WorldWideScience

Sample records for amidines

  1. Oxidative Additions of Homoleptic Tin(II) Amidinate

    Czech Academy of Sciences Publication Activity Database

    Chlupatý, T.; Růžičková, Z.; Horáček, Michal; Alonso, M.; de Proft, F.; Kampová, H.; Brus, Jiří; Růžička, A.

    2015-01-01

    Roč. 34, č. 3 (2015), s. 606-615. ISSN 0276-7333 Institutional support: RVO:61388955 ; RVO:61389013 Keywords : oxidative additions * homoleptic Tin(II) amidinate * DFT methods Subject RIV: CF - Physical ; Theoretical Chemistry; CD - Macromolecular Chemistry (UMCH-V) Impact factor: 4.126, year: 2014

  2. Synthesis of Calcium(II) Amidinate Precursors for Atomic Layer Deposition through a Redox Reaction between Calcium and Amidines.

    Science.gov (United States)

    Kim, Sang Bok; Yang, Chuanxi; Powers, Tamara; Davis, Luke M; Lou, Xiabing; Gordon, Roy G

    2016-08-22

    We have prepared two new Ca(II) amidinates, which comprise a new class of ALD precursors. The syntheses proceed by a direct reaction between Ca metal and the amidine ligands in the presence of ammonia. Bis(N,N'-diisopropylformamidinato)calcium(II) (1) and bis(N,N'-diisopropylacetamidinato)calcium(II) (2) adopt dimeric structures in solution and in the solid state. X-ray crystallography revealed asymmetry in one of the bridging ligands to afford the structure [(η(2) -L)Ca(μ-η(2) :η(2) -L)(μ-η(2) :η(1) -L)Ca(η(2) -L)]. These amidinate complexes showed unprecedentedly high volatility as compared to the widely employed and commercially available Ca(II) precursor, [Ca3 (tmhd)6 ]. In CaS ALD with 1 and H2 S, the ALD window was approximately two times wider and lower in temperature by about 150 °C than previously reported with [Ca3 (tmhd)6 ] and H2 S. Complexes 1 and 2, with their excellent volatility and thermal stability (up to at least 350 °C), are the first homoleptic Ca(II) amidinates suitable for use as ALD precursors. PMID:27351794

  3. Synthetic and structural chemistry of amidinate-substituted boron halides.

    Science.gov (United States)

    Hill, Nicholas J; Findlater, Michael; Cowley, Alan H

    2005-10-01

    The following new amidinate-substituted boron halides are reported: [PhC{N(SiMe(3))}(2)]BCl(2)(6), [MeC{NCy}(2)]BCl(2)(10), [Mes*C{NCy}(2)]BCl(2)(11), [MeC{N(i)Pr}(2)]BCl(2)(12), and [FcC{NCy}(2)]BBr(2)(13). Compound 6 was prepared via the trimethylsilyl chloride elimination reaction of BCl(3) with N,N,N'-tris(trimethylsilyl)benzamidine, and compounds 10-12 were prepared by salt metathesis between the lithium amidinates [RC(NR')(2)]Li and BX(3). Compound 13 was prepared via the insertion of 1,3-dicyclohexylcarbodiimide into the B-C bond of ferrocenyldibromoborane FcBBr(2). The molecular structures of 6, 10, 11, 13 and the known compound [PhC{N(SiMe(3))}(2)]BBr(2)(1) were established by single-crystal X-ray diffraction. PMID:16172649

  4. Amidinate Ligands in Zinc coordination sphere: Synthesis and structural diversity

    Indian Academy of Sciences (India)

    SRINIVAS ANGA; INDRANI BANERJEE; TARUN K PANDA

    2016-06-01

    A one-pot reaction involving neosilyllithium and three different carbodiimides (RN=C=NR, R =cyclohexyl, isopropyl and tert-butyl) in diethyl ether, followed by the addition of anhydrous $ZnCl_{2}$, afforded,in high yield, corresponding homoleptic zinc amidinate complexes having the molecular formulae$[Zn{CyN=C(CH_{2}SiMe_{3})NCy}_{2}]$ (1),$[Zn^{{i}PrN=C(CH_{2}SiMe_{3})N^{i}Pr}_{2}]$ (2) and [Zn$^{{t}BuN=C(CH_{2}SiMe_{3})N^{t}Bu}_{2}]$ (3), respectively, and amidinato moieties in the zinc coordination sphere. Solid state structures of complexes1-3 are reported thereafter - all the three complexes are isostructural, and each of them consists of twofour-membered metallacycles.

  5. Synthesis and Characterization of Ruthenium Amidinate Complexes as Precursors for Vapor Deposition

    OpenAIRE

    Gordon, Roy Gerald; Lim, Booyong S.; Li, Zhengwen; Aaltonen, Titta; Li, Huazhi

    2008-01-01

    Three new ruthenium amidinate complexes were prepared: tris(diisopropylacetamidinato)-ruthenium(III), Ru(iPrNC(Me)NiPr)3 4; bis(diisopropyl-acetamidinato)ruthenium(II) dicarbonyl, Ru(iPrNC(Me)NiPr)2(CO)2 5; and bis(ditert- butylacetamidinato)ruthenium(II) dicarbonyl, Ru(tBuNC(Me)NtBu)2(CO)2 6. They have been synthesized and characterized by 1H NMR, TG and X-ray structure analysis. These three complexes were found to be monomeric and air stable. Compound 6 was found to have sufficient volatili...

  6. Protein kinase A of Leishmania amazonensis as a potential target for methoxy-amidine.

    Science.gov (United States)

    Genestra, M; Echevarria, A; Cysne-Finkelstein, L; Leon, L L

    2001-11-01

    Cyclic 3',5'-adenosine monophosphate (cAMP) is one of the most important signaling molecules for cell growth and differentiation in several systems including protozoal parasites such as Trypanosoma cruzi and Leishmania species. The most important event during Leishmania developmental cycle is the differentiation of procyclic into metacyclic promastigotes, which is associated with the appearance of pathogenicity. As previously demonstrated Leishmania amazonensis metacyclogenesis is associated with an increase of a protein kinase A activity, and therefore further studies on the activity of this phosphorylating enzyme as a target for chemotherapy were performed. Among several amidine derivatives tested by the authors against trypanosomatids (T. cruzi, T. evansi and L. amazonensis) the most effective compounds was defined as that with a methoxy group as substituent. In this work the inhibitory effect of this derivative on the phosphorylating activity of cAMP-dependent protein kinase (PKA) of promastigotes (containing high amounts of metacyclic forms) and axenic amastigotes of L. amazonensis is demonstrated. Soluble fractions (SF) and enriched membrane fractions (MF) were submitted to anion exchange chromatography in a DEAE-cellulose column and the collected fractions used to evaluate the phosphorylating activity associated with cAMP, in the presence/absence of methoxy-amidine and pentamidine (CAS 100-33-4), the latter being used as reference drug. PMID:11765595

  7. Solid-phase synthesis of amidine-substituted phenylbenzimidazoles and incorporation of this DNA binding and recognition motif into amino acid and peptide conjugates.

    Science.gov (United States)

    Garner, Matthew L; Georgiadis, Taxiarchis M; Li, Jessica Bo; Wang, Tianxiu; Long, Eric C

    2014-05-01

    Amidine-substituted phenylbenzimidazoles are well-established DNA-binding structural motifs that have contributed to the development of diverse classes of DNA-targeted agents; this ring system not only assists in increasing the overall DNA affinity of an agent, but can also influence its site selectivity. Seeking a means to conveniently exploit these attributes, a protocol for the on-resin synthesis of amino acid- and peptide-phenylbenzimidazole-amidine conjugates was developed to facilitate installation of phenylbenzimidazole-amidines into peptide chains during the course of standard solid-phase syntheses. Building from a resin-bound amino acid or peptide on Rink amide resin, 4-formyl benzoic acid was coupled to the resin-bound free amine followed by introduction of 3,4-diamino-N'-hydroxybenzimidamide (in the presence of 1,4-benzoquinone) to construct the benzimidazole heterocycle. Finally, the resin-bound N'-hydroxybenzimidamide functionality was reduced to an amidine via 1 M SnCl2·2H2O in DMF prior to resin cleavage to release final product. This procedure permits the straightforward synthesis of amino acids or peptides that are N-terminally capped by a phenylbenzimidazole-amidine ring system. Employing this protocol, a series of amino acid-phenylbenzimidazole-amidine (Xaa-R) conjugates was synthesized as well as dipeptide conjugates of the general form Xaa-Gly-R (where R is the phenylbenzimidazole-amidine and Xaa is any amino acid). PMID:24562478

  8. Amidines for Versatile Cobalt(III)-Catalyzed Synthesis of Isoquinolines through C-H Functionalization with Diazo Compounds.

    Science.gov (United States)

    Li, Jie; Tang, Mengyao; Zang, Lei; Zhang, Xiaolei; Zhang, Zhao; Ackermann, Lutz

    2016-06-01

    A cobalt(III)-catalyzed C-H/N-H bond functionalization for the synthesis of 1-aminoisoquinolines from aryl amidines and diazo compounds has been developed. The reaction proceeds under mild reaction conditions, obviates the need for oxidants, produces only N2 and H2O as the byproducts, and features a broad substrate scope. PMID:27219713

  9. The amidine based colorimetric sensor for Fe(3+), Fe (2+), and Cu (2+) in aqueous medium.

    Science.gov (United States)

    Nandre, Jitendra; Patil, Samadhan; Patil, Prashant; Sahoo, Suban; Redshaw, Carl; Mahulikar, Pramod; Patil, Umesh

    2014-11-01

    An amidine based chemosensor AM-1 was synthesized and characterized by various spectroscopic (FT-IR, (1)H-NMR and mass) data and elemental analyses. Sensor AM-1 exhibited high selectivity and sensitivity towards Fe(3+), Fe(2+) and Cu(2+) in the presence of other surveyed ions (such as Sr(2+), Cr(3+), Co(2+), Ni(2+), Zn(2+), Ag(+), Al(3+), Ba(2+), Ca(2+), Cd(2+), Cs(+), Hg(2+), K(+), Li(+), Mg(2+), Mn(2+), Na(+) and Pb(2+)) with a distinct naked-eye detectable color change and a shift in the absorption band. Moreover, the emission of AM-1 was quenched selectively only in the presence of Fe(3+). PMID:25209201

  10. Synthesis and copper-dependent antimycoplasmal activity of amides and amidines derived from 2-amino-1,10-phenanthroline.

    Science.gov (United States)

    de Zwart, M A; Bastiaans, H M; van der Goot, H; Timmerman, H

    1991-03-01

    A series of both aliphatic and aromatic amides and aromatic amidines derived from 2-amino-1,10-phenanthroline (3) according to the Topliss scheme were synthesized and subsequently tested for antimycoplasmal potency. Although the compounds themselves showed no activity, in the presence of a nontoxic copper concentration of 40 microM all compounds appeared to be very active against Mycoplasma gallisepticum K154. The most active compounds were found in the amide series and show growth inhibition in the nanomolar range. These compounds are 4 times more active than tylosin, a macrolide antibiotic, which is used therapeutically in veterinary practice. In the presence of copper, amides derived from 3 are more active than corresponding amidines. Increased activity following derivatization of 3 may be due to the presence of a third coordination site for copper in the title compounds. Evaluation of biological data revealed that antimycoplasmal activity of amides derived from 3 is dependent on lipophilicity. For these amides a good linear correlation was found between antimycoplasmal activity and hydrophobic fragmental values for substituents considered. This quantitative structure-activity relationship study indicated that antimycoplasmal activity was increased upon a decrease of these hydrophobic fragmental values. PMID:2002460

  11. Reactivity of lithium n-butyl amidinates towards group 14 metal(II) chlorides providing series of hetero- and homoleptic tetrylenes

    Czech Academy of Sciences Publication Activity Database

    Chlupatý, T.; Padělková, Z.; Lyčka, A.; Brus, Jiří; Růžička, A.

    2012-01-01

    Roč. 41, č. 16 (2012), s. 5010-5019. ISSN 1477-9226 Institutional research plan: CEZ:AV0Z40500505 Keywords : lithium n-butyl amidinates * complexes * structure Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.806, year: 2012

  12. Synthesis of Cu, Zn and Cu/Zn brass alloy nanoparticles from metal amidinate precursors in ionic liquids or propylene carbonate with relevance to methanol synthesis

    OpenAIRE

    Schütte, K.; H. Meyer; Gemel, Chr.; Barthel, Juri; Fischer, R.A.; Janiak,Chr.

    2014-01-01

    Microwave-induced decomposition of the transition metal amidinates {[Me(C(NiPr)2)]Cu}2 (1) and [Me(C(NiPr)2)]2Zn (2) in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIm][BF4]) or in propylene carbonate (PC) gives copper and zinc nanoparticles which are stable in the absence of capping ligands (surfactants) for more than six weeks. Co-decomposition of 1 and 2 yields the intermetallic nano-brass phases β-CuZn and γ-Cu3Zn depending on the chosen molar ratios of the precursor...

  13. Integrated control of acaricide-resistant Boophilus microplus populations on grazing cattle in Mexico using vaccination with Gavac and amidine treatments.

    Science.gov (United States)

    Redondo, M; Fragoso, H; Ortíz, M; Montero, C; Lona, J; Medellín, J A; Fría, R; Hernández, V; Franco, R; Machado, H; Rodríguez, M; de la Fuente, J

    1999-10-01

    Throughout most of the twentieth century, tick infestations on cattle have been controlled with chemical acaricides, typically administered by dipping or spraying. This approach can cause environmental and residue problems and has created a high incidence of acaricide resistance within tick populations in the field. Recently we developed a vaccine against Boophilus microplus employing a recombinant Bm86 antigen preparation (Gavac), (Heber Biotec S.A., Havana, Cuba) which has been shown to induce a protective response in vaccinated animals. Here we show for the first time under field conditions a near 100% control of B. microplus populations resistant to pyrethroids and organophosphates, by an integrated system employing vaccination with Gavac and amidine treatments. This method effectively controls tick infestations while reducing the number of chemical acaricide treatments and consequently the rise of B. microplus populations resistant to chemical acaricides. PMID:10581714

  14. Bis(alkyl) rare-earth complexes supported by a new tridentate amidinate ligand with a pendant diphenylphosphine oxide group. Synthesis, structures and catalytic activity in isoprene polymerization.

    Science.gov (United States)

    Tolpygin, Aleksei O; Glukhova, Tatyana A; Cherkasov, Anton V; Fukin, Georgy K; Aleksanyan, Diana V; Cui, Dongmei; Trifonov, Alexander A

    2015-10-01

    A new tridentate amidine 2-[Ph2P(O)]C6H4NHC(tBu)[double bond, length as m-dash]N(2,6-Me2C6H3) (1) bearing a side chain pendant Ph2P[double bond, length as m-dash]O group was synthesized and proved to be a suitable ligand for coordination to rare-earths ions. Bis(alkyl) complexes {2-[Ph2P(O)]C6H4NC(tBu)N(2,6-Me2C6H3)}Ln(CH2SiMe3)2(THF)n (Ln = Y, n = 1 (3), Ln = Er, n = 1 (4), Ln = Lu, n = 0 (5)) were prepared using alkane elimination reactions of and Ln(CH2SiMe3)3(THF)2 (Ln = Y, Er, Lu) in hexane and were isolated in 50, 70 and 75% yields respectively. The X-ray studies revealed that complexes 2-5 feature intramolecular coordination of P[double bond, length as m-dash]O groups to metal ions. The lutetium complex 5 proved to be rather stable: at 20 °C its half-life time is 1155 h, while for the yttrium analogue the half-life time was found to be 63 h. Complexes 3-5 were evaluated as precatalysts for isoprene polymerization. The systems Ln/borate/AliBu3 (Ln = 3-5, borate = [PhNHMe2][B(C6F5)4], [Ph3C][B(C6F5)4]) turned out to be highly efficient in isoprene polymerization and enable complete conversion of 1000-10,000 equivalents of monomer into polymer at 20 °C within 0.5-2.5 h affording polyisoprenes with a very high content of 1,4-cis units (up to 96.6%) and from narrow (1.49) to moderate (3.54) polydispersities. A comparative study of catalytic performance of the related bis(alkyl) yttrium complexes supported by amidinate ligands of different denticities and structures [tBuC(N-2,6iPr2C6H4)2](-), [tBuC(N-2,6-iPr2C6H4)(N-2-MeOC6H4)](-) and {2-[Ph2P(O)]C6H4NC(tBu)N(2,6-Me2C6H3)}(-) demonstrated that the introduction of a pendant donor group (2-MeOC6H4 or Ph2P(O)) into a side chain of amidinate scaffolds results in a significant increase in catalytic activity. The amidinate ligand bearing a Ph2P(O)-group provides a high isoprene polymerization rate along with excellent control over regio- and stereoselectivities and allows us to obtain polyisoprenes with a reasonable

  15. Synthesis of Cu, Zn and Cu/Zn brass alloy nanoparticles from metal amidinate precursors in ionic liquids or propylene carbonate with relevance to methanol synthesis

    Science.gov (United States)

    Schütte, Kai; Meyer, Hajo; Gemel, Christian; Barthel, Juri; Fischer, Roland A.; Janiak, Christoph

    2014-02-01

    Microwave-induced decomposition of the transition metal amidinates {[Me(C(NiPr)2)]Cu}2 (1) and [Me(C(NiPr)2)]2Zn (2) in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIm][BF4]) or in propylene carbonate (PC) gives copper and zinc nanoparticles which are stable in the absence of capping ligands (surfactants) for more than six weeks. Co-decomposition of 1 and 2 yields the intermetallic nano-brass phases β-CuZn and γ-Cu3Zn depending on the chosen molar ratios of the precursors. Nanoparticles were characterized by high-angle annular dark field-scanning transmission electron microscopy (HAADF-STEM), dynamic light scattering and powder X-ray diffractometry. Microstructure characterizations were complemented by STEM with spatially resolved energy-dispersive X-ray spectrometry and X-ray photoelectron spectroscopy. Synthesis in ILs yields significantly smaller nanoparticles than in PC. β-CuZn alloy nanoparticles are precursors to catalysts for methanol synthesis from the synthesis gas H2/CO/CO2 with a productivity of 10.7 mol(MeOH) (kg(Cu) h)-1.Microwave-induced decomposition of the transition metal amidinates {[Me(C(NiPr)2)]Cu}2 (1) and [Me(C(NiPr)2)]2Zn (2) in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIm][BF4]) or in propylene carbonate (PC) gives copper and zinc nanoparticles which are stable in the absence of capping ligands (surfactants) for more than six weeks. Co-decomposition of 1 and 2 yields the intermetallic nano-brass phases β-CuZn and γ-Cu3Zn depending on the chosen molar ratios of the precursors. Nanoparticles were characterized by high-angle annular dark field-scanning transmission electron microscopy (HAADF-STEM), dynamic light scattering and powder X-ray diffractometry. Microstructure characterizations were complemented by STEM with spatially resolved energy-dispersive X-ray spectrometry and X-ray photoelectron spectroscopy. Synthesis in ILs yields significantly smaller nanoparticles than in PC.

  16. Abiotic amidine and guanidine hydrolysis of lamotrigine-N2-glucuronide and related compounds in wastewater: The role of pH and N2-substitution on reaction kinetics.

    Science.gov (United States)

    Zonja, Bozo; Delgado, Antonio; Abad, J Luis; Pérez, Sandra; Barceló, Damià

    2016-09-01

    The stability of lamotrigine (LMG) and its principal human metabolite, lamotrigine N2-glucuronide (LMG-N2-G), was studied as a function of pH (4-9). While LMG was stable across the entire pH range, under neutral-basic conditions, LMG-N2-G was converted to three transformation products (TPs) which were identified using high resolution mass spectrometry (HRMS). The MS fragmentation studies indicated that two TPs were the result of the hydrolysis of the amidine and guanidine moieties. The third TP detected was an intermediate in the guanidine hydrolysis reaction. In order to evaluate the transformation kinetics of the LMG-N2-G degradation, another set of pH-dependent experiments was carried out in hospital effluent, wastewater influent and effluent spiked at 20 and 200 nM after pH adjustment (pH 6.5, 7, 8, 8.5 and 9), demonstrating that, at higher pH, LMG-N2-G is degraded at higher rate. Later, the pH-dependent stability of related compounds with different nitrogen N2-substituents (N2-R) on the 1,2,4-triazine ring was studied. This revealed that because of different imino tautomer equilibrium LMG (N2-H) and LMG-N2-oxide ((+)N2-O(-)) were stable at all pHs but N2-methyl-LMG (N2-CH3) as well as LMG-N2-G were susceptible to amidine and guanidine hydrolysis at basic pH. Finally, hospital effluent samples collected over the course of one week were monitored for their presence. LMG, LMG-N2-G and two of its TPs were detected with concentrations ranging between 0.01 and 1 μgL(-1). PMID:27232991

  17. Molecular design, synthesis and biological activities of amidines as new ketol-acid reductoisomerase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Bao Lei Wang; Yong Hong Li; Jian Guo Wang; Yi Ma; Zheng Ming Li

    2008-01-01

    Diamidine (A) was identified in our in vitro bio-assay as a possible inhibitor of ketol-acid reductoisomerase (KARI) from the ACD database search based on the known three-dimensional crystal structure of KARI. An investigation on interaction of A on KARI active sites, led to the design and synthesis of 15 novel monoamidines. Some of those showed better biological activity than A on rice KARI (in vitro) and in greenhouse herbicidal tests (in vivo). The structure-biological activity relationship was investigated, which provides valuable information to further study of potential KARI inhibitors.

  18. New amidines from intramolecular cyclization in triflic acid of nitroketene aminals with a tethered phenyl ring

    Indian Academy of Sciences (India)

    Soro Yaya; Bamba Fanté; Siaka Sorho; Coustard Jean-Marie; Adima A Augustin

    2007-05-01

    Nitroketene aminals with a tethered phenyl group underwent an intramolecular cyclization in trifluoromethanesulfonic acid to afford the corresponding N-(3-ethyl-hydrohydroxyiminobenzocycloalkenylidene) methylamine trifluoromethanesulfonate. The yields were fair to good excepted for the starting compound 1-[N-ethyl-N-(2-phenylethyl)amino]-1-methylamino-2-nitroethene.

  19. Development of Amidine-Based Sphingosine Kinase 1 Nanomolar Inhibitors and Reduction of Sphingosine 1-Phosphate in Human Leukemia Cells

    OpenAIRE

    Kennedy, Andrew J.; Mathews, Thomas P.; Kharel, Yugesh; Field, Saundra D.; Moyer, Morgan L.; East, James E.; Houck, Joseph D.; Lynch, Kevin R.; Macdonald, Timothy L.

    2011-01-01

    Sphingosine 1-phosphate (S1P) is a bioactive lipid that has been identified as an accelerant of cancer progression. The sphingosine kinases (SphKs) are the sole producers of S1P and thus SphK inhibitors may prove effective in cancer mitigation and chemosensitization. Of the two SphKs, SphK1 overexpression has been observed in a myriad of cancer cell lines and tissues, and has been recognized as the presumptive target over that of the poorly characterized SphK2. Herein, we present the design a...

  20. Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones.

    Science.gov (United States)

    de Castro, Solange L; Batista, Denise G J; Batista, Marcos M; Batista, Wanderson; Daliry, Anissa; de Souza, Elen M; Menna-Barreto, Rubem F S; Oliveira, Gabriel M; Salomão, Kelly; Silva, Cristiane F; Silva, Patricia B; Soeiro, Maria de Nazaré C

    2011-01-01

    Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (benznidazole (Bz) and nifurtimox (Nf)) developed more than four decades ago. Both are far from ideal due to substantial secondary side effects, limited efficacy against different parasite isolates, long-term therapy, and their well-known poor activity in the late chronic phase. These drawbacks justify the urgent need to identify better drugs to treat chagasic patients. Although several classes of natural and synthetic compounds have been reported to act in vitro and in vivo on T. cruzi, since the introduction of Bz and Nf, only a few drugs, such as allopurinol and a few sterol inhibitors, have moved to clinical trials. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity. In addition, a large number of in vitro studies have been conducted using only epimastigotes and trypomastigotes instead of evaluating compounds' activities against intracellular amastigotes, which are the reproductive forms in the vertebrate host and are thus an important determinant in the selection and identification of effective compounds for further in vivo analysis. In addition, due to pharmacokinetics and absorption, distribution, metabolism, and excretion characteristics, several compounds that were promising in vitro have not been as effective as Nf or Bz in animal models of T. cruzi infection. In the last two decades, our team has collaborated with different medicinal chemistry groups to develop preclinical studies for CD and investigate the in vitro and in vivo efficacy, toxicity, selectivity, and parasite targets of different classes of natural and synthetic compounds. Some of these results will be briefly presented, focusing primarily on diamidines and related compounds and naphthoquinone derivatives that showed the most promising efficacy against T. cruzi. PMID:22091400

  1. Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones

    Directory of Open Access Journals (Sweden)

    Solange L. de Castro

    2011-01-01

    Full Text Available Chagas disease (CD, caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (benznidazole (Bz and nifurtimox (Nf developed more than four decades ago. Both are far from ideal due to substantial secondary side effects, limited efficacy against different parasite isolates, long-term therapy, and their well-known poor activity in the late chronic phase. These drawbacks justify the urgent need to identify better drugs to treat chagasic patients. Although several classes of natural and synthetic compounds have been reported to act in vitro and in vivo on T. cruzi, since the introduction of Bz and Nf, only a few drugs, such as allopurinol and a few sterol inhibitors, have moved to clinical trials. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity. In addition, a large number of in vitro studies have been conducted using only epimastigotes and trypomastigotes instead of evaluating compounds' activities against intracellular amastigotes, which are the reproductive forms in the vertebrate host and are thus an important determinant in the selection and identification of effective compounds for further in vivo analysis. In addition, due to pharmacokinetics and absorption, distribution, metabolism, and excretion characteristics, several compounds that were promising in vitro have not been as effective as Nf or Bz in animal models of T. cruzi infection. In the last two decades, our team has collaborated with different medicinal chemistry groups to develop preclinical studies for CD and investigate the in vitro and in vivo efficacy, toxicity, selectivity, and parasite targets of different classes of natural and synthetic compounds. Some of these results will be briefly presented, focusing primarily on diamidines and related compounds and naphthoquinone derivatives that showed the most promising efficacy against T. cruzi.

  2. Chiral benzamidinate ligands in rare-earth-metal coordination chemistry.

    Science.gov (United States)

    Benndorf, Paul; Kratsch, Jochen; Hartenstein, Larissa; Preuss, Corinna M; Roesky, Peter W

    2012-11-01

    The treatment of the recently reported potassium salt (S)-N,N'-bis-(1-phenylethyl)benzamidinate ((S)-KPEBA) and its racemic isomer (rac-KPEBA) with anhydrous lanthanide trichlorides (Ln = Sm, Er, Yb, Lu) afforded mostly chiral complexes. The tris(amidinate) complex [{(S)-PEBA}(3)Sm], bis(amidinate) complexes [{Ln(PEBA)(2)(μ-Cl)}(2)] (Ln = Sm, Er, Yb, Lu), and mono(amidinate) compounds [Ln(PEBA)(Cl)(2)(thf)(n)] (Ln = Sm, Yb, Lu) were isolated and structurally characterized. As a result of steric effects, the homoleptic 3:1 complexes of the smaller lanthanide atoms Yb and Lu were not accessible. Furthermore, chiral bis(amidinate)-amido complexes [{(S)-PEBA}(2)Ln{N(SiMe(3))(2)}] (Ln = Y, Lu) were synthesized by an amine-elimination reaction and salt metathesis. All of these chiral bis- and tris(amidinate) complexes had additional axial chirality and they all crystallized as diastereomerically pure compounds. By using rac-PEBA as a ligand, an achiral meso arrangement of the ligands was observed. The catalytic activities and enantioselectivities of [{(S)-PEBA}(2)Ln{N(SiMe(3))(2)}] (Ln = Y, Lu) were investigated in hydroamination/cyclization reactions. A clear dependence of the rate of reaction and enantioselectivity on the ionic radius was observed, which showed higher reaction rates but poorer enantioselectivities for the yttrium compound. PMID:23015310

  3. Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa.

    Science.gov (United States)

    Trujillo, John I; Huang, Horng-Chih; Neumann, William L; Mahoney, Matthew W; Long, Scott; Huang, Wei; Garland, Danny J; Kusturin, Carrie; Abbas, Zaheer; South, Michael S; Reitz, David B

    2007-08-15

    Herein is described the design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors were designed to explore replacement and variation of the P1 amidine described previously [J. Med. Chem.2003, 46, 4050]. The P1 needle replacements were selected based upon their reduced basicity compared to the parent phenyl amidine (pKa approximately 12). A contributing factor towards the oral bioavailability of a compound is the ionization state of the compound in the intestinal tract. The desired outcome of the study was to identify an orally bioavailable TF-VIIa inhibitor. PMID:17566736

  4. Chemistry of isoflavone heterocyclic analogs. 10. Synthesis of pyrimidines by recyclization of isoflavones and their heterocyclic analogs

    Energy Technology Data Exchange (ETDEWEB)

    Khilya, V.P.; Kornilov, M.Yu.; Gorbulenko, N.V.; Golubushina, G.M.; Kovtun, E.N.; Kolotusha, N.V.; Panasenko, G.V.

    1986-05-01

    Isoflavones and their thiazole and pyrazole analogs are recyclized into the corresponding 4-(2-hydroxyphenyl)-pyrimidine derivatives under the effect of amidines. Their PMR spectra were studied. The effects related to the formation and strength of the intramolecular hydrogen bond were examined.

  5. Selective Synthesis of Isoquinolines by Rhodium(III)-Catalyzed C-H/N-H Functionalization with α-Substituted Ketones.

    Science.gov (United States)

    Li, Jie; Zhang, Zhao; Tang, Mengyao; Zhang, Xiaolei; Jin, Jian

    2016-08-01

    A rhodium(III)-catalyzed C-H/N-H bond functionalization for the synthesis of 1-aminoisoquinolines from aryl amidines and α-MsO/TsO/Cl ketones was achieved under mild reaction conditions. Thus, this approach provides a practical method for the site-selective synthesis of various synthetically valuable isoquinolines with wide functional group tolerance. PMID:27441726

  6. Carbon-14 labelled nitrogen heterocycles; the syntheses of three phosphodiesterase inhibitors

    International Nuclear Information System (INIS)

    The syntheses of three heterocyclic phosphodiesterase inhibitors are described from a common radiolabelled precursor, namely 2-propoxybenzo[cyano-14C] nitrile. Conversion of the nitrile to the corresponding methyl ketone or amidine allows elaboration of the heterocycles radiolabelled within the ring systems. (Author)

  7. Perfluroaryl azides : Reactivities, Unique Reactions and their Applications in the Synthesis of Theranostic Agents

    OpenAIRE

    Xie, Sheng

    2015-01-01

    The work centersaround perfluoroaryl azides (PFAAs), and theirability to undergo certain fast and robusttransformations. The chemistry was furtherappliedfor biomedical applications. The first section focuses on the azide-aldehyde-amine cycloaddition using PFAAs. Experimental and computational investigations uncovered a fast azide-enamine cycloaddition to form triazolines, which spontaneously rearrange into stable amidine products. In addition, this transformation was explored in the formulati...

  8. Evaluation of the Efficacy of Acaricides Used to Control the Cattle Tick, Rhipicephalus microplus, in Dairy Herds Raised in the Brazilian Southwestern Amazon.

    Science.gov (United States)

    Brito, Luciana G; Barbieri, Fábio S; Rocha, Rodrigo B; Oliveira, Márcia C S; Ribeiro, Elisana Sales

    2011-01-01

    The adult immersion test (AIT) was used to evaluate the efficacy of acaricide molecules used for control of Rhipicephalus microplus on 106 populations collected in five municipalities in the state of Rondônia in the Brazilian South Occidental Amazon region. The analysis of the data showed that the acaricide formulations had different efficacies on the tick populations surveyed. The synthetic pyrethroids (SPs) acaricides were the least effective (48.35-76.84%), followed by SP + organophosphate (OP) associations (68.91-81.47%) and amidine (51.35-100%). For the macrocyclic lactones (MLs), the milbemycin (94.84-100%) was the most effective, followed by spinosad (93.21-100%) and the avermectins (81.34-100%). The phenylpyrazole (PZ) group had similar efficacy (99.90%) to the MLs. Therefore, SP acaricides, including associations with OP, and formulations based on amidine presented low in vitro efficacy to control the R. microplus populations surveyed. PMID:21547224

  9. Reaction of Tosylmethyl Isocyanide with N-Heteroaryl Formamidines: an Alternative Approach to the Synthesis of N-Heteroaryl Tosylimidazoles

    Energy Technology Data Exchange (ETDEWEB)

    Gomezgarcia, Omar; Salgadozamora, Hector; Reyesarellano, Aliciam; Camposaldrete, Elena; Peraltacruz, Javier [Departamento Quimica Organica, Colonia (Mexico)

    2013-09-15

    In conclusion, an alternative procedure was developed under mild conditions for the synthesis of 2-(4-tosylimidazo-1-yl)pyridines and pyrimidines by the reaction of TosMIC with the corresponding heteroaryl N,N'-dimethyl form-amidines. This approach does not involve a nucleophilic displacement of a leaving group and constitutes a further application of amidines, in which TosMIC acts as both a nucleophile and an electrophile on the heteroaryl formamidine. This process offers advantages over previously reported procedures. Tosyl methyl isocyanide (TosMIC), a multipurpose commercially available 3-unit synthon introduced by Van Leusen, reacts with a variety of groups to give heterocycles. It is important to emphasize that treatment of TosMIC with various functional groups leads to the formation of the imidazole nucleus, such as is the case with imines, imidoyl chlorides, isothiocyanates, nitrile and ethoxy methylene amino. However, only the latter group yields N-heterocycle imidazoles.

  10. Acaricide Residues in Laying Hens Naturally Infested by Red Mite Dermanyssus gallinae

    OpenAIRE

    Marangi, Marianna; Morelli, Vincenzo; Pati, Sandra; Camarda, Antonio; Cafiero, Maria Assunta; Giangaspero, Annunziata

    2012-01-01

    In the poultry industry, control of the red mite D. gallinae primarily relies worldwide on acaricides registered for use in agriculture or for livestock, and those most widely used are carbamates, followed by amidines, pyrethroids and organophosphates. Due to the repeated use of acaricides - sometimes in high concentrations - to control infestation, red mites may become resistant, and acaricides may accumulate in chicken organs and tissues, and also in eggs. To highlight some situations of mi...

  11. Cyclic compounds of tetracoordinated boron from 5-aminotetrazole and nitriles

    International Nuclear Information System (INIS)

    New cyclic compounds of tetracoordinated boron - dialkylboryl (tetrazole-5-yl)amidinates - from 5-aminotetrazole, nitriles and trialkylboranes with chemical yield 83-93 %, have been synthesized. Crystal and molecular structure of di propylboryl (N - (tetrazole-5-yl)-o-toluamidinate ( a = 13.990 (1), b 9.730 (2), c = 13.261 (2) A) is determined using X-ray diffraction method

  12. Synthesis of Novel Aliphatic N-sulfonylamidino Thymine Derivatives by Cu(I)-catalyzed Three-component Coupling Reaction

    OpenAIRE

    Krstulović, Luka; Ismaili, Hamit; Višnjevac, Aleksandar; Glavaš-Obrovac, Ljubica; Žinić, Biserka

    2012-01-01

    A series of new aliphatic N-sulfonylamidino thymine derivatives containing nucleobase, N-sulfonyl and amidine pharmacophores in the structure were synthesized by Cu(I)-catalyzed threecomponent coupling of 1-propargyl thymine, benzenesulfonyl azides and amines or ammonium salts. Preliminary in vitro antitumor screening (human cervix adenocarcinoma -HeLa and leukemia cells - Jurkat) revealed promising activities of N,N-diethyl- (2) and N-4-cyanobenzyl- (6) derivatives of 4-acetamido...

  13. Expanding the coordination chemistry of donor-stabilized group-14 metalenes

    OpenAIRE

    Cabeza de Marco, Javier Ángel; García Álvarez, Pablo; Polo Coca, Diego

    2013-01-01

    The transformation of an amidinate germylene, equipped with just one accessible lone pair of electrons on the Ge atom, into a bidentate 4-electron donor κ(2)Ge,N-ligand, has been achieved for the first time, opening new doors to the non-carbene-like coordination chemistry of heavier carbene analogues. [Available from: http://www.researchgate.net/publication/233537999_Expanding_the_coordination_chemistry_of_donor-stabilized_group-14_metalenes [accessed Jul 13, 2015].

  14. Investigação eletroquímica e calorimétrica da interação de novos agentes antitumorais biscatiônicos com DNA

    OpenAIRE

    Láuris Lucia da Silva; Claudio Luis Donnici; Júlio César Dias Lopes; Marília Oliveira Fonseca Goulart; Fabiane Caxico de Abreu; Francine Santos de Paula; Carlos E. Salas Bravo; Marcelo Matos Santoro; Ângelo Márcio Leite Denadai; Alexandre Martins Costa Santos; Carlos Alberto Montanari

    2012-01-01

    Biscationic amidines bind in the DNA minor groove and present biological activity against a range of infectious diseases. Two new biscationic compounds (bis-α,ω-S-thioureido, amino and sulfide analogues) were synthesized in good yields and fully characterized, and their interaction with DNA was also investigated. Isothermal titration calorimetry (ITC) was used to measure the thermodynamic properties of binding interactions between DNA and these ligands. A double stranded calf thymus DNA immob...

  15. Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

    OpenAIRE

    Zapol'skii, Viktor A.; Namyslo, Jan C.; Armin de Meijere; Kaufmann, Dieter E

    2012-01-01

    The nitropolychlorobutadienes 3, 4 are valuable building blocks for various amination and successive heterocyclization products. Nucleophilic substitution reactions of the partially protected, bioactive amines 1, 2 with either vinyl, imidoyl or carbonyl chlorides result in the formation of the enamines 11, 12, 13, 16, 25, the amidine 6, and the amides 20, 21, respectively. In the following, cyclization to the highly functionalized pyrazoles 27, 28, pyrimidine 26 and pyridopyrimidine 24 succee...

  16. Cycloadditions of Noncomplementary Substituted 1,2,3-Triazines

    OpenAIRE

    Anderson, Erin D.; Duerfeldt, Adam S.; Zhu, Kaicheng; Glinkerman, Christopher M.; Boger, Dale L.

    2014-01-01

    The scope of the [4 + 2] cycloaddition reactions of substituted 1,2,3-triazines, bearing noncomplementary substitution with electron-withdrawing groups at C4 and/or C6, is described. The studies define key electronic and steric effects of substituents impacting the reactivity, mode (C4/N1 vs C5/N2), and regioselectivity of the cycloaddition reactions of 1,2,3-triazines with amidines, enamines, and ynamines, providing access to highly functionalized heterocycles.

  17. Size dependent disruption of tethered lipid bilayers by functionalized polystyrene nanoparticles.

    Science.gov (United States)

    Liu, Ying; Mark Worden, R

    2015-01-01

    Molecular interactions between engineered nanomaterials (ENM) and biomembranes are not well understood. This study investigated the effects of particle size and surface functional group on polystyrene nanoparticles' (PNPs) potency for biomembrane disruption. Electrochemical impedance spectroscopy was used to measure changes in the electrical resistance (Rm) of a tethered bilayer lipid membrane BLM (tBLM) composed of 1,2-dioleoyl-sn-glycero-phosphocholine (DOPC) following PNP exposure. All PNPs tested triggered a decline in the Rm that could be described using an exponential-decay model. Statistical hierarchical clustering analysis of two model parameters (exponential rate constant and fractional loss of Rm) could distinguish between the PNPs based on both size and surface functional group. For COOH modified nanoparticles, 20nm PNPs were more potent in reducing Rm than 100nm PNP. However, for amidine modified nanoparticles, 120nm PNPs were more potent in reducing Rm than 23nm PNP. The COOH modified PNPs were more potent in reducing Rm than amidine modified PNP, which tended to aggregate following exposure to a tBLM. Ultra performance liquid chromatography-mass spectroscopy analysis suggested that the aggregation may have been triggered by DOPC that was removed from the tBLM by the amidine PNP. PMID:25285435

  18. Fabrication of CO2 Facilitated Transport Channels in Block Copolymer through Supramolecular Assembly

    Directory of Open Access Journals (Sweden)

    Yao Wang

    2014-05-01

    Full Text Available In this paper, the molecule 12-amidine dodecanoic acid (M with ending groups of carboxyl and amidine groups respectively was designed and synthesized as CO2-responsive guest molecules. The block copolymer polystyrene-b-polyethylene oxide (PS-b-PEO was chosen as the host polymer to fabricate a composite membrane through H-bonding assembly with guest molecule M. We attempted to tune the phase separation structure of the annealed film by varying the amount of M added, and investigated the nanostructures via transmission electron microscope (TEM, fourier transform infrared (FT-IR etc. As a result, a reverse worm-like morphology in TEM image of bright PS phase in dark PEO/M matrix was observed for PS-b-PEO/M1 membrane in which the molar ratio of EO unit to M was 1:1. The following gas permeation measurement indicated that the gas flux of the annealed membranes dramatically increased due to the forming of ordered phase separation structure. As we expected, the obtained composite membrane PS-b-PEO/M1 with EO:M mole ratio of 1:1 presented an evident selectivity for moist CO2 permeance, which is identical with our initial proposal that the guest molecule M in the membranes will play the key role for CO2 facilitated transportation since the amidine groups of M could react reversibly with CO2 molecules in membranes. This work provides a supramolecular approach to fabricating CO2 facilitated transport membranes.

  19. Identification of PADI2 as a potential breast cancer biomarker and therapeutic target

    International Nuclear Information System (INIS)

    We have recently reported that the expression of peptidylarginine deiminase 2 (PADI2) is regulated by EGF in mammary cancer cells and appears to play a role in the proliferation of normal mammary epithelium; however, the role of PADI2 in the pathogenesis of human breast cancer has yet to be investigated. Thus, the goals of this study were to examine whether PADI2 plays a role in mammary tumor progression, and whether the inhibition of PADI activity has anti-tumor effects. RNA-seq data from a collection of 57 breast cancer cell lines was queried for PADI2 levels, and correlations with known subtype and HER2/ERBB2 status were evaluated. To examine PADI2 expression levels during breast cancer progression, the cell lines from the MCF10AT model were used. The efficacy of the PADI inhibitor, Cl-amidine, was tested in vitro using MCF10DCIS cells grown in 2D-monolayers and 3D-spheroids, and in vivo using MCF10DCIS tumor xenografts. Treated MCF10DCIS cells were examined by flow-cytometry to determine the extent of apoptosis and by RT2 Profiler PCR Cell Cycle Array to detect alterations in cell cycle associated genes. We show by RNA-seq that PADI2 mRNA expression is highly correlated with HER2/ERBB2 (p = 2.2 × 106) in luminal breast cancer cell lines. Using the MCF10AT model of breast cancer progression, we then demonstrate that PADI2 expression increases during the transition of normal mammary epithelium to fully malignant breast carcinomas, with a strong peak of PADI2 expression and activity being observed in the MCF10DCIS cell line, which models human comedo-DCIS lesions. Next, we show that a PADI inhibitor, Cl-amidine, strongly suppresses the growth of MCF10DCIS monolayers and tumor spheroids in culture. We then carried out preclinical studies in nude (nu/nu) mice and found that Cl-amidine also suppressed the growth of xenografted MCF10DCIS tumors by more than 3-fold. Lastly, we performed cell cycle array analysis of Cl-amidine treated and control MCF10DCIS cells, and

  20. Identification of PADI2 as a potential breast cancer biomarker and therapeutic target

    Directory of Open Access Journals (Sweden)

    McElwee John L

    2012-10-01

    Full Text Available Abstract Background We have recently reported that the expression of peptidylarginine deiminase 2 (PADI2 is regulated by EGF in mammary cancer cells and appears to play a role in the proliferation of normal mammary epithelium; however, the role of PADI2 in the pathogenesis of human breast cancer has yet to be investigated. Thus, the goals of this study were to examine whether PADI2 plays a role in mammary tumor progression, and whether the inhibition of PADI activity has anti-tumor effects. Methods RNA-seq data from a collection of 57 breast cancer cell lines was queried for PADI2 levels, and correlations with known subtype and HER2/ERBB2 status were evaluated. To examine PADI2 expression levels during breast cancer progression, the cell lines from the MCF10AT model were used. The efficacy of the PADI inhibitor, Cl-amidine, was tested in vitro using MCF10DCIS cells grown in 2D-monolayers and 3D-spheroids, and in vivo using MCF10DCIS tumor xenografts. Treated MCF10DCIS cells were examined by flow-cytometry to determine the extent of apoptosis and by RT2 Profiler PCR Cell Cycle Array to detect alterations in cell cycle associated genes. Results We show by RNA-seq that PADI2 mRNA expression is highly correlated with HER2/ERBB2 (p = 2.2 × 106 in luminal breast cancer cell lines. Using the MCF10AT model of breast cancer progression, we then demonstrate that PADI2 expression increases during the transition of normal mammary epithelium to fully malignant breast carcinomas, with a strong peak of PADI2 expression and activity being observed in the MCF10DCIS cell line, which models human comedo-DCIS lesions. Next, we show that a PADI inhibitor, Cl-amidine, strongly suppresses the growth of MCF10DCIS monolayers and tumor spheroids in culture. We then carried out preclinical studies in nude (nu/nu mice and found that Cl-amidine also suppressed the growth of xenografted MCF10DCIS tumors by more than 3-fold. Lastly, we performed cell cycle array analysis of

  1. Synthesis of Ionic Colloidal Crystals (ICCs)

    Science.gov (United States)

    Maskaly, Garry R.; Garcia, R. Edwin; Carter, W. Craig; Chiang, Yet-Ming

    2003-03-01

    Binary ionic colloidal crystals (ICCs) have been produced by ordered heterocoagulation of colloidal mixtures of silica (negative surface charge) and polystyrene functionalized with amidine (positive surface charge) suspended in isopropanol. Experimental conditions predicted by the theoretical model discussed in a separate talk have been implemented to obtain heterocoagulation of these particles in the rocksalt structure. To our knowledge, this is the first experimental demonstration of the ICC concept. The importance of various experimental parameters on ICC formation is discussed. Particle dynamics simulations are carried out to provide insight into the kinetics of ICCs. Potential applications are discussed.

  2. Multicomponent Synthesis of 3,6-Dihydro-2H-1,3-thiazine-2-thiones

    Directory of Open Access Journals (Sweden)

    Frans J. J. de Kanter

    2012-02-01

    Full Text Available Non-fused 3,6-dihydro-2H-1,3-thiazine-2-thiones constitute a so far rather unexplored class of compounds, with the latest report dating back more than two decades. Thiazine-2-thiones contain an endocyclic dithiocarbamate group, which is often found in pesticides, in substrates for radical chemistry and in synthetic intermediates towards thioureas and amidines. We now report the multicomponent reaction (MCR of in situ-generated 1-azadienes with carbon disulfide. With this reaction, a one-step protocol towards the potentially interesting 3,6-dihydro-2H-1,3-thiazine-2-thiones was established and a small library was synthesized.

  3. N3-[(E-Morpholin-4-ylmethylidene]-1-phenyl-1H-1,2,4-triazole-3,5-diamine monohydrate

    Directory of Open Access Journals (Sweden)

    Z. A. Starikova

    2010-12-01

    Full Text Available In the title compound, C13H16N6O·H2O, the mean planes of the benzene and 1,2,4-triazole rings form a dihedral angle of 54.80 (5°. The N atom of the amino group adopts a trigonal–pyramidal configuration. Conjugation in the amidine N=C—N fragment results in sufficient shortening of the formal single bond. In the crystal, intermolecular N—H...O and O—H...N hydrogen bonds link molecules into double layers parallel to the bc plane.

  4. Design and Synthesis of N1,N5-bis[4-(5-Alkyl-1,2,4-oxadiazol-3-ylphenyl]glutaramides as Potential Antifungal Prodrugs

    Directory of Open Access Journals (Sweden)

    Annie Mayence

    2013-09-01

    Full Text Available A facile three step synthesis of a group of N1,N5-bis[4-(5-alkyl-1,2,4-oxadiazol-3-ylphenyl]glutaramides, N1,N5-bis[4-(1,2,4-oxadiazol-3-ylphenyl]glutaramide and N1,N5-bis[4-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-ylphenyl]glutaramide is described. These products are designed to function as masked bis-amidine prodrugs of a promising N1,N5-bis[4-(N'-(carbamimidoylphenyl]glutaramide antifungal lead.

  5. N-terminal guanidinylation of TIPP (Tyr-Tic-Phe-Phe) peptides results in major changes of the opioid activity profile

    OpenAIRE

    Weltrowska, Grazyna; Nguyen, Thi M.-D.; Chung, Nga N.; Wilkes, Brian C.; Schiller, Peter W.

    2013-01-01

    Derivatives of peptides of the TIPP (Tyr-Tic-Phe-Phe; Tic = 1,2,3,4- tetrahydroisoquinoline-3-carboxylic acid) family containing a guanidino (Guan) function in place of the N-terminal amino group were synthesized in an effort to improve their blood-brain barrier permeability. Unexpectedly, N-terminal amidination significantly altered the in vitro opioid activity profiles. Guan-analogues of TIPP-related δ opioid antagonists showed δ partial agonist or mixed δ partial agonist/μ partial agonist ...

  6. Synthesis of 2-(oxadiazolo, pyrimido, imidazolo, and benzimidazolo) substituted analogues of 1,4-benzodiazepin-5-carboxamides linked through a phenoxyl bridge

    Indian Academy of Sciences (India)

    N Kaur; D Kishore

    2014-11-01

    Exceedingly facile single-step expedient protocols based on the versatility and reactivity of corresponding intermediates amidine and imidate (8 and 9), derived from 5-carboxamido-1,4-benzodiazepin-5-(4'-methylpiperazinyl)-carboxamide have been developed to provide an easy installation of the oxadiazole, pyrimidine, imidazole and benzimidazole (9-14) based privileged templates at 2-position of 5-carboxamido-1,4-benzodiazepin-5-(4'-methylpiperazinyl)-carboxamide (4), through a phenoxyl spacer, by utilizing the synthetic strategy depicted in schemes 1 and 2.

  7. Synthesis, characterization and application of new azo dyes derived from uracil for polyester fibre dyeing

    Science.gov (United States)

    Yazdanbakhsh, Mohamad-reza; Abbasnia, Masoumeh; Sheykhan, Mehdi; Ma'mani, Leila

    2010-08-01

    Some novel uracil derived azo compounds were synthesized by diazotization of substituted aromatic amines, amidine- and guanidine-like amines such as 2-aminopyridine and 2-aminopyrimidine, ortho-hydroxy aniline and ortho-hydroxy naphthyl amines and coupling reaction with 6-amino-1,3-dimethyluracil. Structures of the dyes were fully characterized by spectroscopic techniques (UV, 1H NMR, 13C NMR, CHN and IR). The dyes were applied to polyester, affording orange-yellow shades and the wash fastness of the dyeings was excellent.

  8. Cyclic compounds of tetracoordinated boron from 5-amino-1,2,4-triazole and aromatic nitriles

    International Nuclear Information System (INIS)

    New cyclic compounds of tetracoordinated boron - dialkylboryl-[(1,2,4-triazole-5-yl)-amidinate] from 5-amino-1,2,4-triazole, aromatic nitriles and trialkylborane have been synthesized. It is shown that in dialkylboryl derivatives of 5-amino-1,2,4-triazole forming crystalline dimers, R2B (R=Pr, Bu) groups are bonded to circular nitrogen atoms. The X-ray diffraction method was used to determine crystalline and molecular structures of dipropylboryl-[(1,2,4-triazole-5-yl)benzamidinate

  9. Tuning of the Electronic Levels of Oligothiophene-Naphthalimide Assemblies by Chemical Modification.

    Science.gov (United States)

    de la Peña, Alejandro; Arrechea-Marcos, Iratxe; Mancheño, María J; Ruiz Delgado, M Carmen; López Navarrete, J Teodomiro; Segura, José L; Ponce Ortiz, Rocío

    2016-09-12

    Inversion of the connections of amidine linkers combined with controlled oligothiophene chain catenation in oligothiophene-naphthalimide assemblies provides an efficient method to tune the HOMO and LUMO values in this type of assemblies. This modification also suppresses the intramolecular charge transfer (ICT) band normally found in this type of derivatives, also delocalizing the frontier molecular orbitals over the whole conjugated skeleton. The resultant assemblies were used in the fabrication of field-effect transistors, which showed well-balanced ambipolar transport. PMID:27430480

  10. Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

    Directory of Open Access Journals (Sweden)

    Viktor A. Zapol’skii

    2012-04-01

    Full Text Available The nitropolychlorobutadienes 3, 4 are valuable building blocks for various amination and successive heterocyclization products. Nucleophilic substitution reactions of the partially protected, bioactive amines 1, 2 with either vinyl, imidoyl or carbonyl chlorides result in the formation of the enamines 11, 12, 13, 16, 25, the amidine 6, and the amides 20, 21, respectively. In the following, cyclization to the highly functionalized pyrazoles 27, 28, pyrimidine 26 and pyridopyrimidine 24 succeeded. Deprotection of 21, 12 and 28 proved to be only partially feasible.

  11. Chemist makes enhanced oil, oilsands extraction, greener using waste CO2

    International Nuclear Information System (INIS)

    The Canada Research Chair of green Chemistry at Queen's University and his team of researchers has developed a reversible method of tying together and then separating oil and water using carbon dioxide (CO2). This development has led to the ability to switch back and forth between surfactant and demulsifier. The surfactant used in the studies was a long-chain amidine made of a CO2-activated, air-deactivated soap-like compound. CO2 was bubbled through the amidine to make it act like a surfactant. It was deactivated when CO2 was removed by applying air. The technology for the switchable surfactant has potential as an inexpensive, environmentally sound alternative to existing oil recovery methods that use large quantities of toxic byproducts. It also enables more water recycling. Other applications include cleaning up oil spills and degreasing metal equipment or surfaces. The idea came to the researcher when working in Japan with a Nobel Prize winning chemist who studied the use of supercritical CO2 as a solvent for chemical reactions. 1 ref., 1 fig

  12. Evaluation of the Efficacy of Acaricides Used to Control the Cattle Tick, Rhipicephalus microplus, in Dairy Herds Raised in the Brazilian Southwestern Amazon

    Directory of Open Access Journals (Sweden)

    Luciana G. Brito

    2011-01-01

    Full Text Available The adult immersion test (AIT was used to evaluate the efficacy of acaricide molecules used for control of Rhipicephalus microplus on 106 populations collected in five municipalities in the state of Rondônia in the Brazilian South Occidental Amazon region. The analysis of the data showed that the acaricide formulations had different efficacies on the tick populations surveyed. The synthetic pyrethroids (SPs acaricides were the least effective (48.35–76.84%, followed by SP + organophosphate (OP associations (68.91–81.47% and amidine (51.35–100%. For the macrocyclic lactones (MLs, the milbemycin (94.84–100% was the most effective, followed by spinosad (93.21–100% and the avermectins (81.34–100%. The phenylpyrazole (PZ group had similar efficacy (99.90% to the MLs. Therefore, SP acaricides, including associations with OP, and formulations based on amidine presented low in vitro efficacy to control the R. microplus populations surveyed.

  13. Design, synthesis and biological evaluation of PSMA/hepsin-targeted heterobivalent ligands.

    Science.gov (United States)

    Subedi, Milan; Minn, Il; Chen, Jianbo; Kim, YunHye; Ok, Kiwon; Jung, Yong Woo; Pomper, Martin G; Byun, Youngjoo

    2016-08-01

    Cell surface biomarkers such as prostate-specific membrane antigen (PSMA) and hepsin have received considerable attention as targets for imaging prostate cancer (PCa) due to their high cell surface expression in such tumors and easy access for imaging probes. Novel amidine-containing indole analogs (13-21) as hepsin inhibitors were designed and synthesized. These compounds showed in vitro inhibitory activity against hepsin with IC50 values from 5.9 to 70 μM. Based on the SAR of amidine-derived analogs, the novel heterobivalent compound 30, targeting both hepsin and PSMA, was synthesized by linking compound 18 with Lys-urea-Glu, the key scaffold for the specific binding to PSMA, followed by the conjugation of the optical dye SulfoCy7. Compound 30 exhibited inhibitory activities against PSMA and hepsin, with IC50 values of 28 nM and 2.8 μM, respectively. In vitro cell uptake and preliminary in vivo optical imaging studies of 30 showed selective binding and retention in both PSMA and hepsin high-expressing PC3/ML-PSMA-HPN cells as compared with low-expressing PC3/ML cells. PMID:27128184

  14. Assessment of flavaglines as potential chikungunya virus entry inhibitors.

    Science.gov (United States)

    Wintachai, Phitchayapak; Thuaud, Frédéric; Basmadjian, Christine; Roytrakul, Sittiruk; Ubol, Sukathida; Désaubry, Laurent; Smith, Duncan R

    2015-03-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that recently caused large epidemics in islands in, and countries around, the Indian Ocean. There is currently no specific drug for therapeutic treatment or for use as a prophylactic agent against infection and no commercially available vaccine. Prohibitin has been identified as a receptor protein used by chikungunya virus to enter mammalian cells. Recently, synthetic sulfonyl amidines and flavaglines (FLs), a class of naturally occurring plant compounds with potent anti-cancer and cytoprotective and neuroprotective activities, have been shown to interact directly with prohibitin. This study therefore sought to determine whether three prohibitin ligands (sulfonyl amidine 1 m and the flavaglines FL3 and FL23) were able to inhibit CHIKV infection of mammalian Hek293T/17 cells. All three compounds inhibited infection and reduced virus production when cells were treated before infection but not when added after infection. Pretreatment of cells for only 15 minutes prior to infection followed by washing out of the compound resulted in significant inhibition of entry and virus production. These results suggest that further investigation of prohibitin ligands as potential Chikungunya virus entry inhibitors is warranted. PMID:25643977

  15. Surprisingly Different Reaction Behavior of Alkali and Alkaline Earth Metal Bis(trimethylsilyl)amides toward Bulky N-(2-Pyridylethyl)-N'-(2,6-diisopropylphenyl)pivalamidine.

    Science.gov (United States)

    Kalden, Diana; Oberheide, Ansgar; Loh, Claas; Görls, Helmar; Krieck, Sven; Westerhausen, Matthias

    2016-07-25

    N-(2,6-Diisopropylphenyl)-N'-(2-pyridylethyl)pivalamidine (Dipp-N=C(tBu)-N(H)-C2 H4 -Py) (1), reacts with metalation reagents of lithium, magnesium, calcium, and strontium to give the corresponding pivalamidinates [(tmeda)Li{Dipp-N=C(tBu)-N-C2 H4 -Py}] (6), [Mg{Dipp-N=C(tBu)-N-C2 H4 -Py}2 ] (3), and heteroleptic [{(Me3 Si)2 N}Ae{Dipp-N=C(tBu)-N-C2 H4 -Py}], with Ae being Ca (2 a) and Sr (2 b). In contrast to this straightforward deprotonation of the amidine units, the reaction of 1 with the bis(trimethylsilyl)amides of sodium or potassium unexpectedly leads to a β-metalation and an immediate deamidation reaction yielding [(thf)2 Na{Dipp-N=C(tBu)-N(H)}] (4 a) or [(thf)2 K{Dipp-N=C(tBu)-N(H)}] (4 b), respectively, as well as 2-vinylpyridine in both cases. The lithium derivative shows a similar reaction behavior to the alkaline earth metal congeners, underlining the diagonal relationship in the periodic table. Protonation of 4 a or the metathesis reaction of 4 b with CaI2 in tetrahydrofuran yields N-(2,6-diisopropylphenyl)pivalamidine (Dipp-N=C(tBu)-NH2 ) (5), or [(thf)4 Ca{Dipp-N=C(tBu)-N(H)}2 ] (7), respectively. The reaction of AN(SiMe3 )2 (A=Na, K) with less bulky formamidine Dipp-N=C(H)-N(H)-C2 H4 -Py (8) leads to deprotonation of the amidine functionality, and [(thf)Na{Dipp-N=C(H)-N-C2 H4 -Py}]2 (9 a) or [(thf)K{Dipp-N=C(H)-N-C2 H4 -Py}]2 (9 b), respectively, are isolated as dinuclear complexes. From these experiments it is obvious, that β-metalation/deamidation of N-(2-pyridylethyl)amidines requires bases with soft metal ions and also steric pressure. The isomeric forms of all compounds are verified by single-crystal X-ray structure analysis and are maintained in solution. PMID:27355970

  16. Preparation of aromatic polyamidines and their transformation in polybenzimidazoles

    Directory of Open Access Journals (Sweden)

    B. Ch. Kholkhoev

    2014-09-01

    Full Text Available Polymers with amidine groups –NH–C(=NH– in main chain were synthesized by two different approaches. The first strategy consists in polyaddition of dinitriles and diamines in acidic ionic liquids (ILs which act as catalyst and solvent, while the second approach is based on polycondensation of 4,4'-oxybis(benzoic acid diamide and diamines in Eaton’s reagent (ER. The resulting polyamidines (PADs with Mw up to 25 000 g/mol possess thermal stability on air up to 288°C, and good solubility in polar organic solvents. Moreover dehydrocyclization of obtained PADs into polybenzimidazoles (PBIs under the action of various oxidants was also studied in this work. The crosslinked films based on PBI and poly(amino imide resin (PAIR possess high mechanical characteristics. It has been proved that the crosslinked films based on PBI matrix are perspective materials for design the phosphoric acid electrolyte membranes for the medium temperature fuel cells.

  17. Investigação eletroquímica e calorimétrica da interação de novos agentes antitumorais biscatiônicos com DNA

    Directory of Open Access Journals (Sweden)

    Láuris Lucia da Silva

    2012-01-01

    Full Text Available Biscationic amidines bind in the DNA minor groove and present biological activity against a range of infectious diseases. Two new biscationic compounds (bis-α,ω-S-thioureido, amino and sulfide analogues were synthesized in good yields and fully characterized, and their interaction with DNA was also investigated. Isothermal titration calorimetry (ITC was used to measure the thermodynamic properties of binding interactions between DNA and these ligands. A double stranded calf thymus DNA immobilized on an electrode surface was used to study the possible DNA-interacting abilities of these compounds towards dsDNA in situ. A remarkable interaction of these compounds with DNA was demonstrated and their potential application as anticancer agents was furthered.

  18. A straightforward and efficient synthesis of 3-(pyrimidinyl)propanoates from levulinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Flores, Alex F.C.; Malavolta, Juliana L.; Souto, Alynne A.; Goularte, Rayane B.; Flores, Darlene C., E-mail: alex.fcf@ufsm.br [Universidade Federal de Santa Maria (UFSM/NUQUIMHE), RS (Brazil). Departamento de Quimica. Nucleo de Quimica de Heterociclos

    2013-04-15

    The cyclocondensation of methyl 7,7,7-trifluoro-4-methoxy-6-oxo-4-heptenoate and methyl 7,7,7-trichloro-4-methoxy-6-oxo-4-heptenoate, derived from levulinic acid with amidines [NH{sub 2}CONH{sub 2}, NH{sub 2}CR(NH) (R = H, Me, Ph, NH{sub 2}, SMe and 1H-pyrazol-1-yl), 5-amino-3-methyl-1H-pyrazol and 2-aminothiazole] into pyrimidine and pyrimidine-like derivatives as a new type of glutamate-like 3-(trihalomethylatedpyrimidinyl)propanoate is reported. Preparation of 3-(trihalomethylatedpyrimidinyl) propanohydrazides is also described. The synthetic potential of this straightforward protocol was established by the synthesis of fourteen new 3-(pyrimidinyl) propanoates in regular to good yields (38-92%). The structural assignments were based on the analysis of their {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) data. (author)

  19. Synthesis and reactions with a midines of derivates cycles and of open chain of 2-bromo-3, 4-dioxobutanoic; Sintesis y reacciones con amidinas de derivados ciclicos y de cadena abierta del acido 2-bromo-3, 4-dioxobutanoico

    Energy Technology Data Exchange (ETDEWEB)

    Ancos, B. de; Delgado, F.; Martin, M.R. [Departamento de Quimica Organica, Facultad de Ciencias, Universidad Autonoma, Madrid (Spain)

    1995-12-31

    Bromination of enaminoesters 1 and 5, in appropriate conditions, affords in good yield enamines of the corresponding 2-bromo-3.4-dioxobutanoic acid derivatives 2-3 and 6 or dibromocompounds 4 and 6. The open chain enaminoesters (1-3) are more easily hydrolyzed that enaminofuranones 5 and 6. Prolongated treatment of 6 with hydrochloric acid affords the chlorinated enamine 11. The synthesis of 3-Bromo-4-hydroxy-5-methoxyfuran-2(5H)-one 10 can be achieved by bromination of 12, obtained by hydrolysis of 5. The reaction of methyl 3-bromo-4, 4-dimethoxy-3-oxobutanoate with amidines is a good method for the synthesis of 5-bromo-6-(dimethoxymethyl) pyrimidine-4(3H)-ones substituted at 2 position. Under the same conditions the reaction of furanone 10 with benzamide does not lead to the corresponding imidazoline. (Author) 12 refs.

  20. Electrochemical and calorimetric investigation of interaction of novel biscationic anticancer agents with DNA; Investigacao eletroquimica e calorimetrica da interacao de novos agentes antitumorais biscationicos com DNA

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Lauris Lucia da; Donnici, Claudio Luis; Lopes, Julio Cesar Dias, E-mail: cdonnici@terra.com.br [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Inst. de Ciencias Exatas. Dept. de Quimica; Goulart, Marilia Oliveira Fonseca; Abreu, Fabiane Caxico de; Paula, Francine Santos de [Universidade Federal de Alagoas (UFAL), Maceio, AL (Brazil). Campus A.C. Simoes. Inst. de Quimica e Biotecnologia; Bravo, Carlos E. Salas; Santoro, Marcelo Matos [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia; Denadai, Angelo Marcio Leite [Centro Federal de Educacao Tecnologica, Timoteo, MG (Brazil). Campus VII; Santos, Alexandre Martins Costa [Universidade Federal do Espirito Santo, Vitoria, ES (Brazil). Dept. de Ciencias Fisiologicas; Montanari, Carlos Alberto [Universidade de Sao Paulo, Sao Carlos, SP (Brazil). Inst. de Quimica

    2012-07-01

    Biscationic amidines bind in the DNA minor groove and present biological activity against a range of infectious diseases. Two new biscationic compounds (bis-{alpha}-{omega}-S-thioureido, amino and sulfide analogues) were synthesized in good yields and fully characterized, and their interaction with DNA was also investigated. Isothermal titration calorimetry (ITC) was used to measure the thermodynamic properties of binding interactions between DNA and these ligands. A double stranded calf thymus DNA immobilized on an electrode surface was used to study the possible DNA-interacting abilities of these compounds towards dsDNA in situ. A remarkable interaction of these compounds with DNA was demonstrated and their potential application as anticancer agents was furthered. (author)

  1. Chiral Zn(II-Bisamidine Complex as a Lewis-Brønsted Combined Acid Catalyst: Application to Asymmetric Mukaiyama Aldol Reactions of α-Ketoesters

    Directory of Open Access Journals (Sweden)

    Ryo Gotoh

    2012-07-01

    Full Text Available Focusing on the steric and electronic properties of the resonance-stabilized amidine framework, a cationic metal-bisamidine complex was designed as a conjugated combined Lewis-Brønsted acid catalyst. The chiral Zn(II-bisamidine catalyst prepared from the 2,2'-bipyridyl derived bisamidine ligand, ZnCl2, and AgSbF6 promoted asymmetric Mukaiyama aldol reaction of α-ketoester and α,α-disubstituted silyl enol ether to afford the α-hydroxyester having sequential quarternary carbons in good yield, albeit with low enantioselectivity. Addition of 1.0 equivalent of the fluoroalcohol having suitable acidity and bulkiness dramatically increased the enantioselectivity (up to 68% ee. DFT calculations suggested that this additive effect would be caused by self-assembly of the fluoroalcohol on the Zn(II-bisamidine catalyst.

  2. 1,3-Dipolar cycloaddition reactivities of perfluorinated aryl azides with enamines and strained dipolarophiles.

    Science.gov (United States)

    Xie, Sheng; Lopez, Steven A; Ramström, Olof; Yan, Mingdi; Houk, K N

    2015-03-01

    The reactivities of enamines and predistorted (strained) dipolarophiles toward perfluoroaryl azides (PFAAs) were explored experimentally and computationally. Kinetic analyses indicate that PFAAs undergo (3 + 2) cycloadditions with enamines up to 4 orders of magnitude faster than phenyl azide reacts with these dipolarophiles. DFT calculations were used to identify the origin of this rate acceleration. Orbital interactions between the cycloaddends are larger due to the relatively low-lying LUMO of PFAAs. The triazolines resulting from PFAA-enamine cycloadditions rearrange to amidines at room temperature, while (3 + 2) cycloadditions of enamines and phenyl azide yield stable, isolable triazolines. The 1,3-dipolar cycloadditions of norbornene and DIBAC also show increased reactivity toward PFAAs over phenyl azide but are slower than enamine-azide cycloadditions. PMID:25553488

  3. A Food Effect Study of an Oral Thrombin Inhibitor and Prodrug Approach To Mitigate It.

    Science.gov (United States)

    Lee, Jihye; Kim, Bongchan; Kim, Tae Hun; Lee, Sun Hwa; Park, Hee Dong; Chung, Kyungha; Lee, Sung-Hack; Paek, Seungyup; Kim, Eunice EunKyeong; Yoon, SukKyoon; Kim, Aeri

    2016-04-01

    LB30870, a new direct thrombin inhibitor, showed 80% reduction in oral bioavailability in fed state. The present study aims to propose trypsin binding as a mechanism for such negative food effect and demonstrate a prodrug approach to mitigate food effect. Effect of food composition on fed state oral bioavailability of LB30870 was studied in dogs. Various prodrugs were synthesized, and their solubility, permeability, and trypsin binding affinity were measured. LB30870 and prodrugs were subject to cocrystallization with trypsin, and the X-ray structures of cocrystals were determined. Food effect was studied in dogs for selected prodrugs. Protein or lipid meal appeared to affect oral bioavailability of LB30870 in dogs more than carbohydrate meal. Blocking both carboxyl and amidine groups of LB30870 resulted in trypsin Ki values orders of magnitude higher than that of LB30870. Prodrugs belonged to either Biopharmaceutical Classification System I, II, or III. X-ray crystallography revealed that prodrugs did not bind to trypsin, but instead their hydrolysis product at the amidine blocking group formed cocrystal with trypsin. A prodrug with significantly less food effect than LB30870 was identified. Binding of prodrugs to food components such as dietary fiber appeared to counteract the positive effect brought with the prodrug approach. Further formulation research is warranted to enhance the oral bioavailability of prodrugs. In conclusion, this study is the first to demonstrate that the negative food effect of LB30870 can be attributed to trypsin binding. Trypsin binding study is proposed as a screening tool during lead optimization to minimize food effect. PMID:26886576

  4. Modification of dispersibility of nanodiamond by grafting of polyoxyethylene and by the introduction of ionic groups onto the surface via radical trapping

    Energy Technology Data Exchange (ETDEWEB)

    Cha, I. [Graduate School of Science and Technology, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-2181 (Japan); Hashimoto, K. [Department of Material Science and Technology, Faculty of Engineering, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-218 (Japan); Fujiki, K. [Department of Environmental Science, Niigata Institute of Technology, 1719, Fujihashi, Kashiwazaki, Niigata 945-1195 (Japan); Yamauchi, T. [Graduate School of Science and Technology, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-2181 (Japan); Department of Material Science and Technology, Faculty of Engineering, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-218 (Japan); Tsubokawa, N., E-mail: ntsuboka@eng.niigata-u.ac.jp [Graduate School of Science and Technology, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-2181 (Japan); Department of Material Science and Technology, Faculty of Engineering, Niigata University, 8050, Ikarashi, 2-no-cho, Nishi-ku, Niigata 950-218 (Japan)

    2014-02-14

    To improve the dispersibility of polycrystalline nanodiamond (ND) in solvents, the grafting of polymers and introduction of ionic groups onto ND surface via radical trapping by ND surface were investigated. The grafting of polyoxyethylene (POE) onto ND surface by trapping of POE radicals formed by the thermal decomposition of POE macro azo-initiator (Azo-POE) was examined. The polymer radicals formed by the thermal decomposition of Azo-POE were successfully trapped by ND surface to give POE-grafted ND. The effect of temperature on the grafting of POE onto ND was discussed. In addition, the introduction of cationic protonated amidine groups onto ND was achieved by the trapping of radicals bearing protonated amidine groups formed by thermal decomposition of 2,2′-azobis(2-methylpropionamidine)dihydrochloride (AMPA). The anionic carboxylate groups was introduced onto ND surface by the trapping of the radicals bearing carboxyl groups formed by thermal decomposition of 4,4′-azobis(4-cyonovaleric acid) (ACVA) followed by the treatment with NaOH aqueous solution. The dispersibility of ND in water was remarkably improved by the grafting of POE, based on the steric hindrance of polymer chains and by the introduction of ionic groups, based on the ionic repulsion, onto ND surface. - Highlights: • Grafting of PEG onto nanodiamond was achieved by radical trapping. • Introduction of ionic groups onto nanodiamond was achieved by radical trapping. • Nanodiamond was dispersed by PEG grafting based on steric hindrance of PEG chains. • Nanodiamond was dispersed by introduction of ionic groups based on ionic repulsion.

  5. Modification of dispersibility of nanodiamond by grafting of polyoxyethylene and by the introduction of ionic groups onto the surface via radical trapping

    International Nuclear Information System (INIS)

    To improve the dispersibility of polycrystalline nanodiamond (ND) in solvents, the grafting of polymers and introduction of ionic groups onto ND surface via radical trapping by ND surface were investigated. The grafting of polyoxyethylene (POE) onto ND surface by trapping of POE radicals formed by the thermal decomposition of POE macro azo-initiator (Azo-POE) was examined. The polymer radicals formed by the thermal decomposition of Azo-POE were successfully trapped by ND surface to give POE-grafted ND. The effect of temperature on the grafting of POE onto ND was discussed. In addition, the introduction of cationic protonated amidine groups onto ND was achieved by the trapping of radicals bearing protonated amidine groups formed by thermal decomposition of 2,2′-azobis(2-methylpropionamidine)dihydrochloride (AMPA). The anionic carboxylate groups was introduced onto ND surface by the trapping of the radicals bearing carboxyl groups formed by thermal decomposition of 4,4′-azobis(4-cyonovaleric acid) (ACVA) followed by the treatment with NaOH aqueous solution. The dispersibility of ND in water was remarkably improved by the grafting of POE, based on the steric hindrance of polymer chains and by the introduction of ionic groups, based on the ionic repulsion, onto ND surface. - Highlights: • Grafting of PEG onto nanodiamond was achieved by radical trapping. • Introduction of ionic groups onto nanodiamond was achieved by radical trapping. • Nanodiamond was dispersed by PEG grafting based on steric hindrance of PEG chains. • Nanodiamond was dispersed by introduction of ionic groups based on ionic repulsion

  6. Anticancer, antioxidant activities, and DNA affinity of novel monocationic bithiophenes and analogues

    Directory of Open Access Journals (Sweden)

    Ismail MA

    2014-09-01

    Full Text Available Mohamed A Ismail,1,2 Reem K Arafa,3 Magdy M Youssef,1,2 Wael M El-Sayed1,4 1Departments of Chemistry and Biological Sciences, College of Science, King Faisal University, Hofuf, Saudi Arabia; 2Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt; 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 4Department of Zoology, Faculty of Science, University of Ain Shams, Abbassia, Cairo, Egypt Abstract: A series of 15 monocationic bithiophenes and isosteres were prepared and subjected to in vitro antiproliferative screening using the full National Cancer Institute (NCI-60 cell line panel, representing nine types of cancer. Among the nine types of cancer involved in a five-dose screen, non-small cell lung and breast cancer cell lines were the most responsive to the antiproliferative effect of the tested compounds, especially cell lines A549/ATCC, NCI-H322M, and NCI-H460, whereas compounds 1a, 1c, 1d, and 7 exhibited potent activity, with GI50 values (drug concentration that causes 50% inhibition of cell growth from less than 10 nM to 102 nM. In addition, compounds 1c and 1d gave GI50 values of 73 nM and 79 nM, respectively, against the MDA-MB-468 breast cancer cell line. Structure–activity relationship findings indicated that the mononitriles were far less active than their corresponding monoamidines and, within the amidines series, the bioisosteric replacement of a thiophene ring by a furan led to a reduction in antiproliferative activity. Also, molecular manipulations, involving substitution on the phenyl ring, or its replacement by a pyridyl, or alteration of the position of the amidine group, led to significant alteration in antiproliferative activity. On the other hand, DNA studies demonstrated that these monoamidine bichalcophenes have promising ability to cleave the genomic DNA. These monoamidines show a wide range of DNA affinities, as judged from their DNA cleavage effect

  7. Improvement in the chemistry and synthesis of deoxyoligonucleotides

    International Nuclear Information System (INIS)

    Several new phosphoramidites were evaluated as superior phosphite intermediates for DNA synthesis. Criteria tested were stability, reactivity upon tetrazole activation, and ease in high preparation of purity. Morpholino and diisopropylamino phosphoramidites are observed to be more stable than dimethylamino phosphoramidites especially during silica gel chromatography and are easily synthesized in high yield and purity. Resolution of phosphoramidite diastereomers can be accomplished by medium pressure chromatography on silica gel. Furthermore, the diisopropylaminophosphoramidites are shown to be most reactive upon activation with tetrazole, in spite of an intrinsic stability prior to activation. Possible mechanisms of this activation were also discussed. The existence of a tetrazolide intermediate is consistent with kinetic and 31P NMR studies. Acid catalyzed depurination of N-benzoyl-2'-deoxyadenosine has been a serious problem in nucleic acid chemistry for about twenty years and has been suspected as a problem during DNA synthesis. An alternate class of adenine protecting groups called amidines greatly retards depurination rates of adenine in both model studies and during DNA synthesis

  8. Effect of cell physicochemical characteristics and motility on bacterial transport in groundwater

    Science.gov (United States)

    Becker, M.W.; Collins, S.A.; Metge, D.W.; Harvey, R.W.; Shapiro, A.M.

    2004-01-01

    The influence of physicochemical characteristics and motility on bacterial transport in groundwater were examined in flow-through columns. Four strains of bacteria isolated from a crystalline rock groundwater system were investigated, with carboxylate-modified and amidine-modified latex microspheres and bromide as reference tracers. The bacterial isolates included a gram-positive rod (ML1), a gram-negative motile rod (ML2), a nonmotile mutant of ML2 (ML2m), and a gram-positive coccoid (ML3). Experiments were repeated at two flow velocities, in a glass column packed with glass beads, and in another packed with iron-oxyhydroxide coated glass beads. Bacteria breakthrough curves were interpreted using a transport equation that incorporates a sorption model from microscopic observation of bacterial deposition in flow-cell experiments. The model predicts that bacterial desorption rate will decrease exponentially with the amount of time the cell is attached to the solid surface. Desorption kinetics appeared to influence transport at the lower flow rate, but were not discernable at the higher flow rate. Iron-oxyhydroxide coatings had a lower-than-expected effect on bacterial breakthrough and no effect on the microsphere recovery in the column experiments. Cell wall type and shape also had minor effects on breakthrough. Motility tended to increase the adsorption rate, and decrease the desorption rate. The transport model predicts that at field scale, desorption rate kinetics may be important to the prediction of bacteria transport rates. ?? 2003 Elsevier B.V. All rights reserved.

  9. Studies on 2-Arylhydrazononitriles: Synthesis of 3-Aryl-2-arylhydrazopropanenitriles and Their Utility as Precursors to 2-Substituted Indoles, 2-Substituted-1,2,3-Triazoles, and 1-Substituted Pyrazolo[4,3-d]pyrimidines

    Directory of Open Access Journals (Sweden)

    Khaled D. Khalil

    2012-10-01

    Full Text Available Coupling of 2-benzylmalononitrile with aromatic diazonium salts afforded 3-phenyl-2-arylhydrazonopropanenitriles 4a,b, which were rearranged into 2-cyanoindoles 5a,b upon heating with ZnCl2 in the presence of glacial acetic acid. The produced indole derivatives 5a,b can be successfully used as valuable precursors to synthesize 1,2,4-oxadiazolylindoles 8a,b. The reaction of arylhydrazononitriles 4a,b with hydroxylamine afforded an amidoximes 9a,b that could be cyclized into 1,2,3-triazole-4-amines 10a,b. In addition, 4a,b could be converted into 4-aminopyrazoles 12a,b via condensation with chloroacetonitrile in the presence of triethylamine as a basic catalyst. Finally, compounds 12a,b were refluxed with dimethylformamide dimethylacetal (DMFDMA to afford amidines 13a,b that were readily cyclized to the corresponding pyrazolo[4,3-d]pyrimidines 14a,b when refluxed with ammonium acetate.

  10. N-terminal guanidinylation of TIPP (Tyr-Tic-Phe-Phe) peptides results in major changes of the opioid activity profile.

    Science.gov (United States)

    Weltrowska, Grazyna; Nguyen, Thi M-D; Chung, Nga N; Wilkes, Brian C; Schiller, Peter W

    2013-09-15

    Derivatives of peptides of the TIPP (Tyr-Tic-Phe-Phe; Tic=1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) family containing a guanidino (Guan) function in place of the N-terminal amino group were synthesized in an effort to improve their blood-brain barrier permeability. Unexpectedly, N-terminal amidination significantly altered the in vitro opioid activity profiles. Guan-analogues of TIPP-related δ opioid antagonists showed δ partial agonist or mixed δ partial agonist/μ partial agonist activity. Guanidinylation of the mixed μ agonist/δ antagonists H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) and H-Dmt-TicΨ[CH2NH]Phe-Phe-NH2 (DIPP-NH2[Ψ]) converted them to mixed μ agonist/δ agonists. A docking study revealed distinct positioning of DIPP-NH2 and Guan-DIPP-NH2 in the δ receptor binding site. Lys(3)-analogues of DIPP-NH2 and DIPP-NH2[Ψ] (guanidinylated or non-guanidinylated) turned out to be mixed μ/κ agonists with δ antagonist-, δ partial agonist- or δ full agonist activity. Compounds with some of the observed mixed opioid activity profiles have therapeutic potential as analgesics with reduced side effects or for treatment of cocaine addiction. PMID:23932788

  11. In Vivo Nitric Oxide Synthase Inhibitors Can Be Deprived of This Activity: Unexpected Influence of the Tetrachloroplatinate(II) Counteranion. Crystal Structures of Bis(S-Methyl-Isothiouronium)-N,N'-Bis(3-Guanidinopropyl)Piperazinium and Hexamidinium Tetrachloroplatinates(II) Salts.

    Science.gov (United States)

    Morgant, G; Viossat, B; Roch-Arveiller, M; Prognon, P; Giroud, J P; Lancelot, J C; Robba, M; Huy, D N

    1998-01-01

    The synthesis and crystal structures of bis(S-methylisothiouronium) (MSTUH)(+), N,N'-bis((3- guanidinopropyl)piperazinium (PipeC3GuaH4)(4+) and hexamidinium (HexaH2)(2+) tetrachloro platinate(ll) salts ( called hereafter PtMSTU, PtPipeC3Gua and PtHexa respectively ) were investigated. These compounds contain the "amidine" function ( - C(=NH)NH(2) ) in which the H atoms supplied by the acid have become attached to the imino group of each terminal amidino function. Moreover, in PtPipeC3Gua, the nitrogen atoms of the chair-piperazine moiety are also protonated. The influence of tetrachloroplatinate(ll) counteranion ( versus sulfate, nitrate and diisethionate ) in the in vivo nitrite inhibition by the (MSTUH)(+), (PipeC3GuaH4)(4+) and (HexaH2)(2+) cations was investigated. The three tetrachloroplatinate(ll) salts, unexpectedly, do not inhibit significantly the in vivo nitrite production in comparison with the other salts (sulfate, nitrate and diisethionate and their corresponding previous countercations) which exhibit NO synthase inhibition, especially bis(S-methylisothiouronium) sulfate, a selective and potent inducible NO synthase (iNOS) inhibitor commonly used as standard. PMID:18475834

  12. Magnesium Catalysis for the Hydroboration of Carbodiimides.

    Science.gov (United States)

    Weetman, Catherine; Hill, Michael S; Mahon, Mary F

    2016-05-17

    A β-diketiminato magnesium alkyl complex, [CH{C(Me)NDipp}2 }MgnBu] (Dipp=2,6-iPr2 C6 H3 ), was shown to be an effective pre-catalyst for the first reported catalytic hydroboration of alkyl- and aryl-substituted carbodiimides with pinacol borane (HBpin). The catalytic reactions proceed under mild conditions to afford the corresponding N-borylated formamidine compounds in good yields. The reactions were observed to proceed through the intermediacy of magnesium amidinate and formamidinatoborate intermediates and an example of one of these latter species has been structurally characterised by an X-ray diffraction analysis. Crucially, no formation of the N-boryl formamidine products was observed in the absence of additional equivalents of the carbodiimide and HBpin substrates. This observation, supported by the evolution of a sigmoidal kinetic profile for the hydroboration of dicyclohexylcarbodiimide, has been rationalised as the consequence of an allosteric effect of the pinacol borane and carbodiimide on the magnesium formamidinatoborate intermediates. PMID:27072429

  13. STUDY ON THE SYNTHESIS OF POLYPERFLUOROTRIAZINE——The Synthesis and Polymerization of a Novel α,ω-Diiodoperfluorooxaalkyl s-Triazine Monomer

    Institute of Scientific and Technical Information of China (English)

    HUANG Weiyuan; HUANG Bingnan; HU Changming

    1983-01-01

    In order to investigate synthetic route of polyperfluorotriazine elastomer, 2-trifluoromethyl-4,6-bis(4'-iodo-2'-oxahexafluorobutyl)-1,3,5-triazine (1), a novel triazine monomer, was synthesized from 5-iodo-3-oxa-octafluoropentanesulfonyl fluoride (2) in eight-steps. 2 was reduced by potassium sulfite to the sulfinate (3), which was treated with hydriodic acid to yield 5-iodo-3-oxa-hexafluoropentanoic acid (4). Compound 4 was transformed to 5-iodo-3-oxa-hexafluoropentanenitrile (7) through the corresponding ester 5 and amide 6. The desired product 1 was prepared by acylation-cyclodehydration of the imidoylamidine 9, obtained by condensation of the nitrile 7with the amidine 8.The various methods for the esterification of perfluorocarboxylic acid were studied and a possible mechanism for the transformation of perfluorosulfinate to the corresponding perfluorocarboxylic acid by hydriodic acid was proposed.Crude 1 contained compounds 6, 11, 13, as impurities which were removed by low temperature crystallization followed by filtration through a short alumina column. The monomer 1 was polymerized by UV-irradiation in the presence of Hg with or without solvent. Polyperfluorooxaalkyl triazine 17 thus obtained showed good thermal stability. In the main chain of the polymer there was no weak unit of the uncyclized ring. Polymer 17 had an average molecular weight of ca.1.33-2.0×104 (D. P.=27-42) and the temperature of 10% weight loss in nitrogen was 340℃.

  14. Energetics-Based Methods for Protein Folding and Stability Measurements

    Science.gov (United States)

    Geer, M. Ariel; Fitzgerald, Michael C.

    2014-06-01

    Over the past 15 years, a series of energetics-based techniques have been developed for the thermodynamic analysis of protein folding and stability. These techniques include Stability of Unpurified Proteins from Rates of amide H/D Exchange (SUPREX), pulse proteolysis, Stability of Proteins from Rates of Oxidation (SPROX), slow histidine H/D exchange, lysine amidination, and quantitative cysteine reactivity (QCR). The above techniques, which are the subject of this review, all utilize chemical or enzymatic modification reactions to probe the chemical denaturant- or temperature-induced equilibrium unfolding properties of proteins and protein-ligand complexes. They employ various mass spectrometry-, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)-, and optical spectroscopy-based readouts that are particularly advantageous for high-throughput and in some cases multiplexed analyses. This has created the opportunity to use protein folding and stability measurements in new applications such as in high-throughput screening projects to identify novel protein ligands and in mode-of-action studies to identify protein targets of a particular ligand.

  15. Switchable [3+2] and [4+2] Heteroannulation of Primary Propargylamines with Isonitriles to Imidazoles and 1,6-Dihydropyrimidines: Catalyst Loading Enabled Reaction Divergence.

    Science.gov (United States)

    Tong, Shuo; Wang, Qian; Wang, Mei-Xiang; Zhu, Jieping

    2016-06-01

    Isonitrile 1 due to its carbene-like reactivity serves generally as a one-carbon synthon in a diverse set of organic transformations. We report in this article that the isocyano group can also act as a polarized triple bond to undergo, as a two-atom synthon, heteroannulation with primary propargylamines 15. In addition, we serendipitously discovered that the reaction pathways can be modulated by simply changing the catalyst loading. In the presence of 0.1 equiv of Yb(OTf)3 or TfOH, the reaction between 1 and 15 afforded exclusively imidazoles 16 by a formal [3+2] cycloaddition. At a higher catalyst loading (Yb(OTf)3 (0.4 equiv) or TfOH (0.5 equiv)) under otherwise identical conditions, the same reaction furnished 1,6-dihydropyrimidines 17 in good to excellent yields by way of a formal [4+2] cycloaddition process. Mechanistic investigations indicated that both annulations went through an amidine intermediate resulting from the insertion of the isocyano group to the NH bond of the primary amine. Subsequent catalyst-loading-dependent 5-exo-dig or 6-endo-dig cyclization provided selectively the two heterocycles, respectively. PMID:27142526

  16. Interplay between viscoelastic and chemical tunings in fatty-acid-based polyester adhesives: engineering biomass toward functionalized step-growth polymers and soft networks.

    Science.gov (United States)

    Vendamme, Richard; Olaerts, Katrien; Gomes, Monica; Degens, Marc; Shigematsu, Takayuki; Eevers, Walter

    2012-06-11

    This Article describes the synthesis and characterization of renewable self-adhesive coatings with tunable viscoelastic properties and equipped with well-defined amounts of carboxylic acid "sticker" groups with adhesion promoting characteristics. Hydroxyl-ended polyesters with various architectures (linear, branched) were synthesized by melt polycondensation of dimerized fatty acids and fatty diols and then cured with maleic anhydride-modified triglycerides (such as maleinized soybean oil) in the presence of the amidine catalyst 1,8-diazabicyclo[5.4.0]undec-7-ene. The curing reaction of alcoholysis has the dual effect of chain extending/cross-linking the base polymers via creation of polymeric half-esters linkages while introducing carboxylic acid functions within the gel structure. We demonstrated how the adhesion properties can be finely tuned from molecular design and formulation of the network precursors and how the rheology and functionality of the coatings influence the adhesive bond formation and development. These renewable polyester adhesives proved to be suitable materials for pressure-sensitive adhesives applications with respect to adhesion strength, viscoelasticity, and functionality. In addition, the environmental benefits of such materials are briefly discussed. PMID:22612310

  17. Acaricide residues in laying hens naturally infested by red mite Dermanyssus gallinae.

    Science.gov (United States)

    Marangi, Marianna; Morelli, Vincenzo; Pati, Sandra; Camarda, Antonio; Cafiero, Maria Assunta; Giangaspero, Annunziata

    2012-01-01

    In the poultry industry, control of the red mite D. gallinae primarily relies worldwide on acaricides registered for use in agriculture or for livestock, and those most widely used are carbamates, followed by amidines, pyrethroids and organophosphates. Due to the repeated use of acaricides--sometimes in high concentrations--to control infestation, red mites may become resistant, and acaricides may accumulate in chicken organs and tissues, and also in eggs. To highlight some situations of misuse/abuse of chemicals and of risk to human health, we investigated laying hens, destined to the slaughterhouse, for the presence of acaricide residues in their organs and tissues. We used 45 hens from which we collected a total of 225 samples from the following tissues and organs: skin, fat, liver, muscle, hearth, and kidney. In these samples we analyzed the residual contents of carbaryl and permethrin by LC-MS/MS.Ninety-one (40.4%) samples were positive to carbaryl and four samples (1.7%) were positive to permethrin. Concentrations of carbaryl exceeding the detection limit (0.005 ppm) were registered in the skin and fat of birds from two farms (p<0.01), although these concentrations remained below the maximum residue limit (MRLs) (0.05 ppm) (p<0.01). All organs/tissues of hens from a third farm were significantly more contaminated, with skin and muscle samples exceeding the MRL (0.05 ppm) (p<0.01) of carbaryl in force before its use was banned. Out of 45 chickens tested, 37 (82.2%) were found to be contaminated by carbaryl, and 4 (8.8%) by permethrin. The present study is the first report on the presence of pesticides banned by the EU (carbaryl) or not licensed for use (permethrin) in the organs and tissues of laying hens, which have been treated against red mites, and then slaughtered for human consumption at the end of their life cycle. PMID:22363736

  18. Tracers development for the PET study of nicotinic receptors: [11C]-mecamylamine and [11C]-SIB 1553A. Tritium and carbon-11 radiolabelling of a serine proteinase inhibitor: the t-PAstop

    International Nuclear Information System (INIS)

    In order to develop radiotracers for the Positron Emission Tomography (PET), we labelled both the mecamylamine and SIB-1553A with carbon-11 to study the nicotinic cholinergic receptors (nAChRs). The radiosynthesis of [11C]-t-PAstop and the labelling with tritium of one analogue were realized for cerebral ischemia PET studies. The [11C]-mecamylamine, a non-competitive and non-selective nAChRs antagonist was synthesized in 45 min via a N-[11C]-methylation reaction. In the rat brain, the ex vivo studies showed no radio-metabolite 45 min after the injection of [11C]-mecamylamine. The uptake kinetics in the rat brain or in vivo by PET in the anesthetized baboon or in the conscious monkey, reached a plateau around 45-50 min after injection. However, the saturation or displacement experiments did not permit to exhibit nor a significant difference of labelling between the different cerebral regions nor a specific uptake. In consequence, the [11C]-mecamylamine was not an appropriate radioligand for nAChRs PET study. The labelling of [11C]-SIB 1553A, a selective agonist for the nicotinic β4 subunit, required the synthesis in 5 steps (56% overall yield) of precursor for the incorporation of carbon-11. The radiosynthesis was performed in 36 min by a N-[11C]-methylation reaction (yield: 75%). The [11C]-t-PAstop was obtained from [11C]-KCN with yields from 80 to 90%. For the first time with carbon-11, the formation of an amidine group was realized from a nitrile group. The labelling by isotopic exchange of hydrogen by tritium of the t-PAstop did not permit to obtain the [3H]-t-PAstop but a tritiated analogue. This compound will be used to study its vectorization by micro-encapsulation. (author)

  19. Stabilisation of carbonyl free amidinato-manganese(II) hydride complexes: "masked" sources of manganese(I) in organometallic synthesis.

    Science.gov (United States)

    Fohlmeister, Lea; Jones, Cameron

    2016-01-28

    Reaction of the amidinato-manganese(ii) bromide complex, [{(κ(2)-N,N'-Piso)Mn(μ-Br)}3(THF)2] (Piso = [(DipN)2CBu(t)](-), Dip = 2,6-diisopropylphenyl), with K[BHEt3] affords the first example of a structurally authenticated amidinato-manganese(ii) hydride complex, [{(N-,η(3)-arene-Piso)Mn(μ-H)2}2], via a process which involves a change in the amidinate coordination mode. Treatment of the bulkier precursor complex, [{(Piso'')Mn(μ-Br)}n] (Piso'' = [(Dip''N)2CBu(t)](-), Dip'' = C6H2Pr(i)2(CPh3)-2,6,4), with K[BHEt3] did not lead to an isolable manganese hydride complex, but its reaction with the magnesium(i) complex, [{((Mes)Nacnac)Mg}2] ((Mes)Nacnac = [(MesNCMe)2CH](-), Mes = mesityl), did. This reaction presumably proceeds via a reactive manganese(i) intermediate, which abstracts hydrogen from a reaction component to give [{(κ(2)-N,N'-Piso'')Mn(μ-H)}3]. A comparison of the reactivities of [{(N-,η(3)-arene-Piso)Mn(μ-H)2}2] and the isomorphous manganese(i) complex, [{(N-,η(3)-arene-Piso)Mn}2], toward CO, O2 and N2O was carried out. Reactions with the manganese(i) and manganese(ii) species gave identical results, namely the formation of the manganese(i) carbonyl complex, [(κ(2)-N,N'-Piso)Mn(CO)4] (reactions with CO), and the manganese(iii)-μ-oxo complex, [{(κ(2)-N,N'-Piso)Mn(μ-O)}2] (reactions with O2 and N2O). These results indicate that [{(N-,η(3)-arene-Piso)Mn(μ-H)2}2] can act as a "masked" source of an amidinato-manganese(i) fragment in synthetic transformations. PMID:26674008

  20. Imidate-Based Cross-Linkers for Structural Proteomics: Increased Charge of Protein and Peptide Ions and CID and ECD Fragmentation Studies

    Science.gov (United States)

    Koolen, Hector H. F.; Gomes, Alexandre F.; Schwab, Nicolas V.; Eberlin, Marcos N.; Gozzo, Fabio C.

    2014-07-01

    Chemical cross-linking is an attractive low-resolution technique for structural studies of protein complexes. Distance constraints obtained from cross-linked peptides identified by mass spectrometry (MS) are used to construct and validate protein models. Amidinating cross-linkers such as diethyl suberthioimidate (DEST) have been used successfully in chemical cross-linking experiments. In this work, the application of a commercial diimidate cross-linking reagent, dimethyl suberimidate (DMS), was evaluated with model peptides and proteins. The peptides were designed with acetylated N-termini followed by random sequences containing two Lys residues separated by an Arg residue. After cross-linking reactions, intra- and intermolecular cross-linked species were submitted to CID and ECD dissociations to study their fragmentation features in the gas phase. Fragmentation of intramolecular peptides by collision induced dissociation (CID) demonstrates a unique two-step fragmentation pathway involving formation of a ketimine as intermediate. Electron capture and electron transfer dissociation (ECD and ETD) experiments demonstrated that the cyclic moiety is not dissociated. Intermolecular species demonstrated previously described fragmentation behavior in both CID and ECD experiments. The charge state distributions (CSD) obtained after reaction with DMS were compared with those obtained with disuccinimidyl suberate (DSS). CSDs for peptides and proteins were increased after their reaction with DMS, owing to the higher basicity of DMS modified species. These features were also observed in LC-MS experiments with bovine carbonic anhydrase II (BCA) after cross-linking with DMS and tryptic proteolysis. Cross-linked peptides derived from this protein were identified at high confidence and those species were in agreement with the crystal structure of BCA.

  1. 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

  2. Selectivity in ligand binding to uranyl compounds: A synthetic, structural, thermodynamic and computational study

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, John [Univ. of California, Berkeley, CA (United States)

    2015-01-21

    The uranyl cation (UO₂²⁺) is the most abundant form of uranium on the planet. It is estimated that 4.5 billion tons of uranium in this form exist in sea water. The ability to bind and extract the uranyl cation from aqueous solution while separating it from other elements would provide a limitless source of nuclear fuel. A large body of research concerns the selective recognition and extraction of uranyl. A stable molecule, the cation has a linear O=U=O geometry. The short U-O bonds (1.78 Å) arise from the combination of uranium 5f/6d and oxygen 2p orbitals. Due to the oxygen moieties being multiply bonded, these sites were not thought to be basic enough for Lewis acidic coordination to be a viable approach to sequestration. The goal of this research is thus to broaden the coordination chemistry of the uranyl ion by studying new ligand systems via synthetic, structural, thermodynamic and computational methods. It is anticipated that this fundamental science will find use beyond actinide separation technologies in areas such as nuclear waste remediation and nuclear materials. The focus of this study is to synthesize uranyl complexes incorporating amidinate and guanidinate ligands. Both synthetic and computational methods are used to investigate novel equatorial ligand coordination and how this affects the basicity of the oxo ligands. Such an understanding will later apply to designing ligands incorporating functionalities that can bind uranyl both equatorially and axially for highly selective sequestration. Efficient and durable chromatography supports for lanthanide separation will be generated by (1) identifying robust peptoid-based ligands capable of binding different lanthanides with variable affinities, and (2) developing practical synthetic methods for the attachment of these ligands to Dowex ion exchange resins.

  3. Preparation and properties of pure acrylic polymer latex using novel emulsifying system%新型乳化体系下纯丙聚合物乳液的制备及性能研究

    Institute of Scientific and Technical Information of China (English)

    王太林; 何金国

    2015-01-01

    The acrylic polymer latex was successfully prepared via semi-continuous seeded emulsion polymerization, using methyl methacrylat (MMA) and butyl acrylate (BA)as the monomers monobutyl itaconate (MBI) as the functional monomer, mixture of tetradecyl dimethyl hydroxy propyl betaine and octylphenol polyoxyethylene ether(OP-10) as the emulsifier and 2,2'-azobis (2-methyl propion-amidine) dihydrochloride (V-50) as the initiator. The effects of the amounts of the emulsifiers, V-50 and MBI on the properties of the latex and its film were investigated. The results showed that the optimum conditions for preparing the latex were as follows: the amounts of emulsifier, V-50 and MBI were 7%, 0.5% and 4%,respectively.%采用半连续乳液聚合法,以甲基丙烯酸甲酯(MMA),丙烯酸正丁酯(BA)为主单体,衣康酸单丁酯(MBI)为功能性单体,偶氮二异丁脒盐酸盐(V-50)为引发剂,两性表面活性剂十四烷基二甲基羟丙基甜菜碱与烷基酚聚氧乙烯醚(O P-10)复配作为乳化剂,合成了丙烯酸酯乳液。分别探讨了乳化剂,V-50和MBI的用量对乳液及乳胶膜性能的影响。结果表明当乳化剂的用量占单体质量的7%,V-50为0.5%,MBI为4%时,乳液的综合性能最佳。

  4. Synthesis and radiofluorination of putative NMDA receptor ligands

    International Nuclear Information System (INIS)

    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-[18F]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

  5. ESTUDO DA EFICÁCIA “IN VITRO” DO AMITRAZ E DA DELTAMETRINA COMO CARRAPATICIDA NO CONTROLE DE Boophilus microplus (CANESTRINI, 1887 NA BACIA LEITEIRA DA MICRORREGIÃO DE GOIÂNIA - GOIÁS STUDY ON THE EFFICACY OF AMITRAZ AND DELTAMETHRIN AS ACARACIDES AGAINST Boophilus microplus (CAMESTRINI, 1887 IN THE DAIRY AREA OF GOIÂNIA - GOIÁS

    Directory of Open Access Journals (Sweden)

    Guido Fontgalland Coelho Linhares

    2007-09-01

    Full Text Available

    Para avaliar a eficácia antiixodídica do amitraz e da deltametrina sobre o Boophilus microplus na bacia leiteira da microrregião de Goiânia - Goiás, foram realizados testes in vitro por imersão de teleóginas, colhidas diretamente de bovinos da região. Os princípios ativos foram ensaiados na concentração de 250 ppm, através da avaliação da percentagem de inibição da reprodução (%INR. Entre eles o amitraz apresentou a melhor eficácia, com valor de 97,11%, estando acima do valor mínimo exigido pelo Ministério da Agricultura para produtos carrapaticidas. A deltametrina apresentou o valor de 70,86%, revelando uma eficácia insatisfatória.

    PALAVRAS-CHAVE: Boophilus microplus; carrapaticida; amidinas; piretróides; bovinos.

    The efficacy of amitraz and deltamethrin as acaricides against Boophilus microplus (Canestrini, 1887 was evaluated through an in vitro immersion test using engorged female ticks collected in the dairy area of the microrregion of Goiânia, State of Goiás. The effectiveness of the experimental compounds, on concentrations of 250 ppm, was determined by the effect as measured in percentages of inhibited reproduction (%INR after treatments of the ticks with liquid formulations. The results were: amitraz showed the best efficacy with a percentage of inhibited reproduction (%ITR of 97.11%; for deltamethrin such value was 70.86%, which was considered very low to be used as an acaricide.

    KEY-WORDS: Boophilus microplus; acaricides; amidines; pyrethroids; cattle.

  6. Substrate specificity of formylglycinamidine synthetase

    Energy Technology Data Exchange (ETDEWEB)

    Schendel, F.J.; Stubbe, J.

    1986-04-22

    Formylglycinamidine ribonucleotide (FGAM) synthetase, which catalyzes the conversion of formylglycinamide ribonucleotide (FGAR), glutamine, and ATP to FGAM, ADP, glutamate, and Pi, has been purified to homogeneity (sp act. 0.20 mumol min-1 mg-1) from chicken liver by an alternative procedure to that of Buchanan et al. (Buchanan, J. M., Ohnoki, S., and Hong, B. S. (1978) Methods Enzymol. 51, 193-201) (sp act. 0.12 mumol min-1 mg-1). A variety of new analogues of formylglycinamide ribonucleotide have been prepared in which the formylglycinamide arm (R = CH/sub 2/NHCHO) has been replaced by R = CH/sub 3/, CH/sub 2/OH, CH/sub 2/Cl, CH/sub 2/NH/sub 3/, CH/sub 2/NHCOCH/sub 3/, CH/sub 2/NHCOCH/sub 2/Cl, CH/sub 2/NHCO/sub 2/CH/sub 2/Ph, and L-CHC-H/sub 3/NHCHO. These compounds have been characterized by 1H and 13C NMR spectroscopy. With compounds R = CH/sub 3/, CH/sub 2/OH, and CH/sub 2/NHCOCH/sub 3/ and ATP, in the presence or absence of glutamine, FGAM synthetase catalyzes the production of Pi at 4.5, 48, and 20%, respectively, the rate of production of Pi from formylglycinamide ribonucleotide. Only R = CH/sub 2/NHCOCH/sub 3/ causes glutaminase activity as well as ATPase activity and has been shown to be converted to the amidine analogue. Both FGAR (R = CH/sub 2/NHCHO) and the FGAR analogue (R = CH/sub 2/NHCHOCH/sub 3/) in the presence of ATP and FGAM synthetase and in the absence of glutamine form a complex isolable by Sephadex G-50 chromatography. FGAM synthetase is thus highly specific for its formylglycine side chain. (18O)-beta-FGAR was prepared biosynthetically, and FGAM synthetase was shown by 31P NMR spectroscopy to catalyze the transfer of amide 18O to inorganic phosphate.

  7. Enhancing the Value of Free Metals in the Synthesis of Lanthanoid Formamidinates: Is a Co-oxidant Needed?

    Science.gov (United States)

    Deacon, Glen B; Junk, Peter C; Werner, Daniel

    2016-01-01

    divalent rare-earth amidinate field. PMID:26538406

  8. Factors that influence the prevalence of acaricide resistance and tick-borne diseases.

    Science.gov (United States)

    Foil, L D; Coleman, P; Eisler, M; Fragoso-Sanchez, H; Garcia-Vazquez, Z; Guerrero, F D; Jonsson, N N; Langstaff, I G; Li, A Y; Machila, N; Miller, R J; Morton, J; Pruett, J H; Torr, S

    2004-10-28

    obtain a comprehensive profile of their susceptibility to various pesticides. More outbreaks of clinical bovine babesisois and anaplasmosis have been associated with the presence of synthetic pyrethroid (SP) resistance when compared to OP and amidine resistance. This may be the result of differences in the temporal and geographic patterns of resistance development to the different acaricides. If acaricide resistance develops slowly, herd immunity may not be affected. The use of pesticides for the control of pests of cattle other than ticks can affect the incidence of tick resistance and tick-borne diseases. Simple analytical models of tick- and tsetse-borne diseases suggest that reducing the abundance of ticks, by treating cattle with pyrethroids for example, can have a variety of effects on tick-borne diseases. In the worst-case scenario, the models suggest that treating cattle might not only have no impact on trypanosomosis but could increase the incidence of tick-borne disease. In the best-case, treatment could reduce the incidence of both trypanosomosis and tick-borne diseases Surveys of beef and dairy properties in Queensland for which tick resistance to amitraz was known were intended to provide a clear understanding of the economic and management consequences resistance had on their properties. Farmers continued to use amitraz as the major acaricide for tick control after the diagnosis of resistance, although it was supplemented with moxidectin (dairy farms) or fluazuron, macrocyclic lactones or cypermethrin/chlorfenvinphos. PMID:15476966

  9. Spontaneous rearrangement of aminoalkylisothioureas into mercaptoalkylguanidines, a novel class of nitric oxide synthase inhibitors with selectivity towards the inducible isoform.

    Science.gov (United States)

    Southan, G J; Zingarelli, B; O'Connor, M; Salzman, A L; Szabó, C

    1996-02-01

    1. The generation of nitric oxide (NO) from L-arginine by NO synthases (NOS) can be inhibited by guanidines, amidines and S-alkylisothioureas. Unlike most L-arginine based inhibitors, however, some guanidines and S-alkylisothioureas, in particular aminoethylisothiourea (AETU), show selectivity towards the inducible isoform (iNOS) over the constitutive isoforms (endothelial, ecNOS and brain isoform, bNOS) and so may be of therapeutic benefit. In the present study we have investigated the effects of AETU and other aminoalkylisothioureas on the activities of iNOS, ecNOS and bNOS. 2. AETU, aminopropylisothiourea (APTU) and their derivatives containing alkyl substituents on one of the amidino nitrogens, potently inhibit nitrite formation by immunostimulated J774 macrophages (a model of iNOS activity) with EC50 values ranging from 6-30 microM (EC50 values for NG-methyl-L-arginine (L-NMA) and NG-nitro-L-arginine were 159 and > 1000 microM, respectively). The inhibitory effects of these aminoalkylisothioureas (AATUs) were attentuated by L-arginine in the incubation medium, indicating that these agents may complete with L-arginine for its binding site on NOS. 3. The above AATUs undergo chemical conversion in neutral or basic solution (pH 7 or above) as indicated by (1) the disappearance of AATUs from solution as measured by h.p.l.c., (2) the generation of free thiols not previously present and (3) the isolation of species (as picrate and flavianate salts) from neutral or basic solutions of AATUs that are different from those obtained from acid solutions. 4. Mercaptoalkylguanidines (MAGs) were prepared and shown to be potent inhibitors of iNOS activity with EC50s comparable to those of their isomeric AATUs. 5. These findings suggest that certain AATUs exert their potent inhibitory effects through intramolecular rearrangement to mercaptoalkylguanidines (MAGs) at physiological pH. Those AATUs not capable of such rearrangement do not exhibit the same degree of inhibition of i

  10. Avaliação in vitro da eficácia de acaricidas sobre Boophilus microplus (Canestrini, 1887 (Acari: Ixodidae de bovinos no município de Ilhéus, Bahia, Brasil In vitro valuation of acaricides efficiency to Boophilus microplus (Canestrini, 1887 (Acari: Ixodidae from bovines at the region of Ilhéus, Bahia, Brazil

    Directory of Open Access Journals (Sweden)

    Dunezeu Alves Campos Júnior

    2005-12-01

    were performed with engorged females of B. microplus collected from 30 farms randomly chosen in a group of 96 interviewed at the region. The current study showed the existence of resistance or sensibility of the populations of B. microplus to the contact acaricides commonly used at cattle properties of the region of Ilhéus. The four acaricides tested showed the following levels of efficiency: Amidin - 30.95%; Deltamethrin - 65.04%; Cipermethrin / diclorvos - 75.73%; and Triclorfon / coumaphos / cyfluthrin - 75.13%.

  11. 含氟丙烯酸酯乳液整理剂的合成及其在织物防水防油整理中的应用%Synthesis of fluoridated acrylic emulsion finishing agent and application in water and oil proofing finish on cotton fabric

    Institute of Scientific and Technical Information of China (English)

    何彦萱; 刘金华; 郭玉良; 刘军; 卢霜

    2014-01-01

    以甲基丙烯酸甲酯、丙烯酸异冰片酯、甲基丙烯酸十二烷基酯、六氟丙烯酸丁酯、二甲基丙烯酸丁二醇酯、3-氯-2-羟丙基甲基丙烯酸酯为单体,偶氮二异丁基脒盐酸盐为引发剂,合成阳离子含氟丙烯酸酯乳液,并应用于棉织物的拒水拒油整理.用红外光谱对聚合物进行表征,研究了交联剂对胶膜接触角及整理棉织物拒水拒油性能的影响.结果表明:未加交联剂,胶膜接触角达111.58°;加2%的三官能团氮丙啶交联剂,胶膜接触角可以提高到118.35°.经该乳液整理后的织物不仅具有较好的拒水性能,而且有突出的拒油性能,拒水达100分,拒油达6级;同时,耐久性良好,水洗30次以后,拒水为90分,拒油为5级.%Cationic fluorinated acrylic emulsions were synthesized with methyl methacrylate, isobornyl ac⁃rylate, lauryl methacrylate, hexafluorobutyl acrylate, butylene glycol dimethacrylate, 3- chloro- 2- hydroxypropyl methacrylate as monomers and azobis isobutyl amidine hydrochloride as the initiator, which was applied in wa⁃ter and oil repel ent finishing of cotton fabrics. The polymer emulsion properties were characterized with infra⁃red spectrometer. The effects of the crosslinking agent on the contact angle of the film and the water and oil repel ent properties of the finished fabrics were investigated. The results showed that the contact angle of the film was 111.58°, when 2% tri- functional aziridine crosslinking agent was added, the contact angle of the film was increased to 118.35°. The results showed that the finished fabric not only had good water repel ence but also had outstanding oil repel ence. The waterproofing level was 100 points, the oil repel ent level was grade 6; at the same time, the durability was excellent, after 30 times of washing, the waterproofing level was 90 points, and the oil repel ent level was grade 5.

  12. Suscetibilidade de Rhipicephalus (Boophilus microplus a carrapaticidas em Mato Grosso do Sul, Brasil Susceptibility of Rhipicephalus (Boophilus microplus to acaricides in Mato Grosso do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Alberto Gomes

    2011-08-01

    demonstrada aos distintos produtos testados sugere que a resistência do carrapato a diferentes classes esteja amplamente disseminada no Estado, motivo pelo qual recomenda-se a realização rotineira de testes de suscetibilidade antes da seleção e aplicação de produtos acaricidas para controle do carrapato.The cattle tick, Rhipicephalus (Boophilus microplus, is one of the most important ectoparasites of bovines, requiring adoption of control measures mainly in Bos taurus herds and its crossbreeds. Its control has becoming increasingly difficult due to selection of resistant populations by commercial products. This study aimed to know the status of cattle tick resistance to acaricides in the state of Mato Grosso do Sul. From October 2003 to October 2006 acaricide bioassays were conducted on cattle ticks from eleven of the most important livestock regions of the state. Adult immersion tests using regular commercial products according to label recommendations were followed by the evaluation of biological parameters. Twelve acaricide products containing one or more of seven active ingredients, from three chemical classes: amidine (amitraz, synthetic pyrethroid (cypermethrin, and organophosphates (chlorfenvinphos, chlorpyriphos, diazinon, dichlorvos, and ethion were tested. Low tick susceptibility was observed in all ranches, with several populations showing virtually no susceptibility to one or more products. Despite the great variation of susceptibility shown by the populations to each acaricide, a gradient of efficacy of these products was observed. Regardless of the acaricide class, the average efficacy of products containing a single active ingredient (19.94%-64.27% was generally lower than that showed by the mixtures, pyrethroid-organophosphate (46.38%-82.68% and between organophosphates (85.28%-97.68%. The mixture containing pyrethroid + OF + synergist + repellent (cypermethrin + chlorpyrifos + citronellal + piperonyl butoxide showed 100% efficacy, although it was

  13. Bulk gold catalyzed oxidation reactions of amines and isocyanides and iron porphyrin catalyzed N-H and O-H bond insertion/cyclization reactions of diamines and aminoalcohols

    Energy Technology Data Exchange (ETDEWEB)

    Klobukowski, Erik [Iowa State Univ., Ames, IA (United States)

    2011-01-01

    conditions, it was found that the oxidative dehydrogenation of dibenzylamine to Nbenzylidenebenzylamine, with N-methylmorpholine N-oxide (NMMO), was nearly quantitative (96%) within 24 h. However, the reaction with oxygen was much slower, with only a 52% yield of imine product over the same time period. Moreover, the rate of reaction was found to be influenced by the nature of the amine N-oxide. For example, the use of the weakly basic pyridine N-oxide (PyNO) led to an imine yield of only 6% after 24 h. A comparison of amine N-oxide and O2 was also examined in the oxidation of PhCH{sub 2}OH to PhCHO catalyzed by bulk gold. In this reaction, a 52% yield of the aldehyde was achieved when NMMO was used, while only a 7% product yield was afforded when O{sub 2} was the oxidant after 48 h. The bulk gold-catalyzed oxidative dehydrogenation of cyclic amines generates amidines, which upon treatment with Aerosil and water were found to undergo hydrolysis to produce lactams. Moreover, 5-, 6-, and 7-membered lactams could be prepared through a one-pot reaction of cyclic amines by treatment with oxygen, water, bulk gold, and Aerosil. This method is much more atom economical than industrial processes, does not require corrosive acids, and does not generate undesired byproducts. Additionally, the gold and Aerosil catalysts can be readily separated from the reaction mixture. The second project involved studying iron(III) tetraphenylporphyrin chloride, Fe(TPP)Cl, as a homogeneous catalyst for the generation of carbenes from diazo reagents and their reaction with heteroatom compounds. Fe(TPP)Cl, efficiently catalyzed the insertion of carbenes derived from methyl 2-phenyldiazoacetates into O-H bonds of aliphatic and aromatic alcohols. Fe(TPP)Cl was also found to be an effective catalyst for tandem N-H and O-H insertion/cyclization reactions when 1,2-diamines and 1,2-alcoholamines were treated with diazo reagents. This approach provides a one-pot process for synthesizing piperazinones and