes in fatty acid {beta}-oxidation and synthesis. Black-Right-Pointing-Pointer Catalposdie reduces hepatic triacylglycerides. Black-Right-Pointing-Pointer Theses demonstrate catalposide could ameliorate hyperlipidemia and hepatic steatosis. -- Abstract: Peroxisome proliferator-activated receptor-alpha (PPAR{alpha}) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPAR{alpha} agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPAR{alpha} agonist, identified from reporter gene assay-based activity screening with approximately 900 natural plant and seaweed extracts. Results of time-resolved fluorescence resonance energy transfer analyses suggested that the compound interacted directly with the ligand-binding domain of PPAR{alpha}. Cultured hepatocytes stimulated with catalposide exhibited significantly reduced cellular triglyceride concentrations, by 21%, while cellular uptake of fatty acids was increased, by 70% (P < 0.05). Quantitative PCR analysis revealed that the increase in cellular fatty acid uptake was due to upregulation of fatty acid transporter protein-4 (+19% vs. the control) in cells stimulated with catalposide. Additionally, expression of genes related to fatty acid oxidation and high-density lipoprotein metabolism were upregulated, while that of genes related to fatty acid synthesis were suppressed. In conclusion, catalposide is hypolipidemic by activation of PPAR{alpha} via a ligand-mediated mechanism that modulates the expression of in lipid metabolism genes in hepatocytes.

Synthesis of heterocycles: Indolo (2,1-a) isoquinolines, renewables, and aptamer ligands for cellular imaging

Energy Technology Data Exchange (ETDEWEB)

Beasley, Jonathan [Ames Laboratory (AMES), Ames, IA (United States)

2013-01-01

In this thesis, we explore both total syntheses and methodologies of several aromatic heterocyclic molecules. Extensions of the Kraus indole synthesis toward 2-substituted and 2,3-disubstituted indoles, as well as biologically attractive indolo[2,1-a]isoquinolines are described. Recent renewable efforts directed to commodity maleic acid and the first reported furan-based ionic liquids are described. Our total synthesis of mRNA aptamer ligand PDC-Gly, and its dye coupled forms, plus aminoglycoside dye coupled ligands used in molecular imaging, are described.

Synthesis, Structural Characterization and Antimicrobial Activity of Cu(II and Fe(III Complexes Incorporating Azo-Azomethine Ligand

Directory of Open Access Journals (Sweden)

Mohammad Azam

2018-04-01

Full Text Available We are reporting a novel azo-azomethine ligand, HL and its complexes with Cu(II and Fe(III ions. The ligand and its complexes are characterized by various physico-chemical techniques using C,H,N analyses, FT-IR, 1H-NMR, ESI-MS and UV-Vis studies. TGA analyses reveal complexes are sufficiently stable and undergo two-step degradation processes. The redox behavior of the complexes was evaluated by cyclic voltammetry. Furthermore, the ligand and its complexes were tested for antimicrobial activity against bacterial and fungal strains by determining inhibition zone, minimal inhibitory concentration (MIC and minimal bactericidal concentration (MBC. The complexes showed moderate antimicrobial activity when tested against Gram +ve and Gram −ve bacterial strains. To obtain insights into the structure of ligand, DFT studies are recorded. The results obtained are quite close to the experimental results. In addition, the energy gap, chemical hardness, softness, electronegativity, electrophilic index and chemical potential were calculated using HOMO, LUMO energy value of ligand.

Synthesis, structural characterization and antitumor activity of a Ca(II) coordination polymer based on 4-formyl-1,3-benzenedisulfonate-2-furoic acid hydrazide ligands

Energy Technology Data Exchange (ETDEWEB)

Tai, Xi-Shi, E-mail: taixs@wfu.edu.cn [Weifang University, College of Chemistry and Chemical Engineering (China); Wang, Xin [Qinghai Normal University, Department of Chemistry (China)

2017-03-15

A new Ca(II) coordination polymer, ([CaL(H{sub 2}O){sub 4}] · (H{sub 2}O){sub 4}){sub n} (L = 4-formyl-1,3-benzenedisulfonate-2-furoic acid hydrazide) has been prepared by one-pot synthesis method. And it was characterized by elemental analysis, IR and thermal analysis. The result of X-ray single-crystal diffraction analysis shows that the Ca(II) complex molecules form one-dimensional chain structure by the bridging oxygen atoms. The anti-tumor activity of L ligand and the Ca(II) coordination polymer has also been studied.

Ligand-protected gold clusters: the structure, synthesis and applications

Science.gov (United States)

Pichugina, D. A.; Kuz'menko, N. E.; Shestakov, A. F.

2015-11-01

Modern concepts of the structure and properties of atomic gold clusters protected by thiolate, selenolate, phosphine and phenylacetylene ligands are analyzed. Within the framework of the superatom theory, the 'divide and protect' approach and the structure rule, the stability and composition of a cluster are determined by the structure of the cluster core, the type of ligands and the total number of valence electrons. Methods of selective synthesis of gold clusters in solution and on the surface of inorganic composites based, in particular, on the reaction of Aun with RS, RSe, PhC≡C, Hal ligands or functional groups of proteins, on stabilization of clusters in cavities of the α-, β and γ-cyclodextrin molecules (Au15 and Au25) and on anchorage to a support surface (Au25/SiO2, Au20/C, Au10/FeOx) are reviewed. Problems in this field are also discussed. Among the methods for cluster structure prediction, particular attention is given to the theoretical approaches based on the density functional theory (DFT). The structures of a number of synthesized clusters are described using the results obtained by X-ray diffraction analysis and DFT calculations. A possible mechanism of formation of the SR(AuSR)n 'staple' units in the cluster shell is proposed. The structure and properties of bimetallic clusters MxAunLm (M=Pd, Pt, Ag, Cu) are discussed. The Pd or Pt atom is located at the centre of the cluster, whereas Ag and Cu atoms form bimetallic compounds in which the heteroatom is located on the surface of the cluster core or in the 'staple' units. The optical properties, fluorescence and luminescence of ligand-protected gold clusters originate from the quantum effects of the Au atoms in the cluster core and in the oligomeric SR(AuSR)x units in the cluster shell. Homogeneous and heterogeneous reactions catalyzed by atomic gold clusters are discussed in the context of the reaction mechanism and the nature of the active sites. The bibliography includes 345 references.

Pharmaceutical research at the AAEC Part I: Ligand synthesis and biological studies

Energy Technology Data Exchange (ETDEWEB)

Wilson, J G [Australian Atomic Energy Commission Research Establishment, Lucas Heights

1982-09-01

Work on the synthesis of ligands capable of forming chelate complexes with technetium-99m as part of a search for tumour-localising radiopharmaceuticals is described. An account of the biological evaluation of a range of these compounds, in particular, benzimidazoles, sulphanilamides and acridines, and of the investigation of certain biochemical and biological properties affecting the clinical application of both ligands and radiopharmaceuticals is given. Interactions between therapeutic drugs and diagnostic radiopharmaceuticals are considered. The toxicological evaluation of a prospective hepatobiliary imaging agent, dimethyl-BIMIDA, is described.

Synthesis, physico-chemical properties and complexing abilities of new amphiphilic ligands from D-galacturonic acid.

Science.gov (United States)

Allam, Anas; Behr, Jean-Bernard; Dupont, Laurent; Nardello-Rataj, Véronique; Plantier-Royon, Richard

2010-04-19

This paper describes a convenient and efficient synthesis of new complexing surfactants from d-galacturonic acid and n-octanol as renewable raw materials in a two-step sequence. In the first step, simultaneous O-glycosidation-esterification under Fischer conditions was achieved. The anomeric ratio of the products was studied based on the main experimental parameters and the activation mode (thermal or microwave). In the second step, aminolysis of the n-octyl ester was achieved with various functionalized primary amines under standard thermal or microwave activation. The physico-chemical properties of these new amphiphilic ligands were measured and these compounds were found to exhibit interesting surface properties. Complexing abilities of one uronamide ligand functionalized with a pyridine moiety toward Cu(II) ions was investigated in solution by EPR titrations. A solid compound was also synthesized and characterized, its relative structure was deduced from spectroscopic data. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Electrochemical synthesis of transition element complexes with carboxyl- and carbonyl-containing ligands

International Nuclear Information System (INIS)

Frolov, V.Yu.; Bolotin, S.N.; Panyushkin, V.T.

2005-01-01

Complexes of d- and f-elements (E = Cu, Ni, Zn, Nd, Tb, Pr, Gd, Er) with carboxyl- and carbonyl-containing ligands were synthesized by the electrochemical method. The products were characterized by elemental analysis, thermal gravimetric analysis and IR spectra. The influence exerted by a number of factors on the process course was studied. The dependence of the electro synthesis parameters on the composition of the forming compounds was established. A new method for anodic synthesis of these compounds was developed [ru

A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

KAUST Repository

Li, Huaifeng

2014-12-01

Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands\\' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

KAUST Repository

Li, Huaifeng; Zheng, Bin; Huang, Kuo-Wei

2014-01-01

Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

Synthesis of ligand-free CZTS nanoparticles via a facile hot injection route

DEFF Research Database (Denmark)

Mirbagheri, Naghmehalsadat; Engberg, Sara Lena Josefin; Crovetto, Andrea

2016-01-01

and toxic solvents that otherwise could hinder grain growth and limit the deposition techniques. In addition the synthesis route presented here results in nanoparticles of a large size compared to other ligand-free CZTS nanoparticles, due to the high boiling point of the solvents selected. Large particle...

Redox-​Active Ligand-​Induced Homolytic Bond Activation

NARCIS (Netherlands)

Broere, D.L.J.; Metz, L.L.; de Bruin, B.; Reek, J.N.H.; Siegler, M.A.; van der Vlugt, J.I.

2015-01-01

Coordination of the novel redox-​active phosphine-​appended aminophenol pincer ligand (PNOH2) to PdII generates a paramagnetic complex with a persistent ligand-​centered radical. The complex undergoes fully reversible single-​electron oxidn. and redn. Homolytic bond activation of diphenyldisulfide

Synthesis and complexation of acyclic dithiolate ligands

International Nuclear Information System (INIS)

Ashford, L.

1999-11-01

-[N,N'-bis(p-nitro-o-mereaptobenzyliden)propylenediaminate, Copper- [N,N'-bis(p-nitro-o-mercaptobenzyliden)propylenediaminate and Nickel-[N,N'-bis(o-mercaptobenzyliden)propylenediaminate] are analysed. Comparison of the data of the Ni(II) species show the major effects of the para-nitro group arise from electron withdrawal from the thiolate donors. The synthesis and complexation of the (2-mercaptomethyl)thiophenolato series of ligands, via the corresponding (2-hydroxymethyl)thiophenolato compounds, is detailed. Removal of β-elimination pathways by use of an o-xylyl linker allows the synthesis of α,α'-di[(2-mercaptomethyl)thiophenolato]-o-xylene. Reaction of α,α'-di[(2-mercaptomethyl)thiophenolato]-o-xylene with Group 10 metal ions Ni(II) and Pd(ll) monomers and a Pt(ll) trinuclear complex. Potential causes of the broad and featureless resonances in the 1 H NMR spectra of the complexes are investigated. The Ni(II) and Pd(ll) monomers are reacted with Pt(ll) salts to give trinuclear species. (author)

Ligand-protected gold clusters: the structure, synthesis and applications

International Nuclear Information System (INIS)

Pichugina, D A; Kuz'menko, N E; Shestakov, A F

2015-01-01

Modern concepts of the structure and properties of atomic gold clusters protected by thiolate, selenolate, phosphine and phenylacetylene ligands are analyzed. Within the framework of the superatom theory, the 'divide and protect' approach and the structure rule, the stability and composition of a cluster are determined by the structure of the cluster core, the type of ligands and the total number of valence electrons. Methods of selective synthesis of gold clusters in solution and on the surface of inorganic composites based, in particular, on the reaction of Au n with RS, RSe, PhC≡C, Hal ligands or functional groups of proteins, on stabilization of clusters in cavities of the α-, β and γ-cyclodextrin molecules (Au 15 and Au 25 ) and on anchorage to a support surface (Au 25 /SiO 2 , Au 20 /C, Au 10 /FeO x ) are reviewed. Problems in this field are also discussed. Among the methods for cluster structure prediction, particular attention is given to the theoretical approaches based on the density functional theory (DFT). The structures of a number of synthesized clusters are described using the results obtained by X-ray diffraction analysis and DFT calculations. A possible mechanism of formation of the SR(AuSR) n 'staple' units in the cluster shell is proposed. The structure and properties of bimetallic clusters M x Au n L m (M=Pd, Pt, Ag, Cu) are discussed. The Pd or Pt atom is located at the centre of the cluster, whereas Ag and Cu atoms form bimetallic compounds in which the heteroatom is located on the surface of the cluster core or in the 'staple' units. The optical properties, fluorescence and luminescence of ligand-protected gold clusters originate from the quantum effects of the Au atoms in the cluster core and in the oligomeric SR(AuSR) x units in the cluster shell. Homogeneous and heterogeneous reactions catalyzed by atomic gold clusters are discussed in the context of the reaction mechanism and the nature of the active

Transition metal complexes of some biologically active ligands; synthesis characterization and bioactivities

International Nuclear Information System (INIS)

Rehman, S.; Ali, N.; Nisar, M.

2009-01-01

Transition/representative transition metals complexes of biologically active chelating agent 1,2-dipyrolodinoethane were synthesized and characterized through spectral and analytical data. The complexes are of the formula (M(L)X/sub 2/). Where (M = Co (II), Ni (II), Cu (II), Zn (II), Hg (II) and Cd (II) and X = CI, Br, NO/sub 3/). Tetrahedral geometry has been proposed to these-metal complexes with the help of magnetic measurements, elemental analysis, chemical stoichiometry and spectroscopic data Antibacterial activity of the ligand and its metal complexes were screened against Eschereschi coli, Klebsiello pneumonia, Proteus mirabilis, Proteus vulhari, Streptococcus pneumonia, Salmonella Iyphi, Bacilh,s anthrax, Streptococcus fecalis and Staphylococcus aureus. Complexes were found to be active against Eschereschi coli, Klebsiella pneumonia, Proteus mirabilis and Proteus vulharis. (author)

Synthesis, characterization and biological activity of symmetric dinuclear complexes derived from a novel macrocyclic compartmental ligand

Energy Technology Data Exchange (ETDEWEB)

Mruthyunjayaswamy, B.H.M.; Ijare, Omkar B.; Jadegoud, Y. [Gulbarga University (India). Dept. of Chemistry]. E-mail: bhmmswamy53@rediffmail.com

2005-07-15

A phenol based novel macrocyclic binucleating compartmental ligand N,N-bis(2,6-diiminomethyl-4-methyl-1-hydroxyphenyl)malonoyldicarboxamide was prepared. The complexes were prepared by template method by reacting 2,6-diformyl-4-methylphenol, malonoyl dihydrazide and the metal chlorides of Cu(II), Ni(II), Co(II), Cd(II), Zn(II) and Hg(II) in methanol to get a series of dinuclear complexes. The complexes were characterized by elemental analyses, conductivity measurements, magnetic susceptibility data, IR, UV-Vis, ESR, NMR and FAB mass spectral data. The dinuclear nature of the complexes was confirmed on the basis of elemental analyses, magnetic susceptibility, ESR and FAB mass spectral data. The ligand as well as Cu(II), Ni(II), Co(II) and Zn(II) complexes were tested for their antibacterial and antifungal properties against Escherichia coli, Staphyloccocus aureus, Aspergillus niger and Fusarium oxysporum. Magnetic susceptibility measurements of Cu(II), Ni(II) and Co(II) complexes reveal that these complexes exhibit antiferromagnetic coupling behavior due to the presence of two metal ions in close proximity. FAB mass spectrum of the Cu(II) complex gave a clear evidence for the dinuclear nature. The ligand and the complexes were found to be less active against the tested bacteria, but the ligand alone was found active against the fungus Fusarium oxysporum. (author)

Synthesis, characterization and biological activity of symmetric dinuclear complexes derived from a novel macrocyclic compartmental ligand

International Nuclear Information System (INIS)

Mruthyunjayaswamy, B.H.M.; Ijare, Omkar B.; Jadegoud, Y.

2005-01-01

A phenol based novel macrocyclic binucleating compartmental ligand N,N-bis(2,6-diiminomethyl-4-methyl-1-hydroxyphenyl)malonoyldicarboxamide was prepared. The complexes were prepared by template method by reacting 2,6-diformyl-4-methylphenol, malonoyl dihydrazide and the metal chlorides of Cu(II), Ni(II), Co(II), Cd(II), Zn(II) and Hg(II) in methanol to get a series of dinuclear complexes. The complexes were characterized by elemental analyses, conductivity measurements, magnetic susceptibility data, IR, UV-Vis, ESR, NMR and FAB mass spectral data. The dinuclear nature of the complexes was confirmed on the basis of elemental analyses, magnetic susceptibility, ESR and FAB mass spectral data. The ligand as well as Cu(II), Ni(II), Co(II) and Zn(II) complexes were tested for their antibacterial and antifungal properties against Escherichia coli, Staphyloccocus aureus, Aspergillus niger and Fusarium oxysporum. Magnetic susceptibility measurements of Cu(II), Ni(II) and Co(II) complexes reveal that these complexes exhibit antiferromagnetic coupling behavior due to the presence of two metal ions in close proximity. FAB mass spectrum of the Cu(II) complex gave a clear evidence for the dinuclear nature. The ligand and the complexes were found to be less active against the tested bacteria, but the ligand alone was found active against the fungus Fusarium oxysporum. (author)

Copper(II) Complexes of Phenanthroline and Histidine Containing Ligands: Synthesis, Characterization and Evaluation of their DNA Cleavage and Cytotoxic Activity.

Science.gov (United States)

Leite, Sílvia M G; Lima, Luís M P; Gama, Sofia; Mendes, Filipa; Orio, Maylis; Bento, Isabel; Paulo, António; Delgado, Rita; Iranzo, Olga

2016-11-21

Copper(II) complexes have been intensely investigated in a variety of diseases and pathological conditions due to their therapeutic potential. The development of these complexes requires a good knowledge of metal coordination chemistry and ligand design to control species distribution in solution and tailor the copper(II) centers in the right environment for the desired biological activity. Herein we present the synthesis and characterization of two ligands HL1 and H 2 L2 containing a phenanthroline unit (phen) attached to the amino group of histidine (His). Their copper(II) coordination properties were studied using potentiometry, spectroscopy techniques (UV-vis and EPR), mass spectrometry (ESI-MS) and DFT calculations. The data showed the formation of single copper complexes, [CuL1] + and [CuL2], with high stability within a large pH range (from 3.0 to 9.0 for [CuL1] + and from 4.5 to 10.0 for [CuL2]). In both complexes the Cu 2+ ion is bound to the phen unit, the imidazole ring and the deprotonated amide group, and displays a distorted square pyramidal geometry as confirmed by single crystal X-ray crystallography. Interestingly, despite having similar structures, these copper complexes show different redox potentials, DNA cleavage properties and cytotoxic activity against different cancer cell lines (human ovarian (A2780), its cisplatin-resistant variant (A2780cisR) and human breast (MCF7) cancer cell lines). The [CuL2] complex has lower reduction potential (E pc = -0.722 V vs -0.452 V for [CuL1] + ) but higher biological activity. These results highlight the effect of different pendant functional groups (carboxylate vs amide), placed out of the coordination sphere, in the properties of these copper complexes.

Synthesis of freestanding water-soluble indium oxide nanocrystals capped by alanine nitric acid via ligand exchange for thin film transistors and effects of ligands on the electrical properties

International Nuclear Information System (INIS)

Choi, Jin-Kyu; Koh, Ye-Seul; Jeong, Hyun-Dam

2015-01-01

We demonstrate synthesis of freestanding water-soluble indium oxide nanocrystals (In 2 O 3 NCs) by ligand exchange to β-alanine nitric acid (Ala·HNO 3 ) and its application for active channel layer in thin film transistors (TFTs), with investigation of the effect of curing temperatures on the TFT properties in terms of thermal behaviour of the ligand molecules at 150, 300, and 350 °C. After ligand exchange from long alkyl ligand (myristic acid, MA) to short Ala·HNO 3 , the mobility of NC TFTs cured at 150 °C increased by over 1 order of magnitude, from 1.3 × 10 −4 cm 2 V -1 s −1 to 4.5 × 10 −3 cm 2 V -1 s −1 , due to enhanced tunnelling rate (Γ) between adjective NCs. Higher curing temperatures such as 300 and 350 °C, inducing thermal decomposition of the organic ligands, led to further enhancement of the mobility, particularly up to 2.2 cm 2 V -1 s −1 for the In 2 O 3 NC-Ala·HNO 3 TFT cured at 350 °C. It is also found that the ligand exchange of In 2 O 3 NC in acidic condition (e.g. HNO 3 ) would be simple and effective to reduce the surface defects by surface etching, which may lead to better device performances. - Graphical abstract: Display Omitted - Highlights: • Freestanding water-soluble In 2 O 3 nanocrystals (NCs) were synthesized by ligand exchange. • Thin film transistors (TFTs) of colloidal NCs were fabricated by spin-coating method. • Water-soluble In 2 O 3 NC TFTs showed higher mobilities due to shorter ligand length. • Surface defects of NCs were notably reduced by surface etching during ligand exchange

Synthesis and Crystal Structures of Ni(II)/(III) and Zn(II) Complexes with Schiff Base Ligands

International Nuclear Information System (INIS)

Koo, Bon Kweon

2013-01-01

Coordination polymers are of great interest due to their intriguing structural motifs and potential applications in optical, electronic, magnetic, and porous materials. The most commonly used strategy for designing such materials relies on the utilization of multidentate N- or Odonor ligands which have the capacity to bridge between metal centers to form polymeric structures. The Schiff bases with N,O,S donor atoms are an useful source as they are readily available and easily form stable complexes with most transition metal ions. Schiff bases are also important intermediates in synthesis of some bioactive compounds and are potent anti-bacterial, anti-fungal, anticancer and antiviral compounds. In this work, the Schiff bases, Hapb and Hbpb, derived from 2-acetylpyridene or 2-benzoylpyridine and benzhydrazide were taken as trifunctional (N,N,O) monobasic ligand (Scheme 1). This ligand is of important because the π-delocalization of charge and the configurational flexibility of their molecular chain can give rise to a great variety of coordination modes. Although many metal.Schiff base complexes have been reported, the 1D, 2D, and 3D networks of coordination polymers linked through the bridging of ligands such as dicyanamide, N(CN) 2 - as coligand have been little published. In the process of working to extend the dimensionality of the metal-Schiff base complexes using benzilic acid as a bridging ligand, we obtained three simple metal (II)/(III) complexes of acetylpyridine/2-benzoyl pyridine based benzhydrazide ligand. Therefore, we report here the synthesis and crystal structures of the complexes

A multistep continuous-flow system for rapid on-demand synthesis of receptor ligands

DEFF Research Database (Denmark)

Petersen, Trine P; Ritzén, Andreas; Ulven, Trond

2009-01-01

A multistep continuous-flow system for synthesis of receptor ligands by assembly of three variable building blocks in a single unbroken flow is described. The sequence consists of three reactions and two scavenger steps, where a Cbz-protected diamine is reacted with an isocyanate, deprotected, an......, and reacted further with an alkylating agent....

New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-Affinity γ-Hydroxybutyrate (GHB) Binding Sites

DEFF Research Database (Denmark)

Vogensen, Stine B.; Marek, Ales; Bay, Tina

2013-01-01

3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [3H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screen...

Synthesis and characterization of a uranium(III) complex containing a redox-active 2,2'-bipyridine ligand.

Science.gov (United States)

Kraft, Steven J; Fanwick, Phillip E; Bart, Suzanne C

2010-02-01

Hydrotris(3,5-dimethylpyrazolyl)borate uranium(III) diiodide derivatives have been prepared as an entry into low-valent uranium chemistry with these ligands. The bis(tetrahydrofuran) adduct, Tp*UI(2)(THF)(2) (1) (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate), was synthesized by addition of sodium hydrotris(3,5-dimethylpyrazolyl)borate (NaTp*) to an equivalent of UI(3)(THF)(4). Addition of 2,2'-bipyridine (2,2'-bpy) to 1 displaced the THF molecules producing Tp*UI(2)(2,2'-bpy) (2). Both derivatives were characterized by (1)H NMR and IR spectroscopies, magnetic measurements, and X-ray crystallography. Reduction of both species was attempted with two equivalents of potassium graphite. The reduction of 1 did not result in a clean product, but rather decomposition and ligand redistribution. However, compound 2 was reduced to form Tp*(2)U(2,2'-bpy), 3, which is composed of a uranium(III) ion with a radical monoanionic bipyridine ligand. This was confirmed by X-ray crystallography, which revealed distortions in the bond lengths of the bipyridine consistent with reduction. Further support was obtained by (1)H NMR spectroscopy, which showed resonances shifted far upfield, consistent with radical character on the 2,2'-bipyridine ligand. Future studies will explore the reactivity of this compound as well as the consequences for redox-activity in the bipyridine ligand.

Synthesis of Alkanethiolate-Capped Metal Nanoparticles Using Alkyl Thiosulfate Ligand Precursors: A Method to Generate Promising Reagents for Selective Catalysis

Directory of Open Access Journals (Sweden)

Khin Aye San

2018-05-01

Full Text Available Evaluation of metal nanoparticle catalysts functionalized with well-defined thiolate ligands can be potentially important because such systems can provide a spatial control in the reactivity and selectivity of catalysts. A synthetic method utilizing Bunte salts (sodium S-alkylthiosulfates allows the formation of metal nanoparticles (Au, Ag, Pd, Pt, and Ir capped with alkanethiolate ligands. The catalysis studies on Pd nanoparticles show a strong correlation between the surface ligand structure/composition and the catalytic activity and selectivity for the hydrogenation/isomerization of alkenes, dienes, trienes, and allylic alcohols. The high selectivity of Pd nanoparticles is driven by the controlled electronic properties of the Pd surface limiting the formation of Pd–alkene adducts (or intermediates necessary for (additional hydrogenation. The synthesis of water soluble Pd nanoparticles using ω-carboxylate-S-alkanethiosulfate salts is successfully achieved and these Pd nanoparticles are examined for the hydrogenation of various unsaturated compounds in both homogeneous and heterogeneous environments. Alkanethiolate-capped Pt nanoparticles are also successfully synthesized and further investigated for the hydrogenation of various alkynes to understand their geometric and electronic surface properties. The high catalytic activity of activated terminal alkynes, but the significantly low activity of internal alkynes and unactivated terminal alkynes, are observed for Pt nanoparticles.

Synthesis, spectral, thermal and biological studies of mixed ligand complexes with newly prepared Schiff base and 1,10-phenanthroline ligands

Science.gov (United States)

Abd El-Halim, Hanan F.; Mohamed, Gehad G.; Khalil, Eman A. M.

2017-10-01

A series of mixed ligand complexes were prepared from the Schiff base (L1) as a primary ligand, prepared by condensation of oxamide and furan-2-carbaldehyde, and 1,10-phenanthroline (1,10-phen) as a secondary ligand. The Schiff base ligand and its mixed ligand chelates were characterized based on elemental analysis, IR, 1H NMR, thermal analysis, UV-Visible, mass, molar conductance, magnetic moment. X-ray diffraction, solid reflectance and ESR also have been studied. The mixed ligand complexes were found to have the formulae of [M(L1) (1,10-phen)]Clm.nH2O (M = Cr(III) and Fe(III) (m = 3) (n = 0); M = Mn(II), Cu(II) and Cd(II) (m = 2) (n = 0); and M = Co(II) (m = 2) (n = 1), Ni(II) (m = 2) (n = 2) and Zn(II) (m = 2) (n = 3)) and that the geometrical structure of the complexes were octahedral. The parameters of thermodynamic using Coats-Redfern and Horowitz-Metzger equations were calculated. The synthesized Schiff base ligand, 1,10-phenanthroline ligand and Their mixed ligand complexes were also investigated for their antibacterial and antifungal activity against bacterial species (Gram-Ve bacteria: Pseudomonas aeruginosa and Escherichia coli) and (Gram + Ve bacteria: Bacillus subtilis and Streptococcus pneumonia) and fungi (Aspergillus fumigates and Candida albicans). The anticancer activity of the new compounds had been tested against breast (MFC7) and colon (HCT-116) cell lines. The results showed high activity for the synthesized compounds.

Zinc acetylacetonate hydrate adducted with nitrogen donor ligands: Synthesis, spectroscopic characterization, and thermal analysis

Science.gov (United States)

Brahma, Sanjaya; Shivashankar, S. A.

2015-12-01

We report synthesis, spectroscopic characterization, and thermal analysis of zinc acetylacetonate complex adducted by nitrogen donor ligands, such as pyridine, bipyridine, and phenanthroline. The pyridine adducted complex crystallizes to monoclinic crystal structure, whereas other two adducted complexes have orthorhombic structure. Addition of nitrogen donor ligands enhances the thermal property of these complexes as that with parent metal-organic complex. Zinc acetylacetonate adducted with pyridine shows much higher volatility (106 °C), decomposition temperature (202 °C) as that with zinc acetylacetonate (136 °C, 220 °C), and other adducted complexes. All the adducted complexes are thermally stable, highly volatile and are considered to be suitable precursors for metal organic chemical vapor deposition. The formation of these complexes is confirmed by powder X-ray diffraction, Fourier transform infrared spectroscopy, mass spectroscopy, and elemental analysis. The complexes are widely used as starting precursor materials for the synthesis of ZnO nanostructures by microwave irradiation assisted coating process.

Ligand-Controlled Synthesis of Azoles via Ir-Catalyzed Reactions of Sulfoxonium Ylides with 2-Amino Heterocycles.

Science.gov (United States)

Phelps, Alicia M; Chan, Vincent S; Napolitano, José G; Krabbe, Scott W; Schomaker, Jennifer M; Shekhar, Shashank

2016-05-20

An iridium-catalyzed method was developed for the synthesis of imidazo-fused pyrrolopyrazines. The presence or absence of a nitrogenated ligand controlled the outcome of the reaction, leading to simple β-keto amine products in the absence of added ligand and the cyclized 7- and 8-substituted-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine products in the presence of ligand. This catalyst control was conserved across a variety of ylide and amine coupling partners. The substrate was shown to act as a ligand for the iridium catalyst in the absence of other ligands via NMR spectroscopy. Kinetic studies indicated that formation of the Ir-carbene was reversible and the slow step of the reaction. These mechanistic investigations suggest that the β-keto amine products form via an intramolecular carbene N-H insertion, and the imidazopyrrolopyrazines form via an intermolecular carbene N-H insertion.

Pentamethylcyclopentadienyl-rhodium and iridium complexes containing (N^N and N^O) bound chloroquine analogue ligands: synthesis, characterization and antimalarial properties.

Science.gov (United States)

Ekengard, Erik; Kumar, Kamlesh; Fogeron, Thibault; de Kock, Carmen; Smith, Peter J; Haukka, Matti; Monari, Magda; Nordlander, Ebbe

2016-03-07

The synthesis and characterization of twenty new pentamethylcyclopentadienyl-rhodium and iridium complexes containing N^N and N^O-chelating chloroquine analogue ligands are described. The in vitro antimalarial activity of the new ligands as well as the complexes was evaluated against the chloroquine sensitive (CQS) NF54 and the chloroquine resistant (CQR) Dd2 strains of Plasmodium falciparum. The antimalarial activity was found to be good to moderate; although all complexes are less active than artesunate, some of the ligands and complexes showed better activity than chloroquine (CQ). In particular, rhodium complexes were found to be considerably more active than iridium complexes against the CQS NF54 strain. Salicylaldimine Schiff base ligands having electron-withdrawing groups (F, Cl, Br, I and NO2) in para position of the salicyl moiety and their rhodium complexes showed good antiplasmodial activity against both the CQS-NF54 and the CQR-Dd2 strains. The crystal structures of (η(5)-pentamethylcyclopentadienyl){N(1)-(7-chloroquinolin-4-yl)-N(2)-(pyridin-2-ylmethyl)ethane-1,2-diamine)} chlororhodium(III) chloride and (η(5)-pentamethylcyclopentadienyl){(4-chloro-2-(((2-((7-chloroquinolin-4-yl)amino)ethyl)imino)methyl)phenolate)}chlororhodium(III) chloride are reported. The crystallization of the amino-pyridyl complex (η(5)-pentamethylcyclopentadienyl){(N(1)-(7-chloroquinolin-4-yl)-N(2)-(pyridin-2-ylmethyl)ethane-1,2-diamine)}chloroiridium(III) chloride in acetone resulted in the formation of the imino-pyridyl derivative (η(5)-pentamethylcyclopentadienyl){(N1-(7-chloroquinolin-4-yl)-N2-(pyridin-2-ylmethylene)ethane-1,2-diamine)}chloroiridium(III) chloride, the crystal structure of which is also reported.

EGFR Activation by Spatially Restricted Ligands

National Research Council Canada - National Science Library

Clouse, Katherine N; Goodrich, Jennifer S

2006-01-01

...) activity has been associated with an increased prognosis of breast cancer. During cogenesis in Drosophila melanogaster local Egfr activation by the spatially-restricted TGFalpha-like ligand Gurken (Grk...

EGFR Activation by Spatially Restricted Ligands

National Research Council Canada - National Science Library

Goodrich, Jennifer S

2005-01-01

...) activity has been associated with an increased prognosis of breast cancer. During oogenesis in Drosophila melanogaster, local EGFR activation by the spatially restricted TGF alpha-like ligand, Gurken (Grk...

Metal–organic coordination architectures of tetrazole heterocycle ligands bearing acetate groups: Synthesis, characterization and magnetic properties

International Nuclear Information System (INIS)

Hu, Bo-Wen; Zheng, Xiang-Yu; Ding, Cheng

2015-01-01

Two new coordination complexes with tetrazole heterocycle ligands bearing acetate groups, [Co(L) 2 ] n (1) and [Co 3 (L) 4 (N 3 ) 2 ·2MeOH] n (2) (L=tetrazole-1-acetate) have been synthesized and structurally characterized. Single crystal structure analysis shows that the cobalt-complex 1 has the 3D 3,6-connected (4 2 .6) 2 (4 4 .6 2 .8 8 .10)-ant topology. By introducing azide in this system, complex 2 forms the 2D network containing the [Co 3 ] units. And the magnetic properties of 1 and 2 have been studied. - Graphical abstract: The synthesis, crystal structure, and magnetic properties of the new coordination complexes with tetrazole heterocycle ligands bearing acetate groups are reported. - Highlights: • Two novel Cobalt(II) complexes with tetrazole acetate ligands were synthesized. • The magnetic properties of two complexes were studied. • Azide as co-ligand resulted in different structures and magnetic properties. • The new coordination mode of tetrazole acetate ligand was obtained.

Synthesis of freestanding water-soluble indium oxide nanocrystals capped by alanine nitric acid via ligand exchange for thin film transistors and effects of ligands on the electrical properties

Energy Technology Data Exchange (ETDEWEB)

Choi, Jin-Kyu; Koh, Ye-Seul; Jeong, Hyun-Dam, E-mail: hdjeong@chonnam.ac.kr

2015-07-15

We demonstrate synthesis of freestanding water-soluble indium oxide nanocrystals (In{sub 2}O{sub 3} NCs) by ligand exchange to β-alanine nitric acid (Ala·HNO{sub 3}) and its application for active channel layer in thin film transistors (TFTs), with investigation of the effect of curing temperatures on the TFT properties in terms of thermal behaviour of the ligand molecules at 150, 300, and 350 °C. After ligand exchange from long alkyl ligand (myristic acid, MA) to short Ala·HNO{sub 3}, the mobility of NC TFTs cured at 150 °C increased by over 1 order of magnitude, from 1.3 × 10{sup −4} cm{sup 2}V{sup -1}s{sup −1} to 4.5 × 10{sup −3} cm{sup 2}V{sup -1}s{sup −1}, due to enhanced tunnelling rate (Γ) between adjective NCs. Higher curing temperatures such as 300 and 350 °C, inducing thermal decomposition of the organic ligands, led to further enhancement of the mobility, particularly up to 2.2 cm{sup 2}V{sup -1}s{sup −1} for the In{sub 2}O{sub 3} NC-Ala·HNO{sub 3} TFT cured at 350 °C. It is also found that the ligand exchange of In{sub 2}O{sub 3} NC in acidic condition (e.g. HNO{sub 3}) would be simple and effective to reduce the surface defects by surface etching, which may lead to better device performances. - Graphical abstract: Display Omitted - Highlights: • Freestanding water-soluble In{sub 2}O{sub 3} nanocrystals (NCs) were synthesized by ligand exchange. • Thin film transistors (TFTs) of colloidal NCs were fabricated by spin-coating method. • Water-soluble In{sub 2}O{sub 3} NC TFTs showed higher mobilities due to shorter ligand length. • Surface defects of NCs were notably reduced by surface etching during ligand exchange.

Activation of peroxisome proliferator-activated receptors (PPARs) by their ligands and protein kinase A activators

Science.gov (United States)

Lazennec, Gwendal; Canaple, Laurence; Saugy, Damien; Wahli, Walter

2000-01-01

The nuclear peroxisome proliferator-activated receptors (PPARs) α, β and γ activate the transcription of multiple genes involved in lipid metabolism. Several natural and synthetic ligands have been identified for each PPAR isotype but little is known about the phosphorylation state of these receptors. We show here that activators of protein kinase A (PKA) can enhance mouse PPAR activity in the absence and the presence of exogenous ligands in transient transfection experiments. The activation function 1 (AF-1) of PPARs was dispensable for transcriptional enhancement, whereas the activation function 2 (AF-2) was required for this effect. We also show that several domains of PPAR can be phosphorylated by PKA in vitro. Moreover, gel experiments suggest that PKA stabilizes binding of the liganded PPAR to DNA. PKA inhibitors decreased not only the kinase dependent induction of PPARs but also their ligand-dependent induction, suggesting that the ligands may also mobilize the PKA pathway to lead to maximal transcriptional induction by PPARs. Moreover, comparing PPARα KO with PPARα wild-type mice, we show that the expression of the ACO gene can be regulated by PKA-activated PPARα in liver. These data demonstrate that the PKA pathway is an important modulator of PPAR activity and we propose a model associating this pathway in the control of fatty acid β-oxidation under conditions of fasting, stress and exercise. PMID:11117527

Synthesis and Characterization of a Triphos Ligand Derivative and the Corresponding Pd ^II Complexes: Triphos Ligand Derivative and Corresponding Pd ^II Complexes

Energy Technology Data Exchange (ETDEWEB)

Miller, Deanna L.; Boro, Brian J.; Grubel, Katarzyna; Helm, Monte L.; Appel, Aaron M.

2015-11-16

The synthesis of the new bis(2-(diphenylphosphino)ethyl)methylhydroxyphosphine tridentate phosphine ligand, LCH2OH/Ph, is reported. The ligand reacts with [Pd(Cl)2(PhCN)2 to form [Pd(LCH2OH/Ph)Cl]Cl. Exchange of the chloride ions for triflate (OTf–) using AgOTf yielded pure [Pd(LCH2OH/Ph)OTf]OTf. In addition to spectral characterization the free ligand, LCH2OH/Ph, and Pd(II) complex, [Pd(LCH2OH/Ph)OTf]OTf, are structurally characterized. This research was supported by the US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Biosciences, and Geosciences. Pacific Northwest National Laboratory is a multiprogram national laboratory operated by Battelle for DOE.

Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Novel Protease Inhibitors: Design, Synthesis, Protein-Ligand X-ray Structure and Biological Evaluation

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Arun K.; Takayama, Jun; Rao, Kalapala Venkateswar; Ratia, Kiira; Chaudhuri, Rima; Mulhearn, Debbie C.; Lee, Hyun; Nichols, Daniel B.; Baliji, Surendranath; Baker, Susan C.; Johnson, Michael E.; Mesecar, Andrew D. (Purdue); (UC); (UIC)

2012-02-21

The design, synthesis, X-ray crystal structure, molecular modeling, and biological evaluation of a series of new generation SARS-CoV PLpro inhibitors are described. A new lead compound 3 (6577871) was identified via high-throughput screening of a diverse chemical library. Subsequently, we carried out lead optimization and structure-activity studies to provide a series of improved inhibitors that show potent PLpro inhibition and antiviral activity against SARS-CoV infected Vero E6 cells. Interestingly, the (S)-Me inhibitor 15h (enzyme IC{sub 50} = 0.56 {mu}M; antiviral EC{sub 50} = 9.1 {mu}M) and the corresponding (R)-Me 15g (IC{sub 50} = 0.32 {mu}M; antiviral EC{sub 50} = 9.1 {mu}M) are the most potent compounds in this series, with nearly equivalent enzymatic inhibition and antiviral activity. A protein-ligand X-ray structure of 15g-bound SARS-CoV PLpro and a corresponding model of 15h docked to PLpro provide intriguing molecular insight into the ligand-binding site interactions.

New L-Serine Derivative Ligands as Cocatalysts for Diels-Alder Reaction

Science.gov (United States)

Sousa, Carlos A. D.; Rodríguez-Borges, José E.; Freire, Cristina

2013-01-01

New L-serine derivative ligands were prepared and tested as cocatalyst in the Diels-Alder reactions between cyclopentadiene (CPD) and methyl acrylate, in the presence of several Lewis acids. The catalytic potential of the in situ formed complexes was evaluated based on the reaction yield. Bidentate serine ligands showed good ability to coordinate medium strength Lewis acids, thus boosting their catalytic activity. The synthesis of the L-serine ligands proved to be highly efficient and straightforward. PMID:24383009

Sterically demanding diphosphonite ligands - synthesis and application in nickel-catalyzed isomerization of 2-methyl-3-butenenitrile

NARCIS (Netherlands)

Vlugt, van der J.I.; Hewat, A.C.; Neto, S.; Sablong, R.J.; Mills, A.M.; Lutz, M.; Spek, A.L.; Müller, C.; Vogt, D.

2004-01-01

The synthesis of a novel class of sterically demanding diphosphonites 1-8, based on rigid backbones, is described. The starting materials are all commercially available and the methodology allows for a modular approach. All ligands have been fully characterized, including an X-ray crystal structure

Ligand-selective activation of heterologously-expressed mammalian olfactory receptor.

Science.gov (United States)

Ukhanov, K; Bobkov, Y; Corey, E A; Ache, B W

2014-10-01

Mammalian olfactory receptors (ORs) appear to have the capacity to couple to multiple G protein-coupled signaling pathways in a ligand-dependent selective manner. To better understand the mechanisms and molecular range of such ligand selectivity, we expressed the mouse eugenol OR (mOR-EG) in HEK293T cells together with Gα15 to monitor activation of the phospholipase-C (PLC) signaling pathway and/or Gαolf to monitor activation of the adenylate cyclase (AC) signaling pathway, resulting in intracellular Ca(2+) release and/or Ca(2+) influx through a cyclic nucleotide-gated channel, respectively. PLC-dependent responses differed dynamically from AC-dependent responses, allowing them to be distinguished when Gα15 and Gαolf were co-expressed. The dynamic difference in readout was independent of the receptor, the heterologous expression system, and the ligand concentration. Of 17 reported mOR-EG ligands tested, including eugenol, its analogs, and structurally dissimilar compounds (mousse cristal, nootkatone, orivone), some equally activated both signaling pathways, some differentially activated both signaling pathways, and some had no noticeable effect even at 1-5mM. Our findings argue that mOR-EG, when heterologously expressed, can couple to two different signaling pathways in a ligand selective manner. The challenge now is to determine the potential of mOR-EG, and perhaps other ORs, to activate multiple signaling pathways in a ligand selective manner in native ORNs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Simple activation by acid of latent Ru-NHC-based metathesis initiators bearing 8-quinolinolate co-ligands

KAUST Repository

Wappel, Julia

2016-01-28

A straightforward synthesis utilizing the ring-opening metathesis polymerization (ROMP) reaction is described for acid-triggered N,O-chelating ruthenium-based pre-catalysts bearing one or two 8-quinolinolate ligands. The innovative pre-catalysts were tested regarding their behavior in ROMP and especially for their use in the synthesis of poly(dicyclopentadiene) (pDCPD). Bearing either the common phosphine leaving ligand in the first and second Grubbs olefin metathesis catalysts, or the Ru–O bond cleavage for the next Hoveyda-type catalysts, this work is a step forward towards the control of polymer functionalization and living or switchable polymerizations.

Simple activation by acid of latent Ru-NHC-based metathesis initiators bearing 8-quinolinolate co-ligands

KAUST Repository

Wappel, Julia; Fischer, Roland C; Cavallo, Luigi; Slugovc, Christian; Poater, Albert

2016-01-01

A straightforward synthesis utilizing the ring-opening metathesis polymerization (ROMP) reaction is described for acid-triggered N,O-chelating ruthenium-based pre-catalysts bearing one or two 8-quinolinolate ligands. The innovative pre-catalysts were tested regarding their behavior in ROMP and especially for their use in the synthesis of poly(dicyclopentadiene) (pDCPD). Bearing either the common phosphine leaving ligand in the first and second Grubbs olefin metathesis catalysts, or the Ru–O bond cleavage for the next Hoveyda-type catalysts, this work is a step forward towards the control of polymer functionalization and living or switchable polymerizations.

A Mixed-Ligand Chiral Rhodium(II) Catalyst Enables the Enantioselective Total Synthesis of Piperarborenine B.

Science.gov (United States)

Panish, Robert A; Chintala, Srinivasa R; Fox, Joseph M

2016-04-11

A novel, mixed-ligand chiral rhodium(II) catalyst, Rh2(S-NTTL)3(dCPA), has enabled the first enantioselective total synthesis of the natural product piperarborenine B. A crystal structure of Rh2(S-NTTL)3(dCPA) reveals a "chiral crown" conformation with a bulky dicyclohexylphenyl acetate ligand and three N-naphthalimido groups oriented on the same face of the catalyst. The natural product was prepared on large scale using rhodium-catalyzed bicyclobutanation/ copper-catalyzed homoconjugate addition chemistry in the key step. The route proceeds in ten steps with an 8% overall yield and 92% ee. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Effect of Precursor Ligands and Oxidation State in the Synthesis of Bimetallic Nano-Alloys

KAUST Repository

LaGrow, Alec P.

2015-05-12

The characteristics of bimetallic nanomaterials are dictated by their size, shape and elemental distribution. Solution synthesis is widely utilized to form nanomaterials, such as nanoparticles, with controlled size and shape. However, the effects of variables on the characteristics of bimetallic nanomaterials are not completely understood. In this study, we used a continuous-flow synthetic strategy to explore the effects of the ligands and the oxidation state of a metal precursor in a shape-controlled synthesis on the final shape of the nanomaterials and the elemental distribution within the alloy. We demonstrate that this strategy can tune the size of monodisperse PtM (M=Ni or Cu) alloy nanocrystals ranging from 3 to 16 nm with an octahedral shape using acetylacetonate or halide precursors of Pt(II), Pt(IV) and Ni or Cu (II). The nanoparticles formed from halide precursors showed an enrichment of platinum on their surfaces, and the bromides could oxidatively etch the nanoparticles during synthesis with the O2/Br- pair. The two nanocrystal precursors can be uti-lized independently and can control the size with a trend of Pt(acac)2ligand shell of a precursor during the synthesis of alloy nanoparticles as well as to control, in a scalable manner, the nanomaterial size and surface chemistry.

Nickel(II) and palladium(II) triphenylphosphine complexes incorporating tridentate Schiff base ligands: Synthesis, characterization and biocidal activities

Science.gov (United States)

Shabbir, Muhammad; Akhter, Zareen; Ashraf, Ahmad Raza; Ismail, Hammad; Habib, Anum; Mirza, Bushra

2017-12-01

Nickel(II) and palladium(II) triphenylphosphine complexes incorporating tridentate Schiff bases have been prepared and characterized by elemental analysis as well as by spectroscopic techniques (FTIR & NMR). The synthesized compounds were assessed to check their potential biocidal activity by using different biological assays (brine shrimp cytotoxicity, antimicrobial, antioxidant, antitumor and drug-DNA interaction). Results of brine shrimp cytotoxicity assay showed that ligand molecules are more bioactive than metal complexes with LD50 as low as 12.4 μg/mL. The prominent antitumor activity was shown by nickel complexes while the palladium complexes exhibited moderate activity. The synthesized compounds have shown high propensity for DNA binding either through intercalation or groove binding which represents the mechanism of antitumor effect of these compounds. Additionally, ligand molecules and nickel metal complexes showed significant antioxidant activity with IC50 values as low as 3.1 μg/mL and 18.9 μg/mL respectively while palladium complexes exhibited moderate activity. Moreover, in antimicrobial assays H2L1, Ni(L1)PPh3 and H2L3 showed dual inhibition against bacterial and fungal strains while for the rest of the compounds varying degree of activity was recorded against different strains. Overall comparison of results suggests that the synthesized compounds can be promising candidate for drug formulation and development.

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

Science.gov (United States)

Bhatt, Nikunj B; Pandya, Darpan N; Xu, Jide; Tatum, David; Magda, Darren; Wadas, Thaddeus J

2017-01-01

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.

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.

Oxovanadium (iv) complexes with n/o- and o-donor ligands: their synthesis, characterization, semiempirical study and alkaline phosphatase activity (abstract)

International Nuclear Information System (INIS)

Munawar, K.S.; Ali, S.; Khan, A.N.

2011-01-01

Various N/O- and O-donor ligands and their oxovanadium complexes have been synthesized and characterized by different techniques such as FTIR, elemental analysis, thermogravimetery and conductometry. The IR data show the bidentate nature of the ligands and reveals hexa-coordinated geometry in the solid state which is also confirmed by semi-empirical study. Conductance measurements reveal the non-electrolytic nature of the complexes. These complexes have been checked for their alkaline phosphatase activity in the presence and absence of inhibitor which shows that by the addition of inhibitor the activity of enzyme decreases and at higher concentration it is completely inhibited. (author)

Synthesis and pharmacological properties of new antihypertensive compounds, the [(benzodioxan - 1,4,)yl-5]-1 alkylamino-2 ethanols. Synthesis and properties of reversible ligands of central serotoninergic receptors: oxygenated isosteres of hydroxy-8 di-n-propylamino- 3 tetralin

International Nuclear Information System (INIS)

Perdicakis, Christine

1988-01-01

After some recalls on hypertension and on its various treatments, the first part of this thesis in pharmaceutical sciences addresses the synthesis of new molecules, the [(benzodioxan - 1,4,)yl-5]-1 alkylamino-2 ethanols. The author also explains the choice for this structure, and addresses the pharmacological activity of these molecules. The experimental study notably comprises the study of proton NMR spectra and of mass spectra, percentage analyses, fusion point measurements, and liquid-solid chromatography. Pharmacological tests have been performed on rats and on dogs, and did not completely gave the expected results. Therefore, the second part reports other researches related to the central nervous system with the study of the synthesis of radioactive ligands which allows a better knowledge on central serotoninergic receptors. The author reports the development of a new radio-ligand which selectively labels receptor sites of serotonin in the central nervous system [fr

Synthesis and characterization β-ketoamine ligands

Science.gov (United States)

Zaid, Nurzati Amani Mohamed; Hassan, Nur Hasyareeda; Karim, Nurul Huda Abd

2018-04-01

β-ketoamine ligands are important members of heterodonor ligand because of their ease of preparation and modification of both steric and/or electronic effects. Complexes with β-ketoamine has received much less attention and there has been no study about this complex with β-ketoamine in ionic liquid reported. Two type of β-ketoamine ligands which are 4-amino-3-pentene-2-onato (A) and 3-amino-2-butenoic acid methyl ester (B) have been synthesized in this work. The resulting compound formed was characterized using standard spectroscopic and structural techniques which includes 1H and 13C, NMR spectroscopy and FTIR spectroscopy. The 1H and 13C NMR spectrum displayed all the expected signals with correct integration and multiplicity. And it is proved that there are some differences between two ligands as observed in NMR and FTIR spectrum.

Vanadyl complexes with dansyl-labelled di-picolinic acid ligands: synthesis, phosphatase inhibition activity and cellular uptake studies.

Science.gov (United States)

Collins, Juliet; Cilibrizzi, Agostino; Fedorova, Marina; Whyte, Gillian; Mak, Lok Hang; Guterman, Inna; Leatherbarrow, Robin; Woscholski, Rudiger; Vilar, Ramon

2016-04-28

Vanadium complexes have been previously utilised as potent inhibitors of cysteine based phosphatases (CBPs). Herein, we present the synthesis and characterisation of two new fluorescently labelled vanadyl complexes (14 and 15) with bridged di-picolinic acid ligands. These compounds differ significantly from previous vanadyl complexes with phosphatase inhibition properties in that the metal-chelating part is a single tetradentate unit, which should afford greater stability and scope for synthetic elaboration than the earlier complexes. These new complexes inhibit a selection of cysteine based phosphatases (CBPs) in the nM range with some selectivity. Fluorescence spectroscopic studies (including fluorescence anisotropy) were carried out to demonstrate that the complexes are not simply acting as vanadyl delivery vehicles but they interact with the proteins. Finally, we present preliminary fluorescence microscopy studies to demonstrate that the complexes are cell permeable and localise throughout the cytoplasm of NIH3T3 cells.

Ligand-tailored single-site silica supported titanium catalysts: Synthesis, characterization and towards cyanosilylation reaction

International Nuclear Information System (INIS)

Xu, Wei; Li, Yani; Yu, Bo; Yang, Jindou; Zhang, Ying; Chen, Xi; Zhang, Guofang; Gao, Ziwei

2015-01-01

A successive anchoring of Ti(NMe 2 ) 4 , cyclopentadiene and a O-donor ligand, 1-hydroxyethylbenzene (PEA), 1,1′-bi-2-naphthol (Binol) or 2,3-dihydroxybutanedioic acid diethyl ester (Tartrate), on silica was conducted by SOMC strategy in moderate conditions. The silica, monitored by in-situ Fourier transform infrared spectroscopy (in-situ FT-IR), was pretreated at different temperatures (200, 500 and 800 °C). The ligand tailored silica-supported titanium complexes were characterized by in-situ FT-IR, 13 C CP MAS-NMR, X-ray photoelectron spectroscopy (XPS), X-ray absorption near edge structure (XANES) and elemental analysis in detail, verifying that the surface titanium species are single sited. The catalytic activity of the ligand tailored single-site silica supported titanium complexes was evaluated by a cyanosilylation of benzaldehyde. The results showed that the catalytic activity is dependent strongly on the dehydroxylation temperatures of silica and the configuration of the ligands. - Graphical abstract: The ligand-tailored silica supported “single site” titanium complexes were synthesized by SOMC strategy and fully characterized. Their catalytic activity were evaluated by benzaldehyde silylcyanation. - Highlights: • Single-site silica supported Ti active species was prepared by SOMC technique. • O-donor ligand tailored Ti surface species was synthesized. • The surface species was characterized by XPS, 13 C CP-MAS NMR, XANES etc. • Catalytic activity of the Ti active species in silylcyanation reaction was evaluated

Ligand-tailored single-site silica supported titanium catalysts: Synthesis, characterization and towards cyanosilylation reaction

Energy Technology Data Exchange (ETDEWEB)

Xu, Wei; Li, Yani; Yu, Bo; Yang, Jindou; Zhang, Ying; Chen, Xi; Zhang, Guofang, E-mail: gfzhang@snnu.edu.cn; Gao, Ziwei, E-mail: zwgao@snnu.edu.cn

2015-01-15

A successive anchoring of Ti(NMe{sub 2}){sub 4}, cyclopentadiene and a O-donor ligand, 1-hydroxyethylbenzene (PEA), 1,1′-bi-2-naphthol (Binol) or 2,3-dihydroxybutanedioic acid diethyl ester (Tartrate), on silica was conducted by SOMC strategy in moderate conditions. The silica, monitored by in-situ Fourier transform infrared spectroscopy (in-situ FT-IR), was pretreated at different temperatures (200, 500 and 800 °C). The ligand tailored silica-supported titanium complexes were characterized by in-situ FT-IR, {sup 13}C CP MAS-NMR, X-ray photoelectron spectroscopy (XPS), X-ray absorption near edge structure (XANES) and elemental analysis in detail, verifying that the surface titanium species are single sited. The catalytic activity of the ligand tailored single-site silica supported titanium complexes was evaluated by a cyanosilylation of benzaldehyde. The results showed that the catalytic activity is dependent strongly on the dehydroxylation temperatures of silica and the configuration of the ligands. - Graphical abstract: The ligand-tailored silica supported “single site” titanium complexes were synthesized by SOMC strategy and fully characterized. Their catalytic activity were evaluated by benzaldehyde silylcyanation. - Highlights: • Single-site silica supported Ti active species was prepared by SOMC technique. • O-donor ligand tailored Ti surface species was synthesized. • The surface species was characterized by XPS, {sup 13}C CP-MAS NMR, XANES etc. • Catalytic activity of the Ti active species in silylcyanation reaction was evaluated.

Novel Chemical Strategies for Labeling Small Molecule Ligands for Androgen, Progestin, and Peroxisome Proliferator-Activated Receptors for Imaging Prostate and Breast Cancer and the Heart

International Nuclear Information System (INIS)

Katzenellenbogen, John A.

2007-01-01

Summary of Progress The specific aims of this project can be summarized as follows: Aim 1: Prepare and evaluate radiolabeled ligands for the peroxisome proliferator-activated receptor γ (PPARγ), a new nuclear hormone receptor target for tumor imaging and hormone therapy. Aim 2: Prepare steroids labeled with a cyclopentadienyl tricarbonyl technetium or rhenium unit. Aim 3: Prepare and evaluate other organometallic systems of novel design as ligand mimics and halogenated ligands for nuclear hormone receptor-based tumor imaging. As is described in detail in the report, we made excellent progress on all three of these aims; the highlights of our progress are the following: (1) we have prepared the first fluorine-18 labeled analogs of ligands for the PPARγ receptor and used these in tissue distribution studies in rats; (2) we have developed three new methods for the synthesis of cyclopentadienyltricarbonyl rhenium and technetium (CpRe(CO)3 and CpTc(CO)3) systems and we have adapted these to the synthesis of steroids labeled with these metals, as well as ligands for other receptor systems; (3) we have prepared a number of fluorine-18 labeled steroidal and non-steroidal androgens and measured their tissue distribution in rats; (4) we have prepared iodine and bromine-labeled progestins with high progesterone receptor binding affinity; and (5) we have prepared inorganic metal tricarbonyl complexes and steroid receptor ligands in which the metal tricarbonyl unit is an integral part off the ligand core

Synthesis of molecular complexes for small molecule activation

International Nuclear Information System (INIS)

Andrez, Julie

2016-01-01

The redox chemistry of f-elements is drawing the attention of inorganic chemists due to their unusual reaction pathways. Notably low-valent f-element complexes have been shown to be able to activate small molecules such as CO_2 and N_2 in mild conditions. Compared to d-block metals, f-elements present a coordination chemistry dominated by electrostatic interactions and steric constraints. Molecular complexes of f-elements could thus provide new catalytic routes to transform small molecules into valuable chemicals. However the redox chemistry of low valent f-elements is dominated by single-electron transfers while the reductions of CO_2 and N_2 require multi-electronic processes. Accordingly the first approach of this PhD work was the use of redox active ligands as electron reservoir to support f-element centres increasing the electron number available for reduction events. The coordination of uranium with tridentate Schiff base ligand was investigated and led to isolation of a dinuclear electron-rich species able to undertake up to eight-electron reduction combining the redox activity of the ligands and the uranium centres. In order to obtain electron-rich compounds potentially able to polarize the C=O bond of CO_2, the synthesis of hetero-bimetallic species supported by salophen Schiff base ligand was also studied. In a second approach we have used bulky ligands with strong donor-character to tune the reducing abilities of low valent f-elements. In this case a bimolecular electron-transfer process is often observed. The reactivity of the U(III) siloxid complex [U(OSi(OtBu)_3)_4K] was further investigated. Notably, reaction with Ph_3PS led to the formation of a terminal U(IV) sulfide complex with multiple U-S bond which was analysed by DFT studies to better understand the bonding nature. Preliminary studies on the role of the counter-cation (M) in the system [U(OSi(OtBu)_3)_4M] on the outcome of the reactivity with CS_2 and CO_2 have also been performed. The

New synthetic routes toward enantiopure nitrogen donor ligands.

Science.gov (United States)

Sala, Xavier; Rodríguez, Anna M; Rodríguez, Montserrat; Romero, Isabel; Parella, Teodor; von Zelewsky, Alexander; Llobet, Antoni; Benet-Buchholz, Jordi

2006-12-08

New polypyridylic chiral ligands, having either C3 or lower symmetry, have been prepared via a de novo construction of the pyridine nucleus by means of Kröhnke methodology in the key step. The chiral moieties of these ligands originate from the monoterpen chiral pool, namely (-)-alpha-pinene ((-)-14, (-)-15) and (-)-myrtenal ((-)-9, (-)-10). Extension of the above-mentioned asymmetric synthesis procedure to the preparation of enantiopure derivatives of some commonly used polypyridylic ligands has been achieved through a new aldehyde building block ((-)-16). As an example, the synthesis of a chiral derivative of N,N-bis(2-pyridylmethyl)ethylamine (bpea) ligand, (-)-19, has been performed to illustrate the viability of the method. The coordinative ability of the ligands has been tested through the synthesis and characterization of complexes [Mn((-)-19)Br2], (-)-20, and [RuCl((-)-10)(bpy)](BF4), (-)-21. Some preliminary results related to the enantioselective catalytic epoxidation of styrene with the ruthenium complex are also presented.

Synthesis of the sup 11 C-labelled. beta. -adrenergic receptor ligands atenolol, metoprolol and propanolol

Energy Technology Data Exchange (ETDEWEB)

Antoni, G.; Ulin, J.; Laangstroem, B. (Uppsala Univ. (Sweden). Dept. of Organic Chemistry)

1989-01-01

The {sup 11}C-labelled {beta}-adrenergic receptor ligands atenolol 1, metoprolol 2 and propranolol 3 have been synthesized by an N-alkylation reaction using (2-{sup 11}C)isopropyl iodide. The labelled isopropyl iodide was prepared in a one-pot reactor system from ({sup 11}C)carbon dioxide and obtained in 40% radiochemical yield within 14 min reaction time. The total reaction times for compounds 1-3, counted from the start of the isopropyl iodide synthesis and including purification were 45-55 min. The products were obtained in 5-15% radiochemical yields and with radiochemical purities higher than 98%. The specific activity ranged from 0.4 to 4 GBq/{mu}mol. In a typical experiment starting with 4 GBq around 75 MBq of product was obtained. (author).

Ligand mediated synthesis of AgInSe2 nanoparticles with tetragonal/orthorhombic crystal phases

International Nuclear Information System (INIS)

Abazović, Nadica D.; Čomor, Mirjana I.; Mitrić, Miodrag N.; Piscopiello, Emanuela; Radetić, Tamara; Janković, Ivana A.; Nedeljković, Jovan M.

2012-01-01

Nanosized AgInSe 2 particles (d ∼ 7–25 nm) were synthesized using colloidal chemistry method at 270 °C. As solvents/surface ligands 1-octadecene, trioctylphosphine, and oleylamine were used. It was shown that choice of ligand has crucial impact not only on final crystal phase of nanoparticles, but also at mechanism of crystal growth. X-ray diffraction and TEM/HRTEM techniques were used to identify obtained crystal phases and to measure average size and shape of nanoparticles. UV/Vis data were used to estimate band-gap energies of obtained samples. It was shown that presented routes can provide synthesis of nanoparticles with desired crystal phase (tetragonal and/or orthorhombic), with band-gap energies in the range from 1.25 to 1.53 eV.

New aminoporphyrins bearing urea derivative substituents: synthesis, characterization, antibacterial and antifungal activity

Directory of Open Access Journals (Sweden)

Gholamreza Karimipour

2015-06-01

Full Text Available This work studied the synthesis of 5,10,15-tris(4-aminophenyl-20-(N,N-dialkyl/diaryl-N-phenylurea porphyrins (P1-P4 with alkyl or aryl groups of Ph, iPr, Et and Me, respectively and also the preparation of their manganese (III and cobalt (II complexes (MnP and CoP. The P1-P4 ligands were characterized by different spectroscopic techniques (1H NMR, FTIR, UV-Vis and elemental analysis, and metalated with Mn and Co acetate salts. The antibacterial and antifungal activities of these compounds in vitro were investigated by agar-disc diffusion method against Escherichia coli (-, Pseudomonas aeruginosa (-, Staphylococcus aureus(+, Bacillus subtilis (+ and Aspergillus oryzae and Candida albicans. Results showed that antibacterial and antifungal activity of the test samples increased with increase of their concentrations and the highest activity was obtained when the concentration of porphyrin compounds was 100 µg/mL. The activity for the porphyrin ligands depended on the nature of the urea derivative substituents and increased in the order P1 > P2 > P3 >P4, which was consistent with the order of their liposolubility. MnP and CoP complexes exhibited much higher antibacterial and antifungal activity than P1-P4ligands. Further, the growth inhibitory effects of these compounds was generally in the order CoP complexes > MnP complexes > P1-P4 ligands. Among these porphyrin compounds, CoP1displayed the highest antibacterial and antifungal activity, especially with a concentration of 100 µg/mL, against all the four tested bacteria and two fungi, and therefore it could be potential to be used as drug.

Ligand-Controlled Chemoselective C(acyl)–O Bond vs C(aryl)–C Bond Activation of Aromatic Esters in Nickel Catalyzed C(sp2)–C(sp3) Cross-Couplings

KAUST Repository

Chatupheeraphat, Adisak

2018-02-20

A ligand-controlled and site-selective nickel catalyzed Suzuki-Miyaura cross-coupling reaction with aromatic esters and alkyl organoboron reagents as coupling partners was developed. This methodology provides a facile route for C(sp2)-C(sp3) bond formation in a straightforward fashion by successful suppression of the undesired β-hydride elimination process. By simply switching the phosphorus ligand, the ester substrates are converted into the alkylated arenes and ketone products, respectively. The utility of this newly developed protocol was demonstrated by its wide substrate scope, broad functional group tolerance and application in the synthesis of key intermediates for the synthesis of bioactive compounds. DFT studies on the oxidative addition step helped rationalizing this intriguing reaction chemoselectivity: whereas nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step leading to the alkylated product via a decarbonylative process, nickel complexes with monodentate phosphorus ligands favor activation of the C(acyl)-O bond, which later generates the ketone product.

Preparation, Spectroscopic Investigation and Biological Activity of New Mixed Ligand Chelates

International Nuclear Information System (INIS)

Alassbaly, F.S.; Ajaily, M.M.E.

2014-01-01

Preparation and investigation of new Co(II), Ni(II), Zn(II) and Cr(III) chelates with mixed ligands including Schiff base (L1) formed from the condensation of 4-dimethylaminobenzaldehyde with 2-aminophenol and anthranilic acid (L2) were studied. The obtained Schiff base and mixed ligand chelates were subjected to several physiochemical techniques, in terms of CHN elemental analyses, molar conductivity, magnetic moment measurements, infrared, proton nuclear magnetic resonance, electronic and mass spectra. The analytical data showed the formation of the Schiff base compound and the ratio of metal to ligands of the chelates are 1:1:1(M:L1:L2). The infrared spectral data exhibited that the used ligands behaving as bidentate ligands towards the metal ions. The proton nuclear magnetic resonance spectral data showed the signals of the active groups in the ligands which entered in chelation with Zn(II) metal ion. The electronic spectral results showed the existence of pie (phenyl ring) and n = pie (C=N) of the ligands and suggested the geometrical structures of the chelates. Meanwhile, the mass spectral data revealed the fragmentations of the Schiff base, anthranilic acid and their Ni(II) mixed ligand chelate has been preformed the only chelate conducted for justification. All the prepared mixed chelates were non-electrolyte in nature. The antibacterial activity of the Schiff base, anthranilic acid, metal salts and mixed ligand chelates were studied and found to be that mixed ligand chelates have the most biological activity in comparison to the free ligands and salts. (author)

Ligand modeling and design

Energy Technology Data Exchange (ETDEWEB)

Hay, B.P. [Pacific Northwest National Lab., Richland, WA (United States)

1997-10-01

The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used in the cost-effective removal of specific radionuclides from nuclear waste streams. Organic ligands with metal ion specificity are critical components in the development of solvent extraction and ion exchange processes that are highly selective for targeted radionuclides. The traditional approach to the development of such ligands involves lengthy programs of organic synthesis and testing, which in the absence of reliable methods for screening compounds before synthesis, results in wasted research effort. The author`s approach breaks down and simplifies this costly process with the aid of computer-based molecular modeling techniques. Commercial software for organic molecular modeling is being configured to examine the interactions between organic ligands and metal ions, yielding an inexpensive, commercially or readily available computational tool that can be used to predict the structures and energies of ligand-metal complexes. Users will be able to correlate the large body of existing experimental data on structure, solution binding affinity, and metal ion selectivity to develop structural design criteria. These criteria will provide a basis for selecting ligands that can be implemented in separations technologies through collaboration with other DOE national laboratories and private industry. The initial focus will be to select ether-based ligands that can be applied to the recovery and concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium.

Reactivity of halide and pseudohalide ligands

International Nuclear Information System (INIS)

Kukushkin, Yu.N.

1987-01-01

Reactivity of halide and pseudohalide (cyanide, azide, thiocyanate, cyanate) ligands tending to form bridge bonds in transition metal (Re, Mo, W) complexes is considered. Complexes where transition metal salts are ligands of other, complex-forming ion, are described. Transformation of innerspheric pseudohalide ligands is an important way of directed synthesis of these metal coordination compounds

Synthesis and characterization of mixed ligand chiral nanoclusters

KAUST Repository

Guven, Zekiye P.; Ustbas, Burcin; Harkness, Kellen M.; Coskun, Hikmet; Joshi, Chakra Prasad; Besong, Tabot M.D.; Stellacci, Francesco; Bakr, Osman; Akbulut, Ozge

2016-01-01

Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

Synthesis and characterization of mixed ligand chiral nanoclusters

KAUST Repository

Guven, Zekiye P.

2016-06-22

Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

Synthesis, Characterization, DNA Interaction, and Antitumor Activities of La (III) Complex with Schiff Base Ligand Derived from Kaempferol and Diethylenetriamine.

Science.gov (United States)

Wang, Qin; Huang, Yu; Zhang, Jin-Sheng; Yang, Xin-Bin

2014-01-01

A novel La (III) complex, [LaL(H2O)3]NO3 ·3H2O, with Schiff base ligand L derived from kaempferol and diethylenetriamine, has been synthesized and characterized by elemental analysis, IR, UV-visible, (1)H NMR, thermogravimetric analysis, and molar conductance measurements. The fluorescence spectra, circular dichroism spectra, and viscosity measurements and gel electrophoresis experiments indicated that the ligand L and La (III) complex could bind to CT-DNA presumably via intercalative mode and the La (III) complex showed a stronger ability to bind and cleave DNA than the ligand L alone. The binding constants (K b ) were evaluated from fluorescence data and the values ranged from 0.454 to 0.659 × 10(5) L mol(-1) and 1.71 to 17.3 × 10(5) L mol(-1) for the ligand L and La (III) complex, respectively, in the temperature range of 298-310 K. It was also found that the fluorescence quenching mechanism of EB-DNA by ligand L and La (III) complex was a static quenching process. In comparison to free ligand L, La (III) complex exhibited enhanced cytotoxic activities against tested tumor cell lines HL-60 and HepG-2, which may correlate with the enhanced DNA binding and cleaving abilities of the La (III) complex.

1,2,3-triazolyl amino acids as AMPA receptor ligands

DEFF Research Database (Denmark)

Stanley, Nathan J.; Pedersen, Daniel Sejer; Nielsen, Birgitte

2010-01-01

The central nervous system glutamate receptors are an important target for drug discovery. Herein we report initial investigations into the synthesis and glutamate receptor activity of 1,2,3-triazolyl amino acids. Two compounds were found to be selective AMPA receptor ligands, which warrant further...

Attenuated apoptosis response to Fas-ligand in active ulcerative colitis

DEFF Research Database (Denmark)

Seidelin, Jakob B; Nielsen, Ole H

2008-01-01

BACKGROUND: From mainly carcinoma cell line studies, apoptosis has been thought to play a major role in the pathogenesis of ulcerative colitis (UC). Apoptosis has been suggested to be due to a Fas ligand / Fas receptor interaction, but has never been studied in cells from patients with active UC...... was subsequently reached were included. Cultures of isolated colonic crypts were obtained from biopsies and cultured for 4 to 16 hours with Fas ligand or Fas ligand and costimulation with interferon-gamma (IFN-gamma). Control experiments were performed on HT29 cells. Apoptosis was assessed by independent methods....... RESULTS: Isolated colonocytes from healthy subjects or patients with remission in UC had a dose-dependent response to Fas ligand. This response was abolished in patients with active UC (P

Synthesis of a [sup 11]C-labeled novel, quinuclidine based ligand for the 5-HT[sub 3] receptor

Energy Technology Data Exchange (ETDEWEB)

Rajagopal, S; Diksic, M [Montreal Neurological Inst., PQ (Canada); Francis, B; Burns, H D [Merck Research Labs., West Point, PA (United States). Dept. of Radiopharmacology; Swain, C J [Merck Sharp and Dohme Research Labs., Harlow (United Kingdom). Neuroscience Research Centre

1992-11-01

L-683,877, a high affinity, 5-HT[sub 3] selective receptor ligand has been labeled with [sup 11]C for use in PET studies to measure regional brain kinetics of L-683,877 and to determine if [[sup 11]C]L-683,877 can be used for serotonin 5-HT[sub 3] receptor imaging. [[sup 11]C]L-683,877 was prepared by reacting [[sup 11]C]methyl iodide with the desmethyl, borane-protected precursor, L-686,472, in DMF in the presence of tetrabutyl ammonium hydroxide. The average specific activity of [[sup 11]C]L-683,877 was 2700 Ci/mmol and the average radiochemical yield (decay corrected)was 20% at the end of synthesis. (Author).

Predicting Nanocrystal Shape through Consideration of Surface-Ligand Interactions

KAUST Repository

Bealing, Clive R.

2012-03-27

Density functional calculations for the binding energy of oleic acid-based ligands on Pb-rich {100} and {111} facets of PbSe nanocrystals determine the surface energies as a function of ligand coverage. Oleic acid is expected to bind to the nanocrystal surface in the form of lead oleate. The Wulff construction predicts the thermodynamic equilibrium shape of the PbSe nanocrystals. The equilibrium shape is a function of the ligand surface coverage, which can be controlled by changing the concentration of oleic acid during synthesis. The different binding energy of the ligand on the {100} and {111} facets results in different equilibrium ligand coverages on the facets, and a transition in the equilibrium shape from octahedral to cubic is predicted when increasing the ligand concentration during synthesis. © 2012 American Chemical Society.

New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-affinity γ-Hydroxybutyrate (GHB) Binding Sites

Science.gov (United States)

Vogensen, Stine B.; Marek, Aleš; Bay, Tina; Wellendorph, Petrine; Kehler, Jan; Bundgaard, Christoffer; Frølund, Bente; Pedersen, Martin H.F.; Clausen, Rasmus P.

2013-01-01

3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [3H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity and we demonstrate in vivo brain penetration. In vitro characterization of [3H]-1 binding shows high specificity to the high-affinity GHB binding sites. PMID:24053696

Aziridine- and Azetidine-Pd Catalytic Combinations. Synthesis and Evaluation of the Ligand Ring Size Impact on Suzuki-Miyaura Reaction Issues

Directory of Open Access Journals (Sweden)

Hamza Boufroura

2017-01-01

Full Text Available The synthesis of new vicinal diamines based on aziridine and azetidine cores as well as the comparison of their catalytic activities as ligand in the Suzuki-Miyaura coupling reaction are described in this communication. The synthesis of three- and four-membered ring heterocycles substituted by a methylamine pendant arm is detailed from the parent nitrile derivatives. Complexation to palladium under various conditions has been examined affording vicinal diamines or amine-imidate complexes. The efficiency of four new catalytic systems is compared in the preparation of variously substituted biaryls. Aziridine- and azetidine-based catalytic systems allowed Suzuki-Miyaura reactions from aryl halides including chlorides with catalytic loadings until 0.001% at temperatures ranging from 100 °C to r.t. The evolution of the Pd-metallacycle ring strain moving from azetidine to aziridine in combination with a methylamine or an imidate pendant arm impacted the Suzuki-Miyaura reaction issue.

Evaluation of DNA binding, DNA cleavage, protein binding, radical scavenging and in vitro cytotoxic activities of ruthenium(II) complexes containing 2,4-dihydroxy benzylidene ligands

Energy Technology Data Exchange (ETDEWEB)

Mohanraj, Maruthachalam; Ayyannan, Ganesan; Raja, Gunasekaran; Jayabalakrishnan, Chinnasamy, E-mail: drcjbstar@gmail.com

2016-12-01

The new ruthenium(II) complexes with hydrazone ligands, 4-Methyl-benzoic acid (2,4-dihydroxy-benzylidene)-hydrazide (HL{sup 1}), 4-Methoxy-benzoic acid (2,4-dihydroxy-benzylidene)-hydrazide (HL{sup 2}), 4-Bromo-benzoic acid (2,4-dihydroxy-benzylidene)-hydrazide (HL{sup 3}), were synthesized and characterized by various spectro analytical techniques. The molecular structures of the ligands were confirmed by single crystal X-ray diffraction technique. The DNA binding studies of the ligands and complexes were examined by absorption, fluorescence, viscosity and cyclic voltammetry methods. The results indicated that the ligands and complexes could interact with calf thymus DNA (CT-DNA) through intercalation. The DNA cleavage activity of the complexes was evaluated by gel electrophoresis assay, which revealed that the complexes are good DNA cleaving agents. The binding interaction of the ligands and complexes with bovine serum albumin (BSA) was investigated using fluorescence spectroscopic method. Antioxidant studies showed that the complexes have a strong radical scavenging properties. Further, the cytotoxic effect of the complexes examined on cancerous cell lines showed that the complexes exhibit significant anticancer activity. - Highlights: • Synthesis of ruthenium(II) hydrazone complexes • Molecular structure of the ligands was elucidated by single crystal X-ray diffraction method. • The ligands and complexes interact with CT-DNA via intercalation. • The complexes possess significant antioxidant activity against DPPH, OH and NO radicals. • The complex 6 shows higher IC{sub 50} value than the other complexes against cancer cells.

Combining on-chip synthesis of a focused combinatorial library with computational target prediction reveals imidazopyridine GPCR ligands.

Science.gov (United States)

Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Schneider, Gisbert

2014-01-07

Using the example of the Ugi three-component reaction we report a fast and efficient microfluidic-assisted entry into the imidazopyridine scaffold, where building block prioritization was coupled to a new computational method for predicting ligand-target associations. We identified an innovative GPCR-modulating combinatorial chemotype featuring ligand-efficient adenosine A1/2B and adrenergic α1A/B receptor antagonists. Our results suggest the tight integration of microfluidics-assisted synthesis with computer-based target prediction as a viable approach to rapidly generate bioactivity-focused combinatorial compound libraries with high success rates. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mesoporous organosilica nanotubes containing a chelating ligand in their walls

Energy Technology Data Exchange (ETDEWEB)

Liu, Xiao; Goto, Yasutomo; Maegawa, Yoshifumi; Inagaki, Shinji, E-mail: inagaki@mosk.tytlabs.co.jp [Toyota Central R and D Laboratories, Inc., Nagakute, Aichi 480-1192 (Japan); Japan Science and Technology Agency (JST)/ACT-C, Nagakute, Aichi, 480-1192 (Japan); Ohsuna, Tetsu [Toyota Central R and D Laboratories, Inc., Nagakute, Aichi 480-1192 (Japan)

2014-11-01

We report the synthesis of organosilica nanotubes containing 2,2′-bipyridine chelating ligands within their walls, employing a single-micelle-templating method. These nanotubes have an average pore diameter of 7.8 nm and lengths of several hundred nanometers. UV-vis absorption spectra and scanning transmission electron microscopy observations of immobilized nanotubes with an iridium complex on the bipyridine ligands showed that the 2,2′-bipyridine groups were homogeneously distributed in the benzene-silica walls. The iridium complex, thus, immobilized on the nanotubes exhibited efficient catalytic activity for water oxidation using Ce{sup 4+}, due to the ready access of reactants to the active sites in the nanotubes.

Surface-Bound Ligands Modulate Chemoselectivity and Activity of a Bimetallic Nanoparticle Catalyst

KAUST Repository

Vu, Khanh B.

2015-04-03

"Naked" metal nanoparticles (NPs) are thermodynamically and kinetically unstable in solution. Ligands, surfactants, or polymers, which adsorb at a particle\\'s surface, can be used to stabilize NPs; however, such a mode of stabilization is undesirable for catalytic applications because the adsorbates block the surface active sites. The catalytic activity and the stability of NPs are usually inversely correlated. Here, we describe an example of a bimetallic (PtFe) NP catalyst stabilized by carboxylate surface ligands that bind preferentially to one of the metals (Fe). NPs stabilized by fluorous ligands were found to be remarkably competent in catalyzing the hydrogenation of cinnamaldehyde; NPs stabilized by hydrocarbon ligands were significantly less active. The chain length of the fluorous ligands played a key role in determining the chemoselectivity of the FePt NP catalysts. (Chemical Presented). © 2015 American Chemical Society.

Synthesis, crystal structure, antimicrobial activity and electrochemistry study of chromium(III) and copper(II) complexes based on semicarbazone Schiff base and azide ligands

Czech Academy of Sciences Publication Activity Database

Shaabani, B.; Khandar, A.A.; Dušek, Michal; Pojarová, Michaela; Mahmoudi, F.

2013-01-01

Roč. 394, JAN (2013), s. 563-568 ISSN 0020-1693 Grant - others:AV ČR(CZ) AP0701 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:68378271 Keywords : antimicrobial activity * azide ligand * metal complex * Schiff base ligand * X-ray structure Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.041, year: 2013

Synthesis, Characterization, Luminescence and Biological Activity of Two Lanthanide Complexes Involving Mixed Ligands

Energy Technology Data Exchange (ETDEWEB)

Ma, Deyun; Guo, Haifu; Qin, Liang [Zhaoqing Univ., Zhaoqing (China); Xu, Jun [Jinan Univ., Guangzhou (China)

2013-09-15

Two new isostructural dinuclear complexes, Ln{sub 2}(4-cpa){sub 6}(bpy){sub 2} (Ln = Eu (1); Tb (2), 4-cpa = 4-chlorophenyl-acetate, bpy = 2,2'-bipyridine), have been hydrothermally synthesized and characterized by IR spectroscopy, elemental analysis, thermogravimetric analysis (TGA), powder X-ray diffraction and single-crystal X-ray diffraction. The lanthanide ions are bridged by two bidentate and two terdentate carboxylate groups to give centrosymmetric dimers with Ln···Ln separations of 3.967(2) and 3.956(3) A, respectively. Each metal atom is nine-coordinate and exhibits a distorted tricapped trigonal prismatic geometry. Three-dimensional fluorescence spectra show that both 1 and 2 emit bright red and green luminescence at room temperature, with long lifetimes of up to 0.369 ms (at 614 nm) and 0.432 ms (at 543 nm), respectively. Moreover, poor luminescence efficiency has been noted for complex 2. The 4-Hcpa ligand and complexes 1-2 have been screened for their phytogrowth-inhibitory activities against Brassica napus L. and Echinochloa crusgalli L., and the results are compared with the activity of quizalofop-P-ethyl.

Synthesis, spectral, thermal, potentiometric and antimicrobial studies of transition metal complexes of tridentate ligand

Directory of Open Access Journals (Sweden)

Sarika M. Jadhav

2014-01-01

Full Text Available A series of metal complexes of Cu(II, Ni(II, Co(II, Fe(III and Mn(II have been synthesized with newly synthesized biologically active tridentate ligand. The ligand was synthesized by condensation of dehydroacetic acid (3-acetyl-6-methyl-(2H pyran-2,4(3H-dione or DHA, o-phenylene diamine and fluoro benzaldehyde and characterized by elemental analysis, molar conductivity, magnetic susceptibility, thermal analysis, X-ray diffraction, IR, 1H-NMR, UV–Vis spectroscopy and mass spectra. From the analytical data, the stoichiometry of the complexes was found to be 1:2 (metal:ligand with octahedral geometry. The molar conductance values suggest the non-electrolyte nature of metal complexes. The IR spectral data suggest that the ligand behaves as a dibasic tridentate ligand with ONN donor atoms sequence towards central metal ion. Thermal behaviour (TG/DTA and kinetic parameters calculated by the Coats–Redfern and Horowitz–Metzger method suggest more ordered activated state in complex formation. To investigate the relationship between stability constants of metal complexes and antimicrobial activity, the dissociation constants of Schiff bases and stability constants of their binary metal complexes have been determined potentiometrically in THF–water (60:40% solution at 25 ± 1 °C and at 0.1 M NaClO4 ionic strength. The potentiometric study suggests 1:1 and 1:2 complexation. Antibacterial and antifungal activities in vitro were performed against Staphylococcus aureus, Escherichia coli and Aspergillus niger, Trichoderma, respectively. The stability constants of the metal complexes were calculated by the Irving–Rosotti method. A relation between the stability constant and antimicrobial activity of complexes has been discussed. It is observed that the activity enhances upon complexation and the order of antifungal activity is in accordance with stability order of metal ions.

Synthesis and structural characterization of lithium

Indian Academy of Sciences (India)

synthesis and characterization of two new iminophos- phonamine ligands ... structures. 2.3 General synthetic method for ligands (1 and 2) ... 2.3b General method for the Synthesis of ligands ...... studies are currently underway in our laboratory.

Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

Directory of Open Access Journals (Sweden)

Shinichiro Fuse

2013-11-01

Full Text Available Sterically crowded diimine ligands with five aryl rings were prepared in one step in good yields using a micro-flow technique. X-ray crystallographic analysis revealed the detailed structure of the bulky ligands. The nickel complexes prepared from the ligands exerted high polymerization activity in the ethylene homopolymerization and copolymerization of ethylene with polar monomers.

Synthesis and Structure Determination of a New Au₂₀ Nanocluster Protected by Tripodal Tetraphosphine Ligands

Energy Technology Data Exchange (ETDEWEB)

Chen, Jing [Brown Univ., Providence, RI (United States); Zhang, Qianfan [Brown Univ., Providence, RI (United States); Williard, Paul G. [Brown Univ., Providence, RI (United States); Wang, Lai-Sheng [Brown Univ., Providence, RI (United States)

2014-03-31

We report the synthesis and structure determination of a new Au₂₀ nanocluster coordinated by four tripodal tetraphosphine (PP₃) ligands {PP₃ = tris[2-(diphenylphosphino)ethyl]phosphine}. Single-crystal Xray crystallography and electrospray ionization mass spectrometry show that the cluster assembly can be formulated as [Au₂₀(PP₃)₄]Cl₄. The Au₂₀ cluster consists of an icosahedral Au₁₃ core and a seven-Au-atom partial outer shell arranged in a local C₃ symmetry. One PP₃ ligand coordinates to four Au atoms in the outer shell, while the other three PP₃ ligands coordinate to one Au atom from the outer shell and three Au atoms from the surface of the Au₁₃ core, giving rise to an overall chiral 16-electron Au cluster core with C3 symmetry.

New Mn(II, Ni(II, Cd(II, Pb(II complexes with 2-methylbenzimidazole and other ligands. Synthesis, spectroscopic characterization, crystal structure, magnetic susceptibility and biological activity studies

Directory of Open Access Journals (Sweden)

Shayma A. Shaker

2016-11-01

Full Text Available Synthesis and characterization of Mn(II, Ni(II, Cd(II and Pb(II mixed ligand complexes of 2-methylbenzimidazole with other ligands have been reported. The structure of the ligands and their complexes was investigated using elemental analysis, IR, UV–Vis, (1H, 13C NMR spectroscopy, molar conductivity and magnetic susceptibility measurements. In all the studies of complexes, the 2-methylbenzimidazole behaves as a neutral monodentate ligand which is coordinated with the metal ions through the N atom. While benzotriazole behaves as a neutral bidentate ligand which is coordinated with the Ni(II ion through the two N atoms. Moreover, the N-acetylglycine behaves as a bidentate ligand which is coordinated with the Mn(II, Ni(II and Pb(II ions through the N atom and the terminal carboxyl oxygen atom. The magnetic and spectral data indicate the tetrahedral geometry for Mn(II complex, irregular tetrahedral geometry for Pb(II complex and octahedral geometry for Ni(II complex. The X-ray single crystal diffraction method was used to confirm a centrosymmetric dinuclear Cd(II complex as each two metal ions are linked by a pair of thiocyanate N = S bridge. Two 2-methylbenzimidazole N-atom donors and one terminal thiocyanate N atom complete a highly distorted square pyramid geometry around the Cd atom. Besides, different cell types were used to determine the inhibitory effect of Mn(II, Ni(II, Cd(II and Pb(II complexes on cell growth using MTT assay. Cd(II complex showed cytotoxic effect on various types of cancer cell lines with different EC50 values.

Ammonia formation by metal-ligand cooperative hydrogenolysis of a nitrido ligand

Science.gov (United States)

Askevold, Bjorn; Nieto, Jorge Torres; Tussupbayev, Samat; Diefenbach, Martin; Herdtweck, Eberhardt; Holthausen, Max C.; Schneider, Sven

2011-07-01

Bioinspired hydrogenation of N2 to ammonia at ambient conditions by stepwise nitrogen protonation/reduction with metal complexes in solution has experienced remarkable progress. In contrast, the highly desirable direct hydrogenation with H2 remains difficult. In analogy to the heterogeneously catalysed Haber-Bosch process, such a reaction is conceivable via metal-centred N2 splitting and unprecedented hydrogenolysis of the nitrido ligands to ammonia. We report the synthesis of a ruthenium(IV) nitrido complex. The high nucleophilicity of the nitrido ligand is demonstrated by unusual N-C coupling with π-acidic CO. Furthermore, the terminal nitrido ligand undergoes facile hydrogenolysis with H2 at ambient conditions to produce ammonia in high yield. Kinetic and quantum chemical examinations of this reaction suggest cooperative behaviour of a phosphorus-nitrogen-phosphorus pincer ligand in rate-determining heterolytic hydrogen splitting.

SYNTHESIS AND ANTITUMOR ACTIVITY OF COPPER, NICKEL AND COBALT COORDINATION COMPOUNDS WITH 1-(2-HYDROXYPHENYL)ETHANONE N(4)-ALLYL-3-THIOSEMICARBAZONE

OpenAIRE

Vasilii GRAUR; Serghei SAVCIN; Victor TSAPKOV; Aurelian GULEA

2015-01-01

The paper presents the synthesis of the ligand 1-(2-hydroxyphenyl)ethanone N(4)-allyl-3-thiosemicarbazone (H2L) and six coordination compounds of copper, nickel and cobalt with this ligand. The structure of thiosemicarbazone H2L was studied using 1H and 13С NMR spectroscopy. The synthesized coordination compounds were studied using elemental analysis, gravimetric analysis of water content, molar conductivity, and magnetochemistry. For H2L the antitumor activity towards human leukemia HL-60 ce...

Mesoporous organosilica nanotubes containing a chelating ligand in their walls

Directory of Open Access Journals (Sweden)

Xiao Liu

2014-11-01

Full Text Available We report the synthesis of organosilica nanotubes containing 2,2′-bipyridine chelating ligands within their walls, employing a single-micelle-templating method. These nanotubes have an average pore diameter of 7.8 nm and lengths of several hundred nanometers. UV-vis absorption spectra and scanning transmission electron microscopy observations of immobilized nanotubes with an iridium complex on the bipyridine ligands showed that the 2,2′-bipyridine groups were homogeneously distributed in the benzene-silica walls. The iridium complex, thus, immobilized on the nanotubes exhibited efficient catalytic activity for water oxidation using Ce4+, due to the ready access of reactants to the active sites in the nanotubes.

Ligand binding reduces SUMOylation of the peroxisome proliferator-activated receptor γ (PPARγ activation function 1 (AF1 domain.

Directory of Open Access Journals (Sweden)

Rolf Diezko

Full Text Available Peroxisome proliferator-activated receptor gamma (PPARγ is a ligand-activated nuclear receptor regulating adipogenesis, glucose homeostasis and inflammatory responses. The activity of PPARγ is controlled by post-translational modifications including SUMOylation and phosphorylation that affects its biological and molecular functions. Several important aspects of PPARγ SUMOylation including SUMO isoform-specificity and the impact of ligand binding on SUMOylation remain unresolved or contradictory. Here, we present a comprehensive study of PPARγ1 SUMOylation. We show that PPARγ1 can be modified by SUMO1 and SUMO2. Mutational analyses revealed that SUMOylation occurs exclusively within the N-terminal activation function 1 (AF1 domain predominantly at lysines 33 and 77. Ligand binding to the C-terminal ligand-binding domain (LBD of PPARγ1 reduces SUMOylation of lysine 33 but not of lysine 77. SUMOylation of lysine 33 and lysine 77 represses basal and ligand-induced activation by PPARγ1. We further show that lysine 365 within the LBD is not a target for SUMOylation as suggested in a previous report, but it is essential for full LBD activity. Our results suggest that PPARγ ligands negatively affect SUMOylation by interdomain communication between the C-terminal LBD and the N-terminal AF1 domain. The ability of the LBD to regulate the AF1 domain may have important implications for the evaluation and mechanism of action of therapeutic ligands that bind PPARγ.

Ligand-tailored single-site silica supported titanium catalysts: Synthesis, characterization and towards cyanosilylation reaction

Science.gov (United States)

Xu, Wei; Li, Yani; Yu, Bo; Yang, Jindou; Zhang, Ying; Chen, Xi; Zhang, Guofang; Gao, Ziwei

2015-01-01

A successive anchoring of Ti(NMe2)4, cyclopentadiene and a O-donor ligand, 1-hydroxyethylbenzene (PEA), 1,1‧-bi-2-naphthol (Binol) or 2,3-dihydroxybutanedioic acid diethyl ester (Tartrate), on silica was conducted by SOMC strategy in moderate conditions. The silica, monitored by in-situ Fourier transform infrared spectroscopy (in-situ FT-IR), was pretreated at different temperatures (200, 500 and 800 °C). The ligand tailored silica-supported titanium complexes were characterized by in-situ FT-IR, 13C CP MAS-NMR, X-ray photoelectron spectroscopy (XPS), X-ray absorption near edge structure (XANES) and elemental analysis in detail, verifying that the surface titanium species are single sited. The catalytic activity of the ligand tailored single-site silica supported titanium complexes was evaluated by a cyanosilylation of benzaldehyde. The results showed that the catalytic activity is dependent strongly on the dehydroxylation temperatures of silica and the configuration of the ligands.

Application of a novel design paradigm to generate general nonpeptide combinatorial templates mimicking beta-turns: synthesis of ligands for melanocortin receptors.

Science.gov (United States)

Webb, Thomas R; Jiang, Luyong; Sviridov, Sergey; Venegas, Ruben E; Vlaskina, Anna V; McGrath, Douglas; Tucker, John; Wang, Jian; Deschenes, Alain; Li, Rongshi

2007-01-01

We report the further application of a novel approach to template and ligand design by the synthesis of agonists of the melanocortin receptor. This design method uses the conserved structural data from the three-dimensional conformations of beta-turn peptides to design rigid nonpeptide templates that mimic the orientation of the main chain C-alpha atoms in a peptide beta-turn. We report details on a new synthesis of derivatives of template 1 that are useful for the synthesis of exploratory libraries. The utility of this technique is further exemplified by several iterative rounds of high-throughput synthesis and screening, which result in new partially optimized nonpeptide agonists for several melanocortin receptors.

LASSO-ligand activity by surface similarity order: a new tool for ligand based virtual screening.

Science.gov (United States)

Reid, Darryl; Sadjad, Bashir S; Zsoldos, Zsolt; Simon, Aniko

2008-01-01

Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

LASSO—ligand activity by surface similarity order: a new tool for ligand based virtual screening

Science.gov (United States)

Reid, Darryl; Sadjad, Bashir S.; Zsoldos, Zsolt; Simon, Aniko

2008-06-01

Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

Synthesis and pharmacological characterization of novel xanthine carboxylate amides as A2A adenosine receptor ligands exhibiting bronchospasmolytic activity.

Science.gov (United States)

Yadav, Rakesh; Bansal, Ranju; Rohilla, Suman; Kachler, Sonja; Klotz, Karl-Norbert

2016-04-01

The carboxylate amides of 8-phenyl-1,3-dimethylxanthine described herein represent a new series of selective ligands of the adenosine A2A receptors exhibiting bronchospasmolytic activity. The effects of location of 8-phenyl substitutions on the adenosine receptor (AR) binding affinities of the newly synthesized xanthines have also been studied. The compounds displayed moderate to potent binding affinities toward various adenosine receptor subtypes when evaluated through radioligand binding studies. However, most of the compounds showed the maximum affinity for the A2A subtype, some with high selectivity versus all other subtypes. Xanthine carboxylate amide 13b with a diethylaminoethylamino moiety at the para-position of the 8-phenylxanthine scaffold was identified as the most potent A2A adenosine receptor ligand with Ki=0.06μM. Similarly potent and highly A2A-selective are the isovanillin derivatives 16a and 16d. In addition, the newly synthesized xanthine derivatives showed good in vivo bronchospasmolytic activity when tested in guinea pigs. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis of novel ligands for neuro-inflammation imaging using Positron Emission Tomography

International Nuclear Information System (INIS)

Cacheux, Fanny

2016-01-01

Neuro-inflammation plays an important role in many neuro-degenerative diseases (Alzheimer, Parkinson, Multiple sclerosis..) and recent developments in molecular imaging provide today new insights into the diagnostic and the treatment management of these diseases. Among the existing imaging techniques, the highly sensitive and quantitative nuclear modalities SPECT (single photon emission computed tomography) but especially PET (positron emission tomography) play key roles. My PhD program is devoted to the design and synthesis of novel radioligands, all dedicated to the imaging of specific targets and processes linked to neuro-inflammation. For this, PET and the short-lived positron-emitter fluorine-18 (T 1/2 : 109.8 min) remain the main focuses. The project has been divided into two sections, the first one concentrates on the development of novel ligands targeting the Translocator Protein 18 kDa (TSPO). Indeed, this target is today recognized as an early bio-marker of neuro-inflammatory processes and PK11195, an isoquinoline carboxamide labelled with carbon-11, was, in the late 80's, the first reported PET-radioligand. More recently, new compounds, all belonging to different chemical classes, have emerged and notably the pyrazolopyrimidine acetamide [ 11 C]DPA-713 and the pyridazinoindole acetamide [ 11 C]SSR180575. Within the first section of my PhD, novel derivatives of both DPA-713 and SSR180575 have been synthesized and in vitro characterized. Dedicated precursors for labelling were also developed for the most promising candidates, and radiolabelling has been performed. Some results have been presented at the 21. International Symposium on Radiopharmaceutical Sciences (Columbia, MO, USA - May 26-31, 2015).The second part of my PhD, deals with the development of ligands for alternative targets to the TSPO, like the type-2 cannabinoid receptor (CB2R) and the purinergic P2Y14/P2Y12 receptors, the latter emerging today as a hot topic for imaging opportunities

Synthesis, characterisation and antimicrobial activities of cobalt(II, copper(II and zinc(II mixed-ligand complexes containing 1,10-phenanthroline and 2,2’-bipyridine

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A. Mohamadou

2010-06-01

Full Text Available Three new 1,10-phenanthroline and 2,2’-bipyridine mixed-ligand complexes of [Co(bpy(phen2](NO32.2H2O, [Cu(bpy(phen H2O 2]Cl2.2H2O, and [Zn(bpy2(phen]Cl2.6H2O were synthesized. The complexes were characterized by elemental, IR and visible spectroscopic analyses and the results indicate that both ligands are coordinated to the respective metal ions giving octahedral complexes. Antimicrobial studies showed that there is increased antimicrobial activity of the metal ions on coordination to the ligands. The water soluble complexes showed antimicrobial activities that are higher than those of the metal salts and 2,2’-bipyridine but lower than those of 1,10-phenanthroline. The copper complex [Cu(bpy(phen(H2O 2]Cl2.2H2O shows the highest activity.

Iminobisphosphines to (non-)symmetrical diphosphinoamine ligands : Metal-induced synthesis of diphosphorus nickel complexes and application in ethylene oligomerisation reactions

NARCIS (Netherlands)

Boulens, Pierre; Lutz, Martin|info:eu-repo/dai/nl/304828971; Jeanneau, Erwann; Olivier-Bourbigou, Hélène; Reek, Joost N H; Breuil, Pierre Alain R

2014-01-01

We describe the synthesis of a range of novel iminobisphosphine ligands based on a sulfonamido moiety [R1SO2N=P(R 2)2-P(R3)2]. These molecules rearrange in the presence of nickel by metal-induced breakage of the P-P bond to yield symmetrical and nonsymmetrical diphosphinoamine nickel complexes of

Synthesis of n.c.a. {sup 18}F-fluorinated NMDA- and D{sub 4}-receptor ligands via [{sup 18}F]fluorobenzenes; Traegerarme Synthese {sup 18}F-markierter, ausgewaehlter NMDA- und D{sub 4}-Rezeptorliganden durch Einsatz geeigneter [{sup 18}F]Fluorbenzolderivate

Energy Technology Data Exchange (ETDEWEB)

Ludwig, T

2005-11-01

In this thesis new strategies were developed and evaluated for the no-carrier-added (n.c.a.) {sup 18}F-labelling of receptor ligands as radiodiagnostics for characterization of brain receptors using positron-emission-tomography (PET). Special emphasis was placed on the synthesis of n.c.a. ({+-})-3-(4-hydroxy-4-(4-[{sup 18}F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol, a ligand with high affinity for the NR2B subtype of NMDA receptors and n.c.a. (3-(4-[{sup 18}F]fluorphenoxy)propyl)-(2-(4-tolylphenoxy)ethyl)amine ([{sup 18}F]FPTEA) a dopamine D{sub 4} receptor ligand. In order to synthesize n.c.a. ({+-})-3-(4-hydroxy-4-(4-[{sup 18}F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol the {sup 18}F-fluoroarylation method via metallorganic intermediates was modified and improved. The suitability of the organometallic {sup 18}F-fluoroarylation agents was proven with several model compounds. High radiochemical yields of 20-30% were obtained also with piperidinone-derivatives. The preparation of a suitable precursor for the synthesis of the NMDA receptor ligand, however, could not be achieved by synthesis of appropriate 1,3-dioxolane protected piperidinone derivatives. Further, the synthesis of n.c.a. ([{sup 18}F]fluoroaryloxy)alkylamines via n.c.a. 4-[{sup 18}F]fluorophenol was developed and evaluated. The synthesis of n.c.a. [{sup 18}F]fluoroarylethers with corresponding model compounds was optimized and led to a radiochemical yield of 25-60%, depending on the alkylhalide used. The preparation of n.c.a. 1-(3-bromopropoxy)-4-[{sup 18}F]fluorobenzene proved advantageous in comparison to direct use of 4-[{sup 18}]fluorophenol for coupling with a corresponding N-protected precursor for the synthesis of n.c.a. [{sup 18}F]FPTEA. With regard to the radiochemical yields and the loss of activity during the synthesis and isolation of n.c.a. 4-[{sup 18}F]fluorophenol and n.c.a. 1-(3-bromopropoxy)-4-[{sup 18}F]fluorobenzene, [{sup 18}F]FPTEA was obtained by reaction with 2-(4-tolyloxy

Synthesis, spectroscopic, DFT calculations and biological activity studies of ruthenium carbonyl complexes with 2-picolinic acid and a secondary ligand

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Shohayeb, Shahera M.; Mohamed, Rania G.; Moustafa, H.; El-Medani, Samir M.

2016-09-01

Thermal reaction of [Ru3(CO)12] with 2-picolinic acid (Hpic) in the absence and presence of a secondary ligand (pyridine, Py, bipyridine, Bipy, or thiourea, Tu) was investigated. Four complexes with molecular formulae: [Ru(CO)3(Hpic)], 1, [Ru2(CO)5(Hpic)(Py)], 2, [Ru2(CO)5(Hpic)(Tu)], 3 and [Ru2(CO)4(Hpic)(Bipy)], 4, were isolated. All complexes were characterized based on elemental analyses, IR, 1H NMR, magnetic studies, mass spectrometry and thermal analysis. The ligand and its complexes have been screened for antibacterial activities. Density Functional Theory (DFT) calculations at the B3LYP/6-311G (d,p)_ level of theory have been carried out to investigate the equilibrium geometry of the ligands. The optimized geometry parameters of the complexes were evaluated using B3LYP method and LANL2DZ basis set. The extent of natural charge population (core, valence and rydberg), exact electronic configuration, total Lewis and total non-Lewis are estimated and discussed in terms of natural bond orbitals (NBO) analysis.

Identification and Biological Activity of Synthetic Macrophage Inducible C-Type Lectin Ligands

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Chriselle D. Braganza

2018-01-01

Full Text Available The macrophage inducible C-type lectin (Mincle is a pattern recognition receptor able to recognize both damage-associated and pathogen-associated molecular patterns, and in this respect, there has been much interest in determining the scope of ligands that bind Mincle and how structural modifications to these ligands influence ensuing immune responses. In this review, we will present Mincle ligands of known chemical structure, with a focus on ligands that have been synthetically prepared, such as trehalose glycolipids, glycerol-based ligands, and 6-acylated glucose and mannose derivatives. The ability of the different classes of ligands to influence the innate, and consequently, the adaptive, immune response will be described, and where appropriate, structure–activity relationships within each class of Mincle ligands will be presented.

Synthesis and characterization of ligands and bifunctional chelating agents by modification of cysteine for complexation studies with 99mTc

International Nuclear Information System (INIS)

Pillai, M.R.A.; Kothari, K.; Banerjee, S.; Samuel, G.; Suresh, M.; Sarma, H.D.

1998-01-01

The synthesis of four novel ligands using the amino-acid cysteine and its ethyl carboxylate derivative is described. The synthetic method involves a two-step procedure, wherein the intermediate Schiff base formed by the condensation of the amino group of the cysteine substrate and salicylaldehyde is reduced to give the target ligands. The intermediates and the final products are characterised by high resolution NMR spectroscopy. Complexation studies of the ligands with 99m Tc are standardised using stannous tartrate as the reducing agent at varying reaction conditions. The complexes are characterised using standard quality control techniques such as TLC, paper electrophoresis and PC. Lipophilicities of the complexes are estimated by solvent extraction into chloroform. Substantial changes in net charge and lipophilicity in the 99m Tc complexes are observed on substituting the carboxylic acid residue in ligand I and II with the ethyl carboxylate groups (ligands III and IV). All the ligands formed complexes in high yield. While the complexes of ligand I and II are observed to be hydrophilic in nature and are not extractable into CHCl 3 , ligands III and IV gave neutral and lipophilic complexes. Though the distribution ratios of the complexes of ligands III and IV in CHCl 3 /saline system are observed to be very high, considerable differences in lipophilicities are also observed as evidenced by the difference in their respective extractabilities in chloroform. On storage, the complex of ligand III exhibit a tendency to get converted to a hydrophilic and non-extractable species. The bio-distribution of the complexes of ligands I and II showed that they have predominantly renal clearances whereas the complexes of ligands III and IV exhibited a significant hepatobiliary uptake and did not show much uptake in brain in spite of its favourable properties such as neutrality, lipophilicity and conversion into a hydrophilic species. (author)

Novel methylene bridged ethylenediamine-type ligands: Synthesis and spectral characterization

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Mihajlović-Lalić Ljiljana E.

2014-01-01

Full Text Available Herein we report the synthesis of two new organic compounds, diisobutyl- and diisopentyl N,N′-methylene-(S,S-ethylenediamine-N,N′-di-2-(3-cyclohexylpropanoate. A one-pot procedure was carried out by adding the reducing agent and carbonyl compound into the methanol solution of the parent compounds (iso-butyl and iso-pentyl esters of (S,S-ethylenediamine-N,N′-di-2-(3-cyclohexylpropanoic acid in appropriate stoichiometric ratios. The compounds were fully characterized by infrared, ESI-MS, 1D (1H, 13C and 2D (COSY, HSQC, HMBC NMR spectroscopy and elemental analysis. The spectral data confirm the presence of -CH2- group introduced between nitrogen atoms of the ethylenediamine moiety revealing neutral form of potential bidentate ligand. [Projekat Ministarstva nauke Republike Srbije, br. 172035. The authors also acknowledge the support of the FP7 RegPot project FCUB ERA GA No. 256716. The EC does not share responsibility for the content of the article

Synthesis methodology and applied heterocyclic chemistry

International Nuclear Information System (INIS)

Suzenet, F.

2007-11-01

Among the researches activities presented in this work, is described the synthesis of extracting molecules for the reprocessing of nuclear wastes. The use of some elaborated ligands for the detection of metallic cations has been considered. (O.M.)

Synthesis, characterization and thermal behavior of antibacterial and antifungal active zinc complexes of bis (3(4-dimethylaminophenyl)-allylidene-1,2-diaminoethane

International Nuclear Information System (INIS)

Montazerozohori, Morteza; Zahedi, Saeedeh; Naghiha, Asghar; Zohour, Mostafa Montazer

2014-01-01

In this work, synthesis of a new series of zinc halide/pseudohalide complexes of a bidentate Schiff base ligand entitled as bis (3-(4-dimethylaminophenyl)-allylidene)-1,2-diaminoethane(L) is described. The ligand and its zinc complexes were characterized by various techniques such as elemental analysis, FT-IR, UV–visible, 1 H and 13 C NMR spectra, cyclic voltammetry, and conductometry. Accordingly ZnLX 2 (X = Cl − , Br − , I − , SCN − and N 3 − ) was suggested as molecular formula of the complexes. Redox behaviors of ligand and its zinc complexes were investigated by cyclic voltammetry method. Furthermore, the ligand and its zinc halide/pseudohalide complexes were tested for their in vitro antibacterial activities against two gram positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Also in vitro antifungal activities of them against Candida albicans and Aspergillus niger were investigated. The results indicated that all compounds are antibacterial and antifungal active. Thermal behaviors of ligand and its zinc complexes were studied from room temperature to 1100 °C under argon atmosphere. It was found that the ligand and zinc iodide are decomposed completely via three and four steps respectively while other zinc complexes leave out the metal or organometallic compounds as final residuals after 3–4 decomposition steps at above temperature range. Moreover evaluation of some thermo-kinetic parameters such as activation energy (∆E ⁎ ), enthalpy (∆H ⁎ ), entropy (∆S ⁎ ) and Gibbs free energy change (∆G ⁎ ) of the thermal decomposition steps were performed based on the Coats–Redfern relation. - Highlights: • Some novel complexes of Zn(II) with a bidentate Schiff base ligand have been synthesized. • Redox behavior of ligand and zinc complexes was investigated by cyclic voltammetry. • The ligand and its zinc complexes are antibacterial and

Structural characterization and antimicrobial activities of transition metal complexes of a hydrazone ligand

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Bakale, Raghavendra P.; Naik, Ganesh N.; Machakanur, Shrinath S.; Mangannavar, Chandrashekhar V.; Muchchandi, Iranna S.; Gudasi, Kalagouda B.

2018-02-01

A hydrazone ligand has been synthesized by the condensation of 2-nitrobenzaldehyde and hydralazine, and its Co(II), Ni(II), Cu(II) and Zn(II) complexes have been reported. Structural characterization of the ligand and its metal complexes has been performed by various spectroscopic [IR, NMR, UV-Vis, Mass], thermal and other physicochemical methods. The structure of the ligand and its Ni(II) complex has been characterized by single crystal X-ray diffraction studies. All the synthesized compounds have been screened for in vitro antimicrobial activity. The antibacterial activity is tested against Gram-positive strains Enterococcus faecalis, Streptococcus mutans and Staphylococcus aureus and Gram-negative strains Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae using ciprofloxacin as the reference standard. Antifungal activity is tested against Candida albicans, Aspergillus fumigatus and Aspergillus niger using ketoconazole as the reference standard. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standard. Ligand, Cu(II) and Zn(II) complexes have shown excellent activity against Candida albicans.

Design, Synthesis, and Biological Evaluation of Small, High-Affinity Siglec-7 Ligands: Toward Novel Inhibitors of Cancer Immune Evasion.

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Prescher, Horst; Frank, Martin; Gütgemann, Stephan; Kuhfeldt, Elena; Schweizer, Astrid; Nitschke, Lars; Watzl, Carsten; Brossmer, Reinhard

2017-02-09

Natural killer cells are able to directly lyse tumor cells, thereby participating in the immune surveillance against cancer. Unfortunately, many cancer cells use immune evasion strategies to avoid their eradication by the immune system. A prominent escape strategy of malignant cells is to camouflage themselves with Siglec-7 ligands, thereby recruiting the inhibitory receptor Siglec-7 expressed on the NK cell surface which subsequently inhibits NK-cell-mediated lysis. Here we describe the synthesis and evaluation of the first, high-affinity low molecular weight Siglec-7 ligands to interfere with cancer cell immune evasion. The compounds are Sialic acid derivatives and bind with low micromolar K d values to Siglec-7. They display up to a 5000-fold enhanced affinity over the unmodified sialic acid scaffold αMe Neu5Ac, the smallest known natural Siglec-7 ligand. Our results provide a novel immuno-oncology strategy employing natural immunity in the fight against cancers, in particular blocking Siglec-7 with low molecular weight compounds.

Ruthenium(II) arene complexes with chelating chloroquine analogue ligands: Synthesis, characterization and in vitro antimalarial activity†

Science.gov (United States)

Glans, Lotta; Ehnbom, Andreas; de Kock, Carmen; Martínez, Alberto; Estrada, Jesús; Smith, Peter J.; Haukka, Matti; Sánchez-Delgado, Roberto A.; Nordlander, Ebbe

2012-01-01

Three new ruthenium complexes with bidentate chloroquine analogue ligands, [Ru(η6-cym)(L1)Cl]Cl (1, cym = p-cymene, L1 = N-(2-((pyridin-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine), [Ru(η6-cym)(L2)Cl]Cl (2, L2 = N-(2-((1-methyl-1H-imidazol-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine) and [Ru(η6-cym)(L3)Cl] (3, L3 = N-(2-((2-hydroxyphenyl)methylimino)ethyl)-7-chloroquinolin-4-amine) have been synthesized and characterized. In addition, the X-ray crystal structure of 2 is reported. The antimalarial activity of complexes 1–3 and ligands L1, L2 and L3, as well as the compound N-(2-(bis((pyridin-2-yl)methyl)amino)ethyl)-7-chloroquinolin-4-amine (L4), against chloroquine sensitive and chloroquine resistant Plasmodium falciparum malaria strains was evaluated. While 1 and 2 are less active than the corresponding ligands, 3 exhibits high antimalarial activity. The chloroquine analogue L2 also shows good activity against both the choloroquine sensitive and the chloroquine resistant strains. Heme aggregation inhibition activity (HAIA) at an aqueous buffer/n-octanol interface (HAIR50) and lipophilicity (D, as measured by water/n-octanol distribution coefficients) have been measured for all ligands and metal complexes. A direct correlation between the D and HAIR50 properties cannot be made because of the relative structural diversity of the complexes, but it may be noted that these properties are enhanced upon complexation of the inactive ligand L3 to ruthenium, to give a metal complex (3) with promising antimalarial activity. PMID:22249579

Mixed-ligand Ru(II) complexes with 2,2'-bipyridine and aryldiazo-beta-diketonato auxillary ligands: synthesis, physico-chemical study and antitumour properties.

Science.gov (United States)

Mishra, Lallan; Yadaw, Ajay K; Bhattacharya, Subrato; Dubey, Santosh K

2005-05-01

The complexes of Ru(II)-2,2'-bipyridyl with substituted diazopentane-2,4-diones (L1H-L5H) were synthesized and characterized by elemental analyses, conductance, FAB (fast atom bombardment) mass and spectral (IR, UV/Vis (UV/visible), NMR) studies. Molecular geometry optimization of the complexes was also made. None of the complexes luminesce. However, facilitated oxidation of Ru(II) to Ru(III) was evidenced from their lower reduction potential data. The ligands and their complexes were tested for their antitumour activity against a variety of tumour cell lines. Though activity is found to vary with the type of tumour cell lines used, yet complex 5 with naphtyldiazopentane-2,4-dione as co-ligand was found to be a potential compound as it showed in general significant activity against all cell lines studied.

Chiral ligand-protected gold nanoclusters: Considering the optical activity from a viewpoint of ligand dissymmetric field

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Hiroshi Yao

2016-10-01

Full Text Available Chirality is a geometric property of a physical, chemical, or biological object, which is not superimposable on its mirror image. Its significant presence has led to a strong demand in the development of chiral drugs, sensors, catalysts, and photofunctional materials. In recent years, chirality of nanoscale organic/inorganic hybrids has received tremendous attention owing to potential applications in chiral nanotechnology. In particular, with the recent progress in the syntheses and characterizations of atomically precise gold nanoclusters protected by achiral thiolates, atomic level origins of their chirality have been unveiled. On the other hand, chirality or optical activity in metal nanoclusters can also be introduced via the surface chiral ligands, which should be universal for the nanosystems. This tutorial review presents some optically-active metal (gold nanoclusters protected by chiral thiolates or phosphines, and their chiroptical (or circular dichroism; CD properties are discussed mostly from a viewpoint of the ligand dissymmetric field scheme. The examples are the gold nanoclusters protected by (R-/(S-2-phenylpropane-1-thiol, (R-/(S-mercaptosuccinic acid, phenylboronate-D/L-fructose complexes, phosphine sulfonate-ephedrinium ion pairs, or glutathione. Some methodologies for versatile asymmetric transformation and chiroptical controls of the nanocluster compounds are also described. In the dissymmetric field model as the origin of optical activity, the chiroptical responses of the gold nanoclusters are strongly associated with coupled oscillator and/or CD stealing mechanisms based on the concept of induced CD (ICD derived from a perturbation theory, so on this basis, some characteristic features of the observed CD responses of chiral ligand-protected gold nanoclusters are presented in detail. We believe that various kinds of origins of chirality found in ligand-protected gold nanoclusters may provide models for understanding those of

Ligand mobility modulates immunological synapse formation and T cell activation.

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Chih-Jung Hsu

Full Text Available T cell receptor (TCR engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70 and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76. This molecular rearrangement results in formation of the immunological synapse (IS, a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca(2+ were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses.

Synthesis of Phthalimide Derivatives as Potential PPAR-γ Ligands

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So Hyeon Eom

2016-06-01

Full Text Available Paecilocin A, a phthalide derivative isolated from the jellyfish-derived fungus Paecilomyces variotii, activates PPAR-γ (Peroxisome proliferator-activated receptor gamma in rat liver Ac2F cells. Based on a SAR (Structure-activity relationships study and in silico analysis of paecilocin A-mimetic derivatives, additional N-substituted phthalimide derivatives were synthesized and evaluated for PPAR-γ agonistic activity in both murine liver Ac2F cells and in human liver HepG2 cells by luciferase assay, and for adipogenic activity in 3T3-L1 cells. Docking simulation indicated PD6 was likely to bind most strongly to the ligand binding domain of PPAR-γ by establishing crucial H-bonds with key amino acid residues. However, in in vitro assays, PD1 and PD2 consistently displayed significant PPAR-γ activation in Ac2F and HepG2 cells, and adipogenic activity in 3T3-L1 preadipocytes.

The Effects of Magnesium Ions on the Enzymatic Synthesis of Ligand-Bearing Artificial DNA by Template-Independent Polymerase

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Yusuke Takezawa

2016-06-01

Full Text Available A metal-mediated base pair, composed of two ligand-bearing nucleotides and a bridging metal ion, is one of the most promising components for developing DNA-based functional molecules. We have recently reported an enzymatic method to synthesize hydroxypyridone (H-type ligand-bearing artificial DNA strands. Terminal deoxynucleotidyl transferase (TdT, a template-independent DNA polymerase, was found to oligomerize H nucleotides to afford ligand-bearing DNAs, which were subsequently hybridized through copper-mediated base pairing (H–CuII–H. In this study, we investigated the effects of a metal cofactor, MgII ion, on the TdT-catalyzed polymerization of H nucleotides. At a high MgII concentration (10 mM, the reaction was halted after several H nucleotides were appended. In contrast, at lower MgII concentrations, H nucleotides were further appended to the H-tailed product to afford longer ligand-bearing DNA strands. An electrophoresis mobility shift assay revealed that the binding affinity of TdT to the H-tailed DNAs depends on the MgII concentration. In the presence of excess MgII ions, TdT did not bind to the H-tailed strands; thus, further elongation was impeded. This is possibly because the interaction with MgII ions caused folding of the H-tailed strands into unfavorable secondary structures. This finding provides an insight into the enzymatic synthesis of longer ligand-bearing DNA strands.

Synthesis of imine bond containing insoluble polymeric ligand and its transition metal complexes, structural characterization and catalytic activity on esterification reaction.

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Gönül, İlyas; Ay, Burak; Karaca, Serkan; Saribiyik, Oguz Yunus; Yildiz, Emel; Serin, Selahattin

2017-01-01

In this study, synthesis of insoluble polymeric ligand (L) and its transition metal complexes [Cu(L)Cl 2 ]·2H 2 O (1) , [Co(L)Cl 2 (H 2 O) 2 ] (2) and [Ni(L)Cl 2 (H 2 O) 2 ] (3) , having the azomethine groups, were synthesized by the condensation reactions of the diamines and dialdehydes. The structural properties were characterized by the analytical and spectroscopic methods using by elemental analysis, Fourier Transform Infrared, Thermo Gravimetric Analysis, Powder X-ray Diffraction, magnetic susceptibility and Inductively Coupled Plasma. The solubilities of the synthesized polymeric materials were also investigated and found as insoluble some organic and inorganic solvents. Additionally, their catalytic performance was carried out for the esterification reaction of acetic acid and butyl acetate. The highest conversion rate is 75.75% by using catalyst 1 . The esterification of butanol gave butyl acetate with 100% selectivity.

New synthetic routes toward enantiopure nitrogen donor ligands

OpenAIRE

Sala, Xavier; Rodríguez, Anna M.; Rodríguez, Montserrat; Romero, Isabel; Parella, Teodor; Zelewsky, Alexander von; Llobet, Antoni; Benet-Buchholz, Jordi

2008-01-01

New polypyridylic chiral ligands, having either C₃ or lower symmetry, have been prepared via a de novo construction of the pyridine nucleus by means of Kröhnke methodology in the key step. The chiral moieties of these ligands originate from the monoterpen chiral pool, namely (-)-α-pinene ((-)-14, (-)-15) and (-)-myrtenal ((-)-9, (-)-10). Extension of the above-mentioned asymmetric synthesis procedure to the preparation of enantiopure derivatives of some commonly used polypyridylic ligands has...

PPARα ligands activate antioxidant enzymes and suppress hepatic fibrosis in rats

International Nuclear Information System (INIS)

Toyama, Tetsuya; Nakamura, Hideki; Harano, Yuichi; Yamauchi, Norihito; Morita, Atsuhiro; Kirishima, Toshihiko; Minami, Masahito; Itoh, Yoshito; Okanoue, Takeshi

2004-01-01

Oxidative stress is a major pathogenetic factor in hepatic fibrosis. Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor which is known to affect oxidative stress and PPARα ligands may have rescue effects on hepatic fibrosis. We tested this hypothesis using rat thioacetamide (TAA) models of liver cirrhosis. Rats were given intraperitoneal injection of TAA and treated with a diet containing one of the two PPARα ligands, Wy-14,643 (WY) or fenofibrate. WY treatment dramatically reduced hepatic fibrosis and also prevented the inhibition catalase of mRNA expression caused by TAA. Correspondingly, catalase activity increased in the TAA + WY group but decreased in the control TAA group. The antifibrotic action of fenofibrate in the TAA model was comparable with that of WY. PPARα ligands have an antifibrotic action in the rat TAA model of liver cirrhosis, probably due to an antioxidant effect of enhanced catalase expression and activity in the liver

A Guided Inquiry Activity for Teaching Ligand Field Theory

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Johnson, Brian J.; Graham, Kate J.

2015-01-01

This paper will describe a guided inquiry activity for teaching ligand field theory. Previous research suggests the guided inquiry approach is highly effective for student learning. This activity familiarizes students with the key concepts of molecular orbital theory applied to coordination complexes. Students will learn to identify factors that…

Pokemon decreases the transcriptional activity of RARα in the absence of ligand.

Science.gov (United States)

Yang, Yutao; Li, Yueting; Di, Fei; Cui, Jiajun; Wang, Yue; David Xu, Zhi-Qing

2016-12-20

Pokemon is a transcriptional repressor that belongs to the POZ and Krüppel (POK) protein family. In this study, we investigated the potential interaction between Pokemon and retinoic acid receptor alpha (RARα) and determined the role of Pokemon in regulation of RARα transcriptional activity in the absence of ligand. We found that Pokemon could directly interact with RARα. Moreover, we demonstrated that Pokemon could decrease the transcriptional activity of RARα in the absence of ligand. Furthermore, we showed that Pokemon could repress the transcriptional activity of RARα by increasing the recruitment of nuclear receptor co-repressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) to the retinoic acid response element (RARE) element. Taken together, these data suggest that Pokemon is a novel partner of RARα that acts as a co-repressor to regulate RARα transcriptional activity in the absence of ligand.

Screening the efficient biological prospects of triazole allied mixed ligand metal complexes

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Utthra, Ponnukalai Ponya; Kumaravel, Ganesan; Raman, Natarajan

2017-12-01

Triazole appended mixed ligand complexes (1-8) of the general formula [ML (bpy/phen)2]Cl2, where M = Cu(II), Co(II), Ni(II) and Zn(II), L = triazole appended Schiff base (E)sbnd N-(4-nitrobenzylidene)-1H-1,2,4-triazol-3-amine and bpy/phen = 2,2‧-bipyridine/1,10-phenanthroline, have been synthesized. The design and synthesis of this elaborate ligand has been performed with the aim of increasing stability and conjugation of 1,2,4 triazole, whose Schiff base derivatives are known as biologically active compounds thereby exploring their DNA binding affinity and other biological applications. The compounds have been comprehensively characterized by elemental analysis, spectroscopic methods (IR, UV-Vis, EPR, 1H and 13C NMR spectroscopy), ESI mass spectrometry and magnetic susceptibility measurements. The complexes were found to exhibit octahedral geometry. The complexes 1-8 were subjected to DNA binding techniques evaluated using UV-Vis absorption, CV, CD, Fluorescence spectroscopy and hydrodynamic measurements. Complex 5 showed a Kb value of 3.9 × 105 M-1. The DNA damaging efficacy for the complexes was observed to be high compared to the ligand. The antimicrobial screening of the compounds against bacterial and fungal strains indicates that the complexes possess excellent antimicrobial activity than the ligand. The overall biological activity of the complexes with phen as a co-ligand possessed superior potential than the ligand.

Synthesis of high specific activity carbon-11 labeled tracers for neuroreceptor studies

International Nuclear Information System (INIS)

Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Wagner, H.N. Jr; Johns Hopkins Medical Institutions, Baltimore, MD

1989-01-01

The use of short-lived positron-emitting radiotracers together with positron emission tomography (PET) has allowed scientists to acquire previously inaccessible information regarding problems in physiology, biochemistry, and pharmacology in the living human body. In the past five years, successes in the application of PET to the non-invasive determination of the spatial distribution and regional concentration of a variety of neurotransmitter binding sites within the living brain often followed the successful selections and syntheses of appropriately radiolabeled ligands. This presentation concentrates on the synthesis of these high specific activity radiotracers for neuroreceptor PET studies labeled specifically with carbon-11. (author). 15 refs.; 1 fig

Synthesis, characterization and thermal behavior of antibacterial and antifungal active zinc complexes of bis (3(4-dimethylaminophenyl)-allylidene-1,2-diaminoethane

Energy Technology Data Exchange (ETDEWEB)

Montazerozohori, Morteza, E-mail: mmzohori@mail.yu.ac.ir [Department of Chemistry, Yasouj University, Yasouj 75918-74831 (Iran, Islamic Republic of); Zahedi, Saeedeh [Department of Chemistry, Yasouj University, Yasouj 75918-74831 (Iran, Islamic Republic of); Naghiha, Asghar [Department of Animal Sciences, Faculty of Agriculture, Yasouj University, Yasouj (Iran, Islamic Republic of); Zohour, Mostafa Montazer [Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan (Iran, Islamic Republic of)

2014-02-01

In this work, synthesis of a new series of zinc halide/pseudohalide complexes of a bidentate Schiff base ligand entitled as bis (3-(4-dimethylaminophenyl)-allylidene)-1,2-diaminoethane(L) is described. The ligand and its zinc complexes were characterized by various techniques such as elemental analysis, FT-IR, UV–visible, {sup 1}H and {sup 13}C NMR spectra, cyclic voltammetry, and conductometry. Accordingly ZnLX{sub 2} (X = Cl{sup −}, Br{sup −}, I{sup −}, SCN{sup −} and N{sub 3}{sup −}) was suggested as molecular formula of the complexes. Redox behaviors of ligand and its zinc complexes were investigated by cyclic voltammetry method. Furthermore, the ligand and its zinc halide/pseudohalide complexes were tested for their in vitro antibacterial activities against two gram positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Also in vitro antifungal activities of them against Candida albicans and Aspergillus niger were investigated. The results indicated that all compounds are antibacterial and antifungal active. Thermal behaviors of ligand and its zinc complexes were studied from room temperature to 1100 °C under argon atmosphere. It was found that the ligand and zinc iodide are decomposed completely via three and four steps respectively while other zinc complexes leave out the metal or organometallic compounds as final residuals after 3–4 decomposition steps at above temperature range. Moreover evaluation of some thermo-kinetic parameters such as activation energy (∆E{sup ⁎}), enthalpy (∆H{sup ⁎}), entropy (∆S{sup ⁎}) and Gibbs free energy change (∆G{sup ⁎}) of the thermal decomposition steps were performed based on the Coats–Redfern relation. - Highlights: • Some novel complexes of Zn(II) with a bidentate Schiff base ligand have been synthesized. • Redox behavior of ligand and zinc complexes was investigated by cyclic voltammetry. • The

Synthesis, Radiolabelling and In Vitro Characterization of the Gallium-68-, Yttrium-90- and Lutetium-177-Labelled PSMA Ligand, CHX-A''-DTPA-DUPA-Pep.

Science.gov (United States)

Baur, Benjamin; Solbach, Christoph; Andreolli, Elena; Winter, Gordon; Machulla, Hans-Jürgen; Reske, Sven N

2014-04-29

Since prostate-specific membrane antigen (PSMA) has been identified as a diagnostic target for prostate cancer, many urea-based small PSMA-targeting molecules were developed. First, the clinical application of these Ga-68 labelled compounds in positron emission tomography (PET) showed their diagnostic potential. Besides, the therapy of prostate cancer is a demanding field, and the use of radiometals with PSMA bearing ligands is a valid approach. In this work, we describe the synthesis of a new PSMA ligand, CHX-A''-DTPA-DUPA-Pep, the subsequent labelling with Ga-68, Lu-177 and Y-90 and the first in vitro characterization. In cell investigations with PSMA-positive LNCaP C4-2 cells, KD values of ≤14.67 ± 1.95 nM were determined, indicating high biological activities towards PSMA. Radiosyntheses with Ga-68, Lu-177 and Y-90 were developed under mild reaction conditions (room temperature, moderate pH of 5.5 and 7.4, respectively) and resulted in nearly quantitative radiochemical yields within 5 min.

Synthesis, Radiolabelling and In Vitro Characterization of the Gallium-68-, Yttrium-90- and Lutetium-177-Labelled PSMA Ligand, CHX-A''-DTPA-DUPA-Pep

Directory of Open Access Journals (Sweden)

Benjamin Baur

2014-04-01

Full Text Available Since prostate-specific membrane antigen (PSMA has been identified as a diagnostic target for prostate cancer, many urea-based small PSMA-targeting molecules were developed. First, the clinical application of these Ga-68 labelled compounds in positron emission tomography (PET showed their diagnostic potential. Besides, the therapy of prostate cancer is a demanding field, and the use of radiometals with PSMA bearing ligands is a valid approach. In this work, we describe the synthesis of a new PSMA ligand, CHX-A''-DTPA-DUPA-Pep, the subsequent labelling with Ga-68, Lu-177 and Y-90 and the first in vitro characterization. In cell investigations with PSMA-positive LNCaP C4-2 cells, KD values of ≤14.67 ± 1.95 nM were determined, indicating high biological activities towards PSMA. Radiosyntheses with Ga-68, Lu-177 and Y-90 were developed under mild reaction conditions (room temperature, moderate pH of 5.5 and 7.4, respectively and resulted in nearly quantitative radiochemical yields within 5 min.

Acetylation of pregnane X receptor protein determines selective function independent of ligand activation

International Nuclear Information System (INIS)

Biswas, Arunima; Pasquel, Danielle; Tyagi, Rakesh Kumar; Mani, Sridhar

2011-01-01

Research highlights: → Pregnane X receptor (PXR), a major regulatory protein, is modified by acetylation. → PXR undergoes dynamic deacetylation upon ligand-mediated activation. → SIRT1 partially mediates PXR deacetylation. → PXR deacetylation per se induces lipogenesis mimicking ligand-mediated activation. -- Abstract: Pregnane X receptor (PXR), like other members of its class of nuclear receptors, undergoes post-translational modification [PTM] (e.g., phosphorylation). However, it is unknown if acetylation (a major and common form of protein PTM) is observed on PXR and, if it is, whether it is of functional consequence. PXR has recently emerged as an important regulatory protein with multiple ligand-dependent functions. In the present work we show that PXR is indeed acetylated in vivo. SIRT1 (Sirtuin 1), a NAD-dependent class III histone deacetylase and a member of the sirtuin family of proteins, partially mediates deacetylation of PXR. Most importantly, the acetylation status of PXR regulates its selective function independent of ligand activation.

Effect of ligand activation of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in human lung cancer cell lines

International Nuclear Information System (INIS)

He Pengfei; Borland, Michael G.; Zhu Bokai; Sharma, Arun K.; Amin, Shantu; El-Bayoumy, Karam; Gonzalez, Frank J.; Peters, Jeffrey M.

2008-01-01

There is compelling evidence that peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) mediates terminal differentiation and is associated with inhibition of cell growth. However, it was recently suggested that growth of two human lung cancer cell lines is enhanced by PPARβ/δ. The goal of the present study was to provide insight in resolving this controversy. Therefore, the effect of ligand activation of PPARβ/δ in A549 and H1838 human lung cancer cell lines was examined using two high affinity PPARβ/δ ligands. Ligand activation of PPARβ/δ caused up-regulation of a known PPARβ/δ target gene, angiopoietin-like 4 (Angptl4) but did not influence expression of phosphatase and tensin homolog (PTEN) or phosphorylation of protein kinase B (Akt), and did not affect cell growth. Results from this study demonstrate that two human lung cancer cell lines respond to ligand activation of PPARβ/δ by modulation of target gene expression (Angptl4), but fail to exhibit significant modulation of cell proliferation

Ligand activation of peroxisome proliferator-activated receptor-β/δ suppresses liver tumorigenesis in hepatitis B transgenic mice

International Nuclear Information System (INIS)

Balandaram, Gayathri; Kramer, Lance R.; Kang, Boo-Hyon; Murray, Iain A.; Perdew, Gary H.; Gonzalez, Frank J.; Peters, Jeffrey M.

2016-01-01

Highlights: • The role of PPARβ/δ in HBV-induced liver cancer was examined. • PPARβ/δ inhibits steatosis, inflammation, tumor multiplicity and promotes apoptosis. • Kupffer cell PPARβ/δ mediates these effects independent of DNA binding. - Abstract: Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) inhibits steatosis and inflammation, known risk factors for liver cancer. In this study, the effect of ligand activation of PPARβ/δ in modulating liver tumorigenesis in transgenic hepatitis B virus (HBV) mice was examined. Activation of PPARβ/δ in HBV mice reduced steatosis, the average number of liver foci, and tumor multiplicity. Reduced expression of hepatic CYCLIN D1 and c-MYC, tumor necrosis factor alpha (Tnfa) mRNA, serum levels of alanine aminotransaminase, and an increase in apoptotic signaling was also observed following ligand activation of PPARβ/δ in HBV mice compared to controls. Inhibition of Tnfa mRNA expression was not observed in wild-type hepatocytes. Ligand activation of PPARβ/δ inhibited lipopolysaccharide (LPS)-induced mRNA expression of Tnfa in wild-type, but not in Pparβ/δ-null Kupffer cells. Interestingly, LPS-induced expression of Tnfa mRNA was also inhibited in Kupffer cells from a transgenic mouse line that expressed a DNA binding mutant form of PPARβ/δ compared to controls. Combined, these results suggest that ligand activation of PPARβ/δ attenuates hepatic tumorigenesis in HBV transgenic mice by inhibiting steatosis and cell proliferation, enhancing hepatocyte apoptosis, and modulating anti-inflammatory activity in Kupffer cells.

Synthesis, characterization and thermal study of some transition metal complexes of an asymmetrical tetradentate Schiff base ligand

Directory of Open Access Journals (Sweden)

ACHUT S. MUNDE

2010-03-01

Full Text Available Complexes of Cu(II, Ni(II, Co(II, Mn(II and Fe(III with an asymmetric tetradentate Schiff base ligand derived from dehydroacetic acid, 4-methyl-o-phenylenediamine and salicylic aldehyde were synthesized and characterized by elemental analysis, conductometry, magnetic susceptibility, UV–Vis, IR, 1H-NMR spectroscopy, X-ray diffraction analysis of powdered samples and thermal analysis, and screened for antimicrobial activity. The IR spectral data suggested that the ligand behaves as a dibasic tetadentate ligand towards the central metal ion with an ONNO donor atoms sequence. From the microanalytical data, the stoichiometry of the complexes 1:1 (metal:ligand was found. The physico-chemical data suggested square planar geometry for the Cu(II and Ni(II complexes and octahedral geometry for the Co(II, Mn(II and Fe(III complexes. The thermal behaviour (TGA/DTA of the complexes was studied and kinetic parameters were determined by Horowitz–Metzger and Coats–Redfern methods. The powder X-ray diffraction data suggested a monoclinic crystal system for the Co(II, Mn(II and Fe(III complexes. The ligand and their metal complexes were screened for antibacterial activity against Staphylococcus aureus and Escherichia coli and fungicidal activity against Aspergillus niger and Trichoderma viride.

New chiral phosphinephosphinite ligands: Application to stereoselective synthesis of a key intermediate of 1{beta}-methyl carbapenems by Rh(I)-catalyzed asymmetric hydroformylation

Energy Technology Data Exchange (ETDEWEB)

Saito, Takao; Yoshida, Akifumi; Matsumura, Kazuhiko [Takasago International Corp., Kanagawa (Japan)] [and others

1995-12-31

Transition metal catalyzed asymmetric hydroformylation is an attractive and highly useful homologation process for organic synthesis. Recently, the authors reported that the Rh(I) complexes of phosphinephosphite BINAPHOS are highly efficient catalysts for enantioselective hydroformylation of a variety of olefins. This time, the authors have designed and synthesized new chiral phosphinephosphinite ligands having binaphthyl backbone, (R)-2-diarylphosphino-2{prime}-diarylphosphinoxy-1,1{prime}-binaphthy1 (hereafter abbreviated (R)-BIPNITE). The Rh(I) complexes of these ligands are effective catalysts for the asymmetric hydroformylation of 4-vinylazetidin-2-one to give the corresponding oxo-aldehyde 3{beta} as the major product in very high diastereoselectivities and in good regioselectivities. Interestingly, modifications of the aryl substituents in phosphine and phosphinite moieties afforded higher selectivities. Aldehyde 3{beta} was easily oxidized with NaClO{sub 2} to 4, a key intermediate of 1{beta}-methyl carbapenems. Thus, the present method provides a new practical route to a versatile key intermediate for the synthesis of carbapenem antibiotics.

1,2,4-Triazines in the Synthesis of Bipyridine Bisphenolate ONNO Ligands and Their Highly Luminescent Tetradentate Pt(II) Complexes for Solution-Processable OLEDs.

Science.gov (United States)

Pander, Piotr; Bulmer, Rachel; Martinscroft, Ross; Thompson, Stuart; Lewis, Frank W; Penfold, Thomas J; Dias, Fernando B; Kozhevnikov, Valery N

2018-04-02

This article describes a convenient method for the synthesis of ONNO-type tetradentate 6,6'-bis(2-phenoxy)-2,2'-bipyridine (bipyridine bisphenolate, BpyBph) ligands and their platinum(II) complexes. The methodology includes the synthesis of 1,2,4-triazine precursors followed by their transformation to functionalized pyridines by the Boger reaction. Two complementary routes employing 3,3'- and 5,5'-bis-triazines allow a modification of the central pyridine rings in different positions, which was exemplified by the introduction of cyclopentene rings. The new ligands were used to prepare highly luminescent ONNO-type Pt(II) complexes. The position of the cyclopentene rings significantly influences the solubility and photophysical properties of these complexes. Derivatives with closely positioned cyclopentene rings are soluble in organic solvents and proved to be the best candidate for solution-processable organic light-emitting devices (OLEDs), showing efficient single-dopant candlelight electroluminescence.

Synthesis and thermal decomposition kinetics of Th(IV) complex with unsymmetrical Schiff base ligand

International Nuclear Information System (INIS)

Fan Yuhua; Bi Caifeng; Liu Siquan; Yang Lirong; Liu Feng; Ai Xiaokang

2006-01-01

A new unsymmetrical Schiff base ligand (H 2 LLi) was synthesized using L-lysine, o-vanillin and salicylaladyde. Thorium(IV) complex of this ligand [Th(H 2 L)(NO 3 )](NO 3 ) 2 x 3H 2 O have been prepared and characterized by elemental analyses, IR, UV and molar conductance. The thermal decomposition kinetics of the complex for the second stage was studied under non-isothermal condition by TG and DTG methods. The kinetic equation may be expressed as: dα/dt = A x e -E/RT x 1/2 (1-α) x [-ln(1-α)] -1 . The kinetic parameters (E, A), activation entropy ΔS ≠ and activation free-energy ΔG ≠ were also calculated. (author)

Synthesis of two potential NK1-receptor ligands using [1-11C]ethyl iodide and [1-11C]propyl iodide and initial PET-imaging

Directory of Open Access Journals (Sweden)

Genchel Tove

2007-07-01

Full Text Available Abstract Background The previously validated NK1-receptor ligand [O-methyl-11C]GR205171 binds with a high affinity to the NK1-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK1-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK1-receptor ligands with chemical structures based on [O-methyl-11C]GR205171. Methods [1-11C]Ethyl and [1-11C]propyl iodide with specific radioactivities of 90 GBq/μmol and 270 GBq/μmol, respectively, were used in the synthesis of [O-methyl-11C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S-N-(1-(2- [1-11C]ethoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethyl-2-phenylpiperidin-3-amine (I and (2S,3S-2-phenyl-N-(1-(2- [1-11C]propoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethylpiperidin-3-amine (II was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-11C]GR205171. Results All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II had no specific binding in striatum. Ligand (I had moderate specific binding compared to the [O-methyl-11C]GR205171. The ethyl analogue (I displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-11C]GR205171. Conclusion The propyl-analogue (II cannot be used for detecting changes in NK1-ligand levels, while further studies should be

Activation of autoreactive B cells by endogenous TLR7 and TLR3 RNA ligands.

Science.gov (United States)

Green, Nathaniel M; Moody, Krishna-Sulayman; Debatis, Michelle; Marshak-Rothstein, Ann

2012-11-16

The key step in the activation of autoreactive B cells is the internalization of nucleic acid containing ligands and delivery of these ligands to the Toll-like Receptor (TLR) containing endolysosomal compartment. Ribonucleoproteins represent a large fraction of autoantigens in systemic autoimmune diseases. Here we demonstrate that many uridine-rich mammalian RNA sequences associated with common autoantigens effectively activate autoreactive B cells. Priming with type I IFN increased the magnitude of activation, and the range of which RNAs were stimulatory. A subset of RNAs that contain a high degree of self-complementarity also activated B cells through TLR3. For the RNA sequences that activated predominantly through TLR7, the activation is proportional to uridine-content, and more precisely defined by the frequency of specific uridine-containing motifs. These results identify parameters that define specific mammalian RNAs as ligands for TLRs.

Mononuclear late first row transition metal complexes of ONO donor hydrazone ligand: Synthesis, characterization, crystallographic insight, in vivo and in vitro anti-inflammatory activity

Science.gov (United States)

Kendur, Umashri; Chimmalagi, Geeta H.; Patil, Sunil M.; Gudasi, Kalagouda B.; Frampton, Christopher S.; Mangannavar, Chandrashekhar V.; Muchchandi, Iranna S.

2018-02-01

Air and moisture stable coordination compounds of late first row transition metal ions, viz., Co(II), Ni(II), Cu(II) and Zn(II) with a newly designed ligand, (E)-2-amino-N'-(1-(2-hydroxy-6-methyl-4-oxo-4H-pyran-3-yl)ethylidene)benzohydrazide (H2L) were prepared and extensively characterized using various spectro-analytical techniques. The ligand acts both in mono as well as doubly deprotonated manner. The ligand to metal stoichiometry was found to be 1:2 in case of complexes using chloride salts, whereas 1:1 in case of copper (II) complex using its acetate salt. The molecular structures of H2L, nickel and copper complexes were unambiguously determined by single-crystal X-ray diffraction studies reveal that H2L exists in a zwitterionic form while copper complex has copper centre in a distorted square planar environment. On the other hand, cobalt, nickel and zinc complexes display distorted octahedral coordination around the metal ion. In case of [Ni(HL)2].H2O, intramolecular Csbnd H⋯π stacking interaction were observed between the centroid of five membered chelate ring and phenyl proton C5sbnd H5 and intermolecular Csbnd H⋯π stacking interaction between the centroid of phenyl ring, dehydroacetic acid (DHA) ring and phenyl protons. The [Cu(L)DMF] complex is stabilized by intramolecular hydrogen bonding N1H⋯N2 and by intermolecular hydrogen bonding N1H⋯O4. Intermolecular interactions were investigated by Hirshfeld surfaces. Further, H2L and its metal complexes were screened for their in vivo and in vitro anti-inflammatory activities. The activity of the ligand has enhanced on coordination with transition metals. The tested compounds have shown excellent activity, which is almost equipotent to the standard used in the study.

Mixed-ligand complexes of ruthenium(II) incorporating a diazo ...

Indian Academy of Sciences (India)

Unknown

Dedicated to the memory of the late Professor Bhaskar G Maiya. *For correspondence. Mixed-ligand complexes of ruthenium(II) incorporating a diazo ligand: Synthesis .... water (1 : 1) for 5 h to give a dark red solution. The solution was cooled to room temperature. After eva- poration of the solvent, the solid was collected,.

Structure-based design, synthesis and crystallization of 2-arylquinazolines as lipid pocket ligands of p38α MAPK.

Directory of Open Access Journals (Sweden)

Mike Bührmann

Full Text Available In protein kinase research, identifying and addressing small molecule binding sites other than the highly conserved ATP-pocket are of intense interest because this line of investigation extends our understanding of kinase function beyond the catalytic phosphotransfer. Such alternative binding sites may be involved in altering the activation state through subtle conformational changes, control cellular enzyme localization, or in mediating and disrupting protein-protein interactions. Small organic molecules that target these less conserved regions might serve as tools for chemical biology research and to probe alternative strategies in targeting protein kinases in disease settings. Here, we present the structure-based design and synthesis of a focused library of 2-arylquinazoline derivatives to target the lipophilic C-terminal binding pocket in p38α MAPK, for which a clear biological function has yet to be identified. The interactions of the ligands with p38α MAPK was analyzed by SPR measurements and validated by protein X-ray crystallography.

Ruthenium(II) Complexes Containing Lutidine-Derived Pincer CNC Ligands: Synthesis, Structure, and Catalytic Hydrogenation of C-N bonds.

Science.gov (United States)

Hernández-Juárez, Martín; López-Serrano, Joaquín; Lara, Patricia; Morales-Cerón, Judith P; Vaquero, Mónica; Álvarez, Eleuterio; Salazar, Verónica; Suárez, Andrés

2015-05-11

A series of Ru complexes containing lutidine-derived pincer CNC ligands have been prepared by transmetalation with the corresponding silver-carbene derivatives. Characterization of these derivatives shows both mer and fac coordination of the CNC ligands depending on the wingtips of the N-heterocyclic carbene fragments. In the presence of tBuOK, the Ru-CNC complexes are active in the hydrogenation of a series of imines. In addition, these complexes catalyze the reversible hydrogenation of phenantridine. Detailed NMR spectroscopic studies have shown the capability of the CNC ligand to be deprotonated and get involved in ligand-assisted activation of dihydrogen. More interestingly, upon deprotonation, the Ru-CNC complex 5 e(BF4 ) is able to add aldimines to the metal-ligand framework to yield an amido complex. Finally, investigation of the mechanism of the hydrogenation of imines has been carried out by means of DFT calculations. The calculated mechanism involves outer-sphere stepwise hydrogen transfer to the C-N bond assisted either by the pincer ligand or a second coordinated H2 molecule. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design, Synthesis and Biological Evaluation of Quorum Sensing Modulators

DEFF Research Database (Denmark)

Hansen, Mette Reimert

to intercept the communication system by synthetic non-native ligands and thereby lower the pathogenesis and antibiotic tolerance of a bacterial biofilm. To identify new ligands with quorum sensing modulating activities, three types of AHL analogs were synthesized using different synthetic strategies....... Overall, 17 compounds were identified as quorum sensing activators with EC50 values in the low micromolar range. Two build/couple/pair strategies for the synthesis of structurally diverse small molecules are presented. In the first strategy, the Petasis 3-component reaction (Petasis 3-CR) of hydrazides...

Synthesis of a /sup 11/C-labelled neuroleptic drug: pimozide

Energy Technology Data Exchange (ETDEWEB)

Crouzel, C; Mestelan, G; Kraus, E; Lecomte, J M; Comar, D [CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot

1980-09-01

Pimozide, a neuroleptic drug which is one of the best ligands for brain dopaminergic receptors in mice in vivo, was labelled with /sup 11/C for eventual investigation in man. This synthesis was carried out in 30 min from phosgene as the /sup 11/C precursor. The synthesis, resulting specific activity and the tissue distribution kinetics in mice are presented and discussed.

A structural view of ligand-dependent activation in thermoTRP channels

Directory of Open Access Journals (Sweden)

Ximena eSteinberg

2014-05-01

Full Text Available Transient Receptor Potential (TRP proteins are a large family of ion channels, grouped intoseven sub-families. Although great advances have been made regarding the activation andmodulation of TRP channel activity, detailed molecular mechanisms governing TRPchannel gating are still needed. Sensitive to electric, chemical, mechanical, and thermalcues, TRP channels are tightly associated with the detection and integration of sensoryinput, emerging as a model to study the polymodal activation of ion channel proteins.Among TRP channels, the temperature-activated kind constitute a subgroup by itself,formed by Vanilloid receptors 1-4, Melastatin receptors 2, 4, 5 and 8, TRPC5, and TRPA1.Some of the so-called thermoTRP channels participate in the detection of noxious stimulimaking them an interesting pharmacological target for the treatment of pain. However, thepoor specificity of the compounds available in the market represents an important obstacleto overcome. Understanding the molecular mechanics underlying ligand-dependentmodulation of TRP channels may help with the rational design of novel syntheticanalgesics. The present review focuses on the structural basis of ligand-dependentactivation of TRPV1 and TRPM8 channels. Special attention is drawn to the dissection ofligand-binding sites within TRPV1, PIP 2 -dependent modulation of TRP channels, and thestructure of natural and synthetic ligands.

Peroxisome Proliferator-Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies.

Science.gov (United States)

Yousefi, Bahman; Samadi, Nasser; Baradaran, Behzad; Shafiei-Irannejad, Vahid; Zarghami, Nosratollah

2016-07-01

Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr-Abl. Furthermore, coupling imatinib with peroxisome proliferator-activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator-activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator-activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator-activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail. © 2016 John Wiley & Sons A/S.

Synthesis of mixed ligand europium complexes: Verification of predicted luminescence intensification

International Nuclear Information System (INIS)

Lima, Nathalia B.D.; Silva, Anderson I.S.; Gonçalves, Simone M.C.; Simas, Alfredo M.

2016-01-01

Mixed ligand europium complexes are predicted to be more luminescent than what would be expected from their corresponding repeating ligand compounds according to a conjecture recently advanced by our research group; a conjecture that has already been validated for strongly luminescent europium complexes. In this article, we seek to further verify the validity of this conjecture for complexes which are much more symmetric, and which thus display lower levels of luminescence. Accordingly, we synthesized complexes Eu(DBM) 3 (L) 2 , and all novel mixed ligand combinations Eu(DBM) 3 (L,L') with L and L' equal to DBSO, PTSO, and TPPO. The syntheses were carried out via displacement reactions from the starting complex Eu(DBM) 3 (H 2 O) 2 , passing through the intermediates Eu(DBM) 3 (L) 2 and finally, by displacement of L by L', arriving at Eu(DBM) 3 (L,L'). The ligands L obey the following order of displacement TPPO>PTSO>DBSO>H 2 O, which had been previously described by our group. In the present article, we further show that this displacement order could have been predicted by Sparkle/RM1 thermochemical calculations. Subsequently, we determined the radiative decay rates, A rad , for all six compounds by photophysical measurements. As expected, results show that the measured A rad values for all novel mixed ligand complexes are larger than the average of the A rad values for the corresponding repeating ligand coordination compounds. In conclusion, the present article does broaden the scope of our conjecture, which enunciates that an increase in the diversity of ligands around the europium ion tends to intensify the luminescence. - Highlights: • Mixed ligand europium complexes are predicted to be more luminescent than repeating ligand ones. • Radiative decay rates increase with structural coordination asymmetry. • The non-ionic ligands displacement order in substitution reactions is TPPO>PTSO>DBSO>H 2 O. • Sparkle/RM1 correctly predicts the

Luteolin, a flavonoid, inhibits CD40 ligand expression by activated human basophils.

Science.gov (United States)

Hirano, Toru; Arimitsu, Junsuke; Higa, Shinji; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Ohkawara, Tomoharu; Kuwabara, Yusuke; Kawai, Mari; Kawase, Ichiro; Tanaka, Toshio

2006-01-01

We have previously shown that flavonoids such as luteolin, apigenin and fisetin inhibit interleukin 4 and interleukin 13 production. In this study, we investigated whether luteolin can suppress CD40 ligand expression by basophils. A human basophilic cell line, KU812, was stimulated with A23187 and phorbol myristate acetate (PMA) with or without various concentrations of luteolin or other flavonoids for 12 h, and CD40 ligand expression was analyzed by FACS. The effect of luteolin on CD40 ligand mRNA expression was studied by semiquantitative reverse transcription PCR analysis. In addition, CD40 ligand expression was also measured in purified basophils that had been stimulated for 12 h with A23187 plus PMA with or without various concentrations of luteolin. CD40 ligand expression by KU812 cells was enhanced noticeably in response to A23187 and even more strikingly augmented by A23187 plus PMA. The expression was significantly suppressed by 10 or 30 microM of luteolin, whereas myricetin failed to inhibit. Reverse transcription PCR analyses demonstrated that luteolin inhibited CD40 ligand mRNA expression by stimulated KU812 cells. Of the six flavonoids examined, luteolin, apigenin, fisetin and quercetin at 30 microM showed a significant inhibitory effect on CD40 ligand expression. The incubation of purified basophils with A23187 plus PMA significantly enhanced CD40 ligand expression, and the presence of luteolin again had an inhibitory effect. Luteolin inhibits CD40 ligand expression by activated basophils.

Synthesis, structures, and dearomatization by deprotonation of iron complexes featuring bipyridine-based PNN pincer ligands.

Science.gov (United States)

Zell, Thomas; Langer, Robert; Iron, Mark A; Konstantinovski, Leonid; Shimon, Linda J W; Diskin-Posner, Yael; Leitus, Gregory; Balaraman, Ekambaram; Ben-David, Yehoshoa; Milstein, David

2013-08-19

The synthesis and characterization of new iron pincer complexes bearing bipyridine-based PNN ligands is reported. Three phosphine-substituted pincer ligands, namely, the known (t)Bu-PNN (6-((di-tert-butylphosphino)methyl)-2,2'-bipyridine) and the two new (i)Pr-PNN (6-((di-iso-propylphosphino)methyl)-2,2'-bipyridine) and Ph-PNN (6-((diphenylphosphino)methyl)-2,2'-bipyridine) ligands were synthesized and studied in ligation reactions with iron(II) chloride and bromide. These reactions lead to the formation of two types of complexes: mono-chelated neutral complexes of the type [(R-PNN)Fe(X)2] and bis-chelated dicationic complexes of the type [(R-PNN)2Fe](2+). The complexes [(R-PNN)Fe(X)2] (1: R = (t)Bu, X = Cl, 2: R = (t)Bu, X = Br, 3: R = (i)Pr, X = Cl, and 4: R = (i)Pr, X = Br) are readily prepared from reactions of FeX2 with the free R-PNN ligand in a 1:1 ratio. Magnetic susceptibility measurements show that these complexes have a high-spin ground state (S = 2) at room temperature. Employing a 2-fold or higher excess of (i)Pr-PNN, diamagnetic hexacoordinated dicationic complexes of the type [((i)Pr-PNN)2Fe](X)2 (5: X = Cl, and 6: X = Br) are formed. The reactions of Ph-PNN with FeX2 in a 1:1 ratio lead to similar complexes of the type [(Ph-PNN)2Fe](FeX4) (7: X = Cl, and 8: X = Br). Single crystal X-ray studies of 1, 2, 4, 6, and 8 do not indicate electron transfer from the Fe(II) centers to the neutral bipyridine unit based on the determined bond lengths. Density functional theory (DFT) calculations were performed to compare the relative energies of the mono- and bis-chelated complexes. The doubly deprotonated complexes [(R-PNN*)2Fe] (9: R = (i)Pr, and 10: R = Ph) were synthesized by reactions of the dicationic complexes 6 and 8 with KO(t)Bu. The dearomatized nature of the central pyridine of the pincer ligand was established by X-ray diffraction analysis of single crystals of 10. Reactivity studies show that 9 and 10 have a slightly different behavior in

Synthesis, characterization and anticancer activity of gold(I) complexes that contain tri-tert-butylphosphine and dialkyl dithiocarbamate ligands

KAUST Repository

Altaf, Muhammad

2015-03-10

Two new gold(I) complexes that contain tri-ter-butylphosphine and dialkyl dithiocarbamate ligands were synthesized and characterized by FTIR, NMR spectroscopy, Cyclic voltammetry, elemental analysis and X-ray diffraction. The in vitro cytotoxicity of both complexes was examined against A549 (lung cancer), MCF7 (breast cancer), and HeLa (cervical cancer) human cancer cell lines. Both complexes exhibit very strong in vitro cytotoxic effects against A549, MCF7 and HeLa cell lines. The screening of the cytotoxic activity based on IC50 data against the A549, MCF7, and HeLa lines shows that the synthesized gold(I) complexes are highly effective, particularly against HeLa cancer cell line. Based on IC50 data, the cytotoxic activity of both complexes is better than well-known commercial anticancer drug cisplatin against all the three cancer lines tested.

Palladium-catalyzed Asymmetric Hydrosilylation of Styrene and Its Derivatives with Chiral Phosphoramidite Ligands Containing Chiral Ferrocenyl Amine

Energy Technology Data Exchange (ETDEWEB)

Park, Hyun-Sub; Kim, Min Young; Ahn, Hyo Jin; Han, Jin Wook [Hanyang University, Seoul (Korea, Republic of)

2016-06-15

Asymmetric hydrosilylation was one of the most effective methods, which provided optically active organosilanes as a synthetically useful intermediate in organic synthesis. One useful transformation is the Tamao-Fleming oxidation, which is an oxidation reaction of carbon[BOND]silicone bond to afford optically active alcohols with retention of configuration. It is demonstrated that a palladium catalyst coordinating with phosphoramidite ligand (S {sub a},R {sub c},R {sub c,})-L3a from (S)-BINOL and chiral bis((R)-1-ferrocenylethyl) amine shows a high catalytic activity and enantioselectivity up to 97% ee in asymmetric hydrosilylation of styrene and its derivatives. The hydrosilylation of various olefin substrates using these ligands is in progress.

Synthesis, Characterization and Antimicrobial Activity of Cu(II, Co(II and Ni(II Complexes with O, N, and S Donor Ligands

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Vidyavati Reddy

2008-01-01

Full Text Available The complexes of the type ML2 [where M = Cu(II, Co(II, and Ni(II] L = 1-phenyl-1-ene-3-(2-hydroxyphenyl-prop-2-ene with 3- substituted-5-mercapto-4-amino-1,2,4-triazoles. Schiff base ligands have been prepared by reacting 3-(2-hydroxyphenyl-1-phenylprop-2-en-1-one and 3-phenyl/pyridyl-4-amino-5-mercapto-1,2,4-triazoles in an alcoholic medium. The complexes are non-electrolytes in DMF. The resulting complexes were characterized by elemental analysis, magnetic measurements, conductivity measurements and spectral studies. The Schiff base acts as a tridentate dibasic and coordinating through the deprotonated oxygen, thioenolic sulphur and azomethine nitrogen atoms. It is found that Cu(II, Co(II, and Ni(II complexes exhibited octahedral geometry. The antimicrobial activities of ligands and its complexes were screened by cup plate method.

Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes

Energy Technology Data Exchange (ETDEWEB)

Lynch, Caitlin; Pan, Yongmei; Li, Linhao [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States); Heyward, Scott; Moeller, Timothy [Bioreclamation In Vitro Technologies, Baltimore, MD 21227 (United States); Swaan, Peter W. [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States); Wang, Hongbing, E-mail: hwang@rx.umaryland.edu [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States)

2014-08-15

Objective: Accumulating evidence suggests that activation of mouse constitutive androstane receptor (mCAR) alleviates type 2 diabetes and obesity by inhibiting hepatic gluconeogenesis, lipogenesis, and fatty acid synthesis. However, the role of human (h) CAR in energy metabolism is largely unknown. The present study aims to investigate the effects of selective hCAR activators on hepatic energy metabolism in human primary hepatocytes (HPH). Methods: Ligand-based structure–activity models were used for virtual screening of the Specs database ( (www.specs.net)) followed by biological validation in cell-based luciferase assays. The effects of two novel hCAR activators (UM104 and UM145) on hepatic energy metabolism were evaluated in HPH. Results: Real-time PCR and Western blotting analyses reveal that activation of hCAR by UM104 and UM145 significantly repressed the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, two pivotal gluconeogenic enzymes, while exerting negligible effects on the expression of genes associated with lipogenesis and fatty acid synthesis. Functional experiments show that UM104 and UM145 markedly inhibit hepatic synthesis of glucose but not triglycerides in HPH. In contrast, activation of mCAR by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a selective mCAR activator, repressed the expression of genes associated with gluconeogenesis, lipogenesis, and fatty acid synthesis in mouse primary hepatocytes, which were consistent with previous observations in mouse model in vivo. Conclusion: Our findings uncover an important species difference between hCAR and mCAR in hepatic energy metabolism, where hCAR selectively inhibits gluconeogenesis without suppressing fatty acid synthesis. Implications: Such species selectivity should be considered when exploring CAR as a potential therapeutic target for metabolic disorders. - Highlights: • Novel hCAR activators were identified by computational and biological approaches. • The role

Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes

International Nuclear Information System (INIS)

Lynch, Caitlin; Pan, Yongmei; Li, Linhao; Heyward, Scott; Moeller, Timothy; Swaan, Peter W.; Wang, Hongbing

2014-01-01

Objective: Accumulating evidence suggests that activation of mouse constitutive androstane receptor (mCAR) alleviates type 2 diabetes and obesity by inhibiting hepatic gluconeogenesis, lipogenesis, and fatty acid synthesis. However, the role of human (h) CAR in energy metabolism is largely unknown. The present study aims to investigate the effects of selective hCAR activators on hepatic energy metabolism in human primary hepatocytes (HPH). Methods: Ligand-based structure–activity models were used for virtual screening of the Specs database ( (www.specs.net)) followed by biological validation in cell-based luciferase assays. The effects of two novel hCAR activators (UM104 and UM145) on hepatic energy metabolism were evaluated in HPH. Results: Real-time PCR and Western blotting analyses reveal that activation of hCAR by UM104 and UM145 significantly repressed the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, two pivotal gluconeogenic enzymes, while exerting negligible effects on the expression of genes associated with lipogenesis and fatty acid synthesis. Functional experiments show that UM104 and UM145 markedly inhibit hepatic synthesis of glucose but not triglycerides in HPH. In contrast, activation of mCAR by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a selective mCAR activator, repressed the expression of genes associated with gluconeogenesis, lipogenesis, and fatty acid synthesis in mouse primary hepatocytes, which were consistent with previous observations in mouse model in vivo. Conclusion: Our findings uncover an important species difference between hCAR and mCAR in hepatic energy metabolism, where hCAR selectively inhibits gluconeogenesis without suppressing fatty acid synthesis. Implications: Such species selectivity should be considered when exploring CAR as a potential therapeutic target for metabolic disorders. - Highlights: • Novel hCAR activators were identified by computational and biological approaches. • The role

Synthesis of Poly(hydroxamic Acid-Poly(amidoxime Chelating Ligands for Removal of Metals from Industrial Wastewater

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M. R. Lutfor

2011-01-01

Full Text Available Synthesis of poly(hydroxamic acid-poly(amidoxime chelating ligands were carried out from poly(methyl acrylate-co-acrylonitrile grafted sago starch and hydroxylamine in alkaline medium. The binding property of metal ions was performed and maximum sorption capacity of the copper was 3.20 mmol/ g and the rate of exchange of some metals was faster, i.e. t½ ≈ 7 min (average. Two types of wastewater containing chromium, zinc, nickel, copper and iron, etc. were used and the heavy metal recovery was found to be highly efficient, about 99% of the metals could be removed from the metal plating wastewater.

Metal-Free Alternating Copolymerization of CO2with Epoxides: Fulfilling “Green” Synthesis and Activity

KAUST Repository

Zhang, Dongyue

2016-08-16

Polycarbonates were successfully synthesized for the first time through the anionic copolymerization of epoxides with CO2, under metal-free conditions. Using an approach based on the activation of epoxides by Lewis acids and of CO, by appropriate cations, well-defined alternating copolymers made of CO, and propylene oxide (PO) or cyclohexene oxide (CHO) were indeed obtained. Triethyl borane was the Lewis acid chosen to activate the epoxides, and onium halides or onium alkoxides involving either ammonium, phosphonium, or phosphazenium cations were selected to initiate the copolymerization. In the case of PO, the carbonate content of the poly(propylene carbonate) formed was in the range of 92-99% and turnover numbers (TON) were close to 500; in the case of CHO perfectly alternating poly(cyclohexene carbonate) were obtained and TON values were close to 4000. The advantages of such a copolymerization system are manifold: (i) no need for multistep catalyst/ligand synthesis as in previous works; (ii) no transition metal involved in the copolymer synthesis and therefore no coloration of the samples isolated; and (iii) no necessity for postsynthesis purification.

Interactions of ligands with active and inactive conformations of the dopamine D2 receptor.

Science.gov (United States)

Malmberg, A; Mohell, N; Backlund Höök, B; Johansson, A M; Hacksell, U; Nordvall, G

1998-04-10

The affinities of 19 pharmacologically diverse dopamine D2 receptor ligands were determined for the active and inactive conformations of cloned human dopamine D2 receptors expressed in Ltk cells. The agonist [3H]quinpirole was used to selectively label the guanine nucleotide-binding protein-coupled, active receptor conformation. The antagonist [3H]raclopride, in the presence of the non-hydrolysable GTP-analogue Gpp(NH)p and sodium ions and in the absence of magnesium ions, was used to label the free inactive receptor conformation. The intrinsic activities of the ligands were determined in a forskolin-stimulated cyclic AMP assay using the same cells. An excellent correlation was shown between the affinity ratios (KR/KRG) of the ligands for the two receptor conformations and their intrinsic activity (r=0.96). The ligands included eight structurally related and enantiopure 2-aminotetralin derivatives; the enantiomers of 5-hydroxy-2-(dipropylamino)tetralin, 5-methoxy-2-(dipropylamino)tetralin, 5-fluoro-2-(dipropylamino)tetralin and 2-(dipropylamino)tetralin. The (S)-enantiomers behaved as full agonists in the cyclic AMP assay and displayed a large KR/KRG ratio. The (R)-enantiomers were classified as partial agonists and had lower ratios. The structure-affinity relationships of these compounds at the active and the inactive receptor conformations were analysed separately, and used in conjunction with a homology based receptor model of the dopamine D2 receptor. This led to proposed binding modes for agonists, antagonists and partial agonists in the 2-aminotetralin series. The concepts used in this study should be of value in the design of ligands with predetermined affinity and intrinsic activity.

Activation of Hsp90 Enzymatic Activity and Conformational Dynamics through Rationally Designed Allosteric Ligands.

Science.gov (United States)

Sattin, Sara; Tao, Jiahui; Vettoretti, Gerolamo; Moroni, Elisabetta; Pennati, Marzia; Lopergolo, Alessia; Morelli, Laura; Bugatti, Antonella; Zuehlke, Abbey; Moses, Mike; Prince, Thomas; Kijima, Toshiki; Beebe, Kristin; Rusnati, Marco; Neckers, Len; Zaffaroni, Nadia; Agard, David A; Bernardi, Anna; Colombo, Giorgio

2015-09-21

Hsp90 is a molecular chaperone of pivotal importance for multiple cell pathways. ATP-regulated internal dynamics are critical for its function and current pharmacological approaches block the chaperone with ATP-competitive inhibitors. Herein, a general approach to perturb Hsp90 through design of new allosteric ligands aimed at modulating its functional dynamics is proposed. Based on the characterization of a first set of 2-phenylbenzofurans showing stimulatory effects on Hsp90 ATPase and conformational dynamics, new ligands were developed that activate Hsp90 by targeting an allosteric site, located 65 Å from the active site. Specifically, analysis of protein responses to first-generation activators was exploited to guide the design of novel derivatives with improved ability to stimulate ATP hydrolysis. The molecules' effects on Hsp90 enzymatic, conformational, co-chaperone and client-binding properties were characterized through biochemical, biophysical and cellular approaches. These designed probes act as allosteric activators of the chaperone and affect the viability of cancer cell lines for which proper functioning of Hsp90 is necessary. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells.

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Guomin Jiang

Full Text Available On entering the tissues, infiltrating autoreactive T cells must be reactivated locally to gain pathogenic activity. We have previously reported that, when activated by Toll-like receptor 3 (TLR3 and TLR4 ligands, retinal astrocytes (RACs are able to function as antigen-presenting cells to re-activate uveitogenic T cells and allow responder T cells to induce uveitis in mice. In the present study, we found that, although the triggering of TLR2 or nucleotide-binding oligomerization domain receptor 2 (NOD2 alone did not activate RACs, their combined triggering induced RACs with the phenotypes required to efficiently re-activate interphotoreceptor retinoid-binding protein (IRBP-specific T cells. The synergistic effect of TLR2 and NOD2 ligands on RAC activation might be explained by the observations that bacterial lipoprotein (BLP, a TLR2 ligand was able to upregulate NOD2 expression and the combination of BLP and muramyldipeptide (MDP, a NOD2 ligand enhanced the expression of RICK (Rip2, the signaling molecule of NOD2. Moreover, the synergistic effect of MDP and BLP on RACs was lost when the RACs were derived from NOD2 knockout mice or were pre-treated with Rip2 antagonist. Thus, our data suggest that exogenous or endogenous molecules acting on both TLR2 and NOD2 on RACs might have an enhancing effect on susceptibility to autoimmune uveitis.

Novel multi-target-directed ligands for Alzheimer's disease: Combining cholinesterase inhibitors and 5-HT6 receptor antagonists. Design, synthesis and biological evaluation.

Science.gov (United States)

Więckowska, Anna; Kołaczkowski, Marcin; Bucki, Adam; Godyń, Justyna; Marcinkowska, Monika; Więckowski, Krzysztof; Zaręba, Paula; Siwek, Agata; Kazek, Grzegorz; Głuch-Lutwin, Monika; Mierzejewski, Paweł; Bienkowski, Przemysław; Sienkiewicz-Jarosz, Halina; Knez, Damijan; Wichur, Tomasz; Gobec, Stanislav; Malawska, Barbara

2016-11-29

As currently postulated, a complex treatment may be key to an effective therapy for Alzheimer's disease (AD). Recent clinical trials in patients with moderate AD have shown a superior effect of the combination therapy of donepezil (a selective acetylcholinesterase inhibitor) with idalopirdine (a 5-HT 6 receptor antagonist) over monotherapy with donepezil. Here, we present the first report on the design, synthesis and biological evaluation of a novel class of multifunctional ligands that combines a 5-HT 6 receptor antagonist with a cholinesterase inhibitor. Novel multi-target-directed ligands (MTDLs) were designed by combining pharmacophores directed against the 5-HT 6 receptor (1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-indole) and cholinesterases (tacrine or N-benzylpiperidine analogues). In vitro evaluation led to the identification of tacrine derivative 12 with well-balanced potencies against the 5-HT 6 receptor (K b  = 27 nM), acetylcholinesterase and butyrylcholinesterase (IC 50 hAChE  = 12 nM, IC 50 hBuChE  = 29 nM). The compound also showed good in vitro blood-brain-barrier permeability (PAMPA-BBB assay), which was confirmed in vivo (open field study). Central cholinomimetic activity was confirmed in vivo in rats using a scopolamine-induced hyperlocomotion model. A novel class of multifunctional ligands with compound 12 as the best derivative in a series represents an excellent starting point for the further development of an effective treatment for AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Template synthesis and characterization of biologically active transition metal complexes comprising 14-membered tetraazamacrocyclic ligand

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DHARMPAL SINGH

2010-02-01

Full Text Available A novel series of complexes of the type [M(C28H24N4X2], whereM = Co(II, Ni(II, Cu(II, Zn(II and Cd(II, X = Cl–, NO3–, CH3COO– and (C28H24N4 corresponds to the tetradentate macrocyclic ligand, were synthe¬sized by template condensation of 1,8-diaminonaphthalene and diacetyl in the presence of divalent metal salts in methanolic medium. The complexes were characterized by elemental analyses, conductance and magnetic measurements, as well as by UV/Vis, NMR, IR and MS spectroscopy. The low values of the molar conductance indicate non-electrolyte type of complexes. Based on these spectral data, a distorted octahedral geometry may be proposed for all of these complexes. All the synthesized macrocyclic complexes were tested for in vitro antibacterial activity against some pathogenic bacterial strains, viz Bacillus cereus, Salmonella typhi, Escherichia coli and Staphylococcus aureus. The MIC values shown by the complexes against these bacterial strains were compared with the MIC shown by the standard antibiotics linezolid and cefaclor.

Synthesis, spectroscopic, biological activity and thermal characterization of ceftazidime with transition metals

Science.gov (United States)

Masoud, Mamdouh S.; Ali, Alaa E.; Elasala, Gehan S.; Kolkaila, Sherif A.

2018-03-01

Synthesis, physicochemical characterization and thermal analysis of ceftazidime complexes with transition metals (Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II)) were discussed. It's obtained that ceftazidime act as bidentate ligand. From magnetic measurement and spectral data, octahedral structures were proposed for all complexes except for cobalt, nickel and mercury had tetrahedral structural. Hyper chemistry program confirmed binding sites of ceftazidime. Ceftazidime complexes show higher activity than ceftazidime for some strains. From TG and DTA curves the thermal decomposition mechanisms of ceftazidime and their metal complexes were suggested. The thermal decomposition of the complexes ended with the formation of metal oxides as a final product except in case of Hg complex.

Enantioselective synthesis of α-phenyl- and α-(dimethylphenylsilyl)alkylboronic esters by ligand mediated stereoinductive reagent-controlled homologation using configurationally labile carbenoids.

Science.gov (United States)

Barsamian, Adam L; Wu, Zhenhua; Blakemore, Paul R

2015-03-28

Chain extension of boronic esters by the action of configurationally labile racemic lithium carbenoids in the presence of scalemic bisoxazoline ligands was explored for the enantioselective synthesis of the two title product classes. Enantioenriched 2° carbinols generated by oxidative work-up (NaOOH) of initial α-phenylalkylboronate products were obtained in 35-83% yield and 70-96% ee by reaction of B-alkyl and B-aryl neopentyl glycol boronates with a combination of O-(α-lithiobenzyl)-N,N-diisopropylcarbamate and ligand 3,3-bis[(4S)-4,5-dihydro-4-isopropyloxazol-2-yl] pentane in toluene solvent (-78 °C to rt) with MgBr2·OEt2 additive. Enantioenriched α-(dimethylsilylphenylsilyl)alkylboronates were obtained in 35-69% yield and 9-57% ee by reaction of B-alkyl pinacol boronates with a combination of lithio(dimethylphenylsilyl)methyl 2,4,6-triisopropylbenzoate and ligand 2,2-bis[(4S)-4,5-dihydro-4-isopropyloxazol-2-yl]propane in cumene solvent (-45 °C to -95 °C to rt). The stereochemical outcome of the second type of reaction depended on the temperature history of the organolithium·ligand complex indicating that the stereoinduction mechanism in this case involves some aspect of dynamic thermodynamic resolution.

Synthesis and structure-activity relationship of the first nonpeptidergic inverse agonists for the human cytomegalovirus encoded chemokine receptor US28.

Science.gov (United States)

Hulshof, Janneke W; Casarosa, Paola; Menge, Wiro M P B; Kuusisto, Leena M S; van der Goot, Henk; Smit, Martine J; de Esch, Iwan J P; Leurs, Rob

2005-10-06

US28 is a human cytomegalovirus (HCMV) encoded G-protein-coupled receptor that signals in a constitutively active manner. Recently, we identified 1 [5-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2,2-diphenylpentanenitrile] as the first reported nonpeptidergic inverse agonist for a viral-encoded chemokine receptor. Interestingly, this compound is able to partially inhibit the viral entry of HIV-1. In this study we describe the synthesis of 1 and several of its analogues and unique structure-activity relationships for this first class of small-molecule ligands for the chemokine receptor US28. Moreover, the compounds have been pharmacologically characterized as inverse agonists on US28. By modification of lead structure 1, it is shown that a 4-phenylpiperidine moiety is essential for affinity and activity. Other structural features of 1 are shown to be of less importance. These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection.

Synthesis and studies on Cu(II), Co(II), Ni(II) complexes of Knoevenagel β-diketone ligands

Science.gov (United States)

Sumathi, S.; Tharmaraj, P.; Sheela, C. D.; Anitha, C.

2012-11-01

Transition metal complexes of various acetylacetone based ligands of the type ML [where M = Cu(II), Ni(II), Co(II); L = 3-(aryl)-pentane-2,4-dione] have been synthesized. The structural features have been derived from their elemental analysis, magnetic susceptibility, molar conductance, IR, UV-Vis, 1H NMR, Mass and ESR spectral studies. Conductivity measurements reveal that all the complexes are non-electrolytic in nature. Spectroscopic and other analytical data of the complexes suggest octahedral geometry for other metal(II) complexes. The redox behavior of the copper(II) complexes have been studied by cyclic voltammetry. The free ligands and their metal complexes have been screened for their in vitro biological activities against the bacteria Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus as well as the fungus Candida albicans by well diffusion method. The zone of inhibition value indicates that the most of the metal(II) complexes are found to possess increased activities compared to those of the free ligands. All synthesized compounds may serve as potential photoactive materials as indicated from their characteristic fluorescence properties. The second harmonic generation (SHG) efficiency of the ligands (L1-L3) was found to be considerable effect than that of urea and KDP (potassium dihydrogen phosphate).

Transition metal complexes with oxygen donor ligands: a synthesis, spectral, thermal and antimicrobial study

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VAIBHAV N. PATANGE

2008-10-01

Full Text Available Transition metal complexes of chalcones derived from the conden¬sation of 3-acetyl-6-methyl-2H-pyran-2,4(3H-dione (dehydroacetic acid and p-methoxybenzaldehyde (HL1 or p-nitrobenzaldehyde (HL2 were synthesized and characterized by elemental analysis, conductometry, thermal analysis, magnetic measurements, IR, 1H-NMR, UV–Vis spectroscopy and a microbial study. From the analytical and thermal data, the stoichiometry of the complexes was found to be 1:2 (metal:ligand. The molar conductance data revealed that all the metal chelates were non-electrolytes. The thermal stability of the complexes was studied by thermogravimetry and the decomposition schemes of the complexes are given. The ligands and their metal complexes were screened for antibacterial activity against Staphylococcus aureus and Escherichia coli, and fungicidal activity against Aspergillus flavus, Curvularia lunata and Penicillium notatum.

Ligand-controlled, tunable silver-catalyzed C-H amination.

Science.gov (United States)

Alderson, Juliet M; Phelps, Alicia M; Scamp, Ryan J; Dolan, Nicholas S; Schomaker, Jennifer M

2014-12-03

The development of readily tunable and regioselective C-H functionalization reactions that operate solely through catalyst control remains a challenge in modern organic synthesis. Herein, we report that simple silver catalysts supported by common nitrogenated ligands can be used to tune a nitrene transfer reaction between two different types of C-H bonds. The results reported herein represent the first example of ligand-controlled and site-selective silver-promoted C-H amination.

Synthesis, Spectroscopy, Theoretical, and Electrochemical Studies of Zn(II, Cd(II, and Hg(II Azide and Thiocyanate Complexes of a New Symmetric Schiff-Base Ligand

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Morteza Montazerozohori

2013-01-01

Full Text Available Synthesis of zinc(II/cadmium(II/mercury(II thiocyanate and azide complexes of a new bidentate Schiff-base ligand (L with general formula of MLX2 (M = Zn(II, Cd(II, and Hg(II in ethanol solution at room temperature is reported. The ligand and metal complexes were characterized by using ultraviolet-visible (UV-visible, Fourier transform infrared (FT-IR, 1H- and 13C-NMR spectroscopy and physical characterization, CHN analysis, and molar conductivity. 1H- and 13C-NMR spectra have been studied in DMSO-d6. The reasonable shifts of FT-IR and NMR spectral signals of the complexes with respect to the free ligand confirm well coordination of Schiff-base ligand and anions in an inner sphere coordination space. The conductivity measurements as well as spectral data indicated that the complexes are nonelectrolyte. Theoretical optimization on the structure of ligand and its complexes was performed at the Becke’s three-parameter hybrid functional (B3 with the nonlocal correlation of Lee-Yang-Parr (LYP level of theory with double-zeta valence (LANL2DZ basis set using GAUSSIAN 03 suite of program, and then some theoretical structural parameters such as bond lengths, bond angles, and torsion angles were obtained. Finally, electrochemical behavior of ligand and its complexes was investigated. Cyclic voltammograms of metal complexes showed considerable changes with respect to free ligand.

Quaternary Cu2ZnSnS4 quantum dot-sensitized solar cells: Synthesis, passivation and ligand exchange

Science.gov (United States)

Bai, Bing; Kou, Dongxing; Zhou, Wenhui; Zhou, Zhengji; Tian, Qingwen; Meng, Yuena; Wu, Sixin

2016-06-01

The quaternary Cu2ZnSnS4 (CZTS) QDs had been successfully introduced into quantum dot-sensitized solar cells (QDSC) via hydrolysis approach in our previous work [Green Chem. 2015, vol. 17, p. 4377], but the obtained cell efficiency was still limited by low open-circuit voltage and fill factor. Herein, we use 1-dodecanethiol (DDT) as capping ligand for fairly small-sized CZTS QDs synthesis to improve their intrinsic properties. Since this strong bonded capping ligand can not be replaced by 3-mercaptopropionic acid (MPA) directly, the nature cation (Cu, Zn or Sn)-DDT units of QDs are first exchanged by the preconjugated Cd-oleate via successive ionic layer adsorption and reaction (SILAR) procedure accompanied with the formation of a core/shell structure. The weak bonded oleic acid (OA) can be finally replaced by MPA and the constructed water soluble CZTS/CdSe QDSC achieves an impressive conversion efficiency of 4.70%. The electron transport and recombination dynamic processes are confirmed by intensity-modulated photocurrent spectroscopy (IMPS)/intensity-modulated photovoltage spectroscopy (IMVS) measurements. It is found that the removal of long alkyl chain is conducive to improve the electron transport process and the type-II core/shell structure is beneficial to accelerate electron transport and retard charge recombination. This effective ligand removal strategy is proved to be more convenient for the applying of quaternary QDs in QDSC and would boost a more powerful efficiency in the future work.

Surfactant-ligand co-assisted solvothermal technique for the synthesis of different-shaped CdS nanorod-based materials

International Nuclear Information System (INIS)

Bao Chunyan; Jin Ming; Lu Ran; Xue Pengchong; Zhang Qinglin; Wang Dejun; Zhao Yingying

2003-01-01

1-D nanorods, twinrods, golfclubs, and tripods of CdS were prepared via a surfactant-ligand co-assisted solvothermal method at 160 deg. C. The surfactant of S-dodecylisothiounium bromide (C 12 ) used in the process was favorable for synthesis of different-shaped CdS nanorod with high aspect ratio. X-ray diffraction (XRD) and TEM images showed that the 1-D nanorods had wurtzite phase and others had a zinc blende core and wurtzite arms. The morphologies of CdS prepared under different conditions suggested the 'template-assistance' of the surfactant and that the nonaqueous organic media are important for the self-assembling of inorganic components at atomic level

Internalization mechanisms of the epidermal growth factor receptor after activation with different ligands

DEFF Research Database (Denmark)

Henriksen, Lasse; Grandal, Michael Vibo; Knudsen, Stine Louise Jeppe

2013-01-01

after ligand activation focuses on the effect of epidermal growth factor (EGF) and transforming growth factor-α (TGF-α). For a long time it was believed that clathrin-mediated endocytosis was the major pathway for internalization of the receptor, but recent work suggests that different pathways exist....... Here we show that clathrin ablation completely inhibits internalization of EGF- and TGF-α-stimulated receptor, however the inhibition of receptor internalization in cells treated with heparin-binding EGF-like growth factor (HB-EGF) or betacellulin (BTC) was only partial. In contrast, clathrin knockdown...... fully inhibits EGFR degradation after all ligands tested. Furthermore, inhibition of dynamin function blocked EGFR internalization after stimulation with all ligands. Knocking out a number of clathrin-independent dynamin-dependent pathways of internalization had no effect on the ligand...

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

Directory of Open Access Journals (Sweden)

Burkhard Koenig

2011-01-01

Full Text Available N-Arylated aliphatic and aromatic amines are important substituents in many biologically active compounds. In the last few years, transition-metal-mediated N-aryl bond formation has become a standard procedure for the introduction of amines into aromatic systems. While N-arylation of simple aromatic halides by simple amines works with many of the described methods in high yield, the reactions may require detailed optimization if applied to the synthesis of complex molecules with additional functional groups, such as natural products or drugs. We discuss and compare in this review the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald–Hartwig-type reactions, copper-mediated Ullmann-type and Chan–Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan–Lam reactions. Chan–Lam N-arylations are particularly mild and do not require additional ligands, which facilitates the work-up. However, reaction times can be very long. Ullmann- and Buchwald–Hartwig-type methods have been used in intramolecular reactions, giving access to complex ring structures. All three N-arylation methods have specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C–N bond formation in the course of a total synthesis or drug synthesis.

New chiral ligands in asymmetric catalysis. Application in stabilization of metal nanoparticles

OpenAIRE

Axet Martí, M. Rosa

2006-01-01

Thesis M. Rosa AxetThis thesis deals with the development and application of diphosphite ligands derived from carbohydrates to rhodium-catalysed asymmetric hydroformylation and hydrogenation reactions. The use of various carbohydrate derivative ligands as stabilisers of metal nanoparticles is also studied. The synthesis and the characterisation of the series of diphosphite ligands are described in Chapter 2. The results of the asymmetric hydroformylation of styrene and related vinyl arenes ar...

New pyrimidine based ligand capped gold and platinum nano particles: Synthesis, characterization, antimicrobial, antioxidant, DNA interaction and in vitro anticancer activities.

Science.gov (United States)

Sankarganesh, M; Adwin Jose, P; Dhaveethu Raja, J; Kesavan, M P; Vadivel, M; Rajesh, J; Jeyamurugan, R; Senthil Kumar, R; Karthikeyan, S

2017-11-01

In this research work, we have synthesized new pyrimidine based Schiff base ligand, 2-((4,6-dimethoxypyrimidine-2-yl)methyleneenamino)-6-methoxyphenol (DPMM) capped gold (Au) and platinum (Pt) nanoparticles (NPs) by modified Brust-Schiffrin method. The characteristics of DPMM-Au NPs and DPMM-Pt NPs have been examined by UV-Visible, FTIR, SEM, TEM and powder XRD analysis. SEM analysis result shows that surface morphology of the DPMM-Au NPs and DPMM-Pt NPs are in granular and spherical shape, correspondingly. The size of the DPMM-Au NPs and DPMM-Pt NPs are approximately 38.14±4.5 and 58.64±3.0nm respectively, which confirmed by TEM analysis. The DPMM-Au NPs and DPMM-Pt NPs have potent antimicrobial against Escherichia coli, Klebsiella pneumonia, Pseudomonas fluorescens, Shigella sonnei, Staphylococcus aureus and Aspergillus niger, Candida albicans, Candida tropicalis, Mucor indicus, Rhizopus strains. The DPMM-Au NPs and DPMM-Pt NPs have good antioxidant activities than the free ligand (DPMM). The spectroscopic and viscometric measurement confirms the hydrophobic DNA binding abilities of the newly prepared DPMM capped metal NPs. Moreover, the in vitro anticancer activity of DPMM, DPMM-Au NPs and DPMM-Pt NPs against cancer (MCF-7, HeLa & HEp2) and normal (NHDF) cell lines have performed using MTT assay. These results reveals that, DPMM-Au NPs and DPMM-Pt NPs having significant cytotoxic activity against the cancer cell lines and least toxic effect on normal cell line as compared to standard drug cisplatin. Copyright © 2017 Elsevier B.V. All rights reserved.

Designer ligands. Part 14. Novel Mn(lI), Ni(II) and Zn(II) complexes of benzamide- and biphenyl-derived ligands

CSIR Research Space (South Africa)

Wellington, Kevin W

2009-01-01

Full Text Available . Results and Discussion The ligands 1a-c (Scheme 1) were prepared by treating benzoic acid with carbonyl diimidazole (CDI)13 in dimethylformamide (DMF), followed by the respective primary amines, histamine, 2- (2-aminoethyl)benzimidazole and 2...-(2-aminoethyl)pyridine. [Histamine had to be released from its dihydrochloride salt by treatment with sodium methoxide, while 2-(2- aminoethyl)benzimidazole was prepared from 1,2-diaminobenzene and β-alanine.16] The synthesis of the biphenyl-derived ligand 2...

Room temperature synthesis of PbSe quantum dots in aqueous solution: Stabilization by interactions with ligands

Science.gov (United States)

Primera-Pedrozo, Oliva M.; Arslan, Zikri; Rasulev, Bakhtiyor; Leszczynski, Jerzy

2011-01-01

An aqueous route of synthesis is described for rapid synthesis of lead selenide quantum dots (PbSe QDs) at room temperature in an attempt to produce water-soluble and stable nanocrystals. Several thiol-ligands, including thioglycolic acid (TGA), thioglycerol (TGC), 3-mercaptopropionic acid (MPA), 2-mercaptoethyleamine hydrochloride (MEA), 6-mercaptohexanoic acid (MHA), and L-cysteine (L-cys), were used for capping/stabilization of PbSe QDs. The effects of the ligands on the stability of PbSe QDs were evaluated for a period of two months at room temperature under normal light conditions and at 4 °C in dark. The TGA- and MEA-capped QDs exhibited the highest stability prior to purification, almost two months when kept in dark at 4 °C. However, the stability of TGA-capped QDs was reduced substantially after purification to about 5 days under same conditions, while MEA-capped QDs did not show any significant instability. The stabilization energies of Pb-thiolate complexes determined by theoretical DFT simulations supported the experimental results. The PbSe QDs capped with TGA, MPA and MEA were successfully purified and re-dispersed in water, while those stabilized with TGC, MHA and L-cys aggregated during purification attempts. The purified PbSe QDs possess very susceptible surface resulting in poor stability for about 30 – 45 min after re-dispersion in water. In the presence of an excess of free ligand, the stability increased up to 5 days for TGA-capped QDs at pH 7.19, 9 –12 days for MPA-capped QDs at pH 7.3–7.5 and 45–47 days for MEA-capped QDs at pH 7.35. X-Ray Diffraction (XRD) results showed that the QDs possess a cubic rock salt structure with the most intense peaks located at 2θ = 25.3° (200) and 2θ = 29.2° (100). TEM images showed that the size of the QDs ranges between 5 and 10 nm. ICP-MS results revealed that Pb:Se ratio was 1.26, 1.28, 3.85, 1.18, and 1.31 for the QDs capped with TGA, MPA, MEA, L-Cys, and TGC, respectively. The proposed method

Sensitivity to Flg22 Is Modulated by Ligand-Induced Degradation and de Novo Synthesis of the Endogenous Flagellin-Receptor FLAGELLIN-SENSING2[W][OPEN

Science.gov (United States)

Smith, John M.; Salamango, Daniel J.; Leslie, Michelle E.; Collins, Carina A.; Heese, Antje

2014-01-01

FLAGELLIN-SENSING2 (FLS2) is the plant cell surface receptor that perceives bacterial flagellin or flg22 peptide, initiates flg22-signaling responses, and contributes to bacterial growth restriction. Flg22 elicitation also leads to ligand-induced endocytosis and degradation of FLS2 within 1 h. Why plant cells remove this receptor precisely at the time during which its function is required remains mainly unknown. Here, we assessed in planta flg22-signaling competency in the context of ligand-induced degradation of endogenous FLS2 and chemical interference known to impede flg22-dependent internalization of FLS2 into endocytic vesicles. Within 1 h after an initial flg22 treatment, Arabidopsis (Arabidopsis thaliana) leaf tissue was unable to reelicit flg22 signaling in a ligand-, time-, and dose-dependent manner. These results indicate that flg22-induced degradation of endogenous FLS2 may serve to desensitize cells to the same stimulus (homologous desensitization), likely to prevent continuous signal output upon repetitive flg22 stimulation. In addition to impeding ligand-induced FLS2 degradation, pretreatment with the vesicular trafficking inhibitors Wortmannin or Tyrphostin A23 impaired flg22-elicited reactive oxygen species production that was partially independent of BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE1. Interestingly, these inhibitors did not affect flg22-induced mitogen-activated protein kinase phosphorylation, indicating the ability to utilize vesicular trafficking inhibitors to target different flg22-signaling responses. For Tyrphostin A23, reduced flg22-induced reactive oxygen species could be separated from the defect in FLS2 degradation. At later times (>2 h) after the initial flg22 elicitation, recovery of FLS2 protein levels positively correlated with resensitization to flg22, indicating that flg22-induced new synthesis of FLS2 may prepare cells for a new round of monitoring the environment for flg22. PMID:24220680

Synthesis, characterization, and reactivity of ruthenium hydride complexes of N-centered triphosphine ligands.

Science.gov (United States)

Phanopoulos, Andreas; Brown, Neil J; White, Andrew J P; Long, Nicholas J; Miller, Philip W

2014-04-07

The reactivity of the novel tridentate phosphine ligand N(CH2PCyp2)3 (N-triphos(Cyp), 2; Cyp = cyclopentyl) with various ruthenium complexes was investigated and compared that of to the less sterically bulky and less electron donating phenyl derivative N(CH2PPh2)3 (N-triphos(Ph), 1). One of these complexes was subsequently investigated for reactivity toward levulinic acid, a potentially important biorenewable feedstock. Reaction of ligands 1 and 2 with the precursors [Ru(COD)(methylallyl)2] (COD = 1,5-cycloocatadiene) and [RuH2(PPh3)4] gave the tridentate coordination complexes [Ru(tmm){N(CH2PR2)3-κ(3)P}] (R = Ph (3), Cyp (4); tmm = trimethylenemethane) and [RuH2(PPh3){N(CH2PR2)3-κ(3)P}] (R = Ph (5), Cyp (6)), respectively. Ligands 1 and 2 displayed different reactivities with [Ru3(CO)12]. Ligand 1 gave the tridentate dicarbonyl complex [Ru(CO)2{N(CH2PPh2)3-κ(3)P}] (7), while 2 gave the bidentate, tricarbonyl [Ru(CO)3{N(CH2PCyp2)3-κ(2)P}] (8). This was attributed to the greater electron-donating characteristics of 2, requiring further stabilization on coordination to the electron-rich Ru(0) center by more CO ligands. Complex 7 was activated via oxidation using AgOTf and O2, giving the Ru(II) complexes [Ru(CO)2(OTf){N(CH2PPh2)3-κ(3)P}](OTf) (9) and [Ru(CO3)(CO){N(CH2PPh2)3-κ(3)P}] (11), respectively. Hydrogenation of these complexes under hydrogen pressures of 3-15 bar gave the monohydride and dihydride complexes [RuH(CO)2{N(CH2PPh2)3-κ(3)P}] (10) and [RuH2(CO){N(CH2PPh2)3-κ(3)P}] (12), respectively. Complex 12 was found to be unreactive toward levulinic acid (LA) unless activated by reaction with NH4PF6 in acetonitrile, forming [RuH(CO)(MeCN){N(CH2PPh2)3-κ(3)P}](PF6) (13), which reacted cleanly with LA to form [Ru(CO){N(CH2PPh2)3-κ(3)P}{CH3CO(CH2)2CO2H-κ(2)O}](PF6) (14). Complexes 3, 5, 7, 8, 11, and 12 were characterized by single-crystal X-ray crystallography.

Synthesis and spectroscopic behavior of highly luminescent trinuclear europium complexes with tris-β-diketone ligand

Energy Technology Data Exchange (ETDEWEB)

Wang, Dunjia, E-mail: dunjiawang@163.com; Pi, Yan; Liu, Hua; Wei, Xianhong; Hu, Yanjun; Zheng, Jing

2014-11-15

Highlights: • Synthesis of the tris-β-diketone ligand and its trinuclear europium complexes. • Photoluminescence behavior of trinuclear europium complexes. • Analysis of the Judd–Ofelt intensity parameters (Ω{sub t}), lifetime (τ) and quantum yield (η). - Abstract: A new tris-β-diketone ligand, 2-[4,6-bis-(1-benzoyl-2-oxo-2-phenyl-ethyl)-[1,3,5]triazin-2-yl] -1,3-diphenyl-propane-1,3-dione (H{sub 3}L), and its trinuclear europium complexes, Eu{sub 3}(DBM){sub 6}L (C1), Eu{sub 3}(DBM){sub 6}(Bipy){sub 3}L (C2) and Eu{sub 3}(DBM){sub 6}(Phen){sub 3}L (C3) were synthesized and their spectroscopic behaviors were studied by FT-IR, {sup 1}H NMR, UV–vis and photoluminescence spectroscopic techniques. These europium complexes exhibited the characteristic emission bands that arise from the {sup 5}D{sub 0} → {sup 7}F{sub J} (J = 0–4) transitions of the europium ion in solid state. The Ω{sub 2} and Ω{sub 4} intensity parameters, lifetime (τ) and luminescence quantum yield (η) were calculated according to the emission spectra and luminescence decay curves in solid state. The results indicated that these trinuclear europium complexes displayed a longer lifetime (τ) and higher luminescence quantum efficiency (η), especially complexes C2 (τ = 0.820 ms, η = 46.5%) and C3 (τ = 0.804 ms, η = 47.4%), which due to the effect of two additional europium ion lumophors and the introduction of the third ligands, Bipy or Phen in trinuclear complexes. Their Ω{sub 2} values demonstrated that the europium ion in these complexes is in a highly polarizable chemical environment.

Synthesis, structure and catalytic activities of nickel(II) complexes bearing N4 tetradentate Schiff base ligand

Science.gov (United States)

Sarkar, Saikat; Nag, Sanat Kumar; Chattopadhyay, Asoke Prasun; Dey, Kamalendu; Islam, Sk. Manirul; Sarkar, Avijit; Sarkar, Sougata

2018-05-01

Two new nickel(II) complexes [Ni(L)Cl2] (1) and [Ni(L)(NCS)2] (2) of a neutral tetradentate mono-condensed Schiff base ligand, 3-(2-(2-aminoethylamino)ethylimino)butan-2-one oxime (L) have been synthesized and characterized using different physicochemical techniques e.g. elemental analyses, spectroscopic (IR, Electronic, NMR) methods, conductivity and molecular measurements. The crystal structure of complex (2) has been determined by using single crystal X-ray diffraction method and it suggests a distorted octahedral geometry around nickel(II) having a NiN6 coordinating atmosphere. The non-coordinated Osbnd H group on the ligand L remain engaged in H-bonding interactions with the S end of the coordinated thiocyanate moiety. These H-bonding interactions lead to Osbnd S separations of 3.132 Å and play prominent role in crystal packing. It is observed that the mononuclear units are glued together with such Osbnd H…S interactions and finally results in an 1D supramolecular sheet-like arrangement. DFT/TDDFT based theoretical calculations were also performed on the ligand and the complexes aiming at the accomplishment of idea regarding their optimized geometry, electronic transitions and the molecular energy levels. Finally the catalytic behavior of the complexes for oxidation of styrene has also been carried out. A variety of reaction conditions like the effect of solvent, effect of temperature and time as well as the effect of ratio of substrate to oxidant were thoroughly studied to judge the catalytic efficiency of the Ni(II) coordination entity.

Synthesis and organ distribution of [18F]Fluoro-Org 6141 in the rat: A potential glucocorticoid receptor ligand for positron emission tomography

International Nuclear Information System (INIS)

Visser, G.M.; Krugers, H.J.; Luurtsema, G.; Waarde, A. van; Elsinga, P.H.; DeKloet, E.R.; Groen, M.B.; Bohus, B.; Go, K.G.; Paans, A.M.J.; Korf, J.; Vaalburg, W.

1995-01-01

For the synthesis of [ 18 F]Fluoro-Org 6141 via a nucleophilic substitution reaction with 18 F - , the tosyl group was chosen as the leaving group because of its stability and excellent leaving group ability. The biodistribution of the high affinity and moderate lipophilicity (log P 2.66, calculated value) ligand [ 18 F]Fluoro-Org 6141 (specific activity 8.2 to 37 TBq/mmol, yield 10% at EOB) was examined in sham adrenalectomized (sADX) and adrenalectomized (ADX) male Wistar rats. Two days after ADX or sADX, the animals were anesthetized and 0.37 to 1.85 MBq of [ 18 F]Fluoro-Org 6141 was administered intravenously. Kinetics of 18 F activity uptake were monitored for 3 h using a stationary double-headed positron emission tomography (PET) camera, and the biodistribution was assessed by ex vivo determination of radioactivity in several tissues and different brain areas. One hour after injection of the radioligand, the bladder, kidney, liver, trachea, and bone of sADX animals contained more concentration on a wet weight basis than blood. Three hours post injection, radioactivity was retained in bladder, trachea, and bone. The accumulation of radioactivity in brain corresponded to the concentration of activity in the blood within the first hours after injection. ADX animals showed a higher uptake of 18 F activity in spleen, testes, and brain areas (hippocampus and brainstem) but a lower uptake in bone than sADX rats. PET scans suggested that 18 F activity uptake in the brain had not yet reached a maximum at this interval. Although [ 18 F]Fluoro-Org 6141 is not useful for PET studies of glucocorticoid receptors (GRs), the results obtained with this compound indicate a synthetic strategy suitable for the synthesis of high-affinity radioligands for GRs

Probes for narcotic receptor mediated phenomena 22. Pt.1: Synthesis and characterization of optically pure [3H](+)-4-[(αR)-α-((2S,5R)-4-propyl-2,5-dimethyl-1-pi perazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide, [3H]SNC 121, a novel high affinity and selective ligand for delta opioid receptors

International Nuclear Information System (INIS)

Calderon, S.N.; Bertha, C.M.; Rice, K.C.; Gutkind, J.S.; Heng Xu; Partilla, J.S.; Rothman, R.B.

1996-01-01

The synthesis of unlabelled and labelled SNC 121, a selective nonpeptide ligand for the delta opioid receptor is reported. [ 3 H]SNC 121 of specific activity of 26.8 Ci/mmol, was synthesized by catalytic tritiation of the optically pure precursor SNC 80. (author)

Designer ligands: The search for metal ion selectivity

Directory of Open Access Journals (Sweden)

Perry T. Kaye

2011-03-01

Full Text Available The paper reviews research conducted at Rhodes University towards the development of metal-selective ligands. The research has focused on the rational design, synthesis and evaluation of novel ligands for use in the formation of copper complexes as biomimetic models of the metalloenzyme, tyrosinase, and for the selective extraction of silver, nickel and platinum group metal ions in the presence of contaminating metal ions. Attention has also been given to the development of efficient, metal-selective molecular imprinted polymers.

Inhibition of tumor cell growth by Sigma1 ligand mediated translational repression

International Nuclear Information System (INIS)

Kim, Felix J.; Schrock, Joel M.; Spino, Christina M.; Marino, Jacqueline C.; Pasternak, Gavril W.

2012-01-01

Highlights: ► Sigma1 ligand treatment mediates decrease in tumor cell mass. ► Identification of a Sigma1 ligand with reversible translational repressor actions. ► Demonstration of a role for Sigma1 in cellular protein synthesis. -- Abstract: Treatment with sigma1 receptor (Sigma1) ligands can inhibit cell proliferation in vitro and tumor growth in vivo. However, the cellular pathways engaged in response to Sigma1 ligand treatment that contribute to these outcomes remain largely undefined. Here, we show that treatment with putative antagonists of Sigma1 decreases cell mass. This effect corresponds with repressed cap-dependent translation initiation in multiple breast and prostate cancer cell lines. Sigma1 antagonist treatment suppresses phosphorylation of translational regulator proteins p70S6K, S6, and 4E-BP1. RNAi-mediated knockdown of Sigma1 also results in translational repression, consistent with the effects of antagonist treatment. Sigma1 antagonist mediated translational repression and decreased cell size are both reversible. Together, these data reveal a role for Sigma1 in tumor cell protein synthesis, and demonstrate that small molecule Sigma1 ligands can be used as modulators of protein translation.

Modular Synthesis of Biologically Active Phosphatidic Acid Probes Using Click Chemistry

Science.gov (United States)

Smith, Matthew D.; Sudhahar, Christopher G.; Gong, Denghuang; Stahelin, Robert V.

2018-01-01

Phosphatidic acid (PA) is an important signaling lipid that plays roles in a range of biological processes including both physiological and pathophysiological events. PA is one of a number of signaling lipids that can act as site-specific ligands for protein receptors in binding events that enforce membrane-association and generally regulate both receptor function and subcellular localization. However, elucidation of the full scope of PA activities has proven problematic, primarily due to the lack of a consensus sequence among PA-binding receptors. Thus, experimental approaches, such as those employing lipid probes, are necessary for characterizing interactions at the molecular level. Herein, we describe an efficient modular approach to the synthesis of a range of PA probes that employs a late stage introduction of reporter groups. This strategy was exploited in the synthesis of PA probes bearing fluorescent and photoaffinity tags as well as a bifunctional probe containing both a photoaffinity moiety and an azide as a secondary handle for purification purposes. To discern the ability of these PA analogues to mimic the natural lipid in protein binding properties, each compound was incorporated into vesicles for binding studies using a known PA receptor, the C2 domain of PKCα. In these studies, each compound exhibited binding properties that were comparable to those of synthetic PA, indicating their viability as probes for effectively studying the activities of PA in cellular processes. PMID:19668861

Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric, Multiple Ligands Targeting Cholinesterases and Amyloid Beta

Directory of Open Access Journals (Sweden)

Michalina Hebda

2016-03-01

Full Text Available Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer’s disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention—compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC50 = 70 nM. Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE (EeAChE IC50 = 0.76 μM, EqBuChE IC50 = 0.618 μM, and it inhibits amyloid beta aggregation (35.8% at 10 μM. Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors. According to molecular modelling studies, they are able to interact with both catalytic and peripheral active sites of the acetylcholinesterase. Their ability to cross the blood-brain barrier (BBB was confirmed in vitro in the parallel artificial membrane permeability BBB assay. These compounds can be used as a solid starting point for further development of novel multifunctional ligands as potential anti-Alzheimer’s agents.

ALK receptor activation, ligands and therapeutic targeting in glioblastoma and in other cancers

International Nuclear Information System (INIS)

Wellstein, Anton

2012-01-01

The intracellular anaplastic lymphoma kinase (ALK) fragment shows striking homology with members of the insulin receptor family and was initially identified as an oncogenic fusion protein resulting from a translocation in lymphoma and more recently in a range of cancers. The full-length ALK transmembrane receptor of ~220 kDa was identified based on this initial work. This tyrosine kinase receptor and its ligands, the growth factors pleiotrophin (PTN) and midkine (MK) are highly expressed during development of the nervous system and other organs. Each of these genes has been implicated in malignant progression of different tumor types and shown to alter phenotypes as well as signal transduction in cultured normal and tumor cells. Beyond its role in cancer, the ALK receptor pathway is thought to contribute to nervous system development, function, and repair, as well as metabolic homeostasis and the maintenance of tissue regeneration. ALK receptor activity in cancer can be up-regulated by amplification, overexpression, ligand binding, mutations in the intracellular domain of the receptor and by activity of the receptor tyrosine phosphatase PTPRz. Here we discuss the evidence for ligand control of ALK activity as well as the potential prognostic and therapeutic implications from gene expression and functional studies. An analysis of 18 published gene expression data sets from different cancers shows that overexpression of ALK, its smaller homolog LTK (leukocyte tyrosine kinase) and the ligands PTN and MK in cancer tissues from patients correlate significantly with worse course and outcome of the disease. This observation together with preclinical functional studies suggests that this pathway could be a valid therapeutic target for which complementary targeting strategies with small molecule kinase inhibitors as well as antibodies to ligands or the receptors may be used.

Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

Directory of Open Access Journals (Sweden)

Tino Wolter

Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

Versatile phosphite ligands based on silsesquioxane backbones

NARCIS (Netherlands)

van der Vlugt, JI; Ackerstaff, J; Dijkstra, TW; Mills, AM; Kooijman, H; Spek, AL; Meetsma, A; Abbenhuis, HCL; Vogt, D

Silsesquioxanes are employed as ligand backbones for the synthesis of novel phosphite compounds with 3,3'-5,5'-tetrakis(tert-butyl)-2,2'-di-oxa-1,1'-biphenyl substituents. Both mono- and bidentate phosphites are prepared in good yields. Two types of silsesquioxanes are employed as starting

Synthesis, characterization, cytotoxic and antitubercular activities of new gold(I) and gold(III) complexes containing ligands derived from carbohydrates.

Science.gov (United States)

Chaves, Joana Darc Souza; Damasceno, Jaqueline Lopes; Paula, Marcela Cristina Ferreira; de Oliveira, Pollyanna Francielli; Azevedo, Gustavo Chevitarese; Matos, Renato Camargo; Lourenço, Maria Cristina S; Tavares, Denise Crispim; Silva, Heveline; Fontes, Ana Paula Soares; de Almeida, Mauro Vieira

2015-10-01

Novel gold(I) and gold(III) complexes containing derivatives of D-galactose, D-ribose and D-glucono-1,5-lactone as ligands were synthesized and characterized by IR, (1)H, and (13)C NMR, high resolution mass spectra and cyclic voltammetry. The compounds were evaluated in vitro for their cytotoxicity against three types of tumor cells: cervical carcinoma (HeLa) breast adenocarcinoma (MCF-7) and glioblastoma (MO59J) and one non-tumor cell line: human lung fibroblasts (GM07492A). Their antitubercular activity was evaluated as well expressed as the minimum inhibitory concentration (MIC90) in μg/mL. In general, the gold(I) complexes were more active than gold(III) complexes, for example, the gold(I) complex (1) was about 8.8 times and 7.6 times more cytotoxic than gold(III) complex (8) in MO59J and MCF-7 cells, respectively. Ribose and alkyl phosphine derivative complexes were more active than galactose and aryl phosphine complexes. The presence of a thiazolidine ring did not improve the cytotoxicity. The study of the cytotoxic activity revealed effective antitumor activities for the gold(I) complexes, being more active than cisplatin in all the tested tumor cell lines. Gold(I) compounds (1), (2), (3), (4) and (6) exhibited relevant antitubercular activity even when compared with first line drugs such as rifampicin.

Efficient preparation of {sup 99m}Tc(III) '4+1' mixed-ligand complexes for peptide labeling with high specific activity

Energy Technology Data Exchange (ETDEWEB)

Kunstler, Jens-Uwe [Biotectid GmbH, Deutscher Platz 5c, 04103 Leipzig (Germany); Seidel, Gesine [Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, P.O. Box 510 119, 01314 Dresden (Germany); Pietzsch, Hans-Jurgen, E-mail: h.j.pietzsch@fzd.d [Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, P.O. Box 510 119, 01314 Dresden (Germany)

2010-09-15

An improved labeling procedure for peptides attached to organometallic {sup 99m}Tc(III) '4+1' mixed-ligand complexes in which the radiometal is coordinated by a tripodal tetradentate chelator 2,2',2''-nitrilotriethanethiol (NS{sub 3}) and a monodentate isocyanide ligand is presented. The labeling procedure was evaluated by the synthesis of [{sup 99m}Tc(NS{sub 3})(L2-RGD)]. The containing radiopharmaceutically interesting RGD-peptide cyclo[Arg-Gly-Asp-D-Tyr-Lys] was modified with 4-isocyanobutanoic acid (L2) as linker conjugated to N{sup 6}-Lys to get the monodentate ligand L2-RGD. The structural identity of the {sup 99m}Tc-conjugate was confirmed by comparison to a Re reference compound. The Tc- and Re-conjugates had matching retention times under identical HPLC conditions. The {sup 99m}Tc-labeling was performed in a novel one-step procedure using the eluate of a {sup 99}Mo/{sup 99m}Tc generator, NS{sub 3}, the isocyanide modified peptide, SnCl{sub 2}, Na{sub 2}EDTA, mannitol and ascorbic acid in the reaction mixture. Using optimized reagents it is possible to label 50 nmol peptide with {sup 99m}Tc within 60 min at room temperature with a radiochemical yield higher than 95% and a specific activity of {approx}20 GBq/{mu}mol.

Ni(II, Pd(II and Pt(II complexes with ligand containing thiosemicarbazone and semicarbazone moiety: synthesis, characterization and biological investigation

Directory of Open Access Journals (Sweden)

SULEKH CHANDRA

2008-07-01

Full Text Available The synthesis of nickel(II, palladium(II and platinum(II complexes with thiosemicarbazone and semicarbazone of p-tolualdehyde are reported. All the new compounds were characterized by elemental analysis, molar conductance measurements, magnetic susceptibility measurements, mass, 1H-NMR, IR and electronic spectral studies. Based on the molar conductance measurements in DMSO, the complexes may be formulated as [Ni(L2Cl2] and [M(L2]Cl2 (where M = Pd(II and Pt(II due to their non-electrolytic and 1:2 electrolytic nature, respectively. The spectral data are consistent with an octahedral geometry around Ni(II and a square planar geometry for Pd(II and Pt(II, in which the ligands act as bidentate chelating agents, coordinated through the nitrogen and sulphur/oxygen atoms. The ligands and their metal complexes were screened in vitro against fungal species Alternaria alternata, Aspergillus niger and Fusarium odum, using the food poison technique.

Synthesis and Optical Characterization of Mixed Ligands Beryllium Complexes for Display Device Applications

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Vandna Nishal

2015-01-01

Full Text Available Synthesis and photoluminescent behaviour of mixed ligand based beryllium complexes with 2-(2-hydroxyphenylbenzoxazole (HPB and 5-chloro-8-hydroxyquinoline (Clq or 5,7-dichloro-8-hydroxyquinoline (Cl2q or 2-methyl-8-hydroxyquinoline (Meq or 8-hydroxyquinoline (q are reported in this work. These complexes, that is, [BeHPB(Clq], [BeHPB(Cl2q], [BeHPB(Meq], and [BeHPB(q], were prepared and their structures were confirmed by elemental analysis, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and thermal analysis. The beryllium complexes exhibited good thermal stability up to ~300°C temperature. The photophysical properties of beryllium complexes were studied using ultraviolet-visible absorption and photoluminescence emission spectroscopy. The complexes showed absorption peaks due to π-π∗ and n-π∗ electronic transitions. The complexes emitted greenish blue light with peak wavelength at 496 nm, 510 nm, 490 nm, and 505 nm, respectively, consisting of high intensity. Color tuning was observed with changing the substituents in quinoline ring ligand in metal complexes. The emitted light had Commission Internationale d’Eclairage color coordinates values at x=0.15 and y=0.43 for [BeHPB(Clq], x=0.21 and y=0.56 for [BeHPB(Cl2q], x=0.14 and y=0.38 for [BeHPB(Meq], x=0.17 and y=0.41 for [BeHPB(q]. Theoretical calculations using DFT/B3LYP/6-31G(d,p method were performed to reveal the three-dimensional geometries and the frontier molecular orbital energy levels of these synthesized metal complexes.

Ligand-independent canonical Wnt activity in canine mammary tumor cell lines associated with aberrant LEF1 expression.

Directory of Open Access Journals (Sweden)

Ana Gracanin

Full Text Available Pet dogs very frequently develop spontaneous mammary tumors and have been suggested as a good model organism for breast cancer research. In order to obtain an insight into underlying signaling mechanisms during canine mammary tumorigenesis, in this study we assessed the incidence and the mechanism of canonical Wnt activation in a panel of 12 canine mammary tumor cell lines. We show that a subset of canine mammary cell lines exhibit a moderate canonical Wnt activity that is dependent on Wnt ligands, similar to what has been described in human breast cancer cell lines. In addition, three of the tested canine mammary cell lines have a high canonical Wnt activity that is not responsive to inhibitors of Wnt ligand secretion. Tumor cell lines with highly active canonical Wnt signaling often carry mutations in key members of the Wnt signaling cascade. These cell lines, however, carry no mutations in the coding regions of intracellular Wnt pathway components (APC, β-catenin, GSK3β, CK1α and Axin1 and have a functional β-catenin destruction complex. Interestingly, however, the cell lines with high canonical Wnt activity specifically overexpress LEF1 mRNA and the knock-down of LEF1 significantly inhibits TCF-reporter activity. In addition, LEF1 is overexpressed in a subset of canine mammary carcinomas, implicating LEF1 in ligand-independent activation of canonical Wnt signaling in canine mammary tumors. We conclude that canonical Wnt activation may be a frequent event in canine mammary tumors both through Wnt ligand-dependent and novel ligand-independent mechanisms.

Role of the T cell receptor ligand affinity in T cell activation by bacterial superantigens

DEFF Research Database (Denmark)

Andersen, P S; Geisler, C; Buus, S

2001-01-01

Similar to native peptide/MHC ligands, bacterial superantigens have been found to bind with low affinity to the T cell receptor (TCR). It has been hypothesized that low ligand affinity is required to allow optimal TCR signaling. To test this, we generated variants of Staphylococcus enterotoxin C3...... (SEC3) with up to a 150-fold increase in TCR affinity. By stimulating T cells with SEC3 molecules immobilized onto plastic surfaces, we demonstrate that increasing the affinity of the SEC3/TCR interaction caused a proportional increase in the ability of SEC3 to activate T cells. Thus, the potency...... correlation between ligand affinity and ligand potency indicating that it is the density of receptor-ligand complexes in the T cell contact area that determines TCR signaling strength....

Synthesis of mixed-ligand cobalt complexes and their applications in high cis-1,4-selective butadiene polymerization

KAUST Repository

Liu, Wen; Pan, Weijing; Wang, Peng; Li, Wei; Mu, Jingshan; Weng, Gengsheng; Jia, Xiaoyu; Gong, Dirong; Huang, Kuo-Wei

2015-01-01

Incomplete oxidation of (N-di-tert-butylphosphino)-6-(2-methyl-2’H-benzoimidazole)-2-aminepyridine dichlorocobalt (PN3CoCl2) in DMF results in a unique co-crystal I formed with three parts including DMF, unit A and unit B complex with Co1 and Co2, respectively, (PN3 ligand in unit A: (N-di-tert-butylphosphino)-6-(2’-methyl-2’H-benzoimidazole)-2-aminepyridine, and O=PN3 ligand in unit B: (N-di-tert-butylphosphinoxide)-6-(2’-methyl-2’H-benzoimidazole)-2-aminepyridine) with 1:1:1 molar ratio. Co1 and Co2 complexes both display a five-coordinated distorted-square-pyramidal geometry around the metal center. The Co1 center is coordinated with PN3 ligand via two N atoms from pyridine, benzoimidazole moiety as well as one P atom, and the Co2 center is coordinated with the oxidized ligandO=PN3 via two N atoms from pyridine, benzoimidazole moiety as well as one O atom from DMF molecule, while the oxidized phosphine moiety (O=P) being excluded from the coordination sphere. Activated with AlEt2Cl, the co-crystallized complexes I are able to actively convert butadiene to polybutadiene, affording cis-1,4 polybutadiene with cis-1,4 unit up to 95.5-97.8% and number average molecular weight of cal. 105g/mol. The high cis-1,4 selectivity and monomodal GPC curve of resultant polymer imply that the identical active species generated from two distinctive cobalt centers.

Synthesis of mixed-ligand cobalt complexes and their applications in high cis-1,4-selective butadiene polymerization

KAUST Repository

Liu, Wen

2015-08-03

Incomplete oxidation of (N-di-tert-butylphosphino)-6-(2-methyl-2’H-benzoimidazole)-2-aminepyridine dichlorocobalt (PN3CoCl2) in DMF results in a unique co-crystal I formed with three parts including DMF, unit A and unit B complex with Co1 and Co2, respectively, (PN3 ligand in unit A: (N-di-tert-butylphosphino)-6-(2’-methyl-2’H-benzoimidazole)-2-aminepyridine, and O=PN3 ligand in unit B: (N-di-tert-butylphosphinoxide)-6-(2’-methyl-2’H-benzoimidazole)-2-aminepyridine) with 1:1:1 molar ratio. Co1 and Co2 complexes both display a five-coordinated distorted-square-pyramidal geometry around the metal center. The Co1 center is coordinated with PN3 ligand via two N atoms from pyridine, benzoimidazole moiety as well as one P atom, and the Co2 center is coordinated with the oxidized ligandO=PN3 via two N atoms from pyridine, benzoimidazole moiety as well as one O atom from DMF molecule, while the oxidized phosphine moiety (O=P) being excluded from the coordination sphere. Activated with AlEt2Cl, the co-crystallized complexes I are able to actively convert butadiene to polybutadiene, affording cis-1,4 polybutadiene with cis-1,4 unit up to 95.5-97.8% and number average molecular weight of cal. 105g/mol. The high cis-1,4 selectivity and monomodal GPC curve of resultant polymer imply that the identical active species generated from two distinctive cobalt centers.

Probes for narcotic receptor mediated phenomena 22. Pt.1: Synthesis and characterization of optically pure [{sup 3}H](+)-4-[({alpha}R)-{alpha}-((2S,5R)-4-propyl-2,5-dimethyl-1-pi perazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide, [{sup 3}H]SNC 121, a novel high affinity and selective ligand for delta opioid receptors

Energy Technology Data Exchange (ETDEWEB)

Calderon, S.N.; Bertha, C.M.; Rice, K.C. [National Inst. of Diabetes and Digestive and Kidney Diseases, Medicinal Chemistry Lab., Bethesda, MD (United States); Gutkind, J.S. [National Inst. of Dental Research, Bethesda, MD (United States); Heng Xu; Partilla, J.S.; Rothman, R.B. [National Inst. on Drug Abuse, Clinical Psychopharmacology Section, Baltimore, MD (United States)

1996-09-01

The synthesis of unlabelled and labelled SNC 121, a selective nonpeptide ligand for the delta opioid receptor is reported. [{sup 3}H]SNC 121 of specific activity of 26.8 Ci/mmol, was synthesized by catalytic tritiation of the optically pure precursor SNC 80. (author).

Chiral ligands derived from monoterpenes: application in the synthesis of optically pure secondary alcohols via asymmetric catalysis.

Science.gov (United States)

El Alami, Mohammed Samir Ibn; El Amrani, Mohamed Amin; Agbossou-Niedercorn, Francine; Suisse, Isabelle; Mortreux, André

2015-01-19

The preparation of optically pure secondary alcohols in the presence of catalysts based on chiral ligands derived from monoterpenes, such as pinenes, limonenes and carenes, is reviewed. A wide variety of these ligands has been synthesized and used in several catalytic reactions, including hydrogen transfer, C-C bond formation via addition of organozinc compounds to aldehydes, hydrosilylation, and oxazaborolidine reduction, leading to high activities and enantioselectivities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

Directory of Open Access Journals (Sweden)

Jaroslav Padevět

2016-06-01

Full Text Available A synthesis of new NeoPHOX ligands derived from serine or threonine has been developed. The central intermediate is a NeoPHOX derivative bearing a methoxycarbonyl group at the stereogenic center next to the oxazoline N atom. The addition of methylmagnesium chloride leads to a tertiary alcohol, which can be acylated or silylated to produce NeoPHOX ligands with different sterical demand. The new NeoPHOX ligands were tested in the iridium-catalyzed asymmetric hydrogenation and palladium-catalyzed allylic substitution. In both reactions high enantioselectivities were achieved, that were comparable to the enantioselectivities obtained with the up to now best NeoPHOX ligand derived from expensive tert-leucine.

A new class of modular chiral ligands with fluxional groups.

Science.gov (United States)

Sibi, Mukund P; Zhang, Ruzhou; Manyem, Shankar

2003-08-06

In ligand design for asymmetric catalysis, the usual norm is to derive the face shielding elements from a chiral source. New ligands in which the face shielding is determined by fluxional groups are introduced. Their design, modular synthesis, and experiments to demonstrate the significance of the fluxional groups are discussed. The advantage is that the fluxional groups, introduced at a later stage, allow for simple tuning of the face shielding group.

Synthesis of metal complexes involving Schiff base ligand with methylenedioxy moiety: spectral, thermal, XRD and antimicrobial studies.

Science.gov (United States)

Sundararajan, M L; Jeyakumar, T; Anandakumaran, J; Karpanai Selvan, B

2014-10-15

Metal complexes of Zn(II), Cd(II), Ni(II), Cu(II), Fe(III), Co(II), Mn(II) Hg(II), and Ag(I) have been synthesized from Schiff base ligand, prepared by the condensation of 3,4-(methylenedioxy)aniline and 5-bromo salicylaldehyde. All the compounds have been characterized by using elemental analysis, molar conductance, FT-IR, UV-Vis, (1)H NMR, (13)C NMR, mass spectra, powder XRD and thermal analysis (TG/DTA) technique. The elemental analysis suggests the stoichiometry to be 1:1 (metal:ligand). The FT-IR, (1)H NMR, (13)C NMR and UV-Vis spectral data suggest that the ligand coordinate to the metal atom by imino nitrogen and phenolic oxygen as bidentate manner. Mass spectral data further support the molecular mass of the compounds and their structure. Powder XRD indicates the crystalline state and morphology of the ligand and its metal complexes. The thermal behaviors of the complexes prove the presence of lattice as well as coordinated water molecules in the complexes. Melting point supports the thermal stability of all the compounds. The in vitro antimicrobial effects of the synthesized compounds were tested against five bacterial and three fungal species by well diffusion method. Antioxidant activities have also been performed for all the compounds. Metal complexes show more biological activity than the Schiff base. Copyright © 2014 Elsevier B.V. All rights reserved.

A Ligand Structure-Activity Study of DNA-Based Catalytic Asymmetric Hydration and Diels-Alder Reactions

NARCIS (Netherlands)

Rosati, F.; Roelfes, J.G.

A structure-activity relationship study of the first generation ligands for the DNA-based asymmetric hydration of enones and Diels-Alder reaction in water is reported. The design of the ligand was optimized resulting in a maximum ee of 83% in the hydration reaction and 75% in the Diels-Alder

Surface active monomers synthesis, properties, and application

CERN Document Server

Borzenkov, Mykola

2014-01-01

This brief includes information on the background?of and development of synthesis of various types of surface active monomers. The authors explain the importance of utilization of surface active monomers for creation of surface active polymers? and the various biomedical applications of such compounds . This brief introduces techniques for the synthesis of novel types of surface active monomers, their colloidal and polymerizable properties and application for needs of medicine and biology.

Retinal Ligand Mobility Explains Internal Hydration and Reconciles Active Rhodopsin Structures

Science.gov (United States)

Leioatts, Nicholas; Mertz, Blake; Martínez-Mayorga, Karina; Romo, Tod D.; Pitman, Michael C.; Feller, Scott E.; Grossfield, Alan; Brown, Michael F.

2014-01-01

Rhodopsin, the mammalian dim-light receptor, is one of the best-characterized G-protein-coupled receptors, a pharmaceutically important class of membrane proteins that has garnered a great deal of attention because of the recent availability of structural information. Yet the mechanism of rhodopsin activation is not fully understood. Here, we use microsecond-scale all-atom molecular dynamics simulations, validated by solid-state 2H nuclear magnetic resonance spectroscopy, to understand the transition between the dark and metarhodopsin I (Meta I) states. Our analysis of these simulations reveals striking differences in ligand flexibility between the two states. Retinal is much more dynamic in Meta I, adopting an elongated conformation similar to that seen in the recent activelike crystal structures. Surprisingly, this elongation corresponds to both a dramatic influx of bulk water into the hydrophobic core of the protein and a concerted transition in the highly conserved Trp2656.48 residue. In addition, enhanced ligand flexibility upon light activation provides an explanation for the different retinal orientations observed in X-ray crystal structures of active rhodopsin. PMID:24328554

Synthesis, Characterization, and Biological Activity of Nickel (II and Palladium (II Complex with Pyrrolidine Dithiocarbamate (PDTC

Directory of Open Access Journals (Sweden)

Sk Imadul Islam

2016-01-01

Full Text Available The synthesis of square planar Ni(II and Pd(II complexes with pyrrolidine dithiocarbamate (PDTC was characterized by elemental, physiochemical, and spectroscopic methods. Two complexes were prepared by the reaction of nickel acetate and palladium acetate with pyrrolidine dithiocarbamate (PDTC in 1 : 2 molar ratio. The bovine serum albumin (BSA interaction with complexes was examined by absorption and fluorescence spectroscopic techniques at pH 7.4. All the spectral data suggest that coordination of the pyrrolidine dithiocarbamate (PDTC takes place through the two sulphur atoms in a symmetrical bidentate fashion. All the synthesized compounds were screened for their antimicrobial activity against some species of pathogenic bacteria (Escherichia coli, Vibrio cholerae, Streptococcus pneumonia, and Bacillus cereus. It has been observed that complexes have higher activity than the free ligand.

Synthesis of the hexaamine ligand 1,4,7-tris(3-aminopropyl)-1,4,7-triazacyclononane: Reactivity and x-ray crystal structures of the nickel(II) and cobalt(III) complexes

International Nuclear Information System (INIS)

Bushnell, G.W.; Fortier, D.G.; McAuley, A.

1988-01-01

The synthesis of the ligand 1,4,7-tris(3-aminopropyl)-1,4,7-triazacyclononane(tapacn) can be achieved by the reaction of 1,4,7-triazacyclononane with an excess of acetonitrile, followed by reduction of the nitrile with sodium metal in toluene. Halide salts of the cobalt(III)(complex A) and nickel(II)(complex B) ions have been prepared and examined by using x-ray crystallography. The crystal structures are reported. The 13 C NMR spectrum of the dismagnetic d 6 Co(III) complex ion is reported. A discussion of the two ligand structures deals with the ligand opening and with trigonal twist angle as related to metal ion size and mechanism for redox processes of the complex. 45 refs., 6 figs., 9 tabs

Synthesis and Characterization of Acyclic and Cyclic Azabridged Ligands Incorporating 2,2'-Bipyridine Subunits and Their Complexes With Copper(II, Cobalt(II, and Nickel(II

Directory of Open Access Journals (Sweden)

Andrea Pappalardo

2003-07-01

Full Text Available The synthesis of a series of N,N'-disubstituted acyclic (AL and cyclic (CL aza-bridged ligands incorporating 2,2-pipryidine subunits is described. 1H-NMR and IR spectral data support the proposed ligand structures. Dynamic 1H-NMR studies on diurea and diamide derivatives point to the presence of slowly interconverting conformers on the 1H-NMR time-scale, owing to N−H···N hydrogen bonding and/or a restricted rotation around the amide bonds. The ligands synthesized form 1:1 complexes with divalent transition metal ions. Upon complexation, bis-ester derivatives AL5 and CL5 undergo a metal-induced hydrolysis of the ester groups to carboxyl functions, which act as additional binding sites for the metal ion, as well as hydrogen-bonding donor-acceptor binding site to produce dimeric complexes.

Room-temperature synthesis of pure perovskite-related Cs4PbBr6 nanocrystals and their ligand-mediated evolution into highly luminescent CsPbBr3 nanosheets

Science.gov (United States)

Yang, Liu; Li, Dongmei; Wang, Cong; Yao, Wei; Wang, Hao; Huang, Kaixiang

2017-07-01

Currently, all-inorganic cesium lead-halide perovskite nanocrystals have attracted enormous attentions owing to their excellent optical performances. While great efforts have been devoted to CsPbBr3 nanocrystals, the perovskite-related Cs4PbBr6 nanocrystals, which were newly reported, still remained poorly understood. Here, we reported a novel room-temperature reaction strategy to synthesize pure perovskite-related Cs4PbBr6 nanocrystals. Size of the products could be adjusted through altering the amount of ligands, simply. A mixture of two good solvents with different polarity was innovatively used as precursor solvent, being one key to the high-yield Cs4PbBr6 nanocrystals synthesis. Other two keys were Cs+ precursor concentration and surface ligands. Ingenious experiments were designed to reveal the underlying reaction mechanism. No excitonic emission was observed from the prepared Cs4PbBr6 nanocrystals in our work. We considered the green emission which was observed in other reports originated from the avoidless transformation of Cs4PbBr6 into CsPbBr3 nanocrystals. Indeed, the new-prepared Cs4PbBr6 nanocrystals could transform into CsPbBr3 nanosheets with surface ligands mediated. The new-transformed two-dimensional CsPbBr3 nanosheets could evolve into large-size nanosheets. The influences of surface ligand density on the fluorescent intensity and stability of transformed CsPbBr3 nanosheets were also explained. Notably, the photoluminescence quantum yield of the as-transformed CsPbBr3 nanosheets could reach as high as 61.6% in the form of thin film. The fast large-scale synthesis of Cs4PbBr6 nanocrystals and their ligand-mediated transformation into high-fluorescent CsPbBr3 nanosheets will be beneficial to the future optoelectronic applications. Our work provides new approaches to understand the structural evolution and light-emitting principle of perovskite nanocrystals. [Figure not available: see fulltext.

Alkylation and pre-organization of diglycolamide ligands on flexible platforms for nuclear waste treatment

NARCIS (Netherlands)

Leoncini, Andrea

2017-01-01

The research topic of this thesis concerns the synthesis and evaluation of new diglycolamide (DGA) ligands for the extraction and (potential) separation of actinide and lanthanide ions from bulk spent nuclear fuel. This work was aimed at the development of new pre-organised ligands with improved

Direct versus ligand-exchange synthesis of [PtAg28(BDT)12(TPP)4]4− nanoclusters: effect of a single-atom dopant on the optoelectronic and chemical properties

KAUST Repository

Bootharaju, Megalamane Siddaramappa; Kozlov, Sergey M.; Cao, Zhen; Harb, Moussab; Parida, Manas R.; Hedhili, Mohamed N.; Mohammed, Omar F.; Bakr, Osman; Cavallo, Luigi; Basset, Jean-Marie

2017-01-01

to offer monodisperse doped NCs. For instance, the direct synthesis of PtAg28 NCs produces a mixture of [Ag29(BDT)12(TPP)4]3- and [PtAg28(BDT)12(TPP)4]4- NCs (TPP: triphenylphosphine; BDT: 1,3-benzenedithiolate). Here, we designed a ligand-exchange (LE

Synthesis of Ruthenium(III Phthalocyanine with Di-axial Bromo Ligands - A Promising Molecular Conductor with Giant Negative Magnetoresistance

Directory of Open Access Journals (Sweden)

Mario A.V. Gamboa

2015-01-01

Full Text Available The electron transport of Phthalocyanines (Pc with central metal and di-axial ligands (such as FeIII(PcL2; where L = CN, Cl, Br originates from its intermolecular Pc π-π orbital overlap while its giant negative magnetoresistance (GNMR arises from its intramolecular Pc-π(HOMO and Fe-d (s=1/2 interaction. However, the π-d interaction tends to localize itinerant electrons resulting in the decrease in the conductivity of the FeIII(PcL2 series compared to the non-magnetic CoIII(PcL2 where π-d interaction is absent. More so, the axial ligand field energy of the FeIII(PcL2 system is found to have the ability to proportionally modulate the π-d interaction. In reference thereof, theoretical calculations point that isostructural RuIII(PcBr2 would provide the best balance of π-d orbital energy interplay. That is, RuIII(PcBr2 is expected to be a molecule with high electrical conductivity and GNMR which would make it an ideal magnetic molecular conductor. This paper reports on the synthesis of RuIII(PcBr2.

Predicting Efficient Antenna Ligands for Tb(III) Emission

Energy Technology Data Exchange (ETDEWEB)

Samuel, Amanda P.S.; Xu, Jide; Raymond, Kenneth

2008-10-06

A series of highly luminescent Tb(III) complexes of para-substituted 2-hydroxyisophthalamide ligands (5LI-IAM-X) has been prepared (X = H, CH{sub 3}, (C=O)NHCH{sub 3}, SO{sub 3}{sup -}, NO{sub 2}, OCH{sub 3}, F, Cl, Br) to probe the effect of substituting the isophthalamide ring on ligand and Tb(III) emission in order to establish a method for predicting the effects of chromophore modification on Tb(III) luminescence. The energies of the ligand singlet and triplet excited states are found to increase linearly with the {pi}-withdrawing ability of the substituent. The experimental results are supported by time-dependent density functional theory (TD-DFT) calculations performed on model systems, which predict ligand singlet and triplet energies within {approx}5% of the experimental values. The quantum yield ({Phi}) values of the Tb(III) complex increases with the triplet energy of the ligand, which is in part due to the decreased non-radiative deactivation caused by thermal repopulation of the triplet. Together, the experimental and theoretical results serve as a predictive tool that can be used to guide the synthesis of ligands used to sensitize lanthanide luminescence.

synthesis and spectra characterization of mixed- ligand complexes

African Journals Online (AJOL)

BARTH EKWUEME

The Schiff base ligand, N-Propylidene-2-methylpyridylamine was obtained from the condensation of 2- aminomethypyridine and propanal.Also, its complexes with Cu(II),Ni(II),Zn(II),Co(II) .... determined with Thomas–Hoover capillary melting apparatus. RESULTS AND DISCUSSION. N-propylidene-2-methylpyridylamine ...

Fundamental aspects of nucleation and growth in the solution-phase synthesis of germanium nanocrystals

KAUST Repository

Codoluto, Stephen C.

2010-01-01

Colloidal Ge nanocrystals (NCs) were synthesized via the solution phase reduction of germanium(ii) iodide. We report a systematic investigation of the nanocrystal nucleation and growth as a function of synthesis conditions including the nature of coordinating solvents, surface bound ligands, synthesis duration and temperature. NC synthesis in reaction environments with weakly bound phosphine surface ligand led to the coalescence of nascent particles leading to ensembles with broad lognormal particle diameter distributions. Synthesis in the presence of amine or alkene ligands mitigated particle coalescence. High-resolution transmission electron micrographs revealed that NCs grown in the presence of weak ligands had a high crystal defect density whereas NCs grown in amine solutions were predominantly defect-free. We applied infrared spectroscopy to study the NC surface chemistry and showed that alkene ligands project the NCs from surface oxidation. Photoluminescence spectroscopy measurements showed that alkene ligands passivate surface traps, as indicated by infrared fluorescence, conversely oxidized phosphine and amine passivated NCs did not fluoresce. © 2010 The Royal Society of Chemistry.

Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions.

Science.gov (United States)

Lipinski, Christopher A

2016-06-01

The rule of five (Ro5), based on physicochemical profiles of phase II drugs, is consistent with structural limitations in protein targets and the drug target ligands. Three of four parameters in Ro5 are fundamental to the structure of both target and drug binding sites. The chemical structure of the drug ligand depends on the ligand chemistry and design philosophy. Two extremes of chemical structure and design philosophy exist; ligands constructed in the medicinal chemistry synthesis laboratory without input from natural selection and natural product (NP) metabolites biosynthesized based on evolutionary selection. Exceptions to Ro5 are found mostly among NPs. Chemistry chameleon-like behavior of some NPs due to intra-molecular hydrogen bonding as exemplified by cyclosporine A is a strong contributor to NP Ro5 outliers. The fragment derived, drug Navitoclax is an example of the extensive expertise, resources, time and key decisions required for the rare discovery of a non-NP Ro5 outlier. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis and evaluation of [[sup 18]F]fluoroprogestins and [[sup 18]F]fluorometoprolol

Energy Technology Data Exchange (ETDEWEB)

De Groot, T J

1993-05-01

The author investigated if specific radioactively labelled compounds could be applied to gain insight into particular psychic diseases, f.e. Parkinson's disease and schizophrenia, by means of Positron Emission Tomography (PET). No appropriate compounds were found. In this thesis the syntheses of fluorine-18 labelled progestins and [beta][sub 1]-adrenergic ligands are described. Three approaches towards [[sup 18]F]fluorination are investigated. The first method concerns direct S[sub N]2-substitution, the second approach is the opening of an epoxide, and the third approach is [[sup 18]F]fluoroalkylation. The positron emitting radionuclide fluorine-18 was used because of its relatively long decay time and the possibility to produce it in high yields and with high specific activity. The target systems which were applied for the production of fluorine-18 are described in chapter two. Important chemical and physical aspects of [[sup 18]F]fluoride are reviewed in the same chapter. In chapter three the synthesis of 21-[[sup 18]F]fluorinated progestins is discussed. The synthesis of four 21-[[sup 18]F]fluoroprogesterone derivatives is described and the results of an in vivo evaluation of two of these ligands are discussed. Possible routes leading to 6[alpha]-[[sup 18]F]fluoroprogestins are presented in chapter four. The radiochemical approaches towards the synthesis of these ligands are discussed. In chapter five the proposed routes to the fluorine-18 labelled [beta][sub 1]-adrenergic ligands are described and evaluated in the synthesis of two model compounds. 1-[[sup 18]F]fluorometoprolol, the [[sup 18]F]fluorinated analogue of a potent beta-blocker, is prepared using one of the investigated methods. The biological effect of fluorine substitution of a [beta][sub 1]-adrenergic ligand is discussed on the basis of an in vitro and in vivo evaluation. 21 figs., 28 schemes, 19 tabs., 182 refs.

A grand unified model for liganded gold clusters

Science.gov (United States)

Xu, Wen Wu; Zhu, Beien; Zeng, Xiao Cheng; Gao, Yi

2016-12-01

A grand unified model (GUM) is developed to achieve fundamental understanding of rich structures of all 71 liganded gold clusters reported to date. Inspired by the quark model by which composite particles (for example, protons and neutrons) are formed by combining three quarks (or flavours), here gold atoms are assigned three `flavours' (namely, bottom, middle and top) to represent three possible valence states. The `composite particles' in GUM are categorized into two groups: variants of triangular elementary block Au3(2e) and tetrahedral elementary block Au4(2e), all satisfying the duet rule (2e) of the valence shell, akin to the octet rule in general chemistry. The elementary blocks, when packed together, form the cores of liganded gold clusters. With the GUM, structures of 71 liganded gold clusters and their growth mechanism can be deciphered altogether. Although GUM is a predictive heuristic and may not be necessarily reflective of the actual electronic structure, several highly stable liganded gold clusters are predicted, thereby offering GUM-guided synthesis of liganded gold clusters by design.

Cr(III), Fe(III) and Co(III) complexes of tetradentate (ONNO) Schiff base ligands: Synthesis, characterization, properties and biological activity

Science.gov (United States)

Keskioğlu, Eren; Gündüzalp, Ayla Balaban; Çete, Servet; Hamurcu, Fatma; Erk, Birgül

2008-08-01

A series of metal complexes were synthesized from equimolar amounts of Schiff bases: 1,4-bis[3-(2-hydroxy-1-naphthaldimine)propyl]piperazine (bappnaf) and 1,8-bis[3-(2-hydroxy-1-naphthaldimine)- p-menthane (damnaf) with metal chlorides. All of synthesized compounds were characterized by elemental analyses, spectral (UV-vis, IR, 1H- 13C NMR, LC-MS) and thermal (TGA-DTA) methods, magnetic and conductance measurements. Schiff base complexes supposed in tetragonal geometry have the general formula [M(bappnaf or damnaf)]Cl· nH 2O, where M = Cr(III), Co(III) and n = 2, 3. But also Fe(III) complexes have octahedral geometry by the coordination of two water molecules and the formula is [Fe(bappnaf or damnaf)(H 2O) 2]Cl. The changes in the selected vibration bands in FT-IR indicate that Schiff bases behave as (ONNO) tetradentate ligands and coordinate to metal ions from two phenolic oxygen atoms and two azomethine nitrogen atoms. Conductance measurements suggest 1:1 electrolytic nature of the metal complexes. The synthesized compounds except bappnaf ligand have the antimicrobial activity against the bacteria: Escherichia coli (ATCC 11230), Yersinia enterocolitica (ATCC 1501), Bacillus magaterium (RSKK 5117), Bacillus subtilis (RSKK 244), Bacillus cereus (RSKK 863) and the fungi: Candida albicans (ATCC 10239). These results have been considerably interest in piperazine derivatives due to their significant applications in antimicrobial studies.

Synthesis, Characterization and Biological Evaluation of Transition Metal Complexes Derived from N, S Bidentate Ligands

Directory of Open Access Journals (Sweden)

Enis Nadia Md Yusof

2015-05-01

Full Text Available Two bidentate NS ligands were synthesized by the condensation reaction of S-2-methylbenzyldithiocarbazate (S2MBDTC with 2-methoxybenzaldehyde (2MB and 3-methoxybenzaldehyde (3MB. The ligands were reacted separately with acetates of Cu(II, Ni(II and Zn(II yielding 1:2 (metal:ligand complexes. The metal complexes formed were expected to have a general formula of [M(NS2] where M = Cu2+, Ni2+, and Zn2+. These compounds were characterized by elemental analysis, molar conductivity, magnetic susceptibility and various spectroscopic techniques. The magnetic susceptibility measurements and spectral results supported the predicted coordination geometry in which the Schiff bases behaved as bidentate NS donor ligands coordinating via the azomethine nitrogen and thiolate sulfur. The molecular structures of the isomeric S2M2MBH (1 and S2M3MBH (2 were established by X-ray crystallography to have very similar l-shaped structures. The Schiff bases and their metal complexes were evaluated for their biological activities against estrogen receptor-positive (MCF-7 and estrogen receptor-negative (MDA-MB-231 breast cancer cell lines. Only the Cu(II complexes showed marked cytotoxicity against the cancer cell lines. Both Schiff bases and other metal complexes were found to be inactive. In concordance with the cytotoxicity studies, the DNA binding studies indicated that Cu(II complexes have a strong DNA binding affinity.

Exogenous iron and γ-irradiation induce NO-synthase synthesis in mouse liver

International Nuclear Information System (INIS)

Mikoyan, V.D.; Voevodskaya, N.V.; Kubrina, L.N.; Malenkova, I.V.; Vanin, A.F.

1994-01-01

Protein synthesis inhibitor (cycloheximide, CHI) and exogenous antioxidant (phenazan) suppress the synthesis of NO in mouse liver in vivo which is induced by administration to the animals of γ-irradiation, bacterial lipopolysaccharide (LPS), or Fe 2+ -citrate together with LPS. Biosynthesis of NO was monitored by the ESR signal of paramagnetic mononitrosyl iron complexes with the exogenous ligand diethyldithiocarbamate (MNIC-DETC) 30 min after addition of the ligand. The complexes arise from NO binding to DETC complexes with exogenous and endogenous Fe 2+ , which act as selective NO traps. The enhancement of NO biosynthesis after γ-irradiation or LPS or LPS + Fe 2+ -citrate is apparently due to the induction of the synthesis of NO-synthase, which is inhibited by cycloheximide. This process is triggered by reactive oxygen species, presumably through the activation of the transcription factor protein NFkB. The accumulation of free radical oxygen species is inhibited by the antioxidant phenazan

Synthesis, Characterization, and Antibacterial Studies of Mixed Ligand Dioxouranium Complexes with 8-Hydroxyquinoline and Some Amino Acids

Science.gov (United States)

Patil, Sunil S.; Thakur, Ganesh A.; Shaikh, Manzoor M.

2011-01-01

Mixed ligand complexes of dioxouranium (VI) of the type [UO2(Q)(L)·2H2O] have been synthesized using 8-hydroxyquinoline (HQ) as a primary ligand and amino acids (HL) such as L-threonine, L-tryptophan, and L-isoleucine as secondary ligands. The metal complexes have been characterized by elemental analysis, electrical conductance, magnetic susceptibility measurements, and spectral and thermal studies. The electrical conductance studies of the complexes indicate their nonelectrolytic nature. Magnetic susceptibility measurements revealed diamagnetic nature of the complexes. Electronic absorption spectra of the complexes show intraligand and charge transfer transitions, respectively. Bonding of the metal ion through N- and O-donor atoms of the ligands is revealed by IR studies, and the chemical environment of the protons is confirmed by NMR studies. The thermal analysis data of the complexes indicate the presence of coordinated water molecules. The agar cup and tube dilution methods have been used to study the antibacterial activity of the complexes against the pathogenic bacteria S. aureus, C. diphtheriae, S. typhi, and E. coli. PMID:22389843

Cu(II AND Zn(II COMPLEX COMPOUNDS WITH BIGUANIDES AROMATIC DERIVATIVES. SYNTHESIS, CHARACTERIZATION, BIOLOGICAL ACTIVITY

Directory of Open Access Journals (Sweden)

Ticuţa Negreanu-Pîrjol

2011-05-01

Full Text Available In this paper we report the synthesis, physical-chemical characterization and antimicrobial activity of some new complex compounds of hetero-aromatic biguanides ligands, chlorhexidine base (CHX and chlorhexidine diacetate (CHXac2 with metallic ions Cu(II and Zn(II, in different molar ratio. The synthesized complexes were characterized by elemental chemical analysis and differential thermal analysis. The stereochemistry of the metallic ions was determined by infrared spectra, UV-Vis, EPR spectroscopy and magnetic susceptibility in the aim to establish the complexes structures. The biological activity of the new complex compounds was identified in solid technique by measuring minimum inhibition diameter of bacterial and fungal culture, against three standard pathogen strains, Escherichia coli ATCC 25922, Staphilococcus aureus ATCC 25923 and Candida albicans ATCC 10231. The results show an increased specific antimicrobial activity for the complexes chlorhexidine:Cu(II 1:1 and 1:2 compared with the one of the Zn(II complexes.

Melatonin: functions and ligands.

Science.gov (United States)

Singh, Mahaveer; Jadhav, Hemant R

2014-09-01

Melatonin is a chronobiotic substance that acts as synchronizer by stabilizing bodily rhythms. Its synthesis occurs in various locations throughout the body, including the pineal gland, skin, lymphocytes and gastrointestinal tract (GIT). Its synthesis and secretion is controlled by light and dark conditions, whereby light decreases and darkness increases its production. Thus, melatonin is also known as the 'hormone of darkness'. Melatonin and analogs that bind to the melatonin receptors are important because of their role in the management of depression, insomnia, epilepsy, Alzheimer's disease (AD), diabetes, obesity, alopecia, migraine, cancer, and immune and cardiac disorders. In this review, we discuss the mechanism of action of melatonin in these disorders, which could aid in the design of novel melatonin receptor ligands. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis of [N-C[sup 3]H[sub 3

Energy Technology Data Exchange (ETDEWEB)

Wyrick, S D; Myers, A M; Booth, R G; Kula, N S; Baldessarini, R J; Mailman, R B [North Carolina Univ., Chapel Hill, NC (United States). School of Pharmacy and Brain and Development Research Center Harvard Medical School, Boston, MA (United States) Massachusetts General Hospital, Belmont, MA (United States). Mailman Research Center

1994-02-01

Subsequent to the discovery that the (+)-benzomorphan sigma receptor ligands, (+)-pentazocine and (+)-N-allylnormetazocine, stimulated tyrosine hydroxylase activity and dopamine synthesis in rat striatum in vitro, we reported a similar effect on a structurally similar series of 1-phenyl-3-aminotetrahydronaphthalenes (phenylaminotetralins, PAT's). We previously reported the synthesis of tritium labeled Cl,OH-PAT to be used in radioreceptor and autoradiography studies and found that it labeled a sigma-like site in guinea pig brain with an apparent Kd of [approx] 50 pM and with a pharmacological profile unique from other known CNS receptors. Here we report the synthesis of high specific activity tritium labeled trans-(1R,3S)-(-)-H[sub 2]PAT as this enantiomer was found to be more active in the tyrosine hydroxylase assay and possessed approximately 45 fold greater affinity for the novel neuromodulatory sigma-like receptor. (author).

Metal-ligand cooperative activation of nitriles by a ruthenium complex with a de-aromatized PNN pincer ligand

NARCIS (Netherlands)

Eijsink, Linda E; Perdriau, Sébastien C P; de Vries, Johannes G; Otten, Edwin

2016-01-01

The pincer complex (PNN)RuH(CO), with a de-aromatized pyridine in the ligand backbone, is shown to react with nitriles in a metal-ligand cooperative manner. This leads to the formation of a series of complexes with new Ru-N(nitrile) and C(ligand)-C(nitrile) bonds. The initial nitrile cycloaddition

Peroxisome proliferator-activated receptor α ligands and modulators from dietary compounds: Types, screening methods and functions.

Science.gov (United States)

Yang, Haixia; Xiao, Lei; Wang, Nanping

2017-04-01

Peroxisome proliferator-activated receptor α (PPARα) plays a key role in lipid metabolism and glucose homeostasis and a crucial role in the prevention and treatment of metabolic diseases. Natural dietary compounds, including nutrients and phytochemicals, are PPARα ligands or modulators. High-throughput screening assays have been developed to screen for PPARα ligands and modulators in our diet. In the present review, we discuss recent advances in our knowledge of PPARα, including its structure, function, and ligand and modulator screening assays, and summarize the different types of dietary PPARα ligands and modulators. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Short synthesis and antimalarial activity of fagaronine

OpenAIRE

Rivaud, M.; Mendoza, A.; Sauvain, Michel; Valentin, A.; Jullian, Valérie

2012-01-01

Herein, we report a new synthesis of fagaronine 1, inspired by the synthesis reported by Luo for nornitidine. The in vitro biological activity of fagaronine against malaria on several chloroquine-sensitive and resistant Plasmodium falciparum strains was confirmed, and the selectivity index compared to mammalian cells was calculated. Fagaronine was found to have very good antimalarial activity in vivo, comparable to the activity of the reference compound chloroquine. Therefore, fagaronine appe...

Synthesis, structures and Helicobacter pylori urease inhibitory activity of copper(II) complexes with tridentate aroylhydrazone ligands.

Science.gov (United States)

Pan, Lin; Wang, Cunfang; Yan, Kai; Zhao, Kedong; Sheng, Guihua; Zhu, Hailiang; Zhao, Xinlu; Qu, Dan; Niu, Fang; You, Zhonglu

2016-06-01

A series of new copper(II) complexes were prepared. They are [CuL(1)(NCS)] (1), [CuClL(1)]·CH3OH (2), [CuClL(2)]·CH3OH (3), [CuL(3)(NCS)]·CH3OH (4), [CuL(4)(NCS)]·0.4H2O (5), and [CuL(5)(bipy)] (6), where L(1), L(2), L(3) and L(4) are the deprotonated form of N'-(2-hydroxybenzylidene)-3-methylbenzohydrazide, 4-bromo-N'-(2-hydroxy-5-methoxybenzylidene)benzohydrazide, N'-(2-hydroxy-5-methoxybenzylidene)-3-methylbenzohydrazide and 2-chloro-N'-(2-hydroxy-5-methoxybenzylidene)benzohydrazide, respectively, L(5) is the dianionic form of N'-(2-hydroxybenzylidene)-3-methylbenzohydrazide, and bipy is 2,2'-bipyridine. The complexes were characterized by infrared and UV-Vis spectra and single crystal X-ray diffraction. The Cu atoms in complexes 1, 2, 3, 4 and 5 are coordinated by the NOO donor set of the aroylhydrazone ligands, and one Cl or thiocyanate N atom, forming square planar coordination. The Cu atom in complex 6 is in a square pyramidal coordination, with the NOO donor set of L(1), and one N atom of bipy defining the basal plane, and with the other N atom of bipy occupying the apical position. Complexes 1, 2, 3, 4 and 5 show effective urease inhibitory activities, with IC50 values of 5.14, 0.20, 4.06, 5.52 and 0.26μM, respectively. Complex 6 has very weak activity against urease, with IC50 value over 100μM. Molecular docking study of the complexes with the Helicobacter pylori urease was performed. The relationship between structures and urease inhibitory activities indicated that copper complexes with square planar coordination are better models for urease inhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

Unusual saccharin-N,O (carbonyl) coordination in mixed-ligand copper(II) complexes: Synthesis, X-ray crystallography and biological activity

Science.gov (United States)

Mokhtaruddin, Nur Shuhada Mohd; Yusof, Enis Nadia Md; Ravoof, Thahira B. S. A.; Tiekink, Edward R. T.; Veerakumarasivam, Abhi; Tahir, Mohamed Ibrahim Mohamed

2017-07-01

Three tridentate Schiff bases containing N and S donor atoms were synthesized via the condensation reaction between S-2-methylbenzyldithiocarbazate with 2-acetyl-4-methylpyridine (S2APH); 4-methyl-3-thiosemicarbazide with 2-acetylpyridine (MT2APH) and 4-ethyl-3-thiosemicarbazide with 2-acetylpyridine (ET2APH). Three new, binuclear and mixed-ligand copper(II) complexes with the general formula, [Cu(sac)(L)]2 (sac = saccharinate anion; L = anion of the Schiff base) were then synthesized, and subsequently characterized by IR and UV/Vis spectroscopy as well as by molar conductivity and magnetic susceptibility measurements. The Schiff bases were also spectroscopically characterized using NMR and MS to further confirm their structures. The spectroscopic data indicated that the Schiff bases behaved as a tridentate NNS donor ligands coordinating via the pyridyl-nitrogen, azomethine-nitrogen and thiolate-sulphur atoms. Magnetic data indicated a square pyramidal environment for the complexes and the conductivity values showed that the complexes were essentially non-electrolytes in DMSO. The X-ray crystallographic analysis of one complex, [Cu(sac)(S2AP)]2 showed that the Cu(II) atom was coordinated to the thiolate-S, azomethine-N and pyridyl-N donors of the S2AP Schiff base and to the saccharinate-N from one anion, as well as to the carbonyl-O atom from a symmetry related saccharinate anion yielding a centrosymmetric binuclear complex with a penta-coordinate, square pyramidal geometry. All the copper(II) saccharinate complexes were found to display strong cytotoxic activity against the MCF-7 and MDA-MB-231 human breast cancer cell lines.

Internalization mechanisms of the epidermal growth factor receptor after activation with different ligands.

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Lasse Henriksen

Full Text Available The epidermal growth factor receptor (EGFR regulates normal growth and differentiation, but dysregulation of the receptor or one of the EGFR ligands is involved in the pathogenesis of many cancers. There are eight ligands for EGFR, however most of the research into trafficking of the receptor after ligand activation focuses on the effect of epidermal growth factor (EGF and transforming growth factor-α (TGF-α. For a long time it was believed that clathrin-mediated endocytosis was the major pathway for internalization of the receptor, but recent work suggests that different pathways exist. Here we show that clathrin ablation completely inhibits internalization of EGF- and TGF-α-stimulated receptor, however the inhibition of receptor internalization in cells treated with heparin-binding EGF-like growth factor (HB-EGF or betacellulin (BTC was only partial. In contrast, clathrin knockdown fully inhibits EGFR degradation after all ligands tested. Furthermore, inhibition of dynamin function blocked EGFR internalization after stimulation with all ligands. Knocking out a number of clathrin-independent dynamin-dependent pathways of internalization had no effect on the ligand-induced endocytosis of the EGFR. We suggest that EGF and TGF-α lead to EGFR endocytosis mainly via the clathrin-mediated pathway. Furthermore, we suggest that HB-EGF and BTC also lead to EGFR endocytosis via a clathrin-mediated pathway, but can additionally use an unidentified internalization pathway or better recruit the small amount of clathrin remaining after clathrin knockdown.

Internalization Mechanisms of the Epidermal Growth Factor Receptor after Activation with Different Ligands

Science.gov (United States)

Henriksen, Lasse; Grandal, Michael Vibo; Knudsen, Stine Louise Jeppe; van Deurs, Bo; Grøvdal, Lene Melsæther

2013-01-01

The epidermal growth factor receptor (EGFR) regulates normal growth and differentiation, but dysregulation of the receptor or one of the EGFR ligands is involved in the pathogenesis of many cancers. There are eight ligands for EGFR, however most of the research into trafficking of the receptor after ligand activation focuses on the effect of epidermal growth factor (EGF) and transforming growth factor-α (TGF-α). For a long time it was believed that clathrin-mediated endocytosis was the major pathway for internalization of the receptor, but recent work suggests that different pathways exist. Here we show that clathrin ablation completely inhibits internalization of EGF- and TGF-α-stimulated receptor, however the inhibition of receptor internalization in cells treated with heparin-binding EGF-like growth factor (HB-EGF) or betacellulin (BTC) was only partial. In contrast, clathrin knockdown fully inhibits EGFR degradation after all ligands tested. Furthermore, inhibition of dynamin function blocked EGFR internalization after stimulation with all ligands. Knocking out a number of clathrin-independent dynamin-dependent pathways of internalization had no effect on the ligand-induced endocytosis of the EGFR. We suggest that EGF and TGF-α lead to EGFR endocytosis mainly via the clathrin-mediated pathway. Furthermore, we suggest that HB-EGF and BTC also lead to EGFR endocytosis via a clathrin-mediated pathway, but can additionally use an unidentified internalization pathway or better recruit the small amount of clathrin remaining after clathrin knockdown. PMID:23472148

Synthesis and spectral properties of europium phthalocyanine complexes

International Nuclear Information System (INIS)

Maksimova, K.N.; Bazyakina, N.L.; Kutyreva, V.V.; Suvorova, O.N.; Domrachev, G.A.

2008-01-01

Synthesis of europium monophthalocyanic complexes with thenoyltrifluroacetonate (tta) and ferrocenoyltrifluoroacetate (fta) ligands has been considered. Spectral characteristics of complexes PcEu(tta)(ttaH) and PcEu(fta)(ftaH) (Pc - phthalocyanine ligand) have been investigated. One of β-diketonate ligand is proposed to bind with europium ion covalently, and the second ligand saturates coordination sphere of europium due to donor-acceptor binding [ru

Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor.

Science.gov (United States)

Yin, Donghua; He, Yali; Perera, Minoli A; Hong, Seoung Soo; Marhefka, Craig; Stourman, Nina; Kirkovsky, Leonid; Miller, Duane D; Dalton, James T

2003-01-01

The purposes of the present studies were to examine the androgen receptor (AR) binding ability and in vitro functional activity of multiple series of nonsteroidal compounds derived from known antiandrogen pharmacophores and to investigate the structure-activity relationships (SARs) of these nonsteroidal compounds. The AR binding properties of sixty-five nonsteroidal compounds were assessed by a radioligand competitive binding assay with the use of cytosolic AR prepared from rat prostates. The AR agonist and antagonist activities of high-affinity ligands were determined by the ability of the ligand to regulate AR-mediated transcriptional activation in cultured CV-1 cells, using a cotransfection assay. Nonsteroidal compounds with diverse structural features demonstrated a wide range of binding affinity for the AR. Ten compounds, mainly from the bicalutamide-related series, showed a binding affinity superior to the structural pharmacophore from which they were derived. Several SARs regarding nonsteroidal AR binding were revealed from the binding data, including stereoisomeric conformation, steric effect, and electronic effect. The functional activity of high-affinity ligands ranged from antagonist to full agonist for the AR. Several structural features were found to be determinative of agonist and antagonist activities. The nonsteroidal AR agonists identified from the present studies provided a pool of candidates for further development of selective androgen receptor modulators (SARMs) for androgen therapy. Also, these studies uncovered or confirmed numerous important SARs governing AR binding and functional properties by nonsteroidal molecules, which would be valuable in the future structural optimization of SARMs.

New air-stable planar chiral ferrocenyl monophosphine ligands: Suzuki cross-coupling of aryl chlorides and bromides

DEFF Research Database (Denmark)

Jensen, Jakob Feldthusen; Johannsen, Mogens

2003-01-01

GraphicA novel class of planar chiral electron-rich monophosphine ligands has been developed. The modular design allows a short and efficient synthesis of an array of aryl-ferrocenyl derivatives carrying the donating bis(dicyclohexyl)phosphino moiety. These new ligands have successfully been...

Synthesis, spectroscopic characterization, biological screenings, DNA binding study and POM analyses of transition metal carboxylates

Science.gov (United States)

Uddin, Noor; Sirajuddin, Muhammad; Uddin, Nizam; Tariq, Muhammad; Ullah, Hameed; Ali, Saqib; Tirmizi, Syed Ahmed; Khan, Abdur Rehman

2015-04-01

This article contains the synthesis of a novel carboxylic acid derivative, its transition metal complexes and evaluation of biological applications. Six carboxylate complexes of transition metals, Zn(II) and Hg(II), have been successfully synthesized and characterized by FT-IR and NMR (1H, 13C). The ligand, HL, (4-[(2,6-Diethylphenyl)amino]-4-oxobutanoic acid) was also characterized by single crystal X-ray analysis. The complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date show the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than that of the free ligand. The ligand and its complexes were screened for antifungal and antileishmanial activities. The results showed that the ligand and its complexes are active with few exceptions. UV-visible spectroscopy and viscometry results reveal that the ligand and its complexes interact with the DNA via intercalative mode of interaction. A new and efficient strategy to identify the pharmacophores and anti-pharmacophores sites in carboxylate derivatives for the antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.

Design, synthesis and evaluation of 4,7-diamino-1,10-phenanthroline G-quadruplex ligands

DEFF Research Database (Denmark)

Nielsen, Mads Corvinius; Borch, Jonas; Ulven, Trond

2009-01-01

the central ionic column. Introduction of positively charged side chains results in compounds with appreciable G-quadruplex stabilizing properties and high aqueous solubility, with the longer side chains giving more potent compounds. Ligands carrying guanidine side chains in general show higher quadruplex...... stabilizing activity and distinctly slower kinetic properties than their amino and dimethylamino analogues, possibly due to specific hydrogen bond interactions with the G-quadruplex loops....

Synthesis and spectroscopic behavior of highly luminescent Eu 3+-dibenzoylmethanate (DBM) complexes with sulfoxide ligands

Science.gov (United States)

Niyama, E.; Brito, H. F.; Cremona, M.; Teotonio, E. E. S.; Reyes, R.; Brito, G. E. S.; Felinto, M. C. F. C.

2005-09-01

In this paper the synthesis, characterization and photoluminescent behavior of the [RE(DBM) 3L 2] complexes (RE = Gd and Eu) with a variety of sulfoxide ligands; L = benzyl sulfoxide (DBSO), methyl sulfoxide (DMSO), phenyl sulfoxide (DPSO) and p-tolyl sulfoxide (PTSO) have been investigated in solid state. The emission spectra of the Eu 3+-β-diketonate complexes show characteristics narrow bands arising from the 5D 0 → 7F J ( J = 0-4) transitions, which are split according to the selection rule for C n, C nv or C s site symmetries. The experimental Judd-Ofelt intensity parameters ( Ω2 and Ω4), radiative ( Arad) and non-radiative ( Anrad) decay rates, and R02 for the europium complexes have been determined and compared. The highest value of Ω2 (61.9 × 10 -20 cm 2) was obtained to the complex with PTSO ligand, indicating that Eu 3+ ion is in the highly polarizable chemical environment. The higher values of the experimental quantum yield ( q) and emission quantum efficiency of the emitter 5D 0 level ( η) for the Eu-complexes with DMSO, DBSO and PTSO sulfoxides suggest that these complexes are promising Light Conversion Molecular Devices (LCMDs). The lower value of quantum yield ( q = 1%), for the hydrated complex [Eu(DBM) 3(H 2O)], indicates that the luminescence quenching occurs via multiphonon relaxation by coupling with the OH-oscillators from water molecule coordinated to rare earth ion. The pure red emission of the Eu-complexes has been confirmed by ( x, y) color coordinates.

Two novel mixed-ligand complexes containing organosulfonate ligands.

Science.gov (United States)

Li, Mingtian; Huang, Jun; Zhou, Xuan; Fang, Hua; Ding, Liyun

2008-07-01

The structures reported herein, viz. bis(4-aminonaphthalene-1-sulfonato-kappaO)bis(4,5-diazafluoren-9-one-kappa(2)N,N')copper(II), [Cu(C(10)H(8)NO(3)S)(2)(C(11)H(6)N(2)O)(2)], (I), and poly[[[diaquacadmium(II)]-bis(mu-4-aminonaphthalene-1-sulfonato)-kappa(2)O:N;kappa(2)N:O] dihydrate], {[Cd(C(10)H(8)NO(3)S)(2)(H(2)O)(2)].2H(2)O}(n), (II), are rare examples of sulfonate-containing complexes where the anion does not fulfill a passive charge-balancing role, but takes an active part in coordination as a monodentate and/or bridging ligand. Monomeric complex (I) possesses a crystallographic inversion center at the Cu(II) atom, and the asymmetric unit contains one-half of a Cu atom, one complete 4-aminonaphthalene-1-sulfonate (ans) ligand and one 4,5-diazafluoren-9-one (DAFO) ligand. The Cu(II) atom has an elongated distorted octahedral coordination geometry formed by two O atoms from two monodentate ans ligands and by four N atoms from two DAFO molecules. Complex (II) is polymeric and its crystal structure is built up by one-dimensional chains and solvent water molecules. Here also the cation (a Cd(II) atom) lies on a crystallographic inversion center and adopts a slightly distorted octahedral geometry. Each ans anion serves as a bridging ligand linking two Cd(II) atoms into one-dimensional infinite chains along the [010] direction, with each Cd(II) center coordinated by four ans ligands via O and N atoms and by two aqua ligands. In both structures, there are significant pi-pi stacking interactions between adjacent ligands and hydrogen bonds contribute to the formation of two- and three-dimensional networks.

Regulation of the synthesis of the angucyclinone antibiotic alpomycin in Streptomyces ambofaciens by the autoregulator receptor AlpZ and its specific ligand.

Science.gov (United States)

Bunet, Robert; Mendes, Marta V; Rouhier, Nicolas; Pang, Xiuhua; Hotel, Laurence; Leblond, Pierre; Aigle, Bertrand

2008-05-01

Streptomyces ambofaciens produces an orange pigment and the antibiotic alpomycin, both of which are products of a type II polyketide synthase gene cluster identified in each of the terminal inverted repeats of the linear chromosome. Five regulatory genes encoding Streptomyces antibiotic regulatory proteins (alpV, previously shown to be an essential activator gene; alpT; and alpU) and TetR family receptors (alpZ and alpW) were detected in this cluster. Here, we demonstrate that AlpZ, which shows high similarity to gamma-butyrolactone receptors, is at the top of a pathway-specific regulatory hierarchy that prevents synthesis of the alp polyketide products. Deletion of the two copies of alpZ resulted in the precocious production of both alpomycin and the orange pigment, suggesting a repressor role for AlpZ. Consistent with this, expression of the five alp-located regulatory genes and of two representative biosynthetic structural genes (alpA and alpR) was induced earlier in the alpZ deletion strain. Furthermore, recombinant AlpZ was shown to bind to specific DNA sequences within the promoter regions of alpZ, alpV, and alpXW, suggesting direct transcriptional control of these genes by AlpZ. Analysis of solvent extracts of S. ambofaciens cultures identified the existence of a factor which induces precocious production of alpomycin and pigment in the wild-type strain and which can disrupt the binding of AlpZ to its DNA targets. This activity is reminiscent of gamma-butyrolactone-type molecules. However, the AlpZ-interacting molecule(s) was shown to be resistant to an alkali treatment capable of inactivating gamma-butyrolactones, suggesting that the AlpZ ligand(s) does not possess a lactone functional group.

Tetrathiafulvalene-based azine ligands for anion and metal cation coordination

Directory of Open Access Journals (Sweden)

Awatef Ayadi

2015-08-01

Full Text Available The synthesis and full characterization of two tetrathiafulvalene-appended azine ligands, namely 2-([2,2’-bi(1,3-dithiolylidene]-4-yl-6-((2,4-dinitrophenylhydrazonomethylpyridine (L1 and 5-([2,2’-bi(1,3-dithiolylidene]-4-yl-2-((2,4-dinitrophenylhydrazonomethylpyridine (L2 are described. The crystal structure of ligand L1 indicates that the ligand is completely planar with the presence of a strong intramolecular N3–H3···O1 hydrogen bonding. Titration experiments with inorganic anions showed that both ligands are suitable candidates for the sensing of fluoride anions. Ligand L2 was reacted with a Re(I cation to yield the corresponding rhenium tricarbonyl complex 3. In the crystal structure of the newly prepared electroactive rhenium complex the TTF is neutral and the rhenium cation is hexacoordinated. The electrochemical behavior of the three compounds indicates that they are promising for the construction of crystalline radical cation salts.

Syntheses and catalytic oxotransfer activities of oxo molybdenum(vi) complexes of a new aminoalcohol phenolate ligand.

Science.gov (United States)

Hossain, M K; Haukka, M; Sillanpää, R; Hrovat, D A; Richmond, M G; Nordlander, E; Lehtonen, A

2017-05-30

The new aminoalcohol phenol 2,4-di-tert-butyl-6-(((2-hydroxy-2-phenylethyl)amino)methyl)phenol (H2L) was prepared by a facile solvent-free synthesis and used as a tridentate ligand for new cis-dioxomolybdenum(vi)(L) complexes. In the presence of a coordinating solvent (DMSO, MeOH, pyridine), the complexes crystallise as monomeric solvent adducts while in the absence of such molecules, a trimer with asymmetric Mo[double bond, length as m-dash]O→Mo bridges crystallises. The complexes can catalyse epoxidation of cis-cyclooctene and sulfoxidation of methyl-p-tolylsulfide, using tert-butyl hydroperoxide as oxidant.

Potential New Ligand Systems for Binding Uranyl Ions in Seawater Environments

Energy Technology Data Exchange (ETDEWEB)

Arnold, John [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2014-12-13

Work began this quarter on a new project involving a combined computational and biosynthetic approach to selective recognition of uranyl ion in aqueous solution. This project exploits the results of computational studies to discover new ligand classes. Synthetic studies will follow to generate target systems for uranyl binding and determination of binding constants. The process will be iterative, with results from computation informing synthesis, and vice versa. The theme of the ligand classes to be examined initially will be biologically based. New phosphonate-containing α-amino acid N-carboxyanhydride (NCA) monomers were used recently to prepare well-defined phosphonate-containing poly-peptides and block copolypeptides. Our first approach is to utilize these phosphate- and phosphonate-containing NCAs for the coordination of uranyl. The work includes the laboratory-scale preparation of a series of NCAs and the full thermodynamic and spectroscopic characterization of the resulting uranyl complexes. We are also evaluating the sequestering activity in different physiological and environmental conditions of these copolymers as well as their biodegradability.

Synthesis and binding properties of new selective ligands for the nucleobase opposite the AP site.

Science.gov (United States)

Abe, Yukiko; Nakagawa, Osamu; Yamaguchi, Rie; Sasaki, Shigeki

2012-06-01

DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3'-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; that is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site. Copyright © 2012 Elsevier Ltd. All rights reserved.

Digallane with redox-active diimine ligand: dualism of electron-transfer reactions.

Science.gov (United States)

Fedushkin, Igor L; Skatova, Alexandra A; Dodonov, Vladimir A; Chudakova, Valentina A; Bazyakina, Natalia L; Piskunov, Alexander V; Demeshko, Serhiy V; Fukin, Georgy K

2014-05-19

The reactivity of digallane (dpp-Bian)Ga-Ga(dpp-Bian) (1), which consists of redox-active ligand 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene (dpp-Bian), has been studied. The reaction of 1 with I2 proceeds via one-electron oxidation of each of two dpp-Bian ligands to a radical-anionic state and affords complex (dpp-Bian)IGa-GaI(dpp-Bian) (2). Dissolution of complex 2 in pyridine (Py) gives monomeric compound (dpp-Bian)GaI(Py) (3) as a result of a solvent-induced intramolecular electron transfer from the metal-metal bond to the dpp-Bian ligands. Treatment of compound 3 with B(C6F5)3 leads to removal of pyridine and restores compound 2. The reaction of compound 1 with 3,6-di-tert-butyl-ortho-benzoquinone (3,6-Q) proceeds with oxidation of all the redox-active centers in 1 (the Ga-Ga bond and two dpp-Bian dianions) and results in mononuclear catecholate (dpp-Bian)Ga(Cat) (4) (Cat = [3,6-Q](2-)). Treatment of 4 with AgBF4 gives a mixture of [(dpp-Bian)2Ag][BF4] (5) and (dpp-Bian)GaF(Cat) (6), which both consist of neutral dpp-Bian ligands. The reduction of benzylideneacetone (BA) with 1 generates the BA radical-anions, which dimerize, affording (dpp-Bian)Ga-(BA-BA)-Ga(dpp-Bian) (7). In this case the Ga-Ga bond remains unchanged. Within 10 min at 95 °C in solution compound 7 undergoes transformation to paramagnetic complex (dpp-Bian)Ga(BA-BA) (8) and metal-free compound C36H40N2 (9). The latter is a product of intramolecular addition of the C-H bond of one of the iPr groups to the C═N bond in dpp-Bian. Diamagnetic compounds 3, 5, 6, and 9 have been characterized by NMR spectroscopy, and paramagnetic complexes 2, 4, 7, and 8 by ESR spectroscopy. Molecular structures of 2-7 and 9 have been established by single-crystal X-ray analysis.

Peroxisome Proliferator-Activated Receptor-γ Ligands: Potential Pharmacological Agents for Targeting the Angiogenesis Signaling Cascade in Cancer

Directory of Open Access Journals (Sweden)

Costas Giaginis

2008-01-01

Full Text Available Peroxisome proliferator-activated receptor-γ (PPAR-γ has currently been considered as molecular target for the treatment of human metabolic disorders. Experimental data from in vitro cultures, animal models, and clinical trials have shown that PPAR-γ ligand activation regulates differentiation and induces cell growth arrest and apoptosis in a variety of cancer types. Tumor angiogenesis constitutes a multifaceted process implicated in complex downstream signaling pathways that triggers tumor growth, invasion, and metastasis. In this aspect, accumulating in vitro and in vivo studies have provided extensive evidence that PPAR-γ ligands can function as modulators of the angiogenic signaling cascade. In the current review, the crucial role of PPAR-γ ligands and the underlying mechanisms participating in tumor angiogenesis are summarized. Targeting PPAR-γ may prove to be a potential therapeutic strategy in combined treatments with conventional chemotherapy; however, special attention should be taken as there is also substantial evidence to support that PPAR-γ ligands can enhance angiogenic phenotype in tumoral cells.

Characterization of Colloidal Quantum Dot Ligand Exchange by X-ray Photoelectron Spectroscopy

Science.gov (United States)

Atewologun, Ayomide; Ge, Wangyao; Stiff-Roberts, Adrienne D.

2013-05-01

Colloidal quantum dots (CQDs) are chemically synthesized semiconductor nanoparticles with size-dependent wavelength tunability. Chemical synthesis of CQDs involves the attachment of long organic surface ligands to prevent aggregation; however, these ligands also impede charge transport. Therefore, it is beneficial to exchange longer surface ligands for shorter ones for optoelectronic devices. Typical characterization techniques used to analyze surface ligand exchange include Fourier-transform infrared spectroscopy, x-ray diffraction, transmission electron microscopy, and nuclear magnetic resonance spectroscopy, yet these techniques do not provide a simultaneously direct, quantitative, and sensitive method for evaluating surface ligands on CQDs. In contrast, x-ray photoelectron spectroscopy (XPS) can provide nanoscale sensitivity for quantitative analysis of CQD surface ligand exchange. A unique aspect of this work is that a fingerprint is identified for shorter surface ligands by resolving the regional XPS spectrum corresponding to different types of carbon bonds. In addition, a deposition technique known as resonant infrared matrix-assisted pulsed laser evaporation is used to improve the CQD film uniformity such that stronger XPS signals are obtained, enabling more accurate analysis of the ligand exchange process.

Synthesis of nano-sized amorphous boron powders through active dilution self-propagating high-temperature synthesis method

Energy Technology Data Exchange (ETDEWEB)

Wang, Jilin [The State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China); Gu, Yunle [School of Material Science and Engineering, Wuhan Institute of Technology, Wuhan 430073 (China); Li, Zili [The State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China); Wang, Weimin, E-mail: wangwm@hotmail.com [The State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China); Fu, Zhengyi [The State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China)

2013-06-01

Graphical abstract: Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis (SHS) method. The effects of endothermic reaction rate, the possible chemical reaction mechanism and active dilution model for synthesis of the product were also discussed. Highlights: ► Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis method. ► The morphology, particle size and purity of the samples could be effectively controlled via changing the endothermic rate. ► The diluter KBH{sub 4} played an important role in active dilution synthesis of amorphous nano-sized boron powders. ► The active dilution method could be further popularized and become a common approach to prepare various inorganic materials. - Abstract: Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis (SHS) method at temperatures ranging from 700 °C to 850 °C in a SHS furnace using Mg, B{sub 2}O{sub 3} and KBH{sub 4} as raw materials. Samples were characterized by X-ray powder diffraction (XRD), Laser particle size analyzer, Fourier transform infrared spectra (FTIR), X-ray energy dispersive spectroscopy (EDX), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-resolution transmission TEM (HRTEM). The boron powders demonstrated an average particle size of 50 nm with a purity of 95.64 wt.%. The diluter KBH{sub 4} played an important role in the active dilution synthesis of amorphous nano-sized boron powders. The effects of endothermic reaction rate, the possible chemical reaction mechanism and active dilution model for synthesis of the product were also discussed.

Synthesis of nano-sized amorphous boron powders through active dilution self-propagating high-temperature synthesis method

International Nuclear Information System (INIS)

Wang, Jilin; Gu, Yunle; Li, Zili; Wang, Weimin; Fu, Zhengyi

2013-01-01

Graphical abstract: Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis (SHS) method. The effects of endothermic reaction rate, the possible chemical reaction mechanism and active dilution model for synthesis of the product were also discussed. Highlights: ► Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis method. ► The morphology, particle size and purity of the samples could be effectively controlled via changing the endothermic rate. ► The diluter KBH 4 played an important role in active dilution synthesis of amorphous nano-sized boron powders. ► The active dilution method could be further popularized and become a common approach to prepare various inorganic materials. - Abstract: Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis (SHS) method at temperatures ranging from 700 °C to 850 °C in a SHS furnace using Mg, B 2 O 3 and KBH 4 as raw materials. Samples were characterized by X-ray powder diffraction (XRD), Laser particle size analyzer, Fourier transform infrared spectra (FTIR), X-ray energy dispersive spectroscopy (EDX), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-resolution transmission TEM (HRTEM). The boron powders demonstrated an average particle size of 50 nm with a purity of 95.64 wt.%. The diluter KBH 4 played an important role in the active dilution synthesis of amorphous nano-sized boron powders. The effects of endothermic reaction rate, the possible chemical reaction mechanism and active dilution model for synthesis of the product were also discussed

Novel metal complexes of mixed piperaquine-acetaminophen and piperaquine-acetylsalicylic acid: Synthesis, characterization and antimicrobial activities

Directory of Open Access Journals (Sweden)

Yusuf Oloruntoyin Ayipo

2016-11-01

Full Text Available Synthesis of coordination compounds of Zinc(II, Copper(II, Nickel(II, Cobalt(II and Iron(II with mixed piperaquine-acetaminophen and piperaquine-acetylsalicylic acid has been studied. The complexes were characterized via: solubility test, melting point determination, conductivity measurement, Atomic Absorption Spectroscopy, UV-Visible Spectroscopy, FTIR Spectroscopy and magnetic susceptibility. The complexes were proposed to have a stoichiometry ratio of 1:1:1 between each metal salt and the ligands with tetrahedral and octahedral geometry following the reaction pattern of MX.yH2O + L1L2/3 to give ML1L2/3X.yH2O. Biological activities of the synthesized complexes have been evaluated against Escherichia coli and Staphylococcus aureus.

Synthesis and characterization of tantalum organometallic complexes. Catalytic activity for olefins

International Nuclear Information System (INIS)

Baley, A.S.

1990-11-01

Synthesis of monoaryloxy (alcoxy) neopentyl compounds is investigated. The tantalum-oxygen bond is formed by two parallel ways from TaCl 5 or TaR 2 Cl 3 with R = neopentyl and the tantalum carbon bond from a neopentyl derivative of the main series. Some compounds were isolated and characterized by NMR, elemental analysis and sometimes X-ray structure, some others are characterized in solution only. Catalytic effect is tested by ethylene dimerization and olefin polymerization. Reactivity of tantalum aryloxy neopentyl in respect to complexing and chelating ligands is studied for preparation of neopentylidene complexes

Synthesis and characterization of complexes of early actinides with tridentate Schiff base ligands

International Nuclear Information System (INIS)

Mansingh, P.S.; Dash, K.C.

1995-01-01

A series of thorium(IV) and dioxouranium(VI) complexes have been synthesised with tridentate Schiff base ligands (N 2 O donor set) obtained by in-situ condensation of N, N-dimethylethylenediamine with o-hydroxy aromatic aldehydes such as salicylaldehyde (HL) or o-hydroxy naphthaldehyde (HL'). While with dioxouranium(VI), the ligands are coordinated in a neutral manner and act as tridentate donors forming complexes of the type UO 2 (HL)X 2 or UO 2 (HL')X 2 (X=Cl,I,NCS,NO 3 ,CH 3 COO) with thorium(IV) they are coordinated as deprotonated tridentate ligands yielding complexes of the type Th(L') 2 X 2 (X=I,NCS,NO 3 ). The IR spectra show that the thiocyanate group is actually N-bonded unidentate isothiocyanate and both the nitrate and the acetate groups are bonded in bidentate manner while the ligands are bonded in tridentate manner in these complexes. The PMR spectra confirm the mode of bonding of the ligands either as neutral or as deprotonated species. The thermogravimetric analyses indicate the stability of the complexes. (author). 22 refs., 1 tab

Synthesis, spectroscopic characterization, electrochemistry and biological evaluation of some metal (II) complexes with ONO donor ligand containing benzo[b]thiophene and coumarin moieties

Science.gov (United States)

Mahendra Raj, K.; Mruthyunjayaswamy, B. H. M.

2014-09-01

Schiff base ligand 3-chloro-N‧-((7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)methylene)benzo[b]thiophene-2-carbohydrazide and its Cu(II), Co(II), Ni(II) and Zn(II) complexes were synthesized, characterized by elemental analysis and various physico-chemical techniques like, IR, 1H NMR, ESI-mass, UV-Visible, thermogravimetry - differential thermal analysis, magnetic measurements and molar conductance. Spectral analysis indicates octahedral geometry for all the complexes. Cu(II) complex have 1:1 stoichiometry of the type [M(L)(Cl)(H2O)2], whereas Co(II), Ni(II) and Zn(II) complexes have 1:2 stoichiometric ratio of the type [M(L)2]. The bonding sites are the oxygen atom of amide carbonyl, nitrogen of azomethine function and phenolic oxygen of the Schiff base ligand via deprotonation. The thermogravimetry - differential thermal analysis studies gave evidence for the presence of coordinated water molecules in the composition of Cu(II) complex which was further supported by IR measurements. All the complexes were investigated for their electrochemical activity, but only the Cu(II) complex showed the redox property. In order to evaluate the effect of antimicrobial potency of metal ions upon chelation, ligand and its metal complexes along with their respective metal chlorides were screened for their antibacterial and antifungal activities by minimum inhibitory concentration (MIC) method. The results showed that the metal complexes were found to be more active than free ligand. Ligand and its complexes were screened for free radical scavenging activity by DPPH method and DNA cleavage activity using Calf-thymus DNA (Cat. No-105850).

Free-energy relationships in ion channels activated by voltage and ligand

Science.gov (United States)

Chowdhury, Sandipan

2013-01-01

Many ion channels are modulated by multiple stimuli, which allow them to integrate a variety of cellular signals and precisely respond to physiological needs. Understanding how these different signaling pathways interact has been a challenge in part because of the complexity of underlying models. In this study, we analyzed the energetic relationships in polymodal ion channels using linkage principles. We first show that in proteins dually modulated by voltage and ligand, the net free-energy change can be obtained by measuring the charge-voltage (Q-V) relationship in zero ligand condition and the ligand binding curve at highly depolarizing membrane voltages. Next, we show that the voltage-dependent changes in ligand occupancy of the protein can be directly obtained by measuring the Q-V curves at multiple ligand concentrations. When a single reference ligand binding curve is available, this relationship allows us to reconstruct ligand binding curves at different voltages. More significantly, we establish that the shift of the Q-V curve between zero and saturating ligand concentration is a direct estimate of the interaction energy between the ligand- and voltage-dependent pathway. These free-energy relationships were tested by numerical simulations of a detailed gating model of the BK channel. Furthermore, as a proof of principle, we estimate the interaction energy between the ligand binding and voltage-dependent pathways for HCN2 channels whose ligand binding curves at various voltages are available. These emerging principles will be useful for high-throughput mutagenesis studies aimed at identifying interaction pathways between various regulatory domains in a polymodal ion channel. PMID:23250866

Macrocyclic G-quadruplex ligands

DEFF Research Database (Denmark)

Nielsen, M C; Ulven, Trond

2010-01-01

are macrocyclic structures which have been modeled after the natural product telomestatin or from porphyrin-based ligands discovered in the late 1990s. These two structural classes of G-quadruplex ligands are reviewed here with special attention to selectivity and structure-activity relationships, and with focus...

Synthesis and structure of unprecedented samarium complex with bulky bis-iminopyrrolyl ligand via intramolecular C=N bond activation

Energy Technology Data Exchange (ETDEWEB)

Das, Suman; Anga, Srinivas; Harinath, Adimulam; Panda, Tarun K. [Department of Chemistry, Indian Institute of Technology, Hyderabad (India); Pada Nayek, Hari [Department of Applied Chemistry, Indian Institute of Technology, (ISM) Dhanbad, Jharkhand (India)

2017-12-29

An unprecedentate samarium complex of the molecular composition [{κ"3-{(Ph_2CH)N=CH}{sub 2}C{sub 4}H{sub 2}N}{κ"3-{(Ph_2CHN=CH)(Ph_2CHNCH)C_4H_2N}Sm}{sub 2}] (2), which was isolated by the reaction of a potassium salt of 2,5-bis{N-(diphenylmethyl)-iminomethyl}pyrrolyl ligand [K(THF){sub 2}{(Ph_2CH)N=CH}{sub 2}C{sub 4}H{sub 2}N] (1) with anhydrous samarium diiodide in THF at 60 C through the in situ reduction of imine bond is presented. The homoleptic samarium complex [[κ{sup 3}-{(Ph_2CH)-N=CH}{sub 2}C{sub 4}H{sub 2}N]{sub 3}Sm] (3) can also be obtained from the reaction of compound 1 with anhydrous samarium triiodide (SmI{sub 3}) in THF at 60 C. The molecular structures of complexes 2 and 3 were established by single-crystal X-ray diffraction analysis. The molecular structure of complex 2 reveals the formation of a C-C bond in the 2,5-bis{N-(diphenylmethyl)iminomethyl}pyrrole ligand moiety (Ph{sub 2}Py{sup -}). However, complex 3 is a homoleptic samarium complex of three bis-iminopyrrolyl ligands. In complex 2, the samarium ion adopts an octahedral arrangement, whereas in complex 3, a distorted three face-centered trigonal prismatic mode of nine coordination is observed around the metal ion. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Supramolecular architectures constructed using angular bipyridyl ligands

International Nuclear Information System (INIS)

Barnett, Sarah Ann

2003-01-01

This work details the synthesis and characterization of a series of coordination frameworks that are formed using bidentate angular N-donor ligands. Pyrimidine was reacted with metal(ll) nitrate salts. Reactions using Cd(NO 3 ) 2 receive particular focus and the analogous reactions using the linear ligand, pyrazine, were studied for comparison. In all cases, two-dimensional coordination networks were prepared. Structural diversity is observed for the Cd(ll) centres including metal-nitrate bridging. In contrast, first row transition metal nitrates form isostructural one-dimensional chains with only the bridging N-donor ligands generating polymeric propagation. The angular ligand, 2,4-bis(4-pyridyl)-1,3,5-triazine (dpt), was reacted with Cd(NO 3 ) 2 and Zn(NO 3 ) 2 . Whereas Zn(NO 3 ) 2 compounds exhibit solvent mediated polymorphism, a range of structures were obtained for the reactions with Cd(NO 3 ) 2 , including the first example of a doubly parallel interpenetrated 4.8 2 net. 4,7-phenanthroline, was reacted with various metal(ll) nitrates as well as cobalt(ll) and copper(ll) halides. The ability of 4,7-phenanthroline to act as both a N-donor ligand and a hydrogen bond acceptor has been discussed. Reactions of CuSCN with pyrimidine yield an unusual three-dimensional structure in which polymeric propagation is not a result of ligand bridging. The reaction of CuSCN with dpt yielded structural supramolecular isomers. (author)

Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines

International Nuclear Information System (INIS)

Girroir, Elizabeth E.; Hollingshead, Holly E.; Billin, Andrew N.; Willson, Timothy M.; Robertson, Gavin P.; Sharma, Arun K.; Amin, Shantu; Gonzalez, Frank J.; Peters, Jeffrey M.

2008-01-01

The development of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands for the treatment of diseases including metabolic syndrome, diabetes and obesity has been hampered due to contradictory findings on their potential safety. For example, while some reports show that ligand activation of PPARβ/δ promotes the induction of terminal differentiation and inhibition of cell growth, other reports suggest that PPARβ/δ ligands potentiate tumorigenesis by increasing cell proliferation. Some of the contradictory findings could be due in part to differences in the ligand examined, the presence or absence of serum in cell cultures, differences in cell lines or differences in the method used to quantify cell growth. For these reasons, this study examined the effect of ligand activation of PPARβ/δ on cell growth of two human cancer cell lines, MCF7 (breast cancer) and UACC903 (melanoma) in the presence or absence of serum using two highly specific PPARβ/δ ligands, GW0742 or GW501516. Culturing cells in the presence of either GW0742 or GW501516 caused upregulation of the known PPARβ/δ target gene angiopoietin-like protein 4 (ANGPTL4). Inhibition of cell growth was observed in both cell lines cultured in the presence of either GW0742 or GW501516, and the presence or absence of serum had little influence on this inhibition. Results from the present studies demonstrate that ligand activation of PPARβ/δ inhibits the growth of both MCF7 and UACC903 cell lines and provide further evidence that PPARβ/δ ligands are not mitogenic in human cancer cell lines

Synthesis and radiofluorination of putative NMDA receptor ligands

Energy Technology Data Exchange (ETDEWEB)

Kronenberg, U

2011-01-15

In the course of this work on the synthesis of radioligands for the NMDA receptor the authentic standards and labeling precursors of four compounds with an amidine structure was performed. Synthesis of the precursors followed reaction conditions given in the literature and was successful. The imidoesters used for the synthesis were obtained from their nitriles in a Pinner synthesis, while 2-hydroxybenzylamine was synthesized in a reduction of 2-hydroxybenzonitrile using borane as a reducing agent. After a coupling reaction of the amine and the imidoester in DMF using triethylamine as base the precursors were obtained in good yields and purified by crystallization from methanol. The cyclic standard compound was synthesized directly from 2-(bromomethyl)- benzonitrile and 2-hydroxybenzylamine in a ring closing reaction. Similar to the other precursors, crystallization from methanol produced a pure compound. The authentic standards were synthesized starting from salicylaldehyde. In a four step synthesis the desired ortho-fluoroethoxybenzylamine was obtained in good yield. Coupling of the amine with the respective imidoester or in the case of the cyclic compound 2-(bromomethyl)-benzonitrile gave the desired product which was then purified by column chromatography or by crystallization from ethanol and water. For the labeling procedure 1-bromo-2-[{sub 18}F]fluoroethane was synthesized following a previously published pathway starting from 1,2-dibromoethane. An alternative route of radiosynthesis for this prosthetic group was tested using ethyleneglycole- 1,2-ditosylate. The labeling reaction was performed on one of the precursors testing both DMF and DMSO as solvents and using NaOH as base. Yields of N-(2-fluoroethoxybenzyl)- cinnamamidine were about 78 % at 80 C after 30 minutes in DMSO. The desired product can now be synthesized in sufficient yields for in vitro and in vivo evaluation studies. Labeling on the cyclic precursor was attempted utilizing DMSO as solvent

Synthesis and radiofluorination of putative NMDA receptor ligands

International Nuclear Information System (INIS)

Kronenberg, U.

2011-01-01

In the course of this work on the synthesis of radioligands for the NMDA receptor the authentic standards and labeling precursors of four compounds with an amidine structure was performed. Synthesis of the precursors followed reaction conditions given in the literature and was successful. The imidoesters used for the synthesis were obtained from their nitriles in a Pinner synthesis, while 2-hydroxybenzylamine was synthesized in a reduction of 2-hydroxybenzonitrile using borane as a reducing agent. After a coupling reaction of the amine and the imidoester in DMF using triethylamine as base the precursors were obtained in good yields and purified by crystallization from methanol. The cyclic standard compound was synthesized directly from 2-(bromomethyl)- benzonitrile and 2-hydroxybenzylamine in a ring closing reaction. Similar to the other precursors, crystallization from methanol produced a pure compound. The authentic standards were synthesized starting from salicylaldehyde. In a four step synthesis the desired ortho-fluoroethoxybenzylamine was obtained in good yield. Coupling of the amine with the respective imidoester or in the case of the cyclic compound 2-(bromomethyl)-benzonitrile gave the desired product which was then purified by column chromatography or by crystallization from ethanol and water. For the labeling procedure 1-bromo-2-[ 18 F]fluoroethane was synthesized following a previously published pathway starting from 1,2-dibromoethane. An alternative route of radiosynthesis for this prosthetic group was tested using ethyleneglycole- 1,2-ditosylate. The labeling reaction was performed on one of the precursors testing both DMF and DMSO as solvents and using NaOH as base. Yields of N-(2-fluoroethoxybenzyl)- cinnamamidine were about 78 % at 80 C after 30 minutes in DMSO. The desired product can now be synthesized in sufficient yields for in vitro and in vivo evaluation studies. Labeling on the cyclic precursor was attempted utilizing DMSO as solvent, but no

Latent ruthenium–indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand

Directory of Open Access Journals (Sweden)

Thibault E. Schmid

2015-09-01

Full Text Available A silver-free methodology was developed for the synthesis of unprecedented N-heterocyclic carbene ruthenium indenylidene complexes bearing a bidentate picolinate ligand. The highly stable (SIPr(picolinateRuCl(indenylidene complex 4a (SIPr = 1,3-bis(2-6-diisopropylphenylimidazolidin-2-ylidene demonstrated excellent latent behaviour in ring closing metathesis (RCM reaction and could be activated in the presence of a Brønsted acid. The versatility of the catalyst 4a was subsequently demonstrated in RCM, cross-metathesis (CM and enyne metathesis reactions.

An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

KAUST Repository

Ali, Amal J.

2017-05-03

Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL). Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44/HCELL, and not CD43, cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we demonstrated the relevance of our findings to chronic autoimmune disease, by showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.

Unexpected self-sorting self-assembly formation of a [4:4] sulfate:ligand cage from a preorganized tripodal urea ligand.

Science.gov (United States)

Pandurangan, Komala; Kitchen, Jonathan A; Blasco, Salvador; Boyle, Elaine M; Fitzpatrick, Bella; Feeney, Martin; Kruger, Paul E; Gunnlaugsson, Thorfinnur

2015-04-07

The design and synthesis of tripodal ligands 1-3 based upon the N-methyl-1,3,5-benzenetricarboxamide platform appended with three aryl urea arms is reported. This ligand platform gives rise to highly preorganized structures and is ideally suited for binding SO4 (2-) and H2 PO4 (-) ions through multiple hydrogen-bonding interactions. The solid-state crystal structures of 1-3 with SO4 (2-) show the encapsulation of a single anion within a cage structure, whereas the crystal structure of 1 with H2 PO4 (-) showed that two anions are encapsulated. We further demonstrate that ligand 4, based on the same platform but consisting of two bis-urea moieties and a single ammonium moiety, also recognizes SO4 (2-) to form a self-assembled capsule with [4:4] SO4 (2-) :4 stoichiometry in which the anions are clustered within a cavity formed by the four ligands. This is the first example of a self-sorting self-assembled capsule where four tetrahedrally arranged SO4 (2-) ions are embedded within a hydrophobic cavity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cyanide does more to inhibit heme enzymes, than merely serving as an active-site ligand

Energy Technology Data Exchange (ETDEWEB)

Parashar, Abhinav [Center for Biomedical Research, VIT University, Vellore, Tamil Nadu, 632014 India (India); Venkatachalam, Avanthika [REDOx Lab, PSG Institute of Advanced Studies, Avinashi Road, Peelamedu, Coimbatore, Tamil Nadu, 641004 (India); Gideon, Daniel Andrew [Center for Biomedical Research, VIT University, Vellore, Tamil Nadu, 632014 India (India); Manoj, Kelath Murali, E-mail: satyamjayatu@yahoo.com [REDOx Lab, PSG Institute of Advanced Studies, Avinashi Road, Peelamedu, Coimbatore, Tamil Nadu, 641004 (India)

2014-12-12

Highlights: • Cyanide (CN) is a well-studied toxic principle, known to inhibit heme-enzymes. • Inhibition is supposed to result from CN binding at the active site as a ligand. • Diverse heme enzymes’ CN inhibition profiles challenge prevailing mechanism. • Poor binding efficiency of CN at low enzyme concentrations and ligand pressures. • CN-based diffusible radicals cause ‘non-productive electron transfers’ (inhibition). - Abstract: The toxicity of cyanide is hitherto attributed to its ability to bind to heme proteins’ active site and thereby inhibit their activity. It is shown herein that the long-held interpretation is inadequate to explain several observations in heme-enzyme reaction systems. Generation of cyanide-based diffusible radicals in heme-enzyme reaction milieu could shunt electron transfers (by non-active site processes), and thus be detrimental to the efficiency of oxidative outcomes.

Synthesis, characterization and DNA cleavage activity of nickel(II adducts with aromatic heterocyclic bases

Directory of Open Access Journals (Sweden)

G. H. PHILIP

2010-01-01

Full Text Available Mixed ligand complexes of nickel(II with 2,4-dihydroxyaceto-phenone oxime (DAPO and 2,4-dihydroxybenzophenone oxime (DBPO as primary ligands, and pyridine (Py and imidazole (Im as secondary ligands were synthesized and characterized by molar conductivity, magnetic moments measurements, as well as by electronic, IR, and 1H-NMR spectroscopy. Electrochemical studies were performed by cyclic voltammetry. The active signals are assignable to the NiIII/II and NiII/I redox couples. The binding interactions between the metal complexes and calf thymus DNA were investigated by absorption and thermal denaturation. The cleavage activity of the complexes was determined using double-stranded pBR322 circular plasmid DNA by gel electrophoresis. All complexes showed increased nuclease activity in the presence of the oxidant H2O2. The nuclease activities of mixed ligand complexes were compared with those of the parent copper(II complexes.

Synthesis and characterisation of iron, cobalt and gallium complexes wit the redox-active amide ligand systems pyridinocarboxiamidobenzene and hydroxy phenyl oxamide; Synthese und Charakterisierung von Eisen-, Cobalt- und Galliumkomplexen mit den redoxaktiven Amidligandsystemen Pyridincarboxamidobenzol und Hydroxyphenyloxamid

Energy Technology Data Exchange (ETDEWEB)

Beckmann, U.

2001-07-01

The interactions of the redox-active ligand systems piridinocarboxamidobenzene and hydroxy phenyl oxamide with the metals iron, cobalt and gallium were investigated. It was found that metal complexes with ligands of the pyridinocarboxamidobenzene and hydroxy phenyl oxamide type can be redox-active in the sense of a ligand-centered reaction. This may provide a better understanding of natural catalysis mechanisms and redox processes. [German] In dieser Arbeit wurde die Wechselwirkung der redoxaktiven Ligandsysteme Pyridincarboxamidobenzol und Hydroxyphenyloxamid mit den Metallen Eisen, Cobalt und Gallium untersucht. Es konnte gezeigt werden, dass Metallkomplexe mit Liganden vom Typ Pyridincarboxamidobenzol und Hydroxyphenyloxamid auch im Sinne einer ligandzentrierten Reaktion redoxaktiv sein koennen. Dies kann dazu beitragen, Katalysemechanismen und Redoxprozesse in der Natur besser zu verstehen. (orig.)

Synthesis, characterization, DNA interaction and antimicrobial screening of isatin-based polypyridyl mixed-ligand Cu(II and Zn(II complexes

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NATARAJAN RAMAN

2010-06-01

Full Text Available Several mixed ligand Cu(II/Zn(II complexes using 3-(phenyl-imino-1,3-dihydro-2H-indol-2-one (obtained by the condensation of isatin and aniline as the primary ligand and 1,10-phenanthroline (phen/2,2’-bipyridine (bpy as an additional ligand were synthesized and characterized analytically and spectroscopically by elemental analyses, magnetic susceptibility and molar conductance measurements, as well as by UV–Vis, IR, NMR and FAB mass spectroscopy. The interaction of the complexes with calf thymus (CT DNA was studied using absorption spectra, cyclic voltammetric and viscosity measurements. They exhibit absorption hypochromicity, and the specific viscosity increased during the binding of the complexes to calf thymus DNA. The shifts in the oxidation–reduction potential and changes in peak current on addition of DNA were shown by CV measurements. The Cu(II/Zn(II complexes were found to promote cleavage of pUC19 DNA from the supercoiled form I to the open circular form II and linear form III. The complexes show enhanced antifungal and antibacterial activities compared with the free ligand.

Automated radiochemical synthesis and biodistribution of [11C]l-α-acetylmethadol ([11C]LAAM)

International Nuclear Information System (INIS)

Sai, Kiran Kumar Solingapuram; Fan, Jinda; Tu, Zhude; Zerkel, Patrick; Mach, Robert H.; Kharasch, Evan D.

2014-01-01

Long-acting opioid agonists methadone and l-α-acetylmethadol (LAAM) prevent withdrawal in opioid-dependent persons. Attempts to synthesize [ 11 C]-methadone for PET evaluation of brain disposition were unsuccessful. Owing, however, to structural and pharmacologic similarities, we aimed to develop [ 11 C]LAAM as a PET ligand to probe the brain exposure of long-lasting opioids in humans. This manuscript describes [ 11 C]LAAM synthesis and its biodistribution in mice. The radiochemical synthetic strategy afforded high radiochemical yield, purity and specific activity, thereby making the synthesis adaptable to automated modules. - Highlights: • Radiochemical synthesis of opioid [ 11 C]l-α-acetylmethadol (LAAM) described for the first time. • High radiochemical yield, purity and specific activity. • Easily reproducible and adaptable synthesis to any C-11 automated modules. • [ 11 C]LAAM utility as a PET radiopharmaceutical for assessing brain penetration

C-H functionalization: thoroughly tuning ligands at a metal ion, a chemist can greatly enhance catalyst's activity and selectivity.

Science.gov (United States)

Shul'pin, Georgiy B

2013-09-28

This brief essay consists of a few "exciting stories" devoted to relations within a metal-complex catalyst between a metal ion and a coordinated ligand. When, as in the case of a human couple, the rapport of the partners is cordial and a love cements these relations, a chemist finds an ideal married couple, in other words he obtains a catalyst of choice which allows him to functionalize C-H bonds very efficiently and selectively. Examples of such lucky marriages in the catalytic world of ions and ligands are discussed here. Activity of the catalyst is characterized by turnover number (TON) or turnover frequency (TOF) as well as by yield of a target product. Introducing a chelating N,N- or N,O-ligand to the catalyst molecule (this can be an iron or manganese derivative) sharply enhances its activity. However, the activity of vanadium derivatives (with additionally added to the solution pyrazinecarboxylic acid, PCA) as well as of various osmium complexes does not dramatically depend on the nature of ligands surrounding metal ions. Complexes of these metals are very efficient catalysts in oxidations with H2O2. Osmium derivatives are record-holders exhibiting extremely high TONs whereas vanadium complexes are on the second position. Finally, elegant examples of alkane functionalization on the ions of non-transition metals (aluminium, gallium etc.) are described when one ligand within the metal complex (namely, hydroperoxyl ligand HOO(-)) helps other ligand of this complex (H2O2 molecule coordinated to the metal) to disintegrate into two species, generating very reactive hydroxyl radical. Hydrogen peroxide molecule, even ligated to the metal ion, is perfectly stable without the assistance of the neighboring HOO(-) ligand. This ligand can be easily oxidized donating an electron to its partner ligand (H2O2). In an analogous case, when the central ion in the catalyst is a transition metal, this ion changing its oxidation state can donate an electron to the coordinated H2O2

Synthesis, physicochemical studies and biological evaluation of unimetallic and heterobimetallic complexes of hexadentate dihydrazone ligands

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Fathy A. El Saied

2017-03-01

Full Text Available A new coordination unimetallic and heterobimetallic complexes of hexadentate N2O4 donor dihydrazone ligands were prepared by the condensation of 4-formyl antipyrine with adipic dihydrazide and succinic dihydrazide. The ligands (1 and (11 and their complexes thoroughly characterized using various analytical, physical and spectroscopic techniques, which indicate a distorted octahedral geometry around the metal ions. The ESR spectra of solid copper(II complexes (2–4 and (12–14 showed axial symmetry with g||>g⊥ > ge, indicating distorted octahedral structure and the presence of the unpaired electron in a d(x2−y2 orbital with significant covalent bond character. The antimicrobial activity results of the metal compounds (2–5, (7, (10, (12–15 and (17 show that, all these complexes exhibit inhibitory moderate to mild effects towards Bacillus subtilis, Escherichia coli and Aspergillus niger.

Cephalostatin analogues--synthesis and biological activity.

Science.gov (United States)

Flessner, Timo; Jautelat, Rolf; Scholz, Ulrich; Winterfeldt, Ekkehard

2004-01-01

Starting off in the early 90's the field of cephalostatin analogues has continually expanded over the last 10 years. First syntheses prepared symmetric analogues like 14b (119) and 26 (65), which were subsequently desymmetrized to provide analogues like beta-hydroxy ketone 31 (19). Importantly the straightforward approach provided already compounds with mu-molar potency and the same pattern of activity as cephalostatin 1 (1) (see Chapter 2.1). Chemically more demanding, two new methods for the directed synthesis of (bissteroidal) pyrazines were devised and subsequently applied to a wide variety of differently functionalized coupling partners. These new methods allowed for the synthesis of various analogues (Chapter 2.2.; and, last but not least, for the totals synthesis of several cephalostatin natural products; Chapter 1.). Functionalization and derivatization of the 12-position was performed (Chapter 2.1 and 3) and synthetic approaches to establish the D-ring double bond were successfully investigated (Chapter 3). [figure: see text] Dealing synthetically with the spiroketal moiety, novel oxidative opening procedures on monomeric delta 14, 15-steroids were devised as well as intensive studies regarding spiroketal synthesis and spiroketal rearrangements were conducted (Chapter 3.2. and 4.). Last but not least direct chemical modification of ritterazines and cephalostatins were studied, which provided a limited number of ritterazine analogues (Chapter 4.). All these synthetic activities towards analogues are summarized in Fig. 18. During this period of time the growing number of cephalostatins and ritterazines on the one hand and of analogues on the other hand provided several SAR trends, which can guide future analogue synthesis. The combined SAR findings are displayed in Fig. 19. So far it is apparent that: Additional methoxylations or hydroxylations in the steroidal A ring core structure (1-position) are slightly decreasing activity (compare cephalostatin 1 1 to

Synthesis, characterization and antimicrobial activity of some ...

African Journals Online (AJOL)

Thermogravimetric analyses were also carried out. The data obtained agree with the proposed structures and show that the complexes decomposed to the corresponding metal oxide. The ligand and their metal complexes were screened for their antimicrobial activities by the agar-well diffusion technique using DMSO as a ...

Synthesis, spectroscopy and antimicrobial activity of vanadium(III) and vanadium(IV) complexes involving Schiff bases derived from tranexamic acid and X-ray structure of Zwitter ion of tranexamic acid

International Nuclear Information System (INIS)

Shahzadi, S.; Ali, S.; Badshah, A.; Parvez, M.; Ahmed, E.; Malik, A.

2007-01-01

The synthesis of six new vanadium complexes of Schiff base derived from Tranexamic acid is reported. All the complexes were characterized by elemental analysis, infrared, electronic spectra, and mass spectrometry. FTIR data reveals that the Schiff base acts as a bidentate and the complexes exhibit the hexa-coordinated geometry in solid state. These complexes were screened for their biological activity against various bacterial and fungal strains. All the ligands show higher activity after complexation. The crystal structure of the Zwitter ion of the Tranexamic acid has been determined by X-ray single crystal diffraction [ru

Microwave assisted synthesis, spectral, magnetic and bioevolution of few Mn (II)-amide complexes

Energy Technology Data Exchange (ETDEWEB)

Joshi, Gaurav [Department of Chemistry, Govt. Engineering College, Bikaner (India); Verma, K. K.; Gudesaria, D. D.; Bhojak, N., E-mail: drbhojak@rediffmail.com [GCRC, Department of Chemistry, Govt Dungar College, Bikaner-334003, Rajasthan (India)

2016-05-06

The importance and versatility of amide group containing ligands have promoted the selection of this class of ligands and their complexes for the study. The present work describes the synthesis, spectral and biological investigations on the complexes of amides derived from heterocyclic amines with Mn (II) ions. Four ligands derived 2-aminopyridine and their complexes with Mn (II) have been synthesized. A method for the synthesis of complexes has been developed by the use of microwave irradiation which is in agreement to Green chemistry approach. The complexes have been characterized on the basis of elemental analysis, infrared, electronic, ESR spectra and magnetic susceptibility studies. The diffuse reflectance spectrum of the complexes show bands in the region 20,000 cm{sup −1} to 26,000 cm{sup −1} assignable to {sup 6}A{sub 1g} → {sup 4}T{sub 2g} and {sup 6}A{sub 1g} → {sup 4}E{sub 1g} transitions. These are also typical of tetrahedral environment around the manganese. The magnetic moment (5.80 BM) of the complex indicates high spin tetrahedral environment. The microwave method of synthesis of complexes have been found easier, convenient and ecofriendly. Antimicrobial activities of compounds were also carried out against bacteria and fungi. Further minimal inhibitory concentration (MIC) was also determined for each compound.

New 15-membered tetraaza (N4) macrocyclic ligand and its transition metal complexes: Spectral, magnetic, thermal and anticancer activity

Science.gov (United States)

El-Boraey, Hanaa A.; EL-Gammal, Ohyla A.

2015-03-01

Novel tetraamidemacrocyclic 15-membered ligand [L] i.e. naphthyl-dibenzo[1,5,9,12]tetraazacyclopentadecine-6,10,11,15-tetraoneand its transition metal complexes with Fe(II), Co(II), Ni(II), Cu(II), Ru(III) and Pd(II) have been synthesized and characterized by elemental analysis, spectral, thermal as well as magnetic and molar conductivity measurements. On the basis of analytical, spectral (IR, MS, UV-Vis, 1H NMR and EPR) and thermal studies distorted octahedral or square planar geometry has been proposed for the complexes. The antitumor activity of the synthesized ligand and some complexes against human breast cancer cell lines (MCF-7) and human hepatocarcinoma cell lines (HepG2) has been studied. The complexes (IC50 = 2.27-2.7, 8.33-31.1 μg/mL, respectively) showed potent antitumor activity, towards the former cell lines comparable with their ligand (IC50 = 13, 26 μg/mL, respectively). The results show that the activity of the ligand towards breast cancer cell line becomes more pronounced and significant when coordinated to the metal ion.

Green synthesis and structural control of metal and mineral nanostructures

DEFF Research Database (Denmark)

Engelbrekt, Christian

of nanoparticle formation which, however, entails the development of new methods. Two approaches to the advancement of solution synthesis of gold nanomaterials for energy technology were exploited, namely the development of techniques to study nanoparticle formation and the synthesis of active, composite...... nanomaterials. In the first approach, time-resolved chronopotentiometry, pH, conductivity and turbidity, and ultraviolet-visible light spectroscopy were employed to follow the green synthesis of gold nanoparticles. Several distinct phases were observed with all techniques providing a broad picture...... of the complex processes. Strong indications of sequential reduction were found and details about ligands and surface immobilized molecules disclosed. This platform is a widely available alternative to traditionally used synchrotron techniques. In the second approach, systematic efforts toward size and shape...

ProBiS-ligands: a web server for prediction of ligands by examination of protein binding sites.

Science.gov (United States)

Konc, Janez; Janežič, Dušanka

2014-07-01

The ProBiS-ligands web server predicts binding of ligands to a protein structure. Starting with a protein structure or binding site, ProBiS-ligands first identifies template proteins in the Protein Data Bank that share similar binding sites. Based on the superimpositions of the query protein and the similar binding sites found, the server then transposes the ligand structures from those sites to the query protein. Such ligand prediction supports many activities, e.g. drug repurposing. The ProBiS-ligands web server, an extension of the ProBiS web server, is open and free to all users at http://probis.cmm.ki.si/ligands. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Molecular evolution of a peptide GPCR ligand driven by artificial neural networks.

Directory of Open Access Journals (Sweden)

Sebastian Bandholtz

Full Text Available Peptide ligands of G protein-coupled receptors constitute valuable natural lead structures for the development of highly selective drugs and high-affinity tools to probe ligand-receptor interaction. Currently, pharmacological and metabolic modification of natural peptides involves either an iterative trial-and-error process based on structure-activity relationships or screening of peptide libraries that contain many structural variants of the native molecule. Here, we present a novel neural network architecture for the improvement of metabolic stability without loss of bioactivity. In this approach the peptide sequence determines the topology of the neural network and each cell corresponds one-to-one to a single amino acid of the peptide chain. Using a training set, the learning algorithm calculated weights for each cell. The resulting network calculated the fitness function in a genetic algorithm to explore the virtual space of all possible peptides. The network training was based on gradient descent techniques which rely on the efficient calculation of the gradient by back-propagation. After three consecutive cycles of sequence design by the neural network, peptide synthesis and bioassay this new approach yielded a ligand with 70fold higher metabolic stability compared to the wild type peptide without loss of the subnanomolar activity in the biological assay. Combining specialized neural networks with an exploration of the combinatorial amino acid sequence space by genetic algorithms represents a novel rational strategy for peptide design and optimization.

Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: synthesis and biological properties.

Science.gov (United States)

Thomann, Jean-Sébastien; Monneaux, Fanny; Creusat, Gaëlle; Spanedda, Maria Vittoria; Heurtault, Béatrice; Habermacher, Chloé; Schuber, Francis; Bourel-Bonnet, Line; Frisch, Benoît

2012-05-01

A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-α-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an α-Galactosylpyranose or an α-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (α/β ratio>9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Preparation and characterizations of new U(IV) and U(VI) complexes with carboxylate ligands

Energy Technology Data Exchange (ETDEWEB)

Sbrignadello, G; Tomat, G; Battiston, G; Vigato, P A [Consiglio Nazionale delle Ricerche, Padua (Italy). Lab. di Chimica e Tecnologia dei Radioelementi

1978-01-01

The synthesis and characterization of some uranyl(VI) complexes containing glycolate (gly = CH/sub 2/OHCOO/sup -/) and methoxyacetate (MeOAc = CH/sub 3/OCH/sub 2/COO/sup -/) ligands with metal:ligand ratios of 1:1 and 1:2 are reported. In addition, new stable uranium(IV) complexes containing the same ligands, or the oxydiacetate (oda = /sup -/OOCCH/sub 2/OCH/sub 2/COO/sup -/) anion, have been prepared by photolysing aqueous solutions of uranyl(VI) nitrate in the presence of an excess of ligand. The possible structures of these complexes are discussed on the basis of IR results. The photoproduction mechanism of U(IV) complexes is proposed from electronic and spectrofluorimetric spectra and quantum yield data.

Chiral phosphites as ligands in asymmetric metal complex catalysis and synthesis of coordination compounds

International Nuclear Information System (INIS)

Gavrilov, Konstantin N; Bondarev, Oleg G; Polosukhin, Aleksei I

2004-01-01

The data published during the last five years on the application of chiral derivatives of phosphorous acid in coordination chemistry and enantioselective catalysis are summarised and discussed. The effect of the nature of these ligands on the structure of metal complexes and on the efficiency of catalytic organic syntheses is shown. Hydroformylation, hydrogenation, allylic substitution and conjugate addition catalysed by transition metal complexes with optically active phosphites and hydrophosphoranes are considered. The prospects for the development of this field of research are demonstrated.

Discovery of peroxisome proliferator-activated receptor α (PPARα) activators with a ligand-screening system using a human PPARα-expressing cell line.

Science.gov (United States)

Tachibana, Keisuke; Yuzuriha, Tomohiro; Tabata, Ryotaro; Fukuda, Syohei; Maegawa, Takashi; Takahashi, Rika; Tanimoto, Keiichi; Tsujino, Hirofumi; Nunomura, Kazuto; Lin, Bangzhong; Matsuura, Yoshiharu; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro Js; Kodama, Tatsuhiko; Kobayashi, Tadayuki; Ishimoto, Kenji; Miyachi, Hiroyuki; Doi, Takefumi

2018-05-15

Peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor that belongs to the superfamily of nuclear hormone receptors. PPARα is mainly expressed in the liver, where it activates fatty acid oxidation and lipoprotein metabolism and improves plasma lipid profiles. Therefore, PPARα activators are often used to treat patients with dyslipidemia. To discover additional PPARα activators as potential compounds for use in hypolipidemic drugs, here we established human hepatoblastoma cell lines with luciferase reporter expression from the promoters containing peroxisome proliferator responsive elements (PPRE) and tetracycline-regulated expression of full-length human PPARα to quantify the effects of chemical ligands on PPARα activity. Using the established cell-based PPARα-activator screening system to screen a library of > 12,000 chemical compounds, we identified several hit compounds with basic chemical skeletons different from those of known PPARα agonists. One of the hit compounds, a 1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid derivative we termed compound 3, selectively up-regulated PPARα transcriptional activity, leading to PPARα target gene expression both in vitro and in vivo. Of note, the half-maximal effective concentrations of the hit compounds were lower than that of the known PPARα ligand fenofibrate. Finally, fenofibrate or compound 3 treatment of high fructose-fed rats having elevated plasma triglyceride levels for 14 days indicated that compound 3 reduces plasma triglyceride levels with similar efficiency as fenofibrate. These observations raise the possibility that 1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid derivatives might be effective drug candidates for selective targeting of PPARα to manage dyslipidemia. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Synthesis and characterization of titanium and yttrium precursors with unsaturated ligands: application to the doping of low-density micro-molecular materials oxides

International Nuclear Information System (INIS)

Gamet-Cauro, L.-C.

2001-01-01

The laser-matter interaction experiments for high-power pulsed lasers require doped micro-targets. The ablator is a Low-Density Microcellular Material,foam namely a styrene-divinylbenzene copolymer obtained by a HIPE process (High Internal Polymerisation Emulsion). The spectroscopic tracers selected for doping are titanium, yttrium and aluminium as oxides. For obtaining these hybrid organic-inorganic materials, precursors with polymerizable ligands were introduced during the emulsification step since the unsaturation of the ligands could participate in the copolymerization reaction. We report here in the synthesis and characterization of titanium and yttrium precursors with polymerizable ligands. The structures of [Ti(O i Pr) 3 (AMP)] 2 (HAMP allyl-methylphenol), [Ti(OEt) 3 (AAA)] 2 (HAAA allylacetoacetate), Y 8 O 2 (OH) 4 (OEt) 6 (AAA) 10 were established by X-ray diffraction. Ti 4 O 3 (OR) 8 (AAA) 2 (R Et, i Pr).[TiO(O i Pr)(oleate)] m , Y 4 (OH) 2 (AAA) 5 , Y 4 O(O i Pr) 5 (AAA) 5 , Y 4 (OH) 4 Cl 5 (AAA) 3 (THF) 3 have been prepared as well and characterized by FT-IR, 1 HNMR and elemental analysis. Micro-hydrolysis reactions of titanium derivatives were investigated. The rates of polymerisation and copolymerization with styrene were evaluated for the titanium precursors with polymerizable ligands. The parameters of the HIPE process were adapted to the fabrication of doped foams, only the dopant and initiator change. We discuss incorporation mechanisms of titanium oxide and yttrium oxo-hydroxides: precursor-surfactant interaction, copolymerization of precursors with unsaturated ligands and physical or chemical retention. The foams have been characterized by scanning electron microscopy (morphology), elemental analysis and fluorescence X cartography (amount, distribution of metal oxide), adsorption isotherms (BET, texture), compression tests (mechanical strength). Due to this systematic study, a good control of doping has become possible and allowed us to develop

A response calculus for immobilized T cell receptor ligands

DEFF Research Database (Denmark)

Andersen, P S; Menné, C; Mariuzza, R A

2001-01-01

determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated...

Reactivity of monoolefin ligand in transition metal complexes

International Nuclear Information System (INIS)

Rybinskaya, M.I.

1978-01-01

The main tendencies in the coordinated olefin ligand property changes are discussed in the transition metal complexes in comparison with free olefins. The review includes the papers published from 1951 up to 1976. It has been shown that in complexes with transition metal cations olefin π-base acquires the ability to react with nucleophylic reagents. Olefin π-acids in complexes with zero valent metals are easily subjected to electrophylic reagent action. At coordination with transition metal cations the olefin properties are generally preserved, while in the zero-valent metal complexes the nonsaturated ligand acquires the properties of a saturated compounds. The ability of transition metal cations in complexes to intensify reactions of nucleophylic bimolecular substitution of vinyl halogen is clearly detected in contrast to the zero valent metal complexes. It has been shown that investigations of the coordinated olefin ligand reactivity give large possibilities in the further development of the organic synthesis. Some reactions are taken as the basis of important industrial processes

Interaction of amatoxins with plant cells and RNA polymerases II: selection of amanitin-resistant cell lines and synthesis of amanitin-based affinity ligands

International Nuclear Information System (INIS)

Little, M.C.

1984-01-01

A series of experiments directed toward deriving basic information regarding plant RNA polymerase II is presented. The experiments described relate to the potential of isolating RNA polymerase II mutants in plants, using carrot cell cultures as models. Additionally, the synthesis of amanitin-based affinity ligands to immobilize isolated plant RNA polymerase II and associated transcriptional complexes is described. RNA polymerase II activities have been isolated from suspension cultures of carrot and compared to other plant RNA polymerases II with respect to subunit analysis and inhibition with α-amanitin. RNA polymerase II purified by polymin P absorption, DE52, phosphocellulose, and RNA-agarose chromatography is shown to copurify with proteins of 175 (and 200), 135, 70, 43, 28, 22, and 17 kdaltons apparent molecular weights. Conditions for accurate determination of amanitin inhibition of the enzyme are established using 3 H-amanitin and are presented for the first time for plant RNA polymerase II; RNA polymerase II from these cultures is shown to be inhibited by 50% at 3-5 nM by α-amanitin, a value 10-50 times lower than previously reported

Synthesis and receptor binding studies of novel 4,4-disubstituted arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as a new class of σ1 ligands.

Science.gov (United States)

Sadeghzadeh, Masoud; Sheibani, Shahab; Ghandi, Mehdi; Daha, Fariba Johari; Amanlou, Massoud; Arjmand, Mohammad; Hasani Bozcheloie, Abolfazl

2013-06-01

This study presents the synthesis and biological evaluation of a new series of arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as sigma receptor ligands. It was found that a number of halogen substituted sulfonamides display relatively high and low affinities to σ1 and σ2 receptors, respectively. The σ1 affinities and subtype selectivities of four piperidine derivatives were also found to be generally comparable to those of piperazine analogues. Compared to σ1-Rs compounds with n = 0 and 2, those with n = 1 proved to have optimal length of carbon chain by exhibiting higher affinities. Within this series, the 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine sigma ligand was identified with 96-fold σ1/σ2 selectivity ratio (Kiσ1 = 0.96 ± 0.05 nM and Kiσ2 = 91.8 ± 8.1 nM). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling.

Science.gov (United States)

Grøntved, Lars; Waterfall, Joshua J; Kim, Dong Wook; Baek, Songjoon; Sung, Myong-Hee; Zhao, Li; Park, Jeong Won; Nielsen, Ronni; Walker, Robert L; Zhu, Yuelin J; Meltzer, Paul S; Hager, Gordon L; Cheng, Sheue-yann

2015-04-28

A bimodal switch model is widely used to describe transcriptional regulation by the thyroid hormone receptor (TR). In this model, the unliganded TR forms stable, chromatin-bound complexes with transcriptional co-repressors to repress transcription. Binding of hormone dissociates co-repressors and facilitates recruitment of co-activators to activate transcription. Here we show that in addition to hormone-independent TR occupancy, ChIP-seq against endogenous TR in mouse liver tissue demonstrates considerable hormone-induced TR recruitment to chromatin associated with chromatin remodelling and activated gene transcription. Genome-wide footprinting analysis using DNase-seq provides little evidence for TR footprints both in the absence and presence of hormone, suggesting that unliganded TR engagement with repressive complexes on chromatin is, similar to activating receptor complexes, a highly dynamic process. This dynamic and ligand-dependent interaction with chromatin is likely shared by all steroid hormone receptors regardless of their capacity to repress transcription in the absence of ligand.

Selective Electrocatalytic Activity of Ligand Stabilized Copper Oxide Nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Kauffman, Douglas R; Ohodnicki, Paul R; Kail, Brian W; Matranga, Christopher

2011-01-01

Ligand stabilization can influence the surface chemistry of Cu oxide nanoparticles (NPs) and provide unique product distributions for electrocatalytic methanol (MeOH) oxidation and CO{sub 2} reduction reactions. Oleic acid (OA) stabilized Cu{sub 2}O and CuO NPs promote the MeOH oxidation reaction with 88% and 99.97% selective HCOH formation, respectively. Alternatively, CO{sub 2} is the only reaction product detected for bulk Cu oxides and Cu oxide NPs with no ligands or weakly interacting ligands. We also demonstrate that OA stabilized Cu oxide NPs can reduce CO{sub 2} into CO with a {approx}1.7-fold increase in CO/H{sub 2} production ratios compared to bulk Cu oxides. The OA stabilized Cu oxide NPs also show 7.6 and 9.1-fold increases in CO/H{sub 2} production ratios compared to weakly stabilized and non-stabilized Cu oxide NPs, respectively. Our data illustrates that the presence and type of surface ligand can substantially influence the catalytic product selectivity of Cu oxide NPs.

Coordination behavior of tetraaza [N4] ligand towards Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes: Synthesis, spectroscopic characterization and anticancer activity

Science.gov (United States)

El-Boraey, Hanaa A.

2012-11-01

Novel eight Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes with [N4] ligand (L) i.e. 2-amino-N-{2-[(2-aminobenzoyl)amino]ethyl}benzamide have been synthesized and structurally characterized by elemental analysis, spectral, thermal (TG/DTG), magnetic, and molar conductivity measurements. On the basis of IR, mass, electronic and EPR spectral studies an octahedral geometry has been proposed for Co(II), Ni(II) complexes and Cu(II) chloride complex, square-pyramidal for Cu(I) bromide complex. For Cu(II) nitrate complex (6), Pd(II) complex (8) square planar geometry was proposed. The EPR data of Cu(II) complexes in powdered form indicate dx2-y2 ground state of Cu(II) ion. The antitumor activity of the synthesized ligand and some selected metal complexes has been studied. The palladium(II) complex (8) was found to display cytotoxicity (IC50 = 25.6 and 41 μM) against human breast cancer cell line MCF-7 and human hepatocarcinoma HEPG2 cell line.

The Role of Protein-Ligand Contacts in Allosteric Regulation of the Escherichia coli Catabolite Activator Protein*

Science.gov (United States)

Townsend, Philip D.; Rodgers, Thomas L.; Glover, Laura C.; Korhonen, Heidi J.; Richards, Shane A.; Colwell, Lucy J.; Pohl, Ehmke; Wilson, Mark R.; Hodgson, David R. W.; McLeish, Tom C. B.; Cann, Martin J.

2015-01-01

Allostery is a fundamental process by which ligand binding to a protein alters its activity at a distant site. Both experimental and theoretical evidence demonstrate that allostery can be communicated through altered slow relaxation protein dynamics without conformational change. The catabolite activator protein (CAP) of Escherichia coli is an exemplar for the analysis of such entropically driven allostery. Negative allostery in CAP occurs between identical cAMP binding sites. Changes to the cAMP-binding pocket can therefore impact the allosteric properties of CAP. Here we demonstrate, through a combination of coarse-grained modeling, isothermal calorimetry, and structural analysis, that decreasing the affinity of CAP for cAMP enhances negative cooperativity through an entropic penalty for ligand binding. The use of variant cAMP ligands indicates the data are not explained by structural heterogeneity between protein mutants. We observe computationally that altered interaction strength between CAP and cAMP variously modifies the change in allosteric cooperativity due to second site CAP mutations. As the degree of correlated motion between the cAMP-contacting site and a second site on CAP increases, there is a tendency for computed double mutations at these sites to drive CAP toward noncooperativity. Naturally occurring pairs of covarying residues in CAP do not display this tendency, suggesting a selection pressure to fine tune allostery on changes to the CAP ligand-binding pocket without a drive to a noncooperative state. In general, we hypothesize an evolutionary selection pressure to retain slow relaxation dynamics-induced allostery in proteins in which evolution of the ligand-binding site is occurring. PMID:26187469

Synthesis of 2-Substituted Benzofurans from o-Iodophenols and Terminal Alkynes with a Recyclable Palladium Catalyst Supported on Nano-sized Carbon Balls under Copper- and Ligand-Free Conditions

Energy Technology Data Exchange (ETDEWEB)

Yum, Eul Kgun; Yang, Okkyung; Kim, Jieun; Park, Hee Jank [Chungnam National Univ., Daejeon (Korea, Republic of)

2013-09-15

We have developed a one-step synthesis of benzofurans from o-iodophenol and various terminal alkynes, by using Pd catalyst supported on nano-sized carbon balls (NCB) under copper- and ligand free conditions. This recyclable catalyst could be reused more than 5 times in the same heteroannulation reaction. The results have demonstrated that diverse 2-substituted benzofurans with tolerant functional groups can be prepared simply and conveniently under these conditions.

Synthesis of 2-Substituted Benzofurans from o-Iodophenols and Terminal Alkynes with a Recyclable Palladium Catalyst Supported on Nano-sized Carbon Balls under Copper- and Ligand-Free Conditions

International Nuclear Information System (INIS)

Yum, Eul Kgun; Yang, Okkyung; Kim, Jieun; Park, Hee Jank

2013-01-01

We have developed a one-step synthesis of benzofurans from o-iodophenol and various terminal alkynes, by using Pd catalyst supported on nano-sized carbon balls (NCB) under copper- and ligand free conditions. This recyclable catalyst could be reused more than 5 times in the same heteroannulation reaction. The results have demonstrated that diverse 2-substituted benzofurans with tolerant functional groups can be prepared simply and conveniently under these conditions

Abscisic Acid Regulates Inflammation via Ligand-binding Domain-independent Activation of Peroxisome Proliferator-activated Receptor γ*

Science.gov (United States)

Bassaganya-Riera, Josep; Guri, Amir J.; Lu, Pinyi; Climent, Montse; Carbo, Adria; Sobral, Bruno W.; Horne, William T.; Lewis, Stephanie N.; Bevan, David R.; Hontecillas, Raquel

2011-01-01

Abscisic acid (ABA) has shown efficacy in the treatment of diabetes and inflammation; however, its molecular targets and the mechanisms of action underlying its immunomodulatory effects remain unclear. This study investigates the role of peroxisome proliferator-activated receptor γ (PPAR γ) and lanthionine synthetase C-like 2 (LANCL2) as molecular targets for ABA. We demonstrate that ABA increases PPAR γ reporter activity in RAW 264.7 macrophages and increases ppar γ expression in vivo, although it does not bind to the ligand-binding domain of PPAR γ. LANCL2 knockdown studies provide evidence that ABA-mediated activation of macrophage PPAR γ is dependent on lancl2 expression. Consistent with the association of LANCL2 with G proteins, we provide evidence that ABA increases cAMP accumulation in immune cells. ABA suppresses LPS-induced prostaglandin E2 and MCP-1 production via a PPAR γ-dependent mechanism possibly involving activation of PPAR γ and suppression of NF-κB and nuclear factor of activated T cells. LPS challenge studies in PPAR γ-expressing and immune cell-specific PPAR γ null mice demonstrate that ABA down-regulates toll-like receptor 4 expression in macrophages and T cells in vivo through a PPAR γ-dependent mechanism. Global transcriptomic profiling and confirmatory quantitative RT-PCR suggest novel candidate targets and demonstrate that ABA treatment mitigates the effect of LPS on the expression of genes involved in inflammation, metabolism, and cell signaling, in part, through PPAR γ. In conclusion, ABA decreases LPS-mediated inflammation and regulates innate immune responses through a bifurcating pathway involving LANCL2 and an alternative, ligand-binding domain-independent mechanism of PPAR γ activation. PMID:21088297

Abscisic acid regulates inflammation via ligand-binding domain-independent activation of peroxisome proliferator-activated receptor gamma.

Science.gov (United States)

Bassaganya-Riera, Josep; Guri, Amir J; Lu, Pinyi; Climent, Montse; Carbo, Adria; Sobral, Bruno W; Horne, William T; Lewis, Stephanie N; Bevan, David R; Hontecillas, Raquel

2011-01-28

Abscisic acid (ABA) has shown efficacy in the treatment of diabetes and inflammation; however, its molecular targets and the mechanisms of action underlying its immunomodulatory effects remain unclear. This study investigates the role of peroxisome proliferator-activated receptor γ (PPAR γ) and lanthionine synthetase C-like 2 (LANCL2) as molecular targets for ABA. We demonstrate that ABA increases PPAR γ reporter activity in RAW 264.7 macrophages and increases ppar γ expression in vivo, although it does not bind to the ligand-binding domain of PPAR γ. LANCL2 knockdown studies provide evidence that ABA-mediated activation of macrophage PPAR γ is dependent on lancl2 expression. Consistent with the association of LANCL2 with G proteins, we provide evidence that ABA increases cAMP accumulation in immune cells. ABA suppresses LPS-induced prostaglandin E(2) and MCP-1 production via a PPAR γ-dependent mechanism possibly involving activation of PPAR γ and suppression of NF-κB and nuclear factor of activated T cells. LPS challenge studies in PPAR γ-expressing and immune cell-specific PPAR γ null mice demonstrate that ABA down-regulates toll-like receptor 4 expression in macrophages and T cells in vivo through a PPAR γ-dependent mechanism. Global transcriptomic profiling and confirmatory quantitative RT-PCR suggest novel candidate targets and demonstrate that ABA treatment mitigates the effect of LPS on the expression of genes involved in inflammation, metabolism, and cell signaling, in part, through PPAR γ. In conclusion, ABA decreases LPS-mediated inflammation and regulates innate immune responses through a bifurcating pathway involving LANCL2 and an alternative, ligand-binding domain-independent mechanism of PPAR γ activation.

Synthesis, characterization, and biological activity of a new palladium(II) complex with deoxyalliin

Energy Technology Data Exchange (ETDEWEB)

Corbi, P.P.; Massabni, A.C. [Inst. de Quimica - UNESP, Dept., Dept. de Quimica Geral e Inoganica, Araraquara (Brazil)]. E-mail: pedrocorbi@yahoo.com; Moreira, A.G. [Inst. de Quimica - UNESP, Dept. de Quimica Geral e Inoganica, Araraquara (Brazil); Faculdade de Medicina de Ribeirao Preto - USP, Dept. de Bioquimica e Imunologia, Ribeirao Preto (Brazil); Medrano, F.J. [Laboratorio Nacional de Luz Sincrotron - LNLS, Campinas (Brazil); Jasiulionis, M.G. [Escola Paulista de Medicina - UNIFESP, Dept. de Micro-Imuno-Parasitologia, Sao Paulo (Brazil); Costa-Neto, C.M. [Faculdade de Medicina de Ribeirao Preto - USP, Dept. de Bioquimica e Imunologia, Ribeirao Preto (Brazil)

2005-02-15

Synthesis, characterization, and biological activity of a new water-soluble Pd(II)-deoxyalliin (S-allyl-L-cysteine) complex are described in this article. Elemental and thermal analysis for the complex are consistent with the formula [Pd(C{sub 6}H{sub 10}NO{sub 2}S){sub 2}]. {sup 13}C NMR, {sup 1}H NMR, and IR spectroscopy show coordination of the ligand to Pd(II) through S and N atoms in a square planar geometry. Final residue of the thermal treatment was identified as a mixture of PdO and metallic Pd. Antiproliferative assays using aqueous solutions of the complex against HeLa and TM5 tumor cells showed a pronounced activity of the complex even at low concentrations. After incubation for 24 h, the complex induced cytotoxic effect over HeLa cells when used at concentrations higher than 0.40 mmol/L. At lower concentrations, the complex was nontoxic, indicating its action is probably due to cell cycle arrest, rather than cell death. In agreement with these results, the flow cytometric analysis indicated that after incubation for 24 h at low concentrations of the complex cells are arrested in G0/G1. (author)

Importance of the pharmacological profile of the bound ligand in enrichment on nuclear receptors: toward the use of experimentally validated decoy ligands.

Science.gov (United States)

Lagarde, Nathalie; Zagury, Jean-François; Montes, Matthieu

2014-10-27

The evaluation of virtual ligand screening methods is of major importance to ensure their reliability. Taking into account the agonist/antagonist pharmacological profile should improve the quality of the benchmarking data sets since ligand binding can induce conformational changes in the nuclear receptor structure and such changes may vary according to the agonist/antagonist ligand profile. We indeed found that splitting the agonist and antagonist ligands into two separate data sets for a given nuclear receptor target significantly enhances the quality of the evaluation. The pharmacological profile of the ligand bound in the binding site of the target structure was also found to be an additional critical parameter. We also illustrate that active compound data sets for a given pharmacological activity can be used as a set of experimentally validated decoy ligands for another pharmacological activity to ensure a reliable and challenging evaluation of virtual screening methods.

Activation and Molecular Targets of Peroxisome Proliferator-Activated Receptor-γ Ligands in Lung Cancer

Directory of Open Access Journals (Sweden)

Raphael A. Nemenoff

2008-01-01

Full Text Available Lung cancer is the leading cause of cancer death, and five-year survival remains poor, raising the urgency for new treatment strategies. Activation of PPARγ represents a potential target for both the treatment and prevention of lung cancer. Numerous studies have examined the effect of thiazolidinediones such as rosiglitazone and pioglitazone on lung cancer cells in vitro and in xenograft models. These studies indicate that activation of PPARγ inhibits cancer cell proliferation as well as invasiveness and metastasis. While activation of PPARγ can occur by direct binding of pharmacological ligands to the molecule, emerging data indicate that PPARγ activation can occur through engagement of other signal transduction pathways, including Wnt signaling and prostaglandin production. Data, both from preclinical models and retrospective clinical studies, indicate that activation of PPARγ may represent an attractive chemopreventive strategy. This article reviews the existing biological and mechanistic experiments focusing on the role of PPARγ in lung cancer, focusing specifically on nonsmall cell lung cancer.

Nucleotide-mimetic synthetic ligands for DNA-recognizing enzymes One-step purification of Pfu DNA polymerase.

Science.gov (United States)

Melissis, S; Labrou, N E; Clonis, Y D

2006-07-28

The commercial availability of DNA polymerases has revolutionized molecular biotechnology and certain sectors of the bio-industry. Therefore, the development of affinity adsorbents for purification of DNA polymerases is of academic interest and practical importance. In the present study we describe the design, synthesis and evaluation of a combinatorial library of novel affinity ligands for the purification of DNA polymerases (Pols). Pyrococcus furiosus DNA polymerase (Pfu Pol) was employed as a proof-of-principle example. Affinity ligand design was based on mimicking the natural interactions between deoxynucleoside-triphosphates (dNTPs) and the B-motif, a conserved structural moiety found in Pol-I and Pol-II family of enzymes. Solid-phase 'structure-guided' combinatorial chemistry was used to construct a library of 26 variants of the B-motif-binding 'lead' ligand X-Trz-Y (X is a purine derivative and Y is an aliphatic/aromatic sulphonate or phosphonate derivative) using 1,3,5-triazine (Trz) as the scaffold for assembly. The 'lead' ligand showed complementarity against a Lys and a Tyr residue of the polymerase B-motif. The ligand library was screened for its ability to bind and purify Pfu Pol from Escherichia coli extract. One immobilized ligand (oABSAd), bearing 9-aminoethyladenine (AEAd) and sulfanilic acid (oABS) linked on the triazine scaffold, displayed the highest purifying ability and binding capacity (0,55 mg Pfu Pol/g wet gel). Adsorption equilibrium studies with this affinity ligand and Pfu Pol determined a dissociation constant (K(D)) of 83 nM for the respective complex. The oABSAd affinity adsorbent was exploited in the development of a facile Pfu Pol purification protocol, affording homogeneous enzyme (>99% purity) in a single chromatography step. Quality control tests showed that Pfu Pol purified on the B-motif-complementing ligand is free of nucleic acids and contaminating nuclease activities, therefore, suitable for experimental use.

Neuroblastoma Cell Lines Are Refractory to Genotoxic Drug-Mediated Induction of Ligands for NK Cell-Activating Receptors

Directory of Open Access Journals (Sweden)

Irene Veneziani

2018-01-01

Full Text Available Neuroblastoma (NB, the most common extracranial solid tumor of childhood, causes death in almost 15% of children affected by cancer. Treatment of neuroblastoma is based on the combination of chemotherapy with other therapeutic interventions such as surgery, radiotherapy, use of differentiating agents, and immunotherapy. In particular, adoptive NK cell transfer is a new immune-therapeutic approach whose efficacy may be boosted by several anticancer agents able to induce the expression of ligands for NK cell-activating receptors, thus rendering cancer cells more susceptible to NK cell-mediated lysis. Here, we show that chemotherapeutic drugs commonly used for the treatment of NB such as cisplatin, topotecan, irinotecan, and etoposide are unable to induce the expression of activating ligands in a panel of NB cell lines. Consistently, cisplatin-treated NB cell lines were not more susceptible to NK cells than untreated cells. The refractoriness of NB cell lines to these drugs has been partially associated with the abnormal status of genes for ATM, ATR, Chk1, and Chk2, the major transducers of the DNA damage response (DDR, triggered by several anticancer agents and promoting different antitumor mechanisms including the expression of ligands for NK cell-activating receptors. Moreover, both the impaired production of reactive oxygen species (ROS in some NB cell lines and the transient p53 stabilization in response to our genotoxic drugs under our experimental conditions could contribute to inefficient induction of activating ligands. These data suggest that further investigations, exploiting molecular strategies aimed to potentiate the NK cell-mediated immunotherapy of NB, are warranted.

Neuroblastoma Cell Lines Are Refractory to Genotoxic Drug-Mediated Induction of Ligands for NK Cell-Activating Receptors

Science.gov (United States)

Veneziani, Irene; Brandetti, Elisa; Ognibene, Marzia; Pezzolo, Annalisa; Pistoia, Vito

2018-01-01

Neuroblastoma (NB), the most common extracranial solid tumor of childhood, causes death in almost 15% of children affected by cancer. Treatment of neuroblastoma is based on the combination of chemotherapy with other therapeutic interventions such as surgery, radiotherapy, use of differentiating agents, and immunotherapy. In particular, adoptive NK cell transfer is a new immune-therapeutic approach whose efficacy may be boosted by several anticancer agents able to induce the expression of ligands for NK cell-activating receptors, thus rendering cancer cells more susceptible to NK cell-mediated lysis. Here, we show that chemotherapeutic drugs commonly used for the treatment of NB such as cisplatin, topotecan, irinotecan, and etoposide are unable to induce the expression of activating ligands in a panel of NB cell lines. Consistently, cisplatin-treated NB cell lines were not more susceptible to NK cells than untreated cells. The refractoriness of NB cell lines to these drugs has been partially associated with the abnormal status of genes for ATM, ATR, Chk1, and Chk2, the major transducers of the DNA damage response (DDR), triggered by several anticancer agents and promoting different antitumor mechanisms including the expression of ligands for NK cell-activating receptors. Moreover, both the impaired production of reactive oxygen species (ROS) in some NB cell lines and the transient p53 stabilization in response to our genotoxic drugs under our experimental conditions could contribute to inefficient induction of activating ligands. These data suggest that further investigations, exploiting molecular strategies aimed to potentiate the NK cell-mediated immunotherapy of NB, are warranted. PMID:29805983

Synthesis of MOF having hydroxyl functional side groups and optimization of activation process for the maximization of its BET surface area

International Nuclear Information System (INIS)

Kim, Jongsik; Kim, Dong Ok; Kim, Dong Wook; Sagong, Kil

2013-01-01

To accomplish the postsynthetic modification of MOF with organic-metal precursors (OMPs) described in our previous researches more efficiently, synthesis of MOF (HCC-2) possessing relatively larger pore size as well as higher number of hydroxyl functional side groups per its base unit than those of HCC-1 has been successfully conducted via adopting 1,4-di-(4-carboxy-2,6-dihydroxyphenyl)benzene as an organic ligand and Zn(NO 3 ) 2 ·6H 2 O as a metal source, respectively. Also, optimization about the Activation process of HCC-2 was performed to maximize its BET (Brunauer–Emmett–Teller) surface area which was proved to be proportional to the number of exposed active sites on which its postsynthetic modification occurred. However, Activation process having been validated to be so effective with the acquirement of highly-purified HCC-1 (CO 2 supercritical drying step followed by vacuum drying step) was less satisfactory with the case of HCC-2. This might be attributed to relatively higher hydrophilicity and bulkier molecular structure of organic ligand of HCC-2. However, it was readily settled by simple modification of above Activation process. Moreover, indispensable residues composed of both DMF and its thermally degraded derivatives which were chemically attached via coordination bond with hydroxyl functionalities even after Activation process III might enable their H 2 adsorption properties to be seriously debased compared to that of IRMOF-16 having no hydroxyl functionalities. - Graphical abstract: Synthesis of new-structured MOF (HCC-2) simultaneously possessing relatively larger pore size as well as higher number of hydroxyl functional side groups per its base unit at the same time than those of HCC-1 has been performed via adopting 1,4-di-(4-carboxy-2,6-dihydroxyphenyl)benzene as an organic ligand and Zn(NO 3 ) 2 ·6H 2 O as a metal source, respectively. Also, the optimization of activation process for HCC-2 was conducted to maximize its BET surface area

Ombuin-3-O-β-D-glucopyranoside from Gynostemma pentaphyllum is a dual agonistic ligand of peroxisome proliferator-activated receptors α and δ/β

Energy Technology Data Exchange (ETDEWEB)

Malek, Mastura Abd; Hoang, Minh-Hien; Jia, Yaoyao; Lee, Ji Hae; Jun, Hee Jin [Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Lee, Dong-Ho [Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Lee, Hak Ju [Division of Green Business Management, Department of Forest Resources Utilization, Korean Forest Research Institute, Seoul 130-712 (Korea, Republic of); Lee, Chul; Lee, Myung Koo [College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Hwang, Bang Yeon, E-mail: byhwang@chungbuk.ac.kr [College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Lee, Sung-Joon, E-mail: junelee@korea.ac.kr [Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

2013-01-25

Highlights: ► Ombuin-3-O-β-D-glucopyranoside is a dual ligand for PPARα and δ/β. ► Ombuin-3-O-β-D-glucopyranoside reduces cellular lipid levels in multiple cell types. ► Cells stimulated with ombuine up-regulated target genes in cholesterol efflux. ► Cells stimulated with ombuine regulated target fatty acid β-oxidation and synthesis. ► Ombuin-3-O-β-D-glucopyranoside could ameliorate hyperlipidemia and hepatic steatosis. -- Abstract: We demonstrated that ombuin-3-O-β-D-glucopyranoside (ombuine), a flavonoid from Gynostemma pentaphyllum, is a dual agonist for peroxisome proliferator-activated receptors (PPARs) α and δ/β. Using surface plasmon resonance (SPR), time-resolved fluorescence resonance energy transfer (FRET) analyses, and reporter gene assays, we showed that ombuine bound directly to PPARα and δ/β but not to PPARγ or liver X receptors (LXRs). Cultured HepG2 hepatocytes stimulated with ombuine significantly reduced intracellular concentrations of triglyceride and cholesterol and downregulated the expression of lipogenic genes, including sterol regulatory element binding protein-1c (SREBP1c) and stearoyl-CoA desaturase-1 (SCD-1), with activation of PPARα and δ/β. Activation of LXRs by ombuine was confirmed by reporter gene assays, however, SPR and cell-based FRET assays showed no direct binding of ombuine to either of the LXRs suggesting LXR activation by ombuine may be operated via PPARα stimulation. Ombuine-stimulated macrophages showed significantly induced transcription of ATP binding cassette cholesterol transporter A1 (ABCA1) and G1 (ABCG1), the key genes in reverse cholesterol transport, which led to reduced cellular cholesterol concentrations. These results suggest that ombuine is a dual PPAR ligand for PPARα and δ/β with the ability to decrease lipid concentrations by reducing lipogenic gene expression in hepatocytes and inducing genes involved in cholesterol efflux in macrophages.

Ombuin-3-O-β-D-glucopyranoside from Gynostemma pentaphyllum is a dual agonistic ligand of peroxisome proliferator-activated receptors α and δ/β

International Nuclear Information System (INIS)

Malek, Mastura Abd; Hoang, Minh-Hien; Jia, Yaoyao; Lee, Ji Hae; Jun, Hee Jin; Lee, Dong-Ho; Lee, Hak Ju; Lee, Chul; Lee, Myung Koo; Hwang, Bang Yeon; Lee, Sung-Joon

2013-01-01

Highlights: ► Ombuin-3-O-β-D-glucopyranoside is a dual ligand for PPARα and δ/β. ► Ombuin-3-O-β-D-glucopyranoside reduces cellular lipid levels in multiple cell types. ► Cells stimulated with ombuine up-regulated target genes in cholesterol efflux. ► Cells stimulated with ombuine regulated target fatty acid β-oxidation and synthesis. ► Ombuin-3-O-β-D-glucopyranoside could ameliorate hyperlipidemia and hepatic steatosis. -- Abstract: We demonstrated that ombuin-3-O-β-D-glucopyranoside (ombuine), a flavonoid from Gynostemma pentaphyllum, is a dual agonist for peroxisome proliferator-activated receptors (PPARs) α and δ/β. Using surface plasmon resonance (SPR), time-resolved fluorescence resonance energy transfer (FRET) analyses, and reporter gene assays, we showed that ombuine bound directly to PPARα and δ/β but not to PPARγ or liver X receptors (LXRs). Cultured HepG2 hepatocytes stimulated with ombuine significantly reduced intracellular concentrations of triglyceride and cholesterol and downregulated the expression of lipogenic genes, including sterol regulatory element binding protein-1c (SREBP1c) and stearoyl-CoA desaturase-1 (SCD-1), with activation of PPARα and δ/β. Activation of LXRs by ombuine was confirmed by reporter gene assays, however, SPR and cell-based FRET assays showed no direct binding of ombuine to either of the LXRs suggesting LXR activation by ombuine may be operated via PPARα stimulation. Ombuine-stimulated macrophages showed significantly induced transcription of ATP binding cassette cholesterol transporter A1 (ABCA1) and G1 (ABCG1), the key genes in reverse cholesterol transport, which led to reduced cellular cholesterol concentrations. These results suggest that ombuine is a dual PPAR ligand for PPARα and δ/β with the ability to decrease lipid concentrations by reducing lipogenic gene expression in hepatocytes and inducing genes involved in cholesterol efflux in macrophages

An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

KAUST Repository

Ali, Amal J.; AbuElela, Ayman; Merzaban, Jasmeen

2017-01-01

-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein

Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel.

Science.gov (United States)

Heusser, Stephanie A; Yoluk, Özge; Klement, Göran; Riederer, Erika A; Lindahl, Erik; Howard, Rebecca J

2016-07-01

The superfamily of pentameric ligand-gated ion channels includes neurotransmitter receptors that mediate fast synaptic transmission in vertebrates, and are targets for drugs including alcohols, anesthetics, benzodiazepines, and anticonvulsants. However, the mechanisms of ion channel opening, gating, and modulation in these receptors leave many open questions, despite their pharmacological importance. Subtle conformational changes in both the extracellular and transmembrane domains are likely to influence channel opening, but have been difficult to characterize given the limited structural data available for human membrane proteins. Recent crystal structures of a modified Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in multiple states offer an appealing model system for structure-function studies. However, the pharmacology of the crystallographic GluCl construct is not well established. To establish the functional relevance of this system, we used two-electrode voltage-clamp electrophysiology in Xenopus oocytes to characterize activation of crystallographic and native-like GluCl constructs by L-glutamate and ivermectin. We also tested modulation by ethanol and other anesthetic agents, and used site-directed mutagenesis to explore the role of a region of Loop F which was implicated in ligand gating by molecular dynamics simulations. Our findings indicate that the crystallographic construct functionally models concentration-dependent agonism and allosteric modulation of pharmacologically relevant receptors. Specific substitutions at residue Leu174 in loop F altered direct L-glutamate activation, consistent with computational evidence for this region's role in ligand binding. These insights demonstrate conservation of activation and modulation properties in this receptor family, and establish a framework for GluCl as a model system, including new possibilities for drug discovery. In this study, we elucidate the validity of a modified glutamate

Brassinosteroids: synthesis and biological activities

Czech Academy of Sciences Publication Activity Database

Oklešťková, Jana; Rárová, Lucie; Kvasnica, Miroslav; Strnad, Miroslav

2015-01-01

Roč. 14, č. 6 (2015), s. 1053-1072 ISSN 1568-7767 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Brassinosteroids * Chemical synthesis * Plant biological activity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.686, year: 2015

Concise and diversity-oriented synthesis of ligand arm-functionalized azoamides.

Science.gov (United States)

Urankar, Damijana; Kosmrlj, Janez

2008-01-01

Azoamides, previously established as bioactive intracellular GSH-depleting agents, were decorated with a terminal alkyne moiety to 4 and then were transformed, by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), into different ligand-arm functionalized azoamides 6. Azides 5 having ligand-arms amenable for binding to platinum(II) were selected for this study. Because, for the fragile azoamides 4, the typically employed reaction conditions for CuAAC failed, several alternative solvents and copper catalysts were tested. Excellent results were obtained with copper(II) sulfate pentahydrate/metallic copper and especially with heterogeneous catalysts, such as copper-in-charcoal, cupric oxide, and cuprous oxide. The heterogeneous catalysts were employed to obtain the desired products in almost quantitative yields by a simple three-step "stir-filter-evaporate" protocol with no or negligible contamination with copper impurities. This is of particular importance because compounds 6 have been designed for coordination.

Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats.

Science.gov (United States)

Kurtz, M; Capobianco, E; Careaga, V; Martinez, N; Mazzucco, M B; Maier, M; Jawerbaum, A

2014-03-01

Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4 (LTB4, PPARα ligand) or 15deoxyΔ(12,14)prostaglandin J2 (15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4 and partially restored by 15dPGJ2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

Bio-Inspired Nitrile Hydration by Peptidic Ligands Based on L-Cysteine, L-Methionine or L-Penicillamine and Pyridine-2,6-dicarboxylic Acid

Directory of Open Access Journals (Sweden)

Cillian Byrne

2014-12-01

Full Text Available Nitrile hydratase (NHase, EC 4.2.1.84 is a metalloenzyme which catalyses the conversion of nitriles to amides. The high efficiency and broad substrate range of NHase have led to the successful application of this enzyme as a biocatalyst in the industrial syntheses of acrylamide and nicotinamide and in the bioremediation of nitrile waste. Crystal structures of both cobalt(III- and iron(III-dependent NHases reveal an unusual metal binding motif made up from six sequential amino acids and comprising two amide nitrogens from the peptide backbone and three cysteine-derived sulfur ligands, each at a different oxidation state (thiolate, sulfenate and sulfinate. Based on the active site geometry revealed by these crystal structures, we have designed a series of small-molecule ligands which integrate essential features of the NHase metal binding motif into a readily accessible peptide environment. We report the synthesis of ligands based on a pyridine-2,6-dicarboxylic acid scaffold and L-cysteine, L-S-methylcysteine, L-methionine or L-penicillamine. These ligands have been combined with cobalt(III and iron(III and tested as catalysts for biomimetic nitrile hydration. The highest levels of activity are observed with the L-penicillamine ligand which, in combination with cobalt(III, converts acetonitrile to acetamide at 1.25 turnovers and benzonitrile to benzamide at 1.20 turnovers.

The Role of Protein-Ligand Contacts in Allosteric Regulation of the Escherichia coli Catabolite Activator Protein.

Science.gov (United States)

Townsend, Philip D; Rodgers, Thomas L; Glover, Laura C; Korhonen, Heidi J; Richards, Shane A; Colwell, Lucy J; Pohl, Ehmke; Wilson, Mark R; Hodgson, David R W; McLeish, Tom C B; Cann, Martin J

2015-09-04

Allostery is a fundamental process by which ligand binding to a protein alters its activity at a distant site. Both experimental and theoretical evidence demonstrate that allostery can be communicated through altered slow relaxation protein dynamics without conformational change. The catabolite activator protein (CAP) of Escherichia coli is an exemplar for the analysis of such entropically driven allostery. Negative allostery in CAP occurs between identical cAMP binding sites. Changes to the cAMP-binding pocket can therefore impact the allosteric properties of CAP. Here we demonstrate, through a combination of coarse-grained modeling, isothermal calorimetry, and structural analysis, that decreasing the affinity of CAP for cAMP enhances negative cooperativity through an entropic penalty for ligand binding. The use of variant cAMP ligands indicates the data are not explained by structural heterogeneity between protein mutants. We observe computationally that altered interaction strength between CAP and cAMP variously modifies the change in allosteric cooperativity due to second site CAP mutations. As the degree of correlated motion between the cAMP-contacting site and a second site on CAP increases, there is a tendency for computed double mutations at these sites to drive CAP toward noncooperativity. Naturally occurring pairs of covarying residues in CAP do not display this tendency, suggesting a selection pressure to fine tune allostery on changes to the CAP ligand-binding pocket without a drive to a noncooperative state. In general, we hypothesize an evolutionary selection pressure to retain slow relaxation dynamics-induced allostery in proteins in which evolution of the ligand-binding site is occurring. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: discovery, synthesis, and characterization of their binding mode by protein crystallography.

Science.gov (United States)

Patterson, Stephen; Alphey, Magnus S; Jones, Deuan C; Shanks, Emma J; Street, Ian P; Frearson, Julie A; Wyatt, Paul G; Gilbert, Ian H; Fairlamb, Alan H

2011-10-13

Trypanothione reductase (TryR) is a genetically validated drug target in the parasite Trypanosoma brucei , the causative agent of human African trypanosomiasis. Here we report the discovery, synthesis, and development of a novel series of TryR inhibitors based on a 3,4-dihydroquinazoline scaffold. In addition, a high resolution crystal structure of TryR, alone and in complex with substrates and inhibitors from this series, is presented. This represents the first report of a high resolution complex between a noncovalent ligand and this enzyme. Structural studies revealed that upon ligand binding the enzyme undergoes a conformational change to create a new subpocket which is occupied by an aryl group on the ligand. Therefore, the inhibitor, in effect, creates its own small binding pocket within the otherwise large, solvent exposed active site. The TryR-ligand structure was subsequently used to guide the synthesis of inhibitors, including analogues that challenged the induced subpocket. This resulted in the development of inhibitors with improved potency against both TryR and T. brucei parasites in a whole cell assay.

Synthesis, spectral, thermal and antimicrobial studies on cobalt(II), nickel(II), copper(II), zinc(II) and palladium(II) complexes containing thiosemicarbazone ligand

Science.gov (United States)

El-Sawaf, Ayman K.; El-Essawy, Farag; Nassar, Amal A.; El-Samanody, El-Sayed A.

2018-04-01

The coordination characteristic of new N4-morpholinyl isatin-3-thiosemicarbazone (HL) towards Co(II), Ni(II), Cu(II), Zn(II) and Pd(II) has been studies. The structures of the complexes were described by elemental analyses, molar conductivity, magnetic, thermal and spectral (IR, UV-Vis, 1H and 13C NMR and ESR) studies. On the basis of analytical and spectral studies the ligand behaves as monobasic tridentate ONS donor forming two five membered rings towards cobalt, copper and palladium and afforded complexes of the kind [M(L)X], (Mdbnd Co, Cu or Pd; Xdbnd Cl, Br or OAc). Whereas the ligand bound to NiCl2 as neutral tridentate ONS donor and with ZnCl2 as neutral bidentate NS donor. The newly synthesized thiosemicarbazone ligand and some of its complexes were examined for antimicrobial activity against 2 gram negative bacterial strains (Escherichia coli Pseudomonas and aeruginosa), 2 gram positive bacterial strains (Streptococcus pneumoniae and Staphylococcus aureus)} and two Pathogenic fungi (Aspergillus fumigatus and Candida albicans). All metal complexes possess higher antimicrobial activity comparing with the free thiosemicarbazone ligand. The high potent activities of the complexes may arise from the coordination and chelation, which tends to make metal complexes act as more controlling and potent antimicrobial agents, thus hindering the growing of the microorganisms. The antimicrobial results also show that copper bromide complex is better antimicrobial agent as compared to the Schiff base and its metal complexes.

Identification and characterization of PPARα ligands in the hippocampus.

Science.gov (United States)

Roy, Avik; Kundu, Madhuchhanda; Jana, Malabendu; Mishra, Rama K; Yung, Yeni; Luan, Chi-Hao; Gonzalez, Frank J; Pahan, Kalipada

2016-12-01

Peroxisome proliferator-activated receptor-α (PPARα) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPARα is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPARα ligands-3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide-in mouse brain hippocampus. Mass spectrometric detection of these compounds in mouse hippocampal nuclear extracts, in silico interaction studies, time-resolved FRET analyses, and thermal shift assay results clearly indicated that these three compounds served as ligands of PPARα. Site-directed mutagenesis studies further revealed that PPARα Y464 and Y314 are involved in binding these hippocampal ligands. Moreover, these ligands activated PPARα and upregulated the synaptic function of hippocampal neurons. These results highlight the discovery of hippocampal ligands of PPARα capable of modulating synaptic functions.

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.

Synthesis, characterization and catalytic activity of two novel cis - dioxovanadium(V) complexes: [VO{sub 2}(L)] and [VO{sub 2}(HLox)

Energy Technology Data Exchange (ETDEWEB)

Silva, Natalia M.L.; Chacon, Eluzir P.; Resende, Jackson A.L.C.; Carneiro, Jose Walkimar de M.; Lanznaster, Mauricio, E-mail: mlanz@vm.uff.b [Universidade Federal Fluminense (IQ/UFF), Niteroi, RJ (Brazil). Inst. de Quimica; Pinheiro, Carlos B. [Universidade Federal de Minas Gerais (DF/UFMG), Belo Horizonte (Brazil). Dept. de Fisica; Fernandez, Tatiana L.; Scarpellini, Marciela [Universidade Federal do Rio de Janeiro (IQ/UFRJ), RJ (Brazil). Inst. de Quimica

2011-07-01

Two novel complexes, [VO{sub 2}(L)] (1) and [VO{sub 2}(HLox)] (2), were synthesized and characterized by IV, UV-Vis and NMR spectroscopy, cyclic voltammetry, elemental analysis and X-ray diffraction. The synthesis of a new ligand, H{sub 2}Lox, is also described. Complexes 1 and 2 were obtained by the reaction of [VO(acac){sub 2}] with the ligands HL and H{sub 2}Lox, respectively. Alternatively, 2 was also obtained by the reaction of HL with [VO(acac)2] in the presence of hydroxylamine, and by the reaction of 1 with hydroxylamine. Crystallographic data show that complexes 1 and 2 have similar molecular structures, in which the cis-dioxovanadium(V) center is coordinated to L- or HLox{sup -}, respectively, in a distorted octahedral environment. The catalytic activity of these compounds towards cyclohexane oxidation was evaluated using H{sub 2}O{sub 2} and t-BuOOH as oxidants. Both complexes presented > 70% selectivity for cyclohexylhydroperoxide formation. B3LYP/6.31G(d) calculations were used to confirm the geometry and to help assign the electronic spectra. (author)

Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-γ ligand, rosiglitazone

International Nuclear Information System (INIS)

Wakui, Yuta; Inoue, Jun; Ueno, Yoshiyuki; Fukushima, Koji; Kondo, Yasuteru; Kakazu, Eiji; Obara, Noriyuki; Kimura, Osamu; Shimosegawa, Tooru

2010-01-01

Although chronic infection of hepatitis B virus (HBV) is currently managed with nucleot(s)ide analogues or interferon-α, the control of HBV infection still remains a clinical challenge. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor, that plays a role in glucose and lipid metabolism, immune reactions, and inflammation. In this study, the suppressive effect of PPAR ligands on HBV replication was examined in vitro using a PPARα ligand, bezafibrate, and a PPARγ ligand, rosiglitazone. The effects were examined in HepG2 cells transfected with a plasmid containing 1.3-fold HBV genome. Whereas bezafibrate showed no effect against HBV replication, rosiglitazone reduced the amount of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen in the culture supernatant. Southern blot analysis showed that the replicative intermediates of HBV in the cells were also inhibited. It was confirmed that GW9662, an antagonist of PPARγ, reduced the suppressive effect of rosiglitazone on HBV. Moreover, rosiglitazone showed a synergistic effect on HBV replication with lamivudine or interferon-α-2b. In conclusion, this study showed that rosiglitazone inhibited the replication of HBV in vitro, and suggested that the combination therapy of rosiglitazone and nucleot(s)ide analogues or interferon could be a therapeutic option for chronic HBV infection.

The Evaluation of Novel Camphor-derived Ligands as Catalysts in ...

African Journals Online (AJOL)

The evaluation of a series of camphor-derived ligands as catalysts in the asymmetric Henry reaction is reported. The synthesis of two novel derivatives is detailed and these molecules are also screened as catalysts in this reaction. The single crystal X-ray structure of one of the novel compounds is reported. The reaction is ...

Structural insights into human peroxisome proliferator activated receptor delta (PPAR-delta selective ligand binding.

Directory of Open Access Journals (Sweden)

Fernanda A H Batista

Full Text Available Peroxisome proliferator activated receptors (PPARs δ, α and γ are closely related transcription factors that exert distinct effects on fatty acid and glucose metabolism, cardiac disease, inflammatory response and other processes. Several groups developed PPAR subtype specific modulators to trigger desirable effects of particular PPARs without harmful side effects associated with activation of other subtypes. Presently, however, many compounds that bind to one of the PPARs cross-react with others and rational strategies to obtain highly selective PPAR modulators are far from clear. GW0742 is a synthetic ligand that binds PPARδ more than 300-fold more tightly than PPARα or PPARγ but the structural basis of PPARδ:GW0742 interactions and reasons for strong selectivity are not clear. Here we report the crystal structure of the PPARδ:GW0742 complex. Comparisons of the PPARδ:GW0742 complex with published structures of PPARs in complex with α and γ selective agonists and pan agonists suggests that two residues (Val312 and Ile328 in the buried hormone binding pocket play special roles in PPARδ selective binding and experimental and computational analysis of effects of mutations in these residues confirms this and suggests that bulky substituents that line the PPARα and γ ligand binding pockets as structural barriers for GW0742 binding. This analysis suggests general strategies for selective PPARδ ligand design.

LIBRA: LIgand Binding site Recognition Application.

Science.gov (United States)

Hung, Le Viet; Caprari, Silvia; Bizai, Massimiliano; Toti, Daniele; Polticelli, Fabio

2015-12-15

In recent years, structural genomics and ab initio molecular modeling activities are leading to the availability of a large number of structural models of proteins whose biochemical function is not known. The aim of this study was the development of a novel software tool that, given a protein's structural model, predicts the presence and identity of active sites and/or ligand binding sites. The algorithm implemented by ligand binding site recognition application (LIBRA) is based on a graph theory approach to find the largest subset of similar residues between an input protein and a collection of known functional sites. The algorithm makes use of two predefined databases for active sites and ligand binding sites, respectively, derived from the Catalytic Site Atlas and the Protein Data Bank. Tests indicate that LIBRA is able to identify the correct binding/active site in 90% of the cases analyzed, 90% of which feature the identified site as ranking first. As far as ligand binding site recognition is concerned, LIBRA outperforms other structure-based ligand binding sites detection tools with which it has been compared. The application, developed in Java SE 7 with a Swing GUI embedding a JMol applet, can be run on any OS equipped with a suitable Java Virtual Machine (JVM), and is available at the following URL: http://www.computationalbiology.it/software/LIBRAv1.zip. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dendrimers and polyamino-phenolic ligands: activity of new molecules against Legionella pneumophila biofilms.

Directory of Open Access Journals (Sweden)

Elisa eAndreozzi

2016-03-01

Full Text Available Legionnaires’ disease is a potentially fatal pneumonia caused by Legionella pneumophila, an aquatic bacterium often found within the biofilm niche. In man-made water systems microbial biofilms increase the resistance of legionella to disinfection, posing a significant threat to public health. Disinfection methods currently used in water systems have been shown to be ineffective against legionella over the long-term, allowing recolonization by the biofilm-protected microorganisms. In this study, the anti-biofilm activity of previously fabricated polyamino-phenolic ligands and polyamidoamine dendrimers was investigated against legionella mono-species and multi-species biofilms formed by L. pneumophila in association with other bacteria that can be found in tap water (Aeromonas hydrophila, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae. Bacterial ability to form biofilms was verified using a crystal violet colorimetric assay and testing cell viability by real-time quantitative PCR and Plate Count assay. The concentration of the chemicals tested as anti-biofilm agents was chosen based on cytotoxicity assays: the highest non-cytotoxic chemical concentration was used for biofilm inhibition assays, with dendrimer concentration ten-fold higher than polyamino-phenolic ligands. While Macrophen and Double Macrophen were the most active substances among polyamino-phenolic ligands, dendrimers were overall two-fold more effective than all other compounds with a reduction up to 85% and 73% of legionella and multi-species biofilms, respectively. Chemical interaction with matrix molecules is hypothesized, based on SEM images and considering the low or absent anti-microbial activity on planktonic bacteria showed by flow cytometry. These data suggest that the studied compounds, especially dendrimers, could be considered as novel molecules in the design of research projects aimed at the development of efficacious anti-biofilm disinfection

Synthesis, Crystal Structure and Luminescent Property of A Novel Cd(II) Coordination Polymer with Bis-imidazole Ligand

International Nuclear Information System (INIS)

Zhou, Yong Hong

2013-01-01

The key to the successful design of metal-organic coordination polymers is the judicious selection of organic ligand. Recently, polydentate aromatic nitrogen heterocyclic ligands with five-membered rings have been well-studied in the construction of supramolecular structure for their N-coordinated sites apt to coordinating to transition metals. Similar to six-membered N-heterocyclic ligands, the azole-based five-membered N-heterocyclic ligands, such as imidazoles, triazoles and tetrazoles have been extensively employed in the construction of various coordination polymers with diverse topologies and interesting properties. The bis(azole) ligands in which N-donor azole rings (imidazole, triazole, or tetrazole) are separated by alkyl, (CH 2 ) n , spacers are good choices for flexible bridging ligands. The conformational flexibility of the spacers makes the ligands adaptable to various coordination networks with one-, two-, and three dimensional structures

Nickel(0)-catalyzed enantioselective annulations of alkynes and arylenoates enabled by a chiral NHC ligand: efficient access to cyclopentenones.

Science.gov (United States)

Ahlin, Joachim S E; Donets, Pavel A; Cramer, Nicolai

2014-11-24

Cyclopentenones are versatile structural motifs of natural products as well as reactive synthetic intermediates. The nickel-catalyzed reductive [3+2] cycloaddition of α,β-unsaturated aromatic esters and alkynes constitutes an efficient method for their synthesis. Here, nickel(0) catalysts comprising a chiral bulky C1-symmetric N-heterocyclic carbene ligand were shown to enable an efficient asymmetric synthesis of cyclopentenones from mesityl enoates and internal alkynes under mild conditions. The bulky NHC ligand provided the cyclopentenone products in very high enantioselectivity and led to a regioselective incorporation of unsymmetrically substituted alkynes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and characterization of two polyoxometalates consisting of different Cu-ligand hydrogen phosphate units

Energy Technology Data Exchange (ETDEWEB)

Yan, Jinshuang; Zhao, Xiaofang; Huang, Jiao; Gong, Kaining; Han, Zhangang, E-mail: hanzg116@126.com; Zhai, Xueliang, E-mail: xlzhai253@mail.hebtu.edu.cn

2014-03-15

Two polyoxometalates [(Cu-mbpy){sub 4}(HPO{sub 4}){sub 2}(H{sub 2}O){sub 2}][PMo{sub 12}O{sub 40}]·H{sub 2}O (1) and [(Cu-mbpy){sub 6}(HPO{sub 4}){sub 4}][PW{sub 12}O{sub 40}]·4H{sub 2}O (2) (mbpy=4,4'-dimethyl-2,2'-dipyridyl in 1; 5,5″-dimethyl-2,2'-dipyridyl in 2) have been synthesized and characterized by IR, X-ray powder diffraction, TG analysis and electrochemical property. The structural features of 1–2 are in their cationic moieties consisting of different linkages of [Cu-mbpy]{sup 2+} and HPO{sub 4}{sup 2−} groups. In 1 four Cu-mbpy bridged by two HPO{sub 4}{sup 2−} ions form a discrete cluster with an interesting octahedron of (Cu{sub 4}P{sub 2}), while in 2 Cu-mbpy fragments are bridged by HPO{sub 4}{sup 2−} ions into 1D structure consisting of trigonal bipyramidal polyhedra of (Cu{sub 3}P{sub 2}). Photocatalytic experiments indicate that compounds 1 and 2 are actively photocatalytic for degradation of methyl orange in the presence of H{sub 2}O{sub 2} under UV light irradiation. -- Graphical abstract: Two polyoxometalate-based supramolecular compounds consisting of different linkages based on Cu-ligand and HPO{sub 4}{sup 2−} groups have been synthesized and characterized. The photocatalytic activity are studied. Highlights: • Two polyoxometalate-based supramolecular compounds consisting of different linkages based on Cu-ligand and HPO{sub 4}{sup 2−} groups have been synthesized. • Hydrogen bonding and π…π interactions play important roles in constructing crystal supramolecular frameworks. • Two compounds represent a high photocatalytic activity in the degradation of methyl orange.

Synthesis and Crystal Structure of Dinuclear Cadmium(II) Complex with Dipodal Ligand

International Nuclear Information System (INIS)

Kang, Young Jin; Moon, Suk Hee; Byun, Jong Chul; Park, Ki Min

2010-01-01

the preparation and structural characterization of the discrete dinuclear cadmium(II) complex with the formula [Cd(μ 2 -Cl) 2 Cl 2 ]· 2 (H 2 O)·0.5(CH 3 OH)·0.5(CH 3 CN) obtained from the reaction of CdCl 2 ·2.5H 2 O and podal ligand with quinoline end-groups has been reported. In two cadmium ions are triply bridged by two chloride and one donor atoms of ligand L and adopt distorted pentagonal bipyramidal geometries with seven coordinations. It is notable that example of discrete dinuclear complex which one podal ligand accommodates simultaneously two metal ions is very rare. During the last four decades, the chemistry of macrocyclic and non-cyclic polyethers has attracted an increasing attention because of their selective complexation, cation transport and enzyme chemistry. In the field of coordination chemistry, generally, non-cyclic, crown-type polyether affords the low complexation ability because of its conformational freedom while macrocyclic polyethers such as 18-crown-6 show the excellent complexing ability

Ligand induced shape transformation of thorium dioxide nanocrystals.

Science.gov (United States)

Wang, Gaoxue; Batista, Enrique R; Yang, Ping

2018-04-27

Nanocrystals (NCs) with size and shape dependent properties are a thriving research field. Remarkable progress has been made in the controlled synthesis of NCs of stable elements in the past two decades; however, the knowledge of the NCs of actinide compounds has been considerably limited due the difficulties in handling them both experimentally and theoretically. Actinide compounds, especially actinide oxides, play a critical role in many stages of the nuclear fuel cycle. Recently, a non-aqueous surfactant assisted approach has been developed for the synthesis of actinide oxide NCs with different morphologies, but an understanding of its control factors is still missing to date. Herein we present a comprehensive study on the low index surfaces of thorium dioxide (ThO2) and their interactions with relevant surfactant ligands using density functional calculations. A systematic picture on the thermodynamic stability of ThO2 NCs of different sizes and shapes is obtained employing empirical models based on the calculated surface energies. It is found that bare ThO2 NCs prefer the octahedral shape terminated by (111) surfaces. Oleic acid displays selective adsorption on the (110) surface, leading to the shape transformation from octahedrons to nanorods. Other ligands such as acetylacetone, oleylamine, and trioctylphosphine oxide do not modify the equilibrium shape of ThO2 NCs. This work provides atomic level insights into the anisotropic growth of ThO2 NCs that was recently observed in experiments, and thus may contribute to the controlled synthesis of actinide oxide NCs with well-defined size and shape for future applications.

Designer ligands. Part 15. Synthesis and characterisation of novel Mn(lI), Ni(II) and Zn(II) complexes of 1,10-phenanthroline-derived ligands

CSIR Research Space (South Africa)

Wellington, Kevin W

2009-01-01

Full Text Available Series of manganese(II), nickel(II) and zinc(II) complexes have been prepared using 1,10-phenanthroline-derived ligands, and their coordination geometries have been assigned using infrared data. It is apparent that, depending on the ligand...

SYNTHESIS AND ANTITUMOR ACTIVITY OF COPPER, NICKEL AND COBALT COORDINATION COMPOUNDS WITH 1-(2-HYDROXYPHENYLETHANONE N(4-ALLYL-3-THIOSEMICARBAZONE

Directory of Open Access Journals (Sweden)

Vasilii GRAUR

2015-12-01

Full Text Available The paper presents the synthesis of the ligand 1-(2-hydroxyphenylethanone N(4-allyl-3-thiosemicarbazone (H2L and six coordination compounds of copper, nickel and cobalt with this ligand. The structure of thiosemicarbazone H2L was studied using 1H and 13С NMR spectroscopy. The synthesized coordination compounds were studied using elemental analysis, gravimetric analysis of water content, molar conductivity, and magnetochemistry. For H2L the antitumor activity towards human leukemia HL-60 cells and cervical cancer HeLa cells was determined. It was established that the substitution of hydrogen atom with methyl group in the azomethinic fragment leads to the growth of antitumor activity.SINTEZA ŞI ACTIVITATEA ANTITUMORALĂ A COMPUŞILOR COMPLECŞI AI CUPRULUI, NICHELULUI ŞI COBALTULUI CU N(4-ALIL-3-TIOSEMICARBAZONA 1-(2-HIDROXIFENILETANONEILucrarea conţine descrierea sintezei N(4-alil-3-tiosemicarbazonei 1-(2-hidroxifeniletanonei (H2L şi a şase compuşi coordinativi ai cuprului, nichelului şi cobaltului cu acest ligand. Structura tiosemicarbazonei H2L a fost stabilită în baza datelor spectroscopiei RMN 1H şi 13C. Compuşi coordinativi au fost studiaţi cu ajutorul analizei elementale, analizei gravimetrice a conţinutului de apă, conductivitaţii molare şi magnetochimiei. Pentru H2L a fost determinată activitatea antitumorală faţă de celulele leucemiei umane HL-60 şi ale cancerului cervical HeLa. S-a stabilit că înlocuirea atomului de hidrogen cu o grupare metil în fragmentul azomethinic conduce la creşterea activitaţii antitumorale.

Synthesis, structural studies and antituberculosis evaluation of new hydrazone derivatives of quinoline and their Zn(II complexes

Directory of Open Access Journals (Sweden)

Mustapha C. Mandewale

2018-02-01

Full Text Available The quinoline hydrazone ligands were synthesized through multi-step reactions. The 2-hydroxy-3-formylquinoline derivatives (1a–1c were prepared from acetanilide derivatives as starting materials using Vilsmeier–Haack reaction. Then the condensation of 2-hydroxy-3-formylquinoline derivatives with hydrazide derivatives (2a–2c yielded quinoline hydrazone ligands (3a–3i. The synthesis of a new series of Zn(II complexes carried out by refluxing with these quinoline hydrazone ligands (3a–3i is reported. The molecular structures of the ligands (3a–3i and the Zn complexes were characterized by elemental analysis and spectral studies like FT-IR, 1H and 13C NMR, MS, UV–Visible and fluorescence. The preliminary results of antituberculosis study showed that most of the Zn(II complexes 4a–4i demonstrated very good antituberculosis activity while the ligands 3a–3i showed moderate activity. Among the tested compounds 4e and 4g were found to be most active with minimum inhibitory concentration (MIC of 8.00μM and 7.42 μM respectively against Mycobacterium tuberculosis (H37 RV strain ATCC No-27294 which is comparable to “first and second line” drugs used to treat tuberculosis.

Synthesis of high specific activity tritium labelled compounds

International Nuclear Information System (INIS)

Parent, P.

1986-01-01

Tritiated methyl iodide of high specific activity is synthetized by Fischer-Tropsch reaction of tritium with carbon monoxide, tritiated methanol obtained is reacted with hydriodic acid. It is used for the synthesis of S-adenosyl L-methionine 3 H-methyl and of diazepam 3 H-methyl derivatives. Synthesis of 3-PPP 3 H: (hydroxy-3 phenyl)-3N-n propyl [ 3 H-2.3] piperidine [ 3 H-2.3] with a specific activity of 4.25 T Bq/mM (115 Ci/mM) and of baclofene 3 H with a specific activity of 0.925 TBq (25 Ci/mM) are also described [fr

Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation

Directory of Open Access Journals (Sweden)

Miguel Angel Burguillos

2015-03-01

Full Text Available Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4 in microglia’s inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3 released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.

Synthesis of [11C]PBR170, a novel imidazopyridine, for imaging the translocator protein with PET

International Nuclear Information System (INIS)

Bourdier, Thomas; Henderson, David; Fookes, Christopher J.R.; Lam, Peter; Mattner, Filomena; Fulham, Michael; Katsifis, Andrew

2014-01-01

The translocator protein (TSPO) ligand 2-(6,8-dichloro-2-(4-ethoxyphenyl)imidazo[1,2-a]pyridin-3-yl) –N-(2-fluoropyridin-3-yl)–N-methylacetamide (PBR170), is a novel imidazopyridineacetamide with high affinity (2.6 nm) and selectivity for the TSPO. The synthesis of [ 11 C]PBR170 was accomplished by N-methylation of the corresponding desmethyl precursor with [ 11 C]methyl iodide in the presence of sodium hydroxide in dimethylformamide. [ 11 C]PBR170 was produced in 30–45% radiochemical yield (decay-corrected, based on [ 11 C]methyl iodide) with a radiochemical purity >98% and a specific activity of 90–190 GBq/μmol after 35 min of synthesis time. - Highlights: • Radiosynthesis of a novel ligand PBR170 with carbon-11. • 30–45% radiochemical yield (decay-corrected, based on [ 11 C]methyl iodide). • Radiosynthesis and formulation achieved in 35 min. • High radiochemical purity (>98%) and specific activity (90–190 GBq/µmol). • High affinity and selectivity for the translocator protein (TSPO)

Attenuation of eph receptor kinase activation in cancer cells by coexpressed ephrin ligands.

Directory of Open Access Journals (Sweden)

Giulia Falivelli

Full Text Available The Eph receptor tyrosine kinases mediate juxtacrine signals by interacting "in trans" with ligands anchored to the surface of neighboring cells via a GPI-anchor (ephrin-As or a transmembrane segment (ephrin-Bs, which leads to receptor clustering and increased kinase activity. Additionally, soluble forms of the ephrin-A ligands released from the cell surface by matrix metalloproteases can also activate EphA receptor signaling. Besides these trans interactions, recent studies have revealed that Eph receptors and ephrins coexpressed in neurons can also engage in lateral "cis" associations that attenuate receptor activation by ephrins in trans with critical functional consequences. Despite the importance of the Eph/ephrin system in tumorigenesis, Eph receptor-ephrin cis interactions have not been previously investigated in cancer cells. Here we show that in cancer cells, coexpressed ephrin-A3 can inhibit the ability of EphA2 and EphA3 to bind ephrins in trans and become activated, while ephrin-B2 can inhibit not only EphB4 but also EphA3. The cis inhibition of EphA3 by ephrin-B2 implies that in some cases ephrins that cannot activate a particular Eph receptor in trans can nevertheless inhibit its signaling ability through cis association. We also found that an EphA3 mutation identified in lung cancer enhances cis interaction with ephrin-A3. These results suggest a novel mechanism that may contribute to cancer pathogenesis by attenuating the tumor suppressing effects of Eph receptor signaling pathways activated by ephrins in trans.

Zn and Fe complexes containing a redox active macrocyclic biquinazoline ligand.

Science.gov (United States)

Banerjee, Priyabrata; Company, Anna; Weyhermüller, Thomas; Bill, Eckhard; Hess, Corinna R

2009-04-06

A series of iron and zinc complexes has been synthesized, coordinated by the macrocyclic biquinazoline ligand, 2-4:6-8-bis(3,3,4,4-tetramethyldihydropyrrolo)-10-15-(2,2'-biquinazolino)-[15]-1,3,5,8,10,14-hexaene-1,3,7,9,11,14-N(6) (Mabiq). The Mabiq ligand consists of a bipyrimidine moiety and two dihydropyrrole units. The electronic structures of the metal-Mabiq complexes have been characterized using spectroscopic and density-functional theory (DFT) computational methods. The parent zinc complex exhibits a ligand-centered reduction to generate the metal-coordinated Mabiq radical dianion, establishing the redox non-innocence of this ligand. Iron-Mabiq complexes have been isolated in three oxidation states. This redox series includes low-spin ferric and low-spin ferrous species, as well as an intermediate-spin Fe(II) compound. In the latter complex, the iron ion is antiferromagnetically coupled to a Mabiq-centered pi-radical. The results demonstrate the rich redox chemistry and electronic properties of metal complexes coordinated by the Mabiq ligand.

Ruthenium-bipyridine complexes bearing fullerene or carbon nanotubes: synthesis and impact of different carbon-based ligands on the resulting products.

Science.gov (United States)

Wu, Zhen-yi; Huang, Rong-bin; Xie, Su-yuan; Zheng, Lan-sun

2011-09-07

This paper discusses the synthesis of two carbon-based pyridine ligands of fullerene pyrrolidine pyridine (C(60)-py) and multi-walled carbon nanotube pyrrolidine pyridine (MWCNT-py) via 1,3-dipolar cycloaddition. The two complexes, C(60)-Ru and MWCNT-Ru, were synthesized by ligand substitution in the presence of NH(4)PF(6), and Ru(II)(bpy)(2)Cl(2) was used as a reaction precursor. Both complexes were characterized by mass spectroscopy (MS), elemental analysis, nuclear magnetic resonance (NMR) spectroscopy, infrared spectroscopy (IR), ultraviolet/visible spectroscopy (UV-VIS) spectrometry, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and cyclic voltammetry (CV). The results showed that the substitution way of C(60)-py is different from that of MWCNT-py. The C(60)-py and a NH(3) replaced a Cl(-) and a bipyridine in Ru(II)(bpy)(2)Cl(2) to produce a five-coordinate complex of [Ru(bpy)(NH(3))(C(60)-py)Cl]PF(6), whereas MWCNT-py replaced a Cl(-) to generate a six-coordinate complex of [Ru(bpy)(2)(MWCNT-py)Cl]PF(6). The cyclic voltammetry study showed that the electron-withdrawing ability was different for C(60) and MWCNT. The C(60) showed a relatively stronger electron-withdrawing effect with respect to MWCNT. This journal is © The Royal Society of Chemistry 2011

Synthesis, characterization, antimicrobial activity and molecular ...

African Journals Online (AJOL)

Synthesis, characterization, antimicrobial activity and molecular docking studies of combined pyrazol-barbituric acid pharmacophores. Assem Barakat, Bandar M. Al-Qahtani, Abdullah M. Al-Majid, M. Ali Mohammed Rafi Shaik, Mohamed H.M. Al-Agamy, Abdul Wadood ...

Synthesis, spectroscopic characterization, biological studies and DFT calculations on some transition metal complexes of NO donor ligand

Science.gov (United States)

Zordok, W. A.; Sadeek, S. A.

2018-04-01

Seven new complexes of2-oxo-4,6-diphenyl-1,2-dihyropyridine-3-carbonitrile (L) with Fe(III), Co(II), Cu(II), Zn(II), Y(III), Zr(IV) and La(III) were synthesized. The isolated solid compounds were elucidated from micro analytical, IR, electronic, mass, 1H NMR, magnetic susceptibility measurements and TG/DTG, DTA analyses. The intensity of ν(Ctbnd N) was changed to strong and shifted to around 2200 cm-1. Also, the ν(Cdbnd O) was shifted to higher frequency value (1644 cm-1). The spectra of the complexes indicate that the free ligand is coordinated to the metal ions via nitrogen of carbonitrile group and oxygen of keto group. From DFT calculations the Cu(II) and Fe(III) complexes behave as regular octahedral, while other complexes are distorted octahedral. The value of energy gap of the free ligand (ΔE = 0.3343 eV) is greater than all new complexes, so they are more reactive than free ligand, also the Fe(III) complex (ΔE = 0.0985 eV) is the most reactive complex, while Cu(II) complex (ΔE = 0.3219 eV) is the least reactive complex. The LMCT in case of Zr(IV) complex was resulted from transitions from HOMO-2 (62%), HOMO-1 (16%)and HOMO (25%), while the d-d transition in Fe(III) complex was resulted from HOMO-1(30%), HOMO-2(62%) and HOMO(30%). Also, the metal complexes exhibit antibacterial activity for Gram-positive and Gram-negative and antifungal activity. The Y(III) and Cu(II) complexes are highly significant for Escherichia coli and salmonella typhimurium.

Oxahelicene NHC ligands in the asymmetric synthesis of nonracemic helicenes

Czech Academy of Sciences Publication Activity Database

Gay Sánchez, Isabel; Šámal, Michal; Nejedlý, Jindřich; Karras, Manfred; Klívar, Jiří; Rybáček, Jiří; Buděšínský, Miloš; Bednárová, Lucie; Seidlerová, Beata; Stará, Irena G.; Starý, Ivo

2017-01-01

Roč. 53, č. 31 (2017), s. 4370-4373 ISSN 1359-7345 R&D Projects: GA ČR(CZ) GA14-29667S Institutional support: RVO:61388963 Keywords : helicene-based NHC ligands * enantioselective [2+2+2] cycloisomerisation Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 6.319, year: 2016

The complex compounds of manganese (II) with poly dental ligands and polyhedron borane anions

International Nuclear Information System (INIS)

Buranova, S.A.

1996-01-01

The purpose of the present work is synthesis of complex compounds of manganese with organic ligands. Their studying by spectroscopic methods purposely to determinate the influence of borane anions on composition and structure of coordinating sphere of manganese

Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-{gamma} ligand, rosiglitazone

Energy Technology Data Exchange (ETDEWEB)

Wakui, Yuta; Inoue, Jun [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan); Ueno, Yoshiyuki, E-mail: yueno@mail.tains.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan); Fukushima, Koji; Kondo, Yasuteru; Kakazu, Eiji; Obara, Noriyuki; Kimura, Osamu; Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan)

2010-05-28

Although chronic infection of hepatitis B virus (HBV) is currently managed with nucleot(s)ide analogues or interferon-{alpha}, the control of HBV infection still remains a clinical challenge. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor, that plays a role in glucose and lipid metabolism, immune reactions, and inflammation. In this study, the suppressive effect of PPAR ligands on HBV replication was examined in vitro using a PPAR{alpha} ligand, bezafibrate, and a PPAR{gamma} ligand, rosiglitazone. The effects were examined in HepG2 cells transfected with a plasmid containing 1.3-fold HBV genome. Whereas bezafibrate showed no effect against HBV replication, rosiglitazone reduced the amount of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen in the culture supernatant. Southern blot analysis showed that the replicative intermediates of HBV in the cells were also inhibited. It was confirmed that GW9662, an antagonist of PPAR{gamma}, reduced the suppressive effect of rosiglitazone on HBV. Moreover, rosiglitazone showed a synergistic effect on HBV replication with lamivudine or interferon-{alpha}-2b. In conclusion, this study showed that rosiglitazone inhibited the replication of HBV in vitro, and suggested that the combination therapy of rosiglitazone and nucleot(s)ide analogues or interferon could be a therapeutic option for chronic HBV infection.

Molecular mechanism of ligand recognition by membrane transport protein, Mhp1

Science.gov (United States)

Simmons, Katie J; Jackson, Scott M; Brueckner, Florian; Patching, Simon G; Beckstein, Oliver; Ivanova, Ekaterina; Geng, Tian; Weyand, Simone; Drew, David; Lanigan, Joseph; Sharples, David J; Sansom, Mark SP; Iwata, So; Fishwick, Colin WG; Johnson, A Peter; Cameron, Alexander D; Henderson, Peter JF

2014-01-01

The hydantoin transporter Mhp1 is a sodium-coupled secondary active transport protein of the nucleobase-cation-symport family and a member of the widespread 5-helix inverted repeat superfamily of transporters. The structure of Mhp1 was previously solved in three different conformations providing insight into the molecular basis of the alternating access mechanism. Here, we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands. We show precisely where 5-substituted hydantoin substrates bind in an extended configuration at the interface of the bundle and hash domains. They are recognised through hydrogen bonds to the hydantoin moiety and the complementarity of the 5-substituent for a hydrophobic pocket in the protein. Furthermore, we describe a novel structure of an intermediate state of the protein with the external thin gate locked open by an inhibitor, 5-(2-naphthylmethyl)-L-hydantoin, which becomes a substrate when leucine 363 is changed to an alanine. We deduce the molecular events that underlie acquisition and transport of a ligand by Mhp1. PMID:24952894

Synthesis, structure, theoretical studies and luminescent properties of a ternary erbium(III) complex with acetylacetone and bathophenanthroline ligands

Energy Technology Data Exchange (ETDEWEB)

Martín-Ramos, Pablo [CEMDRX, Department of Physics, Universidade de Coimbra, Rua Larga, P-3004-516 Coimbra (Portugal); Advanced Materials Laboratory, ETSIIAA, Universidad de Valladolid, Avenida de Madrid 44, 34004 Palencia (Spain); Silva, Pedro S. Pereira, E-mail: psidonio@pollux.fis.uc.pt [CEMDRX, Department of Physics, Universidade de Coimbra, Rua Larga, P-3004-516 Coimbra (Portugal); Chamorro-Posada, Pedro [Higher Technical School of Telecommunications Engineering, Universidad de Valladolid, Campus Miguel Delibes, Paseo Belén 15, 47011 Valladolid (Spain); Silva, Manuela Ramos [CEMDRX, Department of Physics, Universidade de Coimbra, Rua Larga, P-3004-516 Coimbra (Portugal); Milne, Bruce F. [Centre for Computational Physics, Department of Physics, Universidade de Coimbra, P-3004-516 Coimbra (Portugal); Donostia International Physics Centre, Paseo Manuel de Lardizabal 4, 20018 Donostia-San Sebastián (Spain); Nogueira, Fernando [Centre for Computational Physics, Department of Physics, Universidade de Coimbra, P-3004-516 Coimbra (Portugal); Martín-Gil, Jesús [Advanced Materials Laboratory, ETSIIAA, Universidad de Valladolid, Avenida de Madrid 44, 34004 Palencia (Spain)

2015-06-15

A novel erbium(III) complex with acetylacetone (Hacac) and bathophenanthroline (4,7-diphenyl-1,10-phenanthroline, bath) ligands, formulated as [Er(acac){sub 3}(bath)], has been characterized by elemental analysis, X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectroscopy, Raman spectroscopy, absorption and emission spectroscopies. In the theoretical part of this study, semi-empirical quantum chemistry methods using AM1, PM3, PM6 and PM7 models have been employed to predict the structure of the complex, calculate the geometric and crystallographic parameters, and make comparisons with spectroscopic data using INDO/S-CI calculations. Real-time time-dependent density-functional theory (TDDFT) has also been used to calculate the optical absorption spectrum of the complex in the gas phase. - Highlights: • Synthesis and structure of a new erbium(III) β-diketonate complex. • TDDFT used for the first time to calculate the optical absorption spectrum. • Complex show strong near-infrared luminescence at 1.53 µm due to antenna effect.

Synthesis, structure, theoretical studies and luminescent properties of a ternary erbium(III) complex with acetylacetone and bathophenanthroline ligands

International Nuclear Information System (INIS)

Martín-Ramos, Pablo; Silva, Pedro S. Pereira; Chamorro-Posada, Pedro; Silva, Manuela Ramos; Milne, Bruce F.; Nogueira, Fernando; Martín-Gil, Jesús

2015-01-01

A novel erbium(III) complex with acetylacetone (Hacac) and bathophenanthroline (4,7-diphenyl-1,10-phenanthroline, bath) ligands, formulated as [Er(acac) 3 (bath)], has been characterized by elemental analysis, X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectroscopy, Raman spectroscopy, absorption and emission spectroscopies. In the theoretical part of this study, semi-empirical quantum chemistry methods using AM1, PM3, PM6 and PM7 models have been employed to predict the structure of the complex, calculate the geometric and crystallographic parameters, and make comparisons with spectroscopic data using INDO/S-CI calculations. Real-time time-dependent density-functional theory (TDDFT) has also been used to calculate the optical absorption spectrum of the complex in the gas phase. - Highlights: • Synthesis and structure of a new erbium(III) β-diketonate complex. • TDDFT used for the first time to calculate the optical absorption spectrum. • Complex show strong near-infrared luminescence at 1.53 µm due to antenna effect

A catechol-like phenolic ligand-functionalized hydrothermal carbon: One-pot synthesis, characterization and sorption behavior toward uranium

Energy Technology Data Exchange (ETDEWEB)

Li, Bo; Ma, Lijian; Tian, Yin; Yang, Xiaodan; Li, Juan; Bai, Chiyao; Yang, Xiaoyu; Zhang, Shuang; Li, Shoujian, E-mail: sjli000616@scu.edu.cn; Jin, Yongdong, E-mail: jinyongdong@scu.edu.cn

2014-04-01

Highlights: • A new catechol-like ligand-functionalized hydrothermal carbon sorbent is synthesized. • A combination of bayberry tannin and glyoxal is firstly used as starting materials. • Simple, economically viable and environment-friendly synthesis method. • The sorbent exhibits high sorption capacity and distinct selectivity for uranium. - Abstract: We proposed a new approach for preparing an efficient uranium-selective solid phase extractant (HTC-btg) by choosing bayberry tannin as the main building block and especially glyoxal as crosslinking agent via a simple, economic, and green one-pot hydrothermal synthesis. The results of characterization and analysis show that after addition of glyoxal into only bayberry tannin-based hydrothermal reaction system, the as-synthesized HTC-btg displayed higher thermal stability, larger specific surface area and more than doubled surface phenolic hydroxyl groups. The sorption behavior of the sorbents toward uranium under various conditions was investigated in detail and the results indicated that the process is fast, endothermic, spontaneous, and pseudo-second-order chemisorption. The U(VI) sorption capacity reached up to 307.3 mg g{sup −1} under the current experimental conditions. The selective sorption in a specially designed multi-ion solution containing 12 co-existing cations over the range of pH 1.0–4.5 shown that the amount of uranium sorbed accounts for about 53% of the total sorption amount at pH 4.5 and distinctively about 85%, unreported so far to our knowledge, at pH 2.0. Finally, a possible mechanism involving interaction between uranyl ions and phenolic hydroxyl groups on HTC-btg was proposed.

A catechol-like phenolic ligand-functionalized hydrothermal carbon: One-pot synthesis, characterization and sorption behavior toward uranium

International Nuclear Information System (INIS)

Li, Bo; Ma, Lijian; Tian, Yin; Yang, Xiaodan; Li, Juan; Bai, Chiyao; Yang, Xiaoyu; Zhang, Shuang; Li, Shoujian; Jin, Yongdong

2014-01-01

Highlights: • A new catechol-like ligand-functionalized hydrothermal carbon sorbent is synthesized. • A combination of bayberry tannin and glyoxal is firstly used as starting materials. • Simple, economically viable and environment-friendly synthesis method. • The sorbent exhibits high sorption capacity and distinct selectivity for uranium. - Abstract: We proposed a new approach for preparing an efficient uranium-selective solid phase extractant (HTC-btg) by choosing bayberry tannin as the main building block and especially glyoxal as crosslinking agent via a simple, economic, and green one-pot hydrothermal synthesis. The results of characterization and analysis show that after addition of glyoxal into only bayberry tannin-based hydrothermal reaction system, the as-synthesized HTC-btg displayed higher thermal stability, larger specific surface area and more than doubled surface phenolic hydroxyl groups. The sorption behavior of the sorbents toward uranium under various conditions was investigated in detail and the results indicated that the process is fast, endothermic, spontaneous, and pseudo-second-order chemisorption. The U(VI) sorption capacity reached up to 307.3 mg g −1 under the current experimental conditions. The selective sorption in a specially designed multi-ion solution containing 12 co-existing cations over the range of pH 1.0–4.5 shown that the amount of uranium sorbed accounts for about 53% of the total sorption amount at pH 4.5 and distinctively about 85%, unreported so far to our knowledge, at pH 2.0. Finally, a possible mechanism involving interaction between uranyl ions and phenolic hydroxyl groups on HTC-btg was proposed

Synthesis and electroluminescence properties of europium (III) complexes with new second ligands

International Nuclear Information System (INIS)

Liu Ze; Wen Fushan; Li Wenlian

2005-01-01

Two novel second ligands, 9,9-Di-(4-methoxyphenyl)-9-H-4,5-' (OMe-Spiro-DF) and 9,9-Di-(2-(4-(4-butyloxy)phenyl)-5-phenyl-1,3,4-oxadiazolyl)-phenyl-9-H-4, 5-Diazafluorene (OXD-Spiro-DF), were successfully prepared. Europium complexes, Eu(DBM) 3 (OMe-Spiro-DF) and Eu(DBM) 3 (OXD-Spiro-DF) (DBM=dibenzolylmethane) based on the two ligands were designed and synthesized. For a double-layer device with configuration of indium tin oxide (ITO)/N, N'-diphenyl-N,N'-bis(3-methylphenyl)-1,1'-biphenyl-4,4'-diamine (TPD)/Eu(DBM) 3 (OXD-Spiro-DF) or Eu(DBM) 3 (OMe-Spiro-DF)/Mg/Ag, compared with the device based on complex Eu(DBM) 3 (OMe-Spiro-DF), the brightness and electroluminescent (EL) efficiency of device based on complex Eu(DBM) 3 (OXD-Spiro-DF) with oxadiazole-functionalized ligand OXD-Spiro-DF are significantly improved due to the improvement of electron-transporting ability. A maximum brightness of 154 cd/m 2 was obtained at 17 V in the complex Eu(DBM) 3 (OXD-Spiro-DF), about four times brighter than the corresponding complex Eu(DBM) 3 (OMe-Spiro-DF)

A General Ligand Design for Gold Catalysis allowing Ligand-Directed Anti Nucleophilic Attack of Alkynes

Science.gov (United States)

Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

2014-01-01

Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding. PMID:24704803

Synthesis, structure, DNA binding and anticancer activity of mixed ligand ruthenium(II) complex

Science.gov (United States)

Gilewska, Agnieszka; Masternak, Joanna; Kazimierczuk, Katarzyna; Trynda, Justyna; Wietrzyk, Joanna; Barszcz, Barbara

2018-03-01

In order to obtain a potential chemotherapeutic which is not affected on the normal BALB/3T3 cell line, a new arene ruthenium(II) complex {[RuCl(L1)(η6-p-cymene)]PF6}2 · H2O has been synthesized by a direct reaction of precursor, [{(η6-p-cymene)Ru(μ-Cl)}2Cl2], with N,N-chelating ligand (L1 - 2,2‧-bis(4,5-dimethylimidazole). The compound has been fully characterized by elemental analysis, X-ray diffraction, IR, UV-Vis and 1H, 13C NMR spectroscopies. X-ray analysis have confirmed that the compound crystallized in the monoclinic group Cc as an inversion twin. The asymmetric unit contains two symmetrically independent cationic complexes [RuCl(L1)(η6-p-cymene)]+ whose charge is balanced by two PF6- counterions. The shape of each cationic coordination polyhedral can be described as a distorted dodecahedron and shows a typical piano-stool geometry. In addition, an analysis of the crystal structure and the Hirshfeld surface analysis were used to detect and visualize important hydrogen bonds and intermolecular interaction. Moreover, the antiproliferative behavior of the obtained complex was assayed against three human cells: MV-4-11, LoVo, MCF-7 and BALB/3T3 - normal mice fibroblast cells. To predict a binding mode, a potential interaction of ruthenium complex with calf thymus DNA (CT-DNA) has been explored using UV absorption and circular dichroism (CD).

A new synthesis route for Os-complex modified redox polymers for potential biofuel cell applications.

Science.gov (United States)

Pöller, Sascha; Beyl, Yvonne; Vivekananthan, Jeevanthi; Guschin, Dmitrii A; Schuhmann, Wolfgang

2012-10-01

A new synthesis route for Os-complex modified redox polymers was developed. Instead of ligand exchange reactions for coordinative binding of suitable precursor Os-complexes at the polymer, Os-complexes already exhibiting the final ligand shell containing a suitable functional group were bound to the polymer via an epoxide opening reaction. By separation of the polymer synthesis from the ligand exchange reaction at the Os-complex, the modification of the same polymer backbone with different Os-complexes or the binding of the same Os-complex to a number of different polymer backbones becomes feasible. In addition, the Os-complex can be purified and characterized prior to its binding to the polymer. In order to further understand and optimize suitable enzyme/redox polymer systems concerning their potential application in biosensors or biofuel cells, a series of redox polymers was synthesized and used as immobilization matrix for Trametes hirsuta laccase. The properties of the obtained biofuel cell cathodes were compared with similar biocatalytic interfaces derived from redox polymers obtained via ligand exchange reaction of the parent Os-complex with a ligand integrated into the polymer backbone during the polymer synthesis. Copyright © 2011 Elsevier B.V. All rights reserved.

Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity*

OpenAIRE

Marty, Caroline; Chaligné, Ronan; Lacout, Catherine; Constantinescu, Stefan N.; Vainchenker, William; Villeval, Jean-Luc

2009-01-01

The activating W515L mutation in the thrombopoietin receptor (MPL) has been identified in primary myelofibrosis and essential thrombocythemia. MPL belongs to a subset of the cytokine receptor superfamily that requires the JAK2 kinase for signaling. We examined whether the ligand-independent MPLW515L mutant could signal intracellularly. Addition of the endoplasmic reticulum (ER) retention KDEL sequence to the receptor C terminus efficiently locked MPLW515L within its na...

Expression Profiles of Ligands for Activating Natural Killer Cell Receptors on HIV Infected and Uninfected CD4⁺ T Cells.

Science.gov (United States)

Tremblay-McLean, Alexandra; Bruneau, Julie; Lebouché, Bertrand; Lisovsky, Irene; Song, Rujun; Bernard, Nicole F

2017-10-12

Natural Killer (NK) cell responses to HIV-infected CD4 T cells (iCD4) depend on the integration of signals received through inhibitory (iNKR) and activating NK receptors (aNKR). iCD4 activate NK cells to inhibit HIV replication. HIV infection-dependent changes in the human leukocyte antigen (HLA) ligands for iNKR on iCD4 are well documented. By contrast, less is known regarding the HIV infection related changes in ligands for aNKR on iCD4. We examined the aNKR ligand profiles HIV p24⁺ HIV iCD4s that maintained cell surface CD4 (iCD4⁺), did not maintain CD4 (iCD4 - ) and uninfected CD4 (unCD4) T cells for expression of unique long (UL)-16 binding proteins-1 (ULBP-1), ULBP-2/5/6, ULBP-3, major histocompatibility complex (MHC) class 1-related (MIC)-A, MIC-B, CD48, CD80, CD86, CD112, CD155, Intercellular adhesion molecule (ICAM)-1, ICAM-2, HLA-E, HLA-F, HLA-A2, HLA-C, and the ligands to NKp30, NKp44, NKp46, and killer immunoglobulin-like receptor 3DS1 (KIR3DS1) by flow cytometry on CD4 T cells from 17 HIV-1 seronegative donors activated and infected with HIV. iCD4⁺ cells had higher expression of aNKR ligands than did unCD4. However, the expression of aNKR ligands on iCD4 where CD4 was downregulated (iCD4 - ) was similar to (ULBP-1, ULBP-2/5/6, ULBP-3, MIC-A, CD48, CD80, CD86 and CD155) or significantly lower than (MIC-B, CD112 and ICAM-2) what was observed on unCD4. Thus, HIV infection can be associated with increased expression of aNKR ligands or either baseline or lower than baseline levels of aNKR ligands, concomitantly with the HIV-mediated downregulation of cell surface CD4 on infected cells.

Tripodal (N-alkylated) CMP(O) and malonamide ligands: synthesis, extraction of metal ions, and potentiometric studies

International Nuclear Information System (INIS)

Janczewski, D.; Reinhoudt, D.N.; Verboom, W.; Malinowska, E.; Pietrzak, M.; Hill, C.; Allignol, C.

2007-01-01

Tripodal ligands build on the C-pivot (9b-e, 13b-d, and 17a-d) and tri-alkyl-benzene platforms (10a,b, 11, 12, 14a,b, and 18a,b) bearing (N-alkylated) carbamoyl-methyl-phosphine oxide (CMPO), carbamoyl-methyl-phosphonate (CMP), and malonamide moieties were synthesized. Extraction studies with Am 3+ and Eu 3+ show that in general there is a positive influence of the N-alkyl substituents in C-pivot CMP(O) ligands on the D(distribution) coefficients. The tri-alkyl-benzene CMPO ligands 10a,b, 11, and 12 have considerably larger D coefficients than the corresponding C-pivot analogues 9a-e, although hardly having any selectivity, while N-alkylation gives rise to smaller D coefficients. Although less effective the extraction behavior of the C-pivot CMP analogues 13b-d shows more or less the same trend as the corresponding CMPO ligands 9b-e upon substitution of the carboxamide N-atom with different alkyl chains. The different malonamide ligands 17a-d and 18a,b are bad extractants, while N-alkylation makes them even worse. Potentiometric studies of CMP(O) and malonamide ligands in polymeric membranes on Pb 2+ , Cu 2+ , Ca 2+ , Mg 2+ , Na + , and K + salts revealed that N-alkyl substituents increase the stability constants of ion-ionophore complexes compared to unsubstituted ligands. In polymeric membrane electrodes the ligands induce a selectivity pattern that differs significantly from the so-called Hofmeister series, giving the highest selectivity coefficients for UO 2 2+ among all examined cations (Pb 2+ , Cu 2+ , Ca 2+ , Mg 2+ , Na + , K + ). (authors)

Methodology in structural determination and synthesis of insect pheromone

Directory of Open Access Journals (Sweden)

Guo-Qiang Lin

1991-01-01

Full Text Available By means of ethereal washing of insect pheromone glands of female moths, GC-MS detection along with microchemical reactions and electroantennogram (EAG survey, six economically important insect species were targeted for pheromone identification. The discovery of a natural pheromone inhibitor, chemo-selectivity and species isolation by pheromone will be described. The modified triple bond migration and triethylamine liganded vinyl cuprate were applied for achiral pheromone synthesis in double bond formation. Some optically active pheromones and their stereoisomers were synthesized through chiral pool or asymmetric synthesis. Some examples of chiral recognition of insects towards their chiral pheromones will be discussed. A CaH2 and silica gel catalyzed Sharpless Expoxidation Reaction was found in shortening the reaction time.

The PPARγ ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

International Nuclear Information System (INIS)

Moss, Patrice E.; Lyles, Besstina E.; Stewart, LaMonica V.

2010-01-01

The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPARγ ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPARγ ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPARγ ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPARγ. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPARγ and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.

Sequestering agent for uranyl chelation: a new family of CAMS ligands

International Nuclear Information System (INIS)

Leydier, A.; Pellet-Rostaing, S.; Favre-Reguillon, A.; Lemaire, M.; Lecercle, D.; Taran, F.

2008-01-01

The synthesis of new dipodal bis-sulfo-catechol-amide uranophiles is presented. Their binding abilities for uranyl cation were determined by UV spectrophotometry in aqueous media under various pH conditions and further studied by 1 H NMR analysis of the resonance signal of both aromatic protons of the sulfo-catechol-amide groups. The results showed that the efficiency of these hydrosoluble chelating agents depends on the nature of the spacers. Each ligand shows a more or less pronounced affinity for uranium. The best receptor is the ligand CYCAMS 5d obtained as a mixture of cis/trans isomers, which achieves the best compromise between rigidity and steric hindrance. (authors)

Macrocyclic ligands for uranium complexation: Progress report, August 15, 1987-present

International Nuclear Information System (INIS)

Potts, K.T.

1988-03-01

The synthesis of several macrocyclic ligands, designed by a computer modeling approach for the complexation of the uranyl ion, has now been completed and their structures established. Preliminary indicate that these macrocycles successfully complex the uranyl ion. Other synthetic efforts have led to a variety of intermediates suitable for final ring closure to the desired macrocycles, providing appreciable potential for variation of the macrocyclic peripheral atoms. A 1:1-uranyl ion complex of one of these precursor products has been shown to undergo a DMSO-induced rearrangement to a 2:1 uranyl ion to ligand complex, both structures having been established by single crystal x-ray data. 10 refs

Computational approaches to screen candidate ligands with anti- Parkinson's activity using R programming.

Science.gov (United States)

Jayadeepa, R M; Niveditha, M S

2012-01-01

It is estimated that by 2050 over 100 million people will be affected by the Parkinson's disease (PD). We propose various computational approaches to screen suitable candidate ligand with anti-Parkinson's activity from phytochemicals. Five different types of dopamine receptors have been identified in the brain, D1-D5. Dopamine receptor D3 was selected as the target receptor. The D3 receptor exists in areas of the brain outside the basal ganglia, such as the limbic system, and thus may play a role in the cognitive and emotional changes noted in Parkinson's disease. A ligand library of 100 molecules with anti-Parkinson's activity was collected from literature survey. Nature is the best combinatorial chemist and possibly has answers to all diseases of mankind. Failure of some synthetic drugs and its side effects have prompted many researches to go back to ancient healing methods which use herbal medicines to give relief. Hence, the candidate ligands with anti-Parkinson's were selected from herbal sources through literature survey. Lipinski rules were applied to screen the suitable molecules for the study, the resulting 88 molecules were energy minimized, and subjected to docking using Autodock Vina. The top eleven molecules were screened according to the docking score generated by Autodock Vina Commercial drug Ropinirole was computed similarly and was compared with the 11 phytochemicals score, the screened molecules were subjected to toxicity analysis and to verify toxic property of phytochemicals. R Programming was applied to remove the bias from the top eleven molecules. Using cluster analysis and Confusion Matrix two phytochemicals were computationally selected namely Rosmarinic acid and Gingkolide A for further studies on the disease Parkinson's.

Expression of nociceptive ligands in canine osteosarcoma.

Science.gov (United States)

Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

2015-01-01

Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

SYNTHESIS OF CHIRAL BINAPHTHYL CROWN ETHERS AND THEIR USE IN ANIONIC POLYMERIZATION OF METHYL METHACRYLATE AS INITIATOR LIGANDS

Institute of Scientific and Technical Information of China (English)

Hong-wei Liu; Chuan-fu Chen; Fu Xi

2004-01-01

Some chiral binaphthyl crown ethers were synthesized. The anionic polymerization of methyl methacrylate (MMA) was carried out in the presence of t-BuOK, Ph2CHK or Ph2CHNa (RM), and RM coordination initiator by using chiral binaphthyl crown ethers as ligands, respectively. The results showed that in the former case the PMMA obtained has mainly isotactic structure but without optical activity, while in the later case the PMMA produced predominately has syndiotactic suucture also without optical activity.

Molecular-weight-enlarged multiple-pincer ligands: synthesis and application in palladium-catalyzed allylic substitution reactions

NARCIS (Netherlands)

Ronde, N.J.; Totev, D.; Müller, Christian; Lutz, M.; Spek, A.L.; Vogt, D.

2009-01-01

Three different pincer ligand systems are synthesized via nucleophilic substitution reactions of polyaromatic benzyl bromides as support molecules and phenol derivatives as ligand precursors. Retention tests using a polymeric nanofiltration membrane show moderate to good retention in THF and CH2Cl2.

PPARγ and Its Ligands: Potential Antitumor Agents in the Digestive System.

Science.gov (United States)

Shu, Linjing; Huang, Renhuan; Wu, Songtao; Chen, Zhaozhao; Sun, Ke; Jiang, Yan; Cai, Xiaoxiao

2016-01-01

Peroxisome proliferator-activated receptor γ (PPARγ) is a versatile member of the ligand-activated nuclear hormone receptor superfamily of transcription factors, with expression in several different cell lines, especially in the digestive system. After being activated by its ligand, PPARγ can suppress the growth of oral, esophageal, gastric, colorectal, liver, biliary, and pancreatic tumor cells, suggesting that PPARγ ligand is a potential anticancer agent in PPARγ-expressing tumors. This review highlights key advances in understanding the effects of PPARγ ligands in the treatment of tumors in the digestive system.

Tripodal (N-alkylated) CMP(O) and malonamide ligands: synthesis, extraction of metal ions, and potentiometric studies

Energy Technology Data Exchange (ETDEWEB)

Janczewski, D.; Reinhoudt, D.N.; Verboom, W. [Twente Univ., Lab. of Supramolecular Chemistry and Technology, Mesa Research Institute for Nanotechnology, Enschede (Netherlands); Malinowska, E.; Pietrzak, M. [Warsaw Univ. of Technology, Dept. of Analytical Chemistry, Faculty of Chemistry (Poland); Hill, C.; Allignol, C. [CEA Valrho, 30 - Marcoule (France)

2007-01-15

Tripodal ligands build on the C-pivot (9b-e, 13b-d, and 17a-d) and tri-alkyl-benzene platforms (10a,b, 11, 12, 14a,b, and 18a,b) bearing (N-alkylated) carbamoyl-methyl-phosphine oxide (CMPO), carbamoyl-methyl-phosphonate (CMP), and malonamide moieties were synthesized. Extraction studies with Am{sup 3+} and Eu{sup 3+} show that in general there is a positive influence of the N-alkyl substituents in C-pivot CMP(O) ligands on the D(distribution) coefficients. The tri-alkyl-benzene CMPO ligands 10a,b, 11, and 12 have considerably larger D coefficients than the corresponding C-pivot analogues 9a-e, although hardly having any selectivity, while N-alkylation gives rise to smaller D coefficients. Although less effective the extraction behavior of the C-pivot CMP analogues 13b-d shows more or less the same trend as the corresponding CMPO ligands 9b-e upon substitution of the carboxamide N-atom with different alkyl chains. The different malonamide ligands 17a-d and 18a,b are bad extractants, while N-alkylation makes them even worse. Potentiometric studies of CMP(O) and malonamide ligands in polymeric membranes on Pb{sup 2+}, Cu{sup 2+}, Ca{sup 2+}, Mg{sup 2+}, Na{sup +}, and K{sup +} salts revealed that N-alkyl substituents increase the stability constants of ion-ionophore complexes compared to unsubstituted ligands. In polymeric membrane electrodes the ligands induce a selectivity pattern that differs significantly from the so-called Hofmeister series, giving the highest selectivity coefficients for UO{sub 2}{sup 2+} among all examined cations (Pb{sup 2+}, Cu{sup 2+}, Ca{sup 2+}, Mg{sup 2+}, Na{sup +}, K{sup +}). (authors)

The cholinergic ligand binding material of axonal membranes

International Nuclear Information System (INIS)

Mautner, H.G.; Coronado, R.; Jumblatt, J.E.

1986-01-01

Choline acetyltransferase and acetylcholinesterase, the enzymes responsible for the synthesis and hydrolysis of ACh, are present in nerve fibers. In crustacean peripheral nerves, release of ACh from cut nerve fibers has been demonstrated. Previously closed membrane vesicles have been prepared from lobster walking leg nerve plasma membrane and saturable binding of cholinergic agonsist and antagonists to such membranes have been demonstrated. This paper studies this axonal cholinergic binding material, and elucidates its functions. The binding of tritium-nicotine to lobster nerve plasma membranes was antagonized by a series of cholinergic ligands as well as by a series of local anesthetics. This preparation was capable of binding I 125-alpha-bungarotoxin, a ligand widely believed to be a specific label for nicotinic ACh receptor. The labelling of 50 K petide band with tritium-MBTA following disulfide reduction is illustrated

Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities.

Science.gov (United States)

Lew, Erin D; Oh, Jennifer; Burrola, Patrick G; Lax, Irit; Zagórska, Anna; Través, Paqui G; Schlessinger, Joseph; Lemke, Greg

2014-09-29

The TAM receptor tyrosine kinases Tyro3, Axl, and Mer regulate key features of cellular physiology, yet the differential activities of the TAM ligands Gas6 and Protein S are poorly understood. We have used biochemical and genetic analyses to delineate the rules for TAM receptor-ligand engagement and find that the TAMs segregate into two groups based on ligand specificity, regulation by phosphatidylserine, and function. Tyro3 and Mer are activated by both ligands but only Gas6 activates Axl. Optimal TAM signaling requires coincident TAM ligand engagement of both its receptor and the phospholipid phosphatidylserine (PtdSer): Gas6 lacking its PtdSer-binding 'Gla domain' is significantly weakened as a Tyro3/Mer agonist and is inert as an Axl agonist, even though it binds to Axl with wild-type affinity. In two settings of TAM-dependent homeostatic phagocytosis, Mer plays a predominant role while Axl is dispensable, and activation of Mer by Protein S is sufficient to drive phagocytosis.

Chiral ferrocenes in asymmetric catalysis: synthesis and applications

National Research Council Canada - National Science Library

Dai, Li-Xin; Hou, Xue-Long

2010-01-01

.... It provides a thorough overview of the synthesis and characterization of different types of chiral ferrocene ligands, their application to various catalytic asymmetric reactions, and versatile chiral...

Synthesis and characterization of Mn(III) chloro complexes with salen-type ligands

International Nuclear Information System (INIS)

Byun, Jong Chul; Han, Chung Hun; Lee, Nam Ho; Baik, Jong Seok; Park, Yu Chul

2002-01-01

A series of novel salen-type complexes ((Mn(III)(L acn )Cl): n=1∼11) containing Cl - ion were obtained by reactions of the Mn(CH 3 COO) 2 ·4H 2 O with the potentially tetradentate compartmental ligand (H 2 L acn ), prepared by condensation the of one mole of diamine (ethylenediamine, 1,3-propanediamine, o-phenylenediamine, and 2,2-dimethyl-1,3-propanediamine) with two moles of aldehyde (salicylaldehyde, 5-chloro- salicylaldehyde, 3,5-dichlorosalicylal-dehyde, and 3,5-di-tert-butyl-2-hydroxy-benzaldehyde) in a methanol solution . The resulting salen-type ligands and their Mn(III) complexes were identified and characterized by elemental analysis, conductivity, thermogravimetry and UV-VIS, IR, and NMR spectroscopy

A 12-Fold ThSi2 Interpenetrated Network Utilizing a Glycine-Based Pseudopeptidic Ligand

Directory of Open Access Journals (Sweden)

Edward Loukopoulos

2018-01-01

Full Text Available We report the synthesis and characterization of a 3D Cu(II coordination polymer, [Cu3(L12(H2O8]·8H2O (1, with the use of a glycine-based tripodal pseudopeptidic ligand (H3L1 = N,N′,N″-tris(carboxymethyl-1,3,5-benzenetricarboxamide or trimesoyl-tris-glycine. This compound presents the first example of a 12-fold interpenetrated ThSi2 (ths net. We attempt to justify the unique topology of 1 through a systematic comparison of the synthetic parameters in all reported structures with H3L1 and similar tripodal pseudopeptidic ligands. We additionally explore the catalytic potential of 1 in the A3 coupling reaction for the synthesis of propargylamines. The compound acts as a very good heterogeneous catalyst with yields up to 99% and loadings as low as 3 mol %.

Ligand-based design and synthesis of novel sodium channel blockers from a combined phenytoin–lidocaine pharmacophore

OpenAIRE

Wang, Yuesheng; Jones, Paulianda J.; Batts, Timothy W.; Landry, Victoria; Patel, Manoj K.; Brown, Milton L.

2008-01-01

The voltage-gated sodium channel remains a rich area for the development of novel blockers. In this study we used comparative molecular field analysis (CoMFA), a ligand-based design strategy, to generate a 3D model based upon local anesthetics, hydantoins, and α-hydroxyphenylamides to elucidate a SAR for their binding site in the neuronal sodium channel. Correlation by partial least squares (PLS) analysis of in vitro sodium channel binding activity (expressed as pIC50) and the CoMFA descripto...

A DFT approach to discriminate the antagonist and partial agonist activity of ligands binding to the NMDA receptor

Science.gov (United States)

Haslak, Zeynep Pinar; Bozkurt, Esra; Dutagaci, Bercem; De Proft, Frank; Aviyente, Viktorya; De Vleeschouwer, Freija

2018-02-01

The activation of N-methyl-D-aspartate receptors is found to be intimately associated with neurodegenerative diseases which make them promising therapeutic targets. Despite the significantly increasing multidisciplinary interests centred on this ionotropic channel, design of new ligands with intended functional activity remains a great challenge. In this article, a computational study based on density functional theory is presented to understand the structural factors of ligands determining their function as antagonists and partial agonists. With this aim, the GluN1 subunit is chosen as being one of the essential components in the activation mechanism, and quantum chemical calculations are implemented for 30 antagonists and 30 partial agonists known to bind to this subunit with different binding affinities. Several quantum chemical descriptors are investigated which might unlock the difference between antagonists and partial agonists.

Microwave-assisted synthesis of bio-active heterocycles in aqueous media

KAUST Repository

Polshettiwar, Vivek; Varma, Rajender S.

2010-01-01

Synthesis of bio-active heterocycles and fine chemicals in aqueous media are one of the best solutions for the development of green and sustainable protocols. To illustrate the advantages of aqueous MW chemistry in heterocycle synthesis

Synthesis, structural characterization and cytotoxic activity of two new organoruthenium(II complexes

Directory of Open Access Journals (Sweden)

SANJA GRGURIC-SIPKA

2008-06-01

Full Text Available Two new p-cymene ruthenium(II complexes containing as additional ligands N-methylpiperazine ([(η6-p-cymeneRuCl2(CH3NH(CH24NH]PF6, complex 1 or vitamin K3-thiosemicarbazone ([(η6-p-cymeneRuCl2(K3tsc], complex 2 were synthesized starting from [(η6-p-cymene2RuCl2]2 and the corresponding ligand. The complexes were characterized by elemental analysis, IR, electronic absorption and NMR spectroscopy. The X-ray crystal structure determination of complex 1 revealed “piano-stool” geometry. The differences in the cytotoxic activity of the two complexes are discussed in terms of the ligand present.

3,4-Dimethyl diphenyldithiophosphate of mononuclear cobalt(II) with N-donor ligands: Synthesis, structural characterization, DFT and antibacterial studies

Science.gov (United States)

Kumar, Sandeep; Kour, Gurpreet; Schreckenbach, Georg; Andotra, Savit; Hundal, Geeta; Sharma, Vishal; Jaglan, Sundeep; Pandey, Sushil K.

2017-08-01

3,4-Dimethyl diphenyldithiophosphate of cobalt(II) with N-donor ligands [{(ArO)2PS2}2CoL2] [Ar = 3,4-(CH3)2C6H3 (1-3); L = C5H5N (1), 3,4-(CH3)2C5H3N (2) and 4-(C2H5)C5H4N (3)] have been synthesized and characterized by elemental analyses, infrared spectroscopy (IR), powder X-ray diffraction (PXRD) and single crystal X-ray analysis. Complex 1 crystallizes in the monoclinic space group P21/n whereas complexes 2 and 3 crystallize in the triclinic space group Pbar1. The crystal structures of complexes 1-3 reveal mononuclear units with the Co(II) center chelated in bidentate fashion by four S atoms of the two diphenyldithiophosphate ligands. The N atoms from two donor ligands are axially coordinated, leading to distorted octahedral geometry around Co(II). The complexes have been optimized using density functional theory (DFT), structural parameters have been calculated, and the energy gaps of the frontier orbitals (HOMO-LUMO) have been predicted. Mayer bond orders have also been calculated. Structural parameters from the crystallographic and DFT studies are in good agreement with each other. To explore the biological potential, complexes were evaluated for their antibacterial activity against three bacterial strains. The bacterial growth inhibition capacity of the ligand and complexes followed the order of 3 > 2 > 1 > L1.

A Readily Accessible Class of Chiral Cp Ligands and their Application in RuII -Catalyzed Enantioselective Syntheses of Dihydrobenzoindoles.

Science.gov (United States)

Wang, Shou-Guo; Park, Sung Hwan; Cramer, Nicolai

2018-05-04

Chiral cyclopentadienyl (Cp x ) ligands have a large application potential in enantioselective transition-metal catalysis. However, the development of concise and practical routes to such ligands remains in its infancy. We present a convenient and efficient two-step synthesis of a novel class of chiral Cp x ligands with tunable steric properties that can be readily used for complexation, giving Cp x Rh I , Cp x Ir I , and Cp x Ru II complexes. The potential of this ligand class is demonstrated with the latter in the enantioselective cyclization of azabenzonorbornadienes with alkynes, affording dihydrobenzoindoles in up to 98:2 e.r., significantly outperforming existing binaphthyl-derived Cp x ligands. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Asymmetric catalysis in organic synthesis

Energy Technology Data Exchange (ETDEWEB)

Reilly, S.D.; Click, D.R.; Grumbine, S.K.; Scott, B.L.; Watkins, J.G.

1998-11-01

This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The goal of the project was to prepare new catalyst systems, which would perform chemical reactions in an enantioselective manner so as to produce only one of the possible optical isomers of the product molecule. The authors have investigated the use of lanthanide metals bearing both diolate and Schiff-base ligands as catalysts for the enantioselective reduction of prochiral ketones to secondary alcohols. The ligands were prepared from cheap, readily available starting materials, and their synthesis was performed in a ''modular'' manner such that tailoring of specific groups within the ligand could be carried out without repeating the entire synthetic procedure. In addition, they have developed a new ligand system for Group IV and lanthanide-based olefin polymerization catalysts. The ligand system is easily prepared from readily available starting materials and offers the opportunity to rapidly prepare a wide range of closely related ligands that differ only in their substitution patterns at an aromatic ring. When attached to a metal center, the ligand system has the potential to carry out polymerization reactions in a stereocontrolled manner.

EGFR Activation by Spatially Restricted Ligands

Science.gov (United States)

2006-06-01

the level of ligand production, that result in human breast cancer. We have integrated genetic and biochemical methods to study (1) the effects of a...and spindle-B encode components of the RAD52 DNA repair pathway and affect meiosis and patterning in Drosophila oogenesis. Genes Dev 12, 2711-2723...findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision

Characteristic molecular vibrations of adenosine receptor ligands.

Science.gov (United States)

Chee, Hyun Keun; Yang, Jin-San; Joung, Je-Gun; Zhang, Byoung-Tak; Oh, S June

2015-02-13

Although the regulation of membrane receptor activation is known to be crucial for molecular signal transduction, the molecular mechanism underlying receptor activation is not fully elucidated. Here we study the physicochemical nature of membrane receptor behavior by investigating the characteristic molecular vibrations of receptor ligands using computational chemistry and informatics methods. By using information gain, t-tests, and support vector machines, we have identified highly informative features of adenosine receptor (AdoR) ligand and corresponding functional amino acid residues such as Asn (6.55) of AdoR that has informative significance and is indispensable for ligand recognition of AdoRs. These findings may provide new perspectives and insights into the fundamental mechanism of class A G protein-coupled receptor activation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Catalyst activity or stability: the dilemma in Pd-catalyzed polyketone synthesis.

Science.gov (United States)

Amoroso, Francesco; Zangrando, Ennio; Carfagna, Carla; Müller, Christian; Vogt, Dieter; Hagar, Mohamed; Ragaini, Fabio; Milani, Barbara

2013-10-28

A series of Pd-complexes containing nonsymmetrical bis(aryl-imino)acenaphthene (Ar-BIAN) ligands, characterized by substituents on the meta positions of the aryl rings, have been synthesized, characterized and applied in CO/vinyl arene copolymerization reactions. Crystal structures of two neutral Pd-complexes have been solved allowing comparison of the bonding properties of the ligand. Kinetic and mechanistic investigations on these complexes have been performed. The kinetic investigations indicate that in general ligands with electron-withdrawing substituents give more active, but less stable, catalytic systems, although steric effects also play a role. The good performance observed with nonsymmetrical ligands is at least in part due to a compromise between catalyst activity and lifetime, leading to a higher overall productivity with respect to catalysts based on their symmetrical counterparts. Additionally, careful analysis of the reaction profiles provided information on the catalyst deactivation pathway. The latter begins with the reduction of a Pd(II) Ar-BIAN complex to the corresponding Pd(0) species, a reaction that can be reverted by the action of benzoquinone. Then the ligand is lost, a process that appears to be facilitated by the contemporary coordination of an olefin or a CO molecule. The so formed Pd(0) complex immediately reacts with another molecule of the initial Pd(II) complex to give a Pd(I) dimeric species that irreversibly evolves to metallic palladium. Mechanistic investigations performed on the complex with a nonsymmetrical Ar-BIAN probe evidence that the detected intermediates are characterized by the Pd-C bond trans to the Pd-N bond of the aryl ring bearing electron-withdrawing substituents. In addition, the intermediate resulting from the insertion of 4-methylstyrene into the Pd-acyl bond is a five-member palladacycle and not the open-chain η(3)-allylic species observed for complexes with Ar-BIANs substituted in ortho position.

Novel types of tripodal CMPO ligands: synthesis and extraction

Energy Technology Data Exchange (ETDEWEB)

Janczewski, D. [Twente Univ., Enschede (Netherlands). Lab. of Supramolecular Chemistry and Technology; Inst. of Materials Research and Engineering, Research Link (Singapore); Rawdanowicz, M.; Reinhoudt, D.N.; Verboom, W. [Twente Univ., Enschede (Netherlands). Lab. of Supramolecular Chemistry and Technology; Hill, C.; Martinez, I. [Commissariat a l' Energie Atomique, CEA-Valrho, DRCP/SCPS/LCSE, Bagnols-sur-Ceze (France)

2008-07-01

Novel tripodal CMPO ligands having either aryl groups at the N-atom or alkyl groups at the CMPO methylene bridge were prepared in good yields. In the latter case one alkyl group per CMPO moiety was selectively introduced. Extraction studies with Am{sup 3+} and Eu{sup 3+} show that there is an influence of the electronic character of the aryl groups on the extraction. Alkylation of the CMPO methylene group gives rise to a considerable decrease of the D-values (about 100-1000 times), dependent on the bulkiness of the alkyl substituent. (orig.)

Synthesis of a novel class of nitrido Tc-99m radiopharmaceuticals with phosphino-thiol ligands showing transient heart uptake

Energy Technology Data Exchange (ETDEWEB)

Bolzati, Cristina; Uccelli, Licia; Boschi, Alessandra; Malago, Erica; Duatti, Adriano E-mail: dta@unife.it; Tisato, Francesco; Refosco, Fiorenzo; Pasqualini, Roberto; Piffanelli, Adriano

2000-05-01

A novel class of technetium-99m radiopharmaceuticals showing high heart uptake is described. These complexes were prepared through a simple and efficient procedure, and their molecular structure fully characterized. They are formed by a terminal Tc{identical_to}N multiple bond and two bidentate phosphine-thiol ligands [R{sub 2}P-(CH{sub 2}){sub n}SH, n=2,3] coordinated to the metal ion through the neutral phosphorus atom and the deprotonated thiol sulfur atom. The resulting geometry was trigonal bipyramidal. Biodistribution studies were carried out in rats. The complexes exhibited high initial heart uptake and elimination through liver and kidneys. The washout kinetic from heart was dependent on the nature of the lateral R groups on the phosphine-thiol ligands. When R=phenyl, heart activity was rapidly eliminated within 10-20 min. Instead, when R=tolyl,cyclohexyl, persistent heart uptake was observed. Extraction of activity from myocardium tissue showed that no change of the chemical identity of the tracer occurred after heart uptake. On the contrary, metabolization to more hydrophilic species occurred in liver and kidneys.

Synthesis and characterization of transition metal complexes derived from some biologically active furoic acid hydrazones

Directory of Open Access Journals (Sweden)

P. Venkateswar Rao

2007-04-01

Full Text Available Two new physiologically active ligands, N’-2-[(E-1-hydroxy-4-methyl-2-oxo-2H-8-chromenyl ethylidene-2-furan carbohydrazide (HMCFCH and N’-2-[(Z-1-(4-hydroxy-6-methyl-2-oxo-2H-pyranyl ethylidene]-furan carbohydrazide (HMPFCH and their VO(II, Mn(II, Fe(II, Co(II, Ni(II and Cu(II complexes have been prepared. The ligands and the metal complexes have been characterized by elemental analyses, electrical conductance, magnetic susceptibility measurements, UV-Vis, IR, and ESR spectroscopic data. Basing on the above data, Fe(II and Co(II complexes of HMCFCH and HMPFCH have been assigned a dimeric octahedral geometry. VO(II complexes of HMCFCH and HMPFCH have been assigned sulfate bridged dimeric square pyramidal geometry. Mn(II complex of HMCFCH has been assigned a dimeric octahedral geometry, where as Mn(II complex of HMPFCH has been ascribed to monomeric octahedral geometry. Cu(II and Ni(II complexes of HMCFCH have been ascribed to a polymeric structure. Ni(II complex of HMPFCH has been assigned a dimeric square planar geometry. Cu(II complex of HMPFCH has been proposed an octahedral geometry. The ligands and their metal chelates were screened against S. aureus and P. aeruginosa. The ligands and the metal complexes have been found to be active against these microorganisms. The ligands show more activity than the metal complexes.

Rhodium, iridium and nickel complexes with a 1,3,5-triphenylbenzene tris-MIC ligand. Study of the electronic properties and catalytic activities

Directory of Open Access Journals (Sweden)

Carmen Mejuto

2015-12-01

Full Text Available The coordination versatility of a 1,3,5-triphenylbenzene-tris-mesoionic carbene ligand is illustrated by the preparation of complexes with three different metals: rhodium, iridium and nickel. The rhodium and iridium complexes contained the [MCl(COD] fragments, while the nickel compound contained [NiCpCl]. The preparation of the tris-MIC (MIC = mesoionic carbene complex with three [IrCl(CO2] fragments, allowed the estimation of the Tolman electronic parameter (TEP for the ligand, which was compared with the TEP value for a related 1,3,5-triphenylbenzene-tris-NHC ligand. The electronic properties of the tris-MIC ligand were studied by cyclic voltammetry measurements. In all cases, the tris-MIC ligand showed a stronger electron-donating character than the corresponding NHC-based ligands. The catalytic activity of the tri-rhodium complex was tested in the addition reaction of arylboronic acids to α,β-unsaturated ketones.

Spectroscopic and electrochemical correlations in triangular ruthenium clusters containing N-heterocyclic ligands

International Nuclear Information System (INIS)

Cunha, C.J. da.

1989-01-01

A series of clusters of general formula [Ru sub(3) O (OOCCH sub(3)) sub(6) L sub(3)] sup(+), where L = N-heterocyclic ligands, were synthesized and characterized based on elemental analysis. UV-VIS and IR spectra. Voltametric studies revealed the existence of up to six acessible oxidation states, with a high degree of electronic delocalization. The Ru sub(3) O trigonal center possesses many delocalized electrons and can be visualized as a source of electrons. The ligands coordinated to the clusters tune their redox potentials, determine the differences in their electronic spectra, and are responsible for the special conditions required for their synthesis. (author)

Electrochemical and spectroscopic studies of tungstencarbonyl complexes containing nitrogen and phosphorous ligands

Directory of Open Access Journals (Sweden)

Haddad Paula S.

2000-01-01

Full Text Available The present work deals with the synthesis, spectroscopic investigation and electrochemical behaviour of the compounds [W(CO4(bipy] (1, [W(CO3(bipy(dppm] (2 and [W(CO3(bipy(dppf] (3, bipy = 2,2'-bipyridine; dppm = bis(diphenylphosphinomethane; dppf = 1,1'-bis(diphenylphosphinoferrocene. The IR and 31P{¹H} NMR spectroscopic data have shown an octahedral coordination geometry for the tungsten atom with the diphosphines acting as monodentate ligands. The electrochemical behaviour of the complexes was investigated by cyclic voltammetry and controlled potential coulometry. Cyclic voltammograms have indicated that the compounds containing diphosphines ligands are more stable towards oxidation than compound (1.

Physico-Chemical and In-vitro Microbial Studies of Newly Synthesis Organometallic Complexes

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Isam Hussain Al-Karkhi

2014-05-01

Full Text Available Drugs normally synthesized to use as medication to treat diseases like cancer and microbial infections, these synthesized drugs were interested more than naturally-derived drugs which have been shows low activity or not as efficient against diseases. A new ligand 3-methylbenzyl (2Z-2-[1-(pyridin-4-ylethylidene]hydrazine carbodithioate (PE3MBC and its Cd(II, Cu(II, Co(II and Zn(II metal complexes. The new ligand and metal complexes were characterized via various physico-chemical and spectroscopic techniques. Cd(II complex show more activity against microbes and against cancer cell line MCF-7, while other complexes does not shows activity like cadmium complex, all the complexes does not shows any activity against MDAMB-231 cell line. The fatal of the cancer and the microbes cell was due to inhibition of DNA synthesis which was probably due to chelating with metals complexes, or could be referred to lipophilicity, presence of hydrophobic moiety in the complex molecule, also could be due to steric effects and electronic effects.

Synthesis and Antimicrobial Activities of Some New Pyrazoles ...

African Journals Online (AJOL)

NICO

29 antimalarial,30 antimicrobial,31,32 antiviral,33,34 hypoglycaemic,35 anti-HIV activity,36 insecticidal,37 and anti- fungal38 activities. In view of these reports and in continuation of our previous work39 we describe here a facile synthesis of.

Synthesis and characterization of organically linked ZnO nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Chory, Christine; Riedel, Ingo; Parisi, Juergen [Energy and Semiconductor Research Laboratory (EHF), University of Oldenburg, Carl-von Ossietzky-Strasse 9-11, 26129 Oldenburg (Germany); Kruska, Carsten; Heimbrodt, Wolfram [Department of Physics and Material Sciences Center, Philipps-University Marburg, Renthof 5, 35032 Marburg (Germany); Feser, Clemens [NEXT ENERGY - EWE Research Centre for Energy Technology e.V., Carl-von Ossietzky-Strasse 15, 26129 Oldenburg (Germany); Beenken, Wichard J.D. [Department of Theoretical Physics I, Ilmenau University of Technology, Weimarer Strasse 25, 98693 Ilmenau (Germany); Hoppe, Harald [Department of Experimental Physics I, Ilmenau University of Technology, Weimarer Strasse 32, 98693 Ilmenau (Germany)

2012-11-15

We report on the solution-based synthesis and characterization of three-dimensional networks of ZnO nanoparticles where the formation of structures is achieved by covalently linking the nanocrystals with bifunctional organic ligands. The colloidal synthesis will be presented with application of two ligands that vary in size and binding sites. Furthermore we report on structural characterization of dried powders and thin films by means of X-ray diffraction and electron microscopy in order to examine the regularity of the structures. We also present first investigations of the optical properties and electrical conductance behavior in lateral direction of the differently linked hybrid ZnO networks. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Synthesis and characterization of organically linked ZnO nanoparticles

International Nuclear Information System (INIS)

Chory, Christine; Riedel, Ingo; Parisi, Juergen; Kruska, Carsten; Heimbrodt, Wolfram; Feser, Clemens; Beenken, Wichard J.D.; Hoppe, Harald

2012-01-01

We report on the solution-based synthesis and characterization of three-dimensional networks of ZnO nanoparticles where the formation of structures is achieved by covalently linking the nanocrystals with bifunctional organic ligands. The colloidal synthesis will be presented with application of two ligands that vary in size and binding sites. Furthermore we report on structural characterization of dried powders and thin films by means of X-ray diffraction and electron microscopy in order to examine the regularity of the structures. We also present first investigations of the optical properties and electrical conductance behavior in lateral direction of the differently linked hybrid ZnO networks. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Catalytic Water Oxidation by a Bio-inspired Nickel Complex with Redox Active Ligand

Science.gov (United States)

Wang, Dong; Bruner, Charlie O.

2017-01-01

The oxidation of water to dioxygen is important in natural photosynthesis. One of nature’s strategies for managing such multi-electron transfer reactions is to employ redox active metal-organic cofactor arrays. One prototype example is the copper-tyrosinate active site found in galactose oxidase. In this work, we have implemented such a strategy to develop a bio-inspired nickel-phenolate complex capable of catalyzing the oxidation of water to O2 electrochemically at neutral pH with a modest overpotential. The employment of the redox-active ligand turned out to be a useful strategy to avoid the formation of high-valent nickel intermediates while a reasonable turnover rate (0.15 s−1) is retained. PMID:29099176

Synthesis and characterisation of nitrogen poly-heterocyclic molecules using as selective complexing agents of metallic cations

International Nuclear Information System (INIS)

Alphonse, F.A.

2003-12-01

Separation of actinides (III) from lanthanides (III) is a crucial problem in the reprocessing of used nuclear fuels. Experimental results shown that soft donor extractants such as nitrogen polydentate heterocycles containing a NCCNCCN coordination site are potentials ligands for selective extraction of actinides (III). In those cases, two types of liquid-liquid extractions are employed: synergistic combination with lipophilic acid extractants and direct extraction. On the basis of the Hard and Soft Acids and Bases theory and basicity evaluation, new extractants were defined. We have first studied the synthesis of potential 1,3,5-triazine ligands designed for extraction in synergy with α-bromodecanoic acid. Secondly, we have examined the synthesis of bis-triazinyl-pyridine ligands for direct extraction studies. Extraction tests were carried out and perspectives of synthesis were deducted from those extraction results. (author)

Glucagon-like peptide-1 receptor ligand interactions: structural cross talk between ligands and the extracellular domain.

Directory of Open Access Journals (Sweden)

Graham M West

Full Text Available Activation of the glucagon-like peptide-1 receptor (GLP-1R in pancreatic β-cells potentiates insulin production and is a current therapeutic target for the treatment of type 2 diabetes mellitus (T2DM. Like other class B G protein-coupled receptors (GPCRs, the GLP-1R contains an N-terminal extracellular ligand binding domain. N-terminal truncations on the peptide agonist generate antagonists capable of binding to the extracellular domain, but not capable of activating full length receptor. The main objective of this study was to use Hydrogen/deuterium exchange (HDX to identify how the amide hydrogen bonding network of peptide ligands and the extracellular domain of GLP-1R (nGLP-1R were altered by binding interactions and to then use this platform to validate direct binding events for putative GLP-1R small molecule ligands. The HDX studies presented here for two glucagon-like peptide-1 receptor (GLP-1R peptide ligands indicates that the antagonist exendin-4[9-39] is significantly destabilized in the presence of nonionic detergents as compared to the agonist exendin-4. Furthermore, HDX can detect stabilization of exendin-4 and exendin-4[9-39] hydrogen bonding networks at the N-terminal helix [Val19 to Lys27] upon binding to the N-terminal extracellular domain of GLP-1R (nGLP-1R. In addition we show hydrogen bonding network stabilization on nGLP-1R in response to ligand binding, and validate direct binding events with the extracellular domain of the receptor for putative GLP-1R small molecule ligands.

Synthesis, physico-chemical characterization and biological activity of 2-aminobenzimidazole complexes with different metal ions

Directory of Open Access Journals (Sweden)

Podunavac-Kuzmanović Sanja O.

2004-01-01

Full Text Available Complexes of 2-aminobenzimidazole (L with nitrates of cobalt(II nickel(II, copper (II, zinc(II and silver(I were synthesized. The molar ratio metal:ligand in the reaction of the complex formation was 1:2. It should be noticed, that the reaction of all the metal salts yielded bis(ligand complexes of the general formula M(L2(NO32 × nH2O (M=Co, Ni Cu, Zn or Ag; n=0, 1, 2 or 6. The complexes were characterized by elemental analysis of the metal, molar conductivity, magnetic susceptibility measurements and IR spectra. Co(II, Ni(II and Cu(II complexes behave as non-electrolytes, whilst Zn(II and Ag(I are 1:1 electrolytes. Cu(II complex has a square-planar stereochemistry, Ag(I complex is linear, whilst the Co(II, Ni(II and Zn(II complexes have a tetrahedral configuration. In all the complexes ligand is coordinated by participation of the pyridine nitrogen of the benzimidazole ring. The antimicrobial activity of the ligand and its complexes against Pseudomonas aeruginosa, Bacillus sp. Staphylococcus aureus and Saccharomyces cerevisiae was investigated. The effect of metal on the ligand antimicrobial activity is discussed.

Adrenoceptor-activated nitric oxide synthesis in salivary acinar cells

DEFF Research Database (Denmark)

Looms, Dagnia; Dissing, Steen; Tritsaris, Katerina

2000-01-01

We investigated the cellular regulation of nitric oxide synthase (NOS) activity in isolated acinar cells from rat parotid and human labial salivary glands, using the newly developed fluorescent nitric oxide (NO) indicator, DAF-2. We found that sympathetic stimulation with norepinephrine (NE) caused...... a strong increase in NO synthesis that was not seen after parasympathetic stimulation with acetylcholine. In rat parotid acinar cells, we furthermore investigated to which extent the NOS activity was dependent on the intracellular free Ca2+ concentration ([Ca2+]i) by simultaneously measuring NO synthesis...

The PPARδ Ligand GW501516 Reduces Growth but Not Apoptosis in Mouse Inner Medullary Collecting Duct Cells

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Jordan Clark

2009-01-01

Full Text Available The collecting duct (CD expresses considerable amounts of PPARδ. While its role is unknown in the CD, in other renal cells it has been shown to regulate both growth and apoptosis. We thus hypothesized that PPARδ reduces apoptotic responses and stimulates cell growth in the mouse CD, and examined the effect of GW501516, a synthetic PPARδ ligand, on these responses in mouse IMCD-K2 cells. High doses of GW501516 decreased both DNA and protein synthesis in these cells by 80%, but had no overall effect on cell viability. Although anisomycin treatment resulted in an increase of caspase-3 levels of about 2.59-fold of control, GW501516 did not affect anisomycin-induced changes in active caspase-3 levels. These results show that a PPARδ ligand inhibits growth but does not affect anisomycin-apoptosis in a mouse IMCD cell line. This could have therapeutic implications for renal diseases associated with increased CD growth responses.

Rosiglitazone stimulates the release and synthesis of insulin by enhancing GLUT-2, glucokinase and BETA2/NeuroD expression

International Nuclear Information System (INIS)

Kim, Hyo-Sup; Noh, Jung-Hyun; Hong, Seung-Hyun; Hwang, You-Cheol; Yang, Tae-Young; Lee, Myung-Shik; Kim, Kwang-Won; Lee, Moon-Kyu

2008-01-01

Peroxisome proliferator-activated receptor (PPAR)-γ is a member of the nuclear receptor superfamily, and its ligands, the thiazolidinediones, might directly stimulate insulin release and insulin synthesis in pancreatic β-cells. In the present study, we examined the effects of rosiglitazone (RGZ) on insulin release and synthesis in pancreatic β-cell (INS-1). Insulin release and synthesis were stimulated by treatment with RGZ for 24 h. RGZ upregulated the expressions of GLUT-2 and glucokinase (GCK). Moreover, it was found that RGZ increased the expression of BETA2/NeuroD gene which could regulate insulin gene expression. These results suggest that RGZ could stimulate the release and synthesis of insulin through the upregulation of GLUT-2, GCK, and BETA2/NeuroD gene expression

Dimeric ligands for GPCRs involved in human reproduction : synthesis and biological evaluation

NARCIS (Netherlands)

Bonger, Kimberly Michelle

2008-01-01

Dimeric ligands for G-protein coupled receptors that are involved in human reproduction, namely the gonadotropin releasing hormone receptor, the luteinizing hormone receptor and the follicle-stimulating hormone receptor, were synthesized and biologically evaluated.

Synthesis, spectral characterization, theoretical, antimicrobial, DNA interaction and in vitro anticancer studies of Cu(II and Zn(II complexes with pyrimidine-morpholine based Schiff base ligand

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M. Sankarganesh

2018-05-01

Full Text Available Novel Cu(II (1 and Zn(II (2 complexes with 4-(1-(4-morpholinophenylethylideneaminopyrimidine-5-carbonitrile (L have been synthesized and characterized by various spectroscopic and analytical techniques. DFT (density functional theory studies result confirms that, LMCT mechanism have been done between L and M(II ions. The antimicrobial studies indicate that the ligand L and complexes 1 & 2 exhibit higher activity against the E. coli bacteria and C. albicans fungi. The groove binding mode of ligand L and complexes 1 & 2 with CT-DNA have been confirmed by electronic absorption, competitive binding, viscometric and cyclic voltammetric studies. The electronic absorption titration of ligand L and complexes 1 & 2 with DNA have been carried out in different buffer solutions (pH 4.0, 7.0 & 10.0. The Kb values of ligand L and complexes 1 & 2 are higher in acidic buffer at pH 4.0 (Kb = 2.42 × 105, L; 2.8 × 105, 1; 2.65 × 105, 2 and the results revealed that, the interaction of synthesized compounds with DNA were higher in the acidic medium than basic and neutral medium. Furthermore, CT-DNA cleavage studies of ligand L and complexes 1 & 2 have been studied. The in vitro anticancer activities results show that complexes 1 & 2 have moderate cytotoxicity against cancer cell lines and low toxicity on normal cell line than ligand L. Keywords: Pyrimidine, Morpholine, DFT, Antimicrobial, DNA binding, Anticancer studies

Ionotropic excitatory amino acid receptor ligands. Synthesis and pharmacology of a new amino acid AMPA antagonist

DEFF Research Database (Denmark)

Madsen, U; Sløk, F A; Stensbøl, T B

2000-01-01

We have previously described the potent and selective (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, (RS)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA), and the AMPA receptor antagonist (RS)-2-amino-3-[3-(carboxymethoxy)-5-methyl-4...... excitatory amino acid (EAA) receptors using receptor binding and electrophysiological techniques, and for activity at metabotropic EAA receptors using second messenger assays. Compounds 1 and 4 were essentially inactive. (RS)-2-Amino-3-[3-(2-carboxyethyl)-5-methyl-4-isoxazolyl]propionic acid (ACMP, 2......-isoxazolyl]propionic acid (AMOA). Using these AMPA receptor ligands as leads, a series of compounds have been developed as tools for further elucidation of the structural requirements for activation and blockade of AMPA receptors. The synthesized compounds have been tested for activity at ionotropic...

Synthesis, characterization and electrochemical investigations of mixed-ligand copper(II)-organic supramolecular frameworks

Science.gov (United States)

Singh, Sandeep K.; Srivastava, Ashish Kumar; Srivastava, Krishna; Banerjee, Rahul; Prasad, Jagdish

2017-11-01

Two mixed-ligand copper(II)-organic coordination compounds with 5,5‧-dimethyl-2,2‧-bipyridine (5,5‧-Me2bpy) as a primary ligand while aliphatic malonate (Hmal) and aromatic 2-hydroxynicotinate (2-OHNA) as secondary ligands, were synthesized. These complexes are formulated as: [Cu(Hmal)(5,5‧-Me2bpy)(H2O)](ClO4) 1 and [Cu2(2-OHNA)2(5,5‧-Me2bpy)2(NO3)](NO3) 2. These two complexes were structurally characterized by single crystal X-ray diffraction analysis. Characterization was further supported by powder X-ray diffraction analysis, elemental analyses, FT-IR, FAB-MASS and TGA, DSC studies. Cyclic voltammetric and UV-visible spectral studies of these two complexes have also been done. The electrochemical studies of complex 1 in DMSO and DMF have shown that this complex undergoes quasi-reversible diffusion-controlled one-electron transfer reaction without any chemical complication while complex 2 in DMSO undergoes quasi-reversible diffusion-controlled one electron transfer reaction, following EC mechanism. The electrochemical behaviour of complex 2 in DMF is complicated probably due to presence of more than one species in solution phase.

Synthesis of aryl-substituted 5-[18F]fluoroalkylbenzamides: High affinity ligands for dopamine D-2 studies

International Nuclear Information System (INIS)

Mathis, C.A.; Bishop, J.E.; Gerdes, J.M.; Faggin, B.; Mailman, R.

1990-01-01

Recent studies of the structure-activity relationship of benzamides have shown that the 2,3-dimethoxy substitution pattern of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,3-dimethoxy-5-iodobenzamide (PDB) resulted in a potent D-2 antagonist. Based upon these results and the concept that the potency of receptor ligands can be preserved when aromatic halogen substituents are replaced by fluoroalkyl functional groups, the authors synthesized a series of aryl-substituted fluoroalkyl PDBs and salicylamides. Synthetic pathways and an in vivo study in rats are outlined

Evaluation of 3-Ethyl-3-(phenylpiperazinylbutyl)oxindoles as PET Ligands for the Serotonin 5-HT7 Receptor

DEFF Research Database (Denmark)

Herth, Matthias M; Andersen, Valdemar L; Hansen, Hanne D

2015-01-01

We have investigated several oxindole derivatives in the pursuit of a 5-HT7 receptor PET ligand. Herein the synthesis, chiral separation, and pharmacological profiling of two possible PET candidates toward a wide selection of CNS-targets are detailed. Subsequent (11)C-labeling and in vivo evaluat...... evaluation in Danish landrace pigs showed that both ligands displayed high brain uptake. However, neither of the radioligands could be displaced by the 5-HT7 receptor selective inverse agonist SB-269970....

Hybrid Pd/Fe{sub 3}O{sub 4} nanowires: Fabrication, characterization, optical properties and application as magnetically reusable catalyst for the synthesis of N-monosubstituted ureas under ligand-free conditions

Energy Technology Data Exchange (ETDEWEB)

Nasrollahzadeh, Mahmoud, E-mail: mahmoudnasr81@gmail.com [Department of Chemistry, Faculty of Science, University of Qom, Qom 37185-359 (Iran, Islamic Republic of); Azarian, Abbas [Department of Physics, University of Qom, Qom (Iran, Islamic Republic of); Ehsani, Ali [Department of Chemistry, Faculty of Science, University of Qom, Qom 37185-359 (Iran, Islamic Republic of); Sajadi, S.Mohammad [Department of Petroleum Geoscience, Faculty of Science, Soran University, PO Box 624, Soran, Kurdistan Regional Government (Iraq); Babaei, Ferydon [Department of Physics, University of Qom, Qom (Iran, Islamic Republic of)

2014-07-01

Highlights: • Preparation of Pd/Fe{sub 3}O{sub 4} nanowires as magnetically reusable catalysts. • The optical properties of the catalyst were studied using Gans theory. • N-arylation of benzylurea and in situ hydrogenolysis of 1-benzyl-3-arylureas. - Abstract: This paper reports the synthesis and use of Pd/Fe{sub 3}O{sub 4} nanowires, as magnetically separable catalysts for ligand-free amidation coupling reactions of aryl halides with benzylurea under microwave irradiation. Then, the in situ hydrogenolysis of the products was performed to afford the N-monosubstituted ureas from good to excellent yields. This method has the advantages of high yields, simple methodology and easy work up. The catalyst can be recovered by using a magnet and reused several times without significant loss of its catalytic activity. The catalyst was characterized using the powder XRD, SEM, EDS and UV–vis spectroscopy. Experimental absorbance spectra was compared with results from the Gans theory.

The selenium metabolite methylselenol regulates the expression of ligands that trigger immune activation through the lymphocyte receptor NKG2D

DEFF Research Database (Denmark)

Hagemann-Jensen, Michael Henrik; Uhlenbrock, Franziska Katharina; Kehlet, Stephanie

2014-01-01

For decades Selenium (Se) research has been focused on the identification of active metabolites, which are crucial for Se chemoprevention of cancer. In this context, the metabolite methylselenol (CH3SeH) is known for its action to selectively kill transformed cells through mechanisms that include...... ligands. A balanced cell-surface expression of NKG2D ligands is considered as an innate barrier against tumor development. Our work therefore indicates that the application of selenium compounds, which are metabolized to CH3SeH, could improve NKG2D-based immune therapy.......: Increased formation of reactive oxygen species (ROS), induction of DNA damage, triggering of apoptosis and the inhibition of angiogenesis. Here, we revealed that CH3SeH modulates cell surface expression of NKG2D ligands. The expression of NKG2D ligands is induced by stress-associated pathways, which occur...