(Tris{2-[(5-hy­droxy­pyridin-2-yl-κN)methyl­idene­imino-κN]eth­yl}amine)­zinc dinitrate

Science.gov (United States)

Seredyuk, Maksym; Znovjyak, Kateryna O.; Haukka, Matti; Pavlenko, Vadim A.; Bokach, Nadezhda A.

2011-01-01

In the complex cation of the title compound, [Zn(C24H27N7O3)](NO3)2, the tripodal tris­{[2-(5-hy­droxy­pyridin-2-yl)methyl­idene­imino]­eth­yl}amine ligand is coordin­ated to the Zn atom through the three pyridine and three imino N atoms. The coordination sphere of the Zn atom is based on an octahedron with a significant distortion towards trigonal prismatic, the twist angle being 45.58 (9)°. The crystal packing is formed by L and D anti­podes arranged in layers disposed parallel to the b axis. Strong O—H⋯O hydrogen bonding exists between the hy­droxy groups of the ligand and the nitrate anion. PMID:22199579

Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yloxy-2-methylpropan-2-yl-2,6-dimethylisonicotinamide (S2218

Directory of Open Access Journals (Sweden)

Donald S. Karanewsky

Full Text Available A toxicological evaluation of N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yloxy-2-methylpropan-2-yl-2,6-dimethylisonicotinamide (S2218; CAS 1622458-34-7, a flavour with modifying properties, was completed for the purpose of assessing its safety for use in food and beverage applications. S2218 exhibited minimal oxidative metabolism in vitro, and in rat pharmacokinetic studies, the compound was poorly orally bioavailable and rapidly eliminated. S2218 was not found to be mutagenic in an in vitro bacterial reverse mutation assay, and was found to be neither clastogenic nor aneugenic in an in vitro mammalian cell micronucleus assay. In subchronic oral toxicity studies in male and female rats, the NOAEL was 140 mg/kg bw/day (highest dose tested for S2218 sulfate salt (S8069 when administered as a food ad-mix for 13 consecutive weeks. Furthermore, S2218 sulfate salt demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats. Keywords: Flavours with modifying properties, S2218, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation, Developmental toxicity evaluation

Design and syntheses of novel N-(benzothiazol-5-yl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione and N-(benzothiazol-5-yl)isoindoline-1,3-dione as potent protoporphyrinogen oxidase inhibitors.

Science.gov (United States)

Jiang, Li-Li; Zuo, Yang; Wang, Zhi-Fang; Tan, Yin; Wu, Qiong-You; Xi, Zhen; Yang, Guang-Fu

2011-06-08

Discovery of protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors has been one of the hottest research areas in the field of herbicide development for many years. As a continuation of our research work on the development of new PPO-inhibiting herbicides, a series of novel N-(benzothiazol-5-yl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-diones (1a-p) and N-(benzothiazol-5-yl)isoindoline-1,3-diones (2a-h) were designed and synthesized according to the ring-closing strategy of two ortho-substituents. The bioassay results indicated that some newly synthesized compounds exhibited higher PPO inhibition activity than the control of sulfentrazone. Compound 1a, S-(5-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-6-fluorobenzothiazol-2-yl) O-methyl carbonothioate, was identified as the most potent inhibitor with k(i) value of 0.08 μM, about 9 times higher than that of sulfentrazone (k(i) = 0.72 μM). Further green house assay showed that compound 1b, methyl 2-((5-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-6-fluorobenzothiazol-2-yl)thio)acetate, exhibited herbicidal activity comparable to that of sulfentrazone even at a concentration of 37.5 g ai/ha. In addition, among six tested crops, wheat exhibited high tolerance to compound 1b even at a dosage of 300 g ai/ha. These results indicated that compound 1b might have the potential to be developed as a new herbicide for weed control of wheat field.

Crystal structure of [2-({4-[2,6-bis(pyridin-2-ylpyridin-4-yl]phenyl}(methylaminoethanol-κ3N,N′,N′′]bis(thiocyanato-κNzinc N,N-dimethylformamide monosolvate

Directory of Open Access Journals (Sweden)

Shi-Chao Wang

2014-10-01

Full Text Available In the title compound, [Zn(NCS2(C24H22N4O]·C3H7NO, the ZnII cation is N,N′,N′′-chelated by one 2-({4-[2,6-bis(pyridin-2-ylpyridin-4-yl]phenyl}(methylaminoethanol ligand and coordinated by two thiocyanate anions in a distorted N5 trigonal–bipyramidal geometry. In the molecule, the three pyridine rings are approximately coplanar [maximum deviation = 0.026 (5 Å], and the mean plane of the three pyridine rings is twisted to the benzene ring with a small dihedral angle of 5.9 (2°. In the crystal, complex molecules are linked by weak C—H...O hydrogen bonds into supramolecular chains propagated along [110]; π–π stacking is observed between adjacent chains [centroid–centroid distance = 3.678 (4 Å]. The dimethylformamide solvent molecules are linked with the complex chains via weak C—H...O hydrogen bonds.

[2,6-Difluoro-3-(pyridin-2-yl-κNpyridin-4-yl-κC4](pentane-2,4-dionato-κ2O,O′iridium(III

Directory of Open Access Journals (Sweden)

Kaijun Luo

2013-11-01

Full Text Available The title compound, [Ir(C10H5F2N22(C5H7O2], has a distorted octahedral coordination geometry around the IrIII atom, retaining the cis-C,C/trans-N,N chelate disposition in two 2,6-difluoro-3-(pyridin-2-yl-κNpyridin-4-yl ligands which are nearly mutually perpendicular [dihedral angle = 82.75 (15°]. The molecular structure is stabilized by weak C—H...O and C—H...F hydrogen-bond interactions. The crystal structure is stabilized by π–π stacking interactions (centroid–centroid distance = 3.951 Å.

Synthesis, crystal structure and properties of [Co(L2](ClO42 (L=1,3-bis(1H-benzimidazol-2-yl-2-oxapropane

Directory of Open Access Journals (Sweden)

Tavman Aydin

2015-01-01

Full Text Available The reaction of 1,3-bis(1H-benzimidazol-2-yl-2-oxapropane (L with Co(ClO42•6H2O in absolute ethanol produces di[1,3-bis(1H-benzimidazol-2-yl-2-oxapropane-k2N,N’]cobalt(IIdiperchlorate chelate complex ([Co(L2](ClO42, 1. The complex 1 was characterized by elemental analysis, magnetic moment, molar conductivity, thermogravimetric analysis, FT-IR, UV-visible, mass spectrometry, and its solid state structure was determined by single crystal X-ray diffraction. According to the thermogravimetric analysis data, there is no any water coordinated or uncoordinated in 1 as well as elemental analysis. The complex 1 has 1:2 M:L ionic characteristic according to the molar conductivity. In the complex, the distances between the cobalt and the ethereal oxygen atoms (Co1-O2: 2.805(3; Co2-O1: 2.752(2 Å show the semi-coordination bonding and the Co(II ion is six-coordinated with a N4O2 ligand set, resulting in a distorted octahedron.

Biocatalytic Asymmetric Synthesis of (1R, 2S)-N-Boc-vinyl-ACCA Ethyl Ester with a Newly Isolated Sphingomonas aquatilis.

Science.gov (United States)

Zhu, Shaozhou; Shi, Ying; Zhang, Xinyu; Zheng, Guojun

2018-02-01

1-amino cyclopropane-1-carboxylic acid (ACCA) and its derivatives are essential pharmacophoric unit that widely used in drug research and development. Specifically, (1R, 2S)-N-Boc-vinyl-ACCA ethyl ester (vinyl-ACCA) is a key chiral intermediate in the synthesis of highly potent hepatitis C virus (HCV) NS3/4A protease inhibitors such as asunaprevir and simeprevir. Developing strategies for the asymmetric synthesis of vinyl-ACCA is thus extremely high demand. In this study, 378 bacterial strains were isolated from soil samples using N-Boc-vinyl-ACCA ethyl ester as the sole carbon source and were screened for esterase activity. Fourteen of which worked effectively for the asymmetric synthesis of (1R, 2S)-N-Boc-1-vinyl ACCA ethyl ester. The strain CY-2, identified as Sphingomonas aquatilis, which showed the highest stability and enantioselectivity was selected as whole cell biocatalyst for further study. A systematic study of all factors influencing the enzymatic hydrolysis was performed. Under optimized conditions, resolution of rac-vinyl-ACCA to (1R, 2S)-N-Boc-1-vinyl ACCA ethyl ester with 88.2% ee and 62.4% conversion (E = 9) was achieved. Besides, S. aquatilis was also used to transform other 10 different substrates. Notably, it was found that 7 of them could be stereoselectively hydrolyzed, especially for (1R,2S)-1-amino-vinyl-ACCA ethyl ester hydrochloride (99.6% ee, E>200). Our investigations provide a new efficient whole cell biocatalyst for resolution of ACCA and might be developed for industry application.

Synthesis of radioiodinated N-succinimidyl 3-[125I] iodobenzoate

International Nuclear Information System (INIS)

Li Junling; Wang Lihua; Zhang Lan; Tian Haibin; Wang Yongxian

2003-01-01

N-Succinimidyl 3-(tri-n-butylstannyl) benzoate (ATE) was radioiodinated using Iodogen as oxidant and useful conjugate S 125 IB of labeling proteins was obtained. ATE and Iodogen affecting labeling proteins were successfully isolated from S 125 IB by Sep-Pak silica. The labeling efficiency was more than 93%. Several factors affecting labeling such as labeling time, the amount of Iodogen and the mole ratio of ATE to Na 125 I, were studied. The better labeling conditions were obtained as follows: mole ratio of ATE to Na 125 I=6:1, Iodogen=7 μg, labeling time=5 min in room temperature

Antimalarial activity of the bisquinoline trans-N1,N2-bis (7- chloroquinolin-4-yl)cyclohexane-1,2-diamine: Comparison of two stereoisomers and detailed evaluation of the S,S enantiomer, Ro 47-7737

NARCIS (Netherlands)

Ridley, R.G.; Matile, H.; Jaquet, C.; Dorn, A.; Hofheinz, W.; Leupin, W.; Masciadri, R.; Theil, F.P.; Richter, W.F.; Girometta, M.A.; Guenzi, A.; Urwyler, H.; Gocke, E.; Potthast, J.M.; Csato, M.; Thomas, A.; Peters, W.

1997-01-01

The S,S enantiomer of the bisquinoline trans-N1,N2-bis(7- chloroquinolin-4-yl)cyclohexane-1,2-diamine, Ro 47-7737, is significantly more potent against chloroquine-resistant Plasmodium falciparum than the R,R enantiomer and the previously described racemate. Both the enantiomers and the racemate are

New optically active and thermally stable poly(amide-imide)s containing N,N'-(Bicyclo[2,2,2]oct-7-ene-2,3,5,6-tetracarboxylic)-bis-L-alanine and aromatic diamines: synthesis and characterization

International Nuclear Information System (INIS)

Faghihi, Khalil; Absalar, Morteza; Hajibeygi, Mohsen

2009-01-01

Five new optically active poly(amide-imide)s (PAIs) 6a-e were prepared by direct polycondensation reaction of the newly synthesized N,N'-(bicyclo[2,2,2]oct-7-ene-2,3,5,6-tetra carboxylic)-bis-L-alanine 4 with various aromatic diamines 5a-e using polar aprotic solvents such as N-methyl-2-pyrrolidone (NMP). In this technique triphenyl phosphite (TPP) and pyridine were used as condensing agents to form poly(amide-imide)s through the N-phosphonium salts of pyridine. All of the polymers were obtained in quantitative yields with inherent viscosities between 0.29-0.46 dL g -1 and were highly soluble in polar aprotic solvents such as N,N-dimethyl acetamide (DMAc), N,N-dimethyl formamide (DMF), dimethyl sulfoxide (DMSO), N-methyl- 2-pyrrolidone (NMP) and solvents such as sulfuric acid. They were fully characterized by means of 1 H NMR, FTIR spectroscopy, elemental analyses, inherent viscosity, solubility test, specific rotation and thermal properties of these polymers were investigated using thermogravimetric analysis techniques (TGA and DTG). (author)

Two-electron capture into autoionising configurations N/sup 4 +/(1snln'l') with n = 2,3,4 and n' >= n, observed by electron spectrometry in collisions of N/sup 6 +/(1s) with He and H/sub 2/, at 4. 2 keV amu/sup -1/

Energy Technology Data Exchange (ETDEWEB)

Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Marrakchi, A.I.; Dousson, S.; Hitz, D.

1984-04-14

Double electron transfer into autoionising states N/sup 4 +/(1snln'l'), with n = 2,3,4 and n' >= n has been observed in a collision between a one-electron highly charged N/sup 6 +/(1s) ion and a two-electron target (He or H/sub 2/), by electron spectrometry. The same configurations are excited in the two collisional systems but with very different probabilities. Electron capture mainly occurs into 1s2ln'l' in He-systems whereas transfer into 1s3ln'l' is stronger in H/sub 2/ systems.

Radiolabelling of isopeptide N epsilon-(gamma-glutamyl)-L-lysine by conjugation with N-succinimidyl-4-[18F]fluorobenzoate.

Science.gov (United States)

Wüst, F; Hultsch, C; Bergmann, R; Johannsen, B; Henle, T

2003-07-01

The isopeptide N(epsilon)-(gamma-glutamyl)-L-lysine 4 was labelled with 18F via N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). A modified approach for the convenient synthesis of [18F]SFB was used, and [18F]SFB could be obtained in decay-corrected radiochemical yields of 44-53% (n = 20) and radiochemical purity >95% within 40 min after EOB. For labelling N(epsilon)-(gamma-glutamyl)-L-lysine with [18F]SFB the effects of isopeptide concentration, temperature, and pH were studied to determine the optimum reaction conditions. The coupling reaction was shown to be temperature and pH independent while being strongly affected by the isopeptide concentration. Using the optimized labelling conditions, in a typical experiment 1.3GBq of [18F]SFB could be converted into 447MBq (46%, decay-corrected) of [18F]fluorobenzoylated isopeptide within 45 min, including HPLC purification.

(μ-Acetato-κ2 O:O′)[μ-2,6-bis­({bis­[(pyri­din-2-yl-κN)meth­yl]amino-κN}meth­yl)-4-methyl­phenolato-κ2 O:O](metha­nol-κO)dizinc bis­(perchlorate)

Science.gov (United States)

Das, Biswanath; Haukka, Matti; Nordlander, Ebbe

2014-01-01

The binuclear title complex, [Zn2(C33H33N6O)(CH3COO2)(CH3OH)](ClO4)2, was synthesized by the reaction between 2,6-bis­({[bis­(pyridin-2-yl)meth­yl]amino}­meth­yl)-4-methyl­phenol (H-BPMP), Zn(OAc)2 and NaClO4. The two ZnII ions are bridged by the phenolate O atom of the octadentate ligand and the acetate group. An additional methanol ligand is terminally coordinated to one of the ZnII ions, rendering the whole structure unsymmetric. Other symmetric dizinc complexes of BPMP have been reported. However, to the best of our knowledge, the present structure, in which the two ZnII ions are distinguishable by the number of coordinating ligands and the coordination geometries (octahedral and square-pyramidal), is unique. The dizinc complex is a dication, and two perchlorate anions balance the charge. The –OH group of the coordinating methanol solvent mol­ecule forms a hydrogen bond with a perchlorate counter-anion. One of the anions is disordered over two sets of sites with an occupancy ratio of 0.734 (2):0.266 (2). PMID:24826088

New optically active and thermally stable poly(amide-imide)s containing N,N'-(Bicyclo[2,2,2]oct-7-ene-2,3,5,6-tetracarboxylic)-bis-L-alanine and aromatic diamines: synthesis and characterization

Energy Technology Data Exchange (ETDEWEB)

Faghihi, Khalil; Absalar, Morteza; Hajibeygi, Mohsen [Arak University (Iran, Islamic Republic of). Faculty of Science. Organic Polymer Chemistry Research Lab.

2009-07-01

Five new optically active poly(amide-imide)s (PAIs) 6a-e were prepared by direct polycondensation reaction of the newly synthesized N,N'-(bicyclo[2,2,2]oct-7-ene-2,3,5,6-tetra carboxylic)-bis-L-alanine 4 with various aromatic diamines 5a-e using polar aprotic solvents such as N-methyl-2-pyrrolidone (NMP). In this technique triphenyl phosphite (TPP) and pyridine were used as condensing agents to form poly(amide-imide)s through the N-phosphonium salts of pyridine. All of the polymers were obtained in quantitative yields with inherent viscosities between 0.29-0.46 dL g{sup -1} and were highly soluble in polar aprotic solvents such as N,N-dimethyl acetamide (DMAc), N,N-dimethyl formamide (DMF), dimethyl sulfoxide (DMSO), N-methyl- 2-pyrrolidone (NMP) and solvents such as sulfuric acid. They were fully characterized by means of {sup 1}H NMR, FTIR spectroscopy, elemental analyses, inherent viscosity, solubility test, specific rotation and thermal properties of these polymers were investigated using thermogravimetric analysis techniques (TGA and DTG). (author)

Synthesis and 125I labeling of N-succinimidyl-3-(tri-n-butylstannyl)benzoate

International Nuclear Information System (INIS)

Liu Zhenfeng; Wang Yongxian; Zhou Wei; Wang Lihua; Xia Jiaoyun; Yin Duanzhi

2005-01-01

N-succinimidyl-3-(tri-n-butylstannyl)benzoate (ATE) and N-succinimidyl-3-iodo-benzoate (SIB) is synthesized. The structures of ATE and SIB are confirmed with 1 HNMR, MS and IR. The yields of ATE and SIB are 45.4% and 71.4%, respectively. ATE is labeled with 125 I. The labeling field is 93.0% and radiochemical purity is over 98.0%. The synthesis and the labeling of ATE have a important value for indirect label of radiopharmaceuticals. (authors)

Technetium-99m labeling of N-[N-(3-diphenylphosphino propionyl)glycyl]cysteine (PN2S-OH) and its methyl ester derivative (PN2S-OMe)

International Nuclear Information System (INIS)

Visentin, Roberta; Giron, Maria Cecilia; Bello, Michele; Mazzi, Ulderico

2004-01-01

N-[N-(3-diphenylphosphinopropionyl)glycyl]cysteine and its methyl ester derivative were labeled with 99m Tc at neutral pH, leading to a single species in high yield (>95%) in 30 min. RP-HPLC comparison with the analogue Re V -oxo complexes identified the labeled compounds as the anti isomers of pentacoordinated 99m TcO[PN 2 S]-OH and 99m TcO[PN 2 S]-OMe complexes. The compounds are stable from pH 7 to pH 9 when 99m TcO[PN 2 S]-OH interconverts to related syn isomer, while 99m TcO[PN 2 S]-OMe undergoes both saponification and interconversion. They exhibit high stability in human plasma and in vivo (mice), and a biodistribution characterized by hepatobiliary excretion

Different hydrogen-bonded chains in the crystal structures of three alkyl N-[(E-1-(2-benzylidene-1-methylhydrazinyl-3-hydroxy-1-oxopropan-2-yl]carbamates

Directory of Open Access Journals (Sweden)

Thais C. M. Noguiera

2015-07-01

Full Text Available The crystal structures of three methylated hydrazine carbamate derivatives prepared by multi-step syntheses from l-serine are presented, namely benzyl N-{(E-1-[2-(4-cyanobenzylidene-1-methylhydrazinyl]-3-hydroxy-1-oxopropan-2-yl}carbamate, C20H20N4O4, tert-butyl N-{(E-1-[2-(4-cyanobenzylidene-1-methylhydrazinyl]-3-hydroxy-1-oxopropan-2-yl}carbamate, C17H22N4O4, and tert-butyl N-[(E-1-(2-benzylidene-1-methylhydrazinyl-3-hydroxy-1-oxopropan-2-yl]carbamate, C16H23N3O4. One of them shows that an unexpected racemization has occurred during the mild-condition methylation reaction. In each crystal structure, the molecules are linked into chains by O—H...O hydrogen bonds, but with significant differences between them.

Crystal structures and Hirshfeld surface analyses of bis-[N,N-bis-(2-meth-oxy-eth-yl)di-thio-carbamato-κ2S,S']di-n-butyl-tin(IV) and [N-(2-meth-oxy-eth-yl)-N-methyl-dithio-carbamato-κ2S,S']tri-phenyl-tin(IV).

Science.gov (United States)

Mohamad, Rapidah; Awang, Normah; Kamaludin, Nurul Farahana; Jotani, Mukesh M; Tiekink, Edward R T

2018-03-01

The crystal and mol-ecular structures of the two title organotin di-thio-carbamate compounds, [Sn(C 4 H 9 ) 2 (C 7 H 14 NO 2 S 2 ) 2 ], (I), and [Sn(C 6 H 5 ) 3 (C 5 H 10 NOS 2 )], (II), are described. Both structures feature asymmetrically bound di-thio-carbamate ligands leading to a skew-trapezoidal bipyramidal geometry for the metal atom in (I) and a distorted tetra-hedral geometry in (II). The complete mol-ecule of (I) is generated by a crystallographic twofold axis (Sn site symmetry 2). In the crystal of (I), mol-ecules self-assemble into a supra-molecular array parallel to (10-1) via methyl-ene-C-H⋯O(meth-oxy) inter-actions. In the crystal of (II), supra-molecular dimers are formed via pairs of weak phenyl-C-H⋯π(phen-yl) contacts. In each of (I) and (II), the specified assemblies connect into a three-dimensional architecture without directional inter-actions between them. Hirshfeld surface analyses confirm the importance of H⋯H contacts in the mol-ecular packing of each of (I) and (II), and in the case of (I), highlight the importance of short meth-oxy-H⋯H(but-yl) contacts between layers.

Pd-catalyzed versus uncatalyzed, PhI(OAc)2-mediated cyclization reactions of N6-([1,1'-biaryl]-2-yl)adenine nucleosides.

Science.gov (United States)

Satishkumar, Sakilam; Poudapally, Suresh; Vuram, Prasanna K; Gurram, Venkateshwarlu; Pottabathini, Narender; Sebastian, Dellamol; Yang, Lijia; Pradhan, Padmanava; Lakshman, Mahesh K

2017-11-09

In this work we have assessed reactions of N 6 -([1,1'-biaryl]-2-yl)adenine nucleosides with Pd(OAc) 2 and PhI(OAc) 2 , via a Pd II /Pd IV redox cycle. The substrates are readily obtained by Pd/Xantphos-catalyzed reaction of adenine nucleosides with 2-bromo-1,1'-biaryls. In PhMe, the N 6 -biarylyl nucleosides gave C6-carbazolyl nucleoside analogues by C-N bond formation with the exocyclic N 6 nitrogen atom. In the solvent screening for the Pd-catalyzed reactions, an uncatalyzed process was found to be operational. It was observed that the carbazolyl products could also be obtained in the absence of a metal catalyst by reaction with PhI(OAc) 2 in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Thus, under Pd catalysis and in HFIP, reactions proceed to provide carbazolyl nucleoside analogues, with some differences. If reactions of N 6 -biarylyl nucleoside substrates were conducted in MeCN, formation of aryl benzimidazopurinyl nucleoside derivatives was observed in many cases by C-N bond formation with the N 1 ring nitrogen atom of the purine (carbazole and benzimidazole isomers are readily separated by chromatography). Whereas Pd II /Pd IV redox is responsible for carbazole formation under the metal-catalyzed conditions, in HFIP and MeCN radical cations and/or nitrenium ions can be intermediates. An extensive set of radical inhibition experiments was conducted and the data are presented.

Mechanistic Study of the sPLA2 Mediated Hydrolysis of a Thio-ester Pro Anticancer Ether Lipid

DEFF Research Database (Denmark)

Linderoth, Lars; Fristrup, Peter; Hansen, Martin

2009-01-01

Secretory phospholipase A2 (sPLA2) is an interesting enzyme for triggered liposomal drug delivery to tumor tissue due the overexpression of sPLA2 in cancerous tissue. A drug delivery system based on the triggered release of therapeutics from sPLA2-sensitive liposomes constituted of pro anticancer...... ether lipids, which become cytotoxic upon sPLA2-catalyzed hydrolysis has previously been established. To optimize the hydrolysis rate of the lipids and thereby optimizing the release profile of the drugs from the liposomes, we have synthesized a thio-ester pro anticancer ether lipid. Liposomes...... constituted of this lipid showed an altered rate of hydrolysis by sPLA2. We have tested the cytotoxicity of the thio-ester pro anticancer ether lipids toward cancer cells, and the results showed that the cytotoxicity is indeed maintained upon sPLA2 exposure. To further understand the origin for the observed...

Radiobromination of humanized anti-HER2 monoclonal antibody trastuzumab using N-succinimidyl 5-bromo-3-pyridinecarboxylate, a potential label for immunoPET

Energy Technology Data Exchange (ETDEWEB)

Mume, Eskender [Organic Chemistry, Department of Chemistry, Uppsala University, S-751 24 Uppsala (Sweden); Orlova, Anna [Affibody AB, S-161 02 Bromma (Sweden); Malmstroem, Per-Uno [Division of Urology, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala (Sweden); Lundqvist, Hans [Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, S-751 85 Uppsala (Sweden); Sjoeberg, Stefan [Organic Chemistry, Department of Chemistry, Uppsala University, S-751 24 Uppsala (Sweden); Tolmachev, Vladimir [Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, S-751 85 Uppsala (Sweden)]. E-mail: vladimir.tolmachev@bms.uu.se

2005-08-01

Combining the specificity of radioimmunoscintigraphy and the high sensitivity of PET in an in vivo detection technique could improve the quality of nuclear diagnostics. Positron-emitting nuclide {sup 76}Br (T {sub 1/2}=16.2 h) might be a possible candidate for labeling monoclonal antibodies (mAbs) and their fragments, provided that the appropriate labeling chemistry has been established. For internalizing antibodies, such as the humanized anti-HER2 monoclonal antibody, trastuzumab, radiobromine label should be residualizing, i.e., ensuring that radiocatabolites are trapped intracellularly after the proteolytic degradation of antibody. This study evaluated the chemistry of indirect radiobromination of trastuzumab using N-succinimidyl 5-(tributylstannyl)-3-pyridinecarboxylate. Literature data indicated that the use of this method provided residualizing properties for iodine and astatine labels on some antibodies. An optimized 'one-pot' procedure produced an overall labeling efficiency of 45.5{+-}1.2% over 15 min. The bromine label was stable under physiological and denaturing conditions. The labeled trastuzumab retained its capacity to bind specifically to HER2-expressing SKOV-3 ovarian carcinoma cells in vitro (immunoreactivity more than 75%). However, in vitro cell test did not demonstrate that the radiobromination of trastuzumab using N-succinimidyl 5-bromo-3-pyridinecarboxylate improves cellular retention of radioactivity in comparison with the use of N-succinimidyl 4-bromobenzoate.

N-succinimidyl 4-methyl-3-(tri-n-butylstannyl)benzoate: synthesis and potential utility for the radioiodination of monoclonal antibodies

International Nuclear Information System (INIS)

Garg, P.K.; Garg, S.; Zalutsky, M.R.

1993-01-01

N-Succinimidyl 4-methyl-3-(tri-n-butylstannyl)benzoate (MATE) was synthesized in two steps from 4-methyl-3-iodobenzoic acid. Radioiododestannylation of MATE proceeded more slowly than N-succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE), but for reaction periods of 10 min, identical yields were obtained. Paired-label biodistribution studies were performed in mice with an intact monoclonal antibody and an F(ab') 2 fragment labeled using MATE, ATE and Iodogen. Thyroid uptake with MATE was low, comparable to that seen with ATE, and considerably lower than that observed when the Iodogen method was used. With the F(ab') 2 fragment, kidney uptake using MATE was 8-fold higher than that observed when either the ATE or Iodogen methods were used. (Author)

Determination of the enthalpy of vaporization and prediction of surface tension for ionic liquid 1-alkyl-3-methylimidazolium propionate [C(n)mim][Pro](n = 4, 5, 6).

Science.gov (United States)

Tong, Jing; Yang, Hong-Xu; Liu, Ru-Jing; Li, Chi; Xia, Li-Xin; Yang, Jia-Zhen

2014-11-13

With the use of isothermogravimetrical analysis, the enthalpies of vaporization, Δ(g)lH(o)m(T(av)), at the average temperature, T(av) = 445.65 K, for the ionic liquids (ILs) 1-alkyl-3-methylimidazolium propionate [C(n)mim][Pro](n = 4, 5, 6) were determined. Using Verevkin's method, the difference of heat capacities between the vapor phase and the liquid phase, Δ(g)lC(p)(o)m, for [C(n)mim][Pro](n = 2, 3, 4, 5, 6), were calculated based on the statistical thermodynamics. Therefore, with the use of Δ(g)lC(p)(o)m, the values of Δ(g)lH(o)m(T(av)) were transformed into Δ(g)lH(o)m(298), 126.8, 130.3, and 136.5 for [C(n)mim][Pro](n = 4, 5, 6), respectively. In terms of the new scale of polarity for ILs, the order of the polarity of [C(n)mim][Pro](n = 2, 3, 4, 5, 6) was predicted, that is, the polarity decreases with increasing methylene. A new model of the relationship between the surface tension and the enthalpy of vaporization for aprotic ILs was put forward and used to predict the surface tension for [C(n)mim][Pro](n = 2, 3, 4, 5, 6) and others. The predicted surface tension for the ILs is in good agreement with the experimental one.

Synthesis and Structural Characterization of 1- and 2-Substituted Indazoles: Ester and Carboxylic Acid Derivatives

Directory of Open Access Journals (Sweden)

Isabel Bento

2006-11-01

Full Text Available A series of indazoles substituted at the N-1 and N-2 positions with ester-containing side chains -(CH2nCO2R of different lengths (n = 0-6, 9, 10 are described.Nucleophilic substitution reactions on halo esters (X(CH2nCO2R by 1H-indazole inalkaline solution lead to mixtures of N-1 and N-2 isomers, in which the N-1 isomerpredominates. Basic hydrolysis of the ester derivatives allowed the synthesis of thecorresponding indazole carboxylic acids. All compounds were fully characterised bymultinuclear NMR and IR spectroscopies, MS spectrometry and elemental analysis; theNMR spectroscopic data were used for structural assignment of the N-1 and N-2 isomers.The molecular structure of indazol-2-yl-acetic acid (5b was determined by X-raydiffraction, which shows a supramolecular architecture involving O2-H...N1intermolecular hydrogen bonds.

Varying the Lewis base coordination of the Y2N2 core in the reduced dinitrogen complexes {[(Me3Si)2N]2(L)Y}2(μ-η2:η2-N2) (L = benzonitrile, pyridines, triphenylphosphine oxide, and trimethylamine N-oxide).

Science.gov (United States)

Corbey, Jordan F; Farnaby, Joy H; Bates, Jefferson E; Ziller, Joseph W; Furche, Filipp; Evans, William J

2012-07-16

The effect of the neutral donor ligand, L, on the Ln(2)N(2) core in the (N═N)(2-) complexes, [A(2)(L)Ln](2)(μ-η(2):η(2)-N(2)) (Ln = Sc, Y, lanthanide; A = monoanion; L = neutral ligand), is unknown since all of the crystallographically characterized examples were obtained with L = tetrahydrofuran (THF). To explore variation in L, displacement reactions between {[(Me(3)Si)(2)N](2)(THF)Y}(2)(μ-η(2):η(2)-N(2)), 1, and benzonitrile, pyridine (py), 4-dimethylaminopyridine (DMAP), triphenylphosphine oxide, and trimethylamine N-oxide were investigated. THF is displaced by all of these ligands to form {[(Me(3)Si)(2)N](2)(L)Y}(2)(μ-η(2):η(2)-N(2)) complexes (L = PhCN, 2; py, 3; DMAP, 4; Ph(3)PO, 5; Me(3)NO, 6) that were fully characterized by analytical, spectroscopic, density functional theory, and X-ray crystallographic methods. The crystal structures of the Y(2)N(2) cores in 2-5 are similar to that in 1 with N-N bond distances between 1.255(3) Å and 1.274(3) Å, but X-ray analysis of the N-N distance in 6 shows it to be shorter: 1.198(3) Å.

2-Methylpyridinium/pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olates as potent anticonvulsant agents—synthesis and crystal structure

Energy Technology Data Exchange (ETDEWEB)

Mangaiyarkarasi, G.; Kalaivani, D., E-mail: kalaivbalaj@yahoo.co.in [Affiliated to Bharathidasan University, Post Graduate and Research Department of Chemistry, Seethalakshmi Ramaswami College, Tiruchirappalli-620 002 (India)

2013-12-15

The molecular salt, 2-methylpyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropy-rimidin-4-olate) (I), is prepared from the ethanolic solution of 1-chloro-2,4-dinitrobenzene, pyrimidine-2,4,6-(1H,3H,5H)-trione (barbituric acid) and 2-methylpyridine at room temperature, and the molecular salt, pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate (II), is prepared from the same reactants, by dissolving them in hot DMSO and ethanol mixture at 70°C. The structures of I and II are characterized by visible, IR, {sup 1}H-NMR, {sup 13}C-NMR and elemental analysis and confirmed by single crystal X-ray analysis. Both the salts crystallize in triclinic crystal system with sp. gr. P-bar1. They possess noticeable anticonvulsant activity even at low concentration (25 mg/kg). Acute toxicity studies of these complexes indicate that LD{sub 50} values are greater than 1500 mg/kg and the tested animals do not show any behavioural changes.

2-Methylpyridinium/pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olates as potent anticonvulsant agents—synthesis and crystal structure

International Nuclear Information System (INIS)

Mangaiyarkarasi, G.; Kalaivani, D.

2013-01-01

The molecular salt, 2-methylpyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropy-rimidin-4-olate) (I), is prepared from the ethanolic solution of 1-chloro-2,4-dinitrobenzene, pyrimidine-2,4,6-(1H,3H,5H)-trione (barbituric acid) and 2-methylpyridine at room temperature, and the molecular salt, pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate (II), is prepared from the same reactants, by dissolving them in hot DMSO and ethanol mixture at 70°C. The structures of I and II are characterized by visible, IR, 1 H-NMR, 13 C-NMR and elemental analysis and confirmed by single crystal X-ray analysis. Both the salts crystallize in triclinic crystal system with sp. gr. P-bar1. They possess noticeable anticonvulsant activity even at low concentration (25 mg/kg). Acute toxicity studies of these complexes indicate that LD 50 values are greater than 1500 mg/kg and the tested animals do not show any behavioural changes

Photochemically activated antiviral halogenated 1,8-naphthalimides: synthesis of N,N'-bis-{2-[(5-bromo-2-[1-14C]hexyl-1H-benz[de]isoquinolin-1,3(2H)-dion-6-yl)amino]ethyl}hexanediamide

International Nuclear Information System (INIS)

Hayes, B.A.; Gupta, Surendra; Shaochieh Chang; Utecht, R.E.; Lewis, D.E.

1996-01-01

The synthesis of N,N'-bis-{2-[(5-bromo-2-[1- 14 C]hexyl-1H-benz[de]isoquinolin-1, 3(2H)-dion-6-yl)amino]ethyl}hexanediamide from 1-[1- 14 C]-hexylamine and 4-chloro-1,8-naphthalic anhydride is described. The anhydride is first converted to the 4-chloro-n-[1- 14 C]hexyl-1,8-naphthalimide by condensation with 1-[1- 14 C]-hexylamine, and the chlorine is then displaced with ethylenediamine to give the 4-(2-aminoethylamino-N-[1- 14 C]hexyl-1,8-naphthalimide. Coupling of this monomeric naphthalimide with adipoyl chloride affords the dimeric naphthalimide which is brominated regiospecifically with elemental bromine in carbon tetrachloride to afford the title compound. (author)

Indirect radioiodination of human IgG with N-succinimidyl-3-iodo[125I] benzoate

International Nuclear Information System (INIS)

Liu Zhenfeng; Wang Yongxian; Dong Mo; Zhou Wei; Xia Jiaoyun; Yin Duanzhi; Li Linfa

2007-01-01

The objective of this study was to develop an acylation method for the radioiodination of monoclonal antibodies that could decrease the loss of radioiodine in vivo. Preparation of N- succinimidyl-3-iodobenzoate(S 125 IB) from the organoth precursor, N-succinimidyl-3-(tri-n-bu- tylstannyl)benzoate(ATE) proceeds in more than 95% labelling yield, when the mass of ATE and NCS are respectively 25-100 μg and 10-20 μg, and the volume of PBS is 10-20 μL, and reaction time is 5 min. IgG is labeled using S 125 IB in up to 75% conjugation efficiency and with well retained immunoreactivity to sheep anti-human IgG. Hepama-1 is also labeled using S 125 IB in more than 75% conjugation efficiency. Paired-label biodistribution studies in normal mice demonstrate that thyroid uptake(a monitor of dehalogenation) of Hepama-1 labeled by S 125 IB method is up to 87.9 times lower than that of Hepama-1 labeled with Iodogen. This result suggests that S 125 IB offers significant advantages for labeling proteins, antibodies over other conventional methods for protein radioiodination. (authors)

Crystal structure of bis(azido-κNbis[2,5-bis(pyridin-2-yl-1,3,4-thiadiazole-κ2N2,N3]nickel(II

Directory of Open Access Journals (Sweden)

Abdelhakim Laachir

2015-02-01

Full Text Available Reaction of 2,5-bis(pyridin-2-yl-1,3,4-thiadiazole and sodium azide with nickel(II triflate yielded the mononuclear title complex, [Ni(N32(C12H8N4S2]. The NiII ion is located on a centre of symmetry and is octahedrally coordinated by four N atoms of the two bidentate heterocyclic ligands in the equatorial plane. The axial positions are occupied by the N atoms of two almost linear azide ions [N—N—N = 178.8 (2°]. The thiadiazole and pyridine rings of the heterocyclic ligand are almost coplanar, with a maximum deviation from the mean plane of 0.0802 (9 Å. The cohesion of the crystal structure is ensured by π–π interactions between parallel pyridine rings of neighbouring molecules [centroid-to-centroid distance = 3.6413 (14 Å], leading to a layered arrangement of the molecules parallel to (001.

Radiolabelling of isopeptide N{sup {epsilon}}-({gamma}-glutamyl)-L-lysine by conjugation with N-succinimidyl-4-[{sup 18}F]fluorobenzoate

Energy Technology Data Exchange (ETDEWEB)

Wuest, F; Hultsch, C; Bergmann, R; Johannsen, B; Henle, T

2003-07-01

The isopeptide N{sup {epsilon}}-({gamma}-glutamyl)-L-lysine 4 was labelled with {sup 18}F via N-succinimidyl-4-[{sup 18}F]fluorobenzoate ([{sup 18}F]SFB). A modified approach for the convenient synthesis of [{sup 18}F]SFB was used, and [{sup 18}F]SFB could be obtained in decay-corrected radiochemical yields of 44-53% (n=20) and radiochemical purity >95% within 40 min after EOB. For labelling N{sup {epsilon}}-({gamma}-glutamyl)-L-lysine with [{sup 18}F]SFB the effects of isopeptide concentration, temperature, and pH were studied to determine the optimum reaction conditions. The coupling reaction was shown to be temperature and pH independent while being strongly affected by the isopeptide concentration. Using the optimized labelling conditions, in a typical experiment 1.3 GBq of [{sup 18}F]SFB could be converted into 447 MBq (46%, decay-corrected) of [{sup 18}F]fluorobenzoylated isopeptide within 45 min, including HPLC purification.

Crystal structures of three co-crystals of 1,2-bis-(pyridin-4-yl)ethane with 4-alk-oxy-benzoic acids: 4-eth-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1), 4-n-propoxybenzoic acid-1,2-bis(pyridin-4-yl)ethane (2/1) and 4-n-but-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1).

Science.gov (United States)

Tabuchi, Yohei; Gotoh, Kazuma; Ishida, Hiroyuki

2015-11-01

The crystal structures of three hydrogen-bonded co-crystals of 4-alk-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1), namely, 2C9H10O3·C12H12N2, (I), 2C10H12O3·C12H12N2, (II), and 2C11H14O3·C12H12N2, (III), have been determined at 93, 290 and 93 K, respectively. In (I), the asymmetric unit consists of one 4-eth-oxy-benzoic acid mol-ecule and one half-mol-ecule of 1,2-bis-(pyridin-4-yl)ethane, which lies on an inversion centre. In (II) and (III), the asymmetric units each comprise two crystallographically independent 4-alk-oxy-benzoic acid mol-ecules and one 1,2-bis-(pyridin-4-yl)ethane mol-ecule. In each crystal, the two components are linked by O-H⋯N hydrogen bonds, forming a linear hydrogen-bonded 2:1unit of the acid and the base. Similar to the structure of 2:1 unit of (I), the units of (II) and (III) adopt nearly pseudo-inversion symmetry. The 2:1 units of (I), (II) and (III) are linked via C-H⋯O hydrogen bonds, forming tape structures.

Crystal structure of tetraaqua[2-(pyridin-2-yl-1H-imidazole-κ2N2,N3]iron(II sulfate

Directory of Open Access Journals (Sweden)

Zouaoui Setifi

2015-04-01

Full Text Available In the title compound, [Fe(C8H7N3(H2O4]SO4, the central FeII ion is octahedrally coordinated by two N atoms from the bidentate 2-(pyridin-2-yl-1H-imidazole ligand and by four O atoms of the aqua ligands. The largest deviation from the ideal octahedral geometry is reflected by the small N—Fe—N bite angle of 76.0 (1°. The Fe—N coordination bonds have markedly different lengths [2.1361 (17 and 2.243 (2 Å], with the shorter one to the pyrimidine N atom. The four Fe—O coordination bond lengths vary from 2.1191 (18 to 2.1340 (17 Å. In the crystal, the cations and anions are arranged by means of medium-strength O—H...O hydrogen bonds into layers parallel to the ab plane. Neighbouring layers further interconnect by N—H...O hydrogen bonds involving the imidazole fragment as donor group to one sulfate O atom as an acceptor. The resulting three-dimensional network is consolidated by C—H...O, C—H...π and π–π interactions.

Room-Temperature Synthesis of Thiostannates from {[Ni(tren)]2[Sn2S6]}n.

Science.gov (United States)

Hilbert, Jessica; Näther, Christian; Weihrich, Richard; Bensch, Wolfgang

2016-08-15

The compound {[Ni(tren)]2[Sn2S6]}n (1) (tren = tris(2-aminoethyl)amine, C6H18N4) was successfully applied as source for the room-temperature synthesis of the new thiostannates [Ni(tren)(ma)(H2O)]2[Sn2S6]·4H2O (2) (ma = methylamine, CH5N) and [Ni(tren)(1,2-dap)]2[Sn2S6]·2H2O (3) (1,2-dap = 1,2-diaminopropane, C3H10N2). The Ni-S bonds in the Ni2S2N8 bioctahedron in the structure of 1 are analyzed with density functional theory calculations demonstrating significantly differing Ni-S bond strengths. Because of this asymmetry they are easily broken in the presence of an excess of ma or 1,2-dap immediately followed by Ni-N bond formation to N donor atoms of the amine ligands thus generating [Ni(tren)(amine)](2+) complexes. The chemical reactions are fast, and compounds 2 and 3 are formed within 1 h. The synthesis concept presented here opens hitherto unknown possibilities for preparation of new thiostannates.

Crystal structure of bis(azido-κNbis[2,5-bis(pyridin-2-yl-1,3,4-thiadiazole-κ2N2,N3]cobalt(II

Directory of Open Access Journals (Sweden)

Abdelhakim Laachir

2015-05-01

Full Text Available In the mononuclear title complex, [Co(N32(C12H8N4S2], the cobalt(II atom is located on an inversion centre and displays an axially weakly compressed octahedral coordination geometry. The equatorial positions are occupied by the N atoms of two 2,5-bis(pyridin-2-yl-1,3,4-thiadiazole ligands, whereas the axial positions are occupied by N atoms of the azide anions. The thiadiazole and pyridine rings linked to the metal are almost coplanar, with a maximum deviation from the mean plane of 0.0273 (16 Å. The cohesion of the crystal is ensured by weak C—H...N hydrogen bonds and by π–π interactions between pyridine rings [intercentroid distance = 3.6356 (11 Å], forming a layered arrangement parallel to (001. The structure of the title compound is isotypic with that of the analogous nickel(II complex [Laachir et al. (2013. Acta Cryst. E69, m351–m352].

Bis[2,6-bis(trimethylsilylaminopyridine-κN1]{[6-bis(trimethylsilylaminopyridin-2-yl-κN1](trimethylsilylazanido-κN}lithium

Directory of Open Access Journals (Sweden)

Justin A. Rave

2016-03-01

Full Text Available The title complex, [Li(C11H22N3Si2(C11H23N3Si22], contains a single lithium cation coordinated to three ligands. This is the first reported example of the ligand 2,6-bis(trimethylsilylaminopyridine supporting a monometallic complex. One ligand is mono-anionic and forms a four-membered chelate ring with the lithium cation via the pyridine and silylamido N atoms. The other two ligands are neutral and bind via the pyridine nitrogen. The lithium cation is coordinated in a tetrahedral environment. No intra- or intermolecular hydrogen bonding is observed in the crystal structure, likely indicating that weak electrostatic interactions are the dominant feature of the crystal packing.

Toxicological evaluation of a novel cooling compound: 2-(4-methylphenoxy-N-(1H-pyrazol-3-yl-N-(2-thienylmethylacetamide

Directory of Open Access Journals (Sweden)

Donald S. Karanewsky

2015-01-01

Full Text Available A toxicological evaluation of a novel cooling agent, 2-(4-methylphenoxy-N-(1H-pyrazol-3-yl-N-(2-thienylmethyl acetamide (S2227; CAS 1374760-95-8, was completed for the purpose of assessing its safety for use in food and beverage applications. S2227 undergoes rapid oxidative metabolism in vitro, and in rat and dog pharmacokinetic studies is rapidly converted to its component carboxylic acid and secondary amine. S2227 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in polychromatic erythrocytes in vivo. The secondary amine hydrolysis product, N-(2-thienylmethyl-1H-pyrazol-3-amine (M179, was also evaluated for genotoxicity. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for S2227 was 100 mg/kg/day (highest dose tested when administered by oral gavage for 90 consecutive days. Furthermore, S2227 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.

Discovery of (1R,2S)-2-{[(2,4-Dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide (E2006): A Potent and Efficacious Oral Orexin Receptor Antagonist.

Science.gov (United States)

Yoshida, Yu; Naoe, Yoshimitsu; Terauchi, Taro; Ozaki, Fumihiro; Doko, Takashi; Takemura, Ayumi; Tanaka, Toshiaki; Sorimachi, Keiichi; Beuckmann, Carsten T; Suzuki, Michiyuki; Ueno, Takashi; Ozaki, Shunsuke; Yonaga, Masahiro

2015-06-11

The orexin/hypocretin receptors are a family of G protein-coupled receptors and consist of orexin-1 (OX1) and orexin-2 (OX2) receptor subtypes. Orexin receptors are expressed throughout the central nervous system and are involved in the regulation of the sleep/wake cycle. Because modulation of these receptors constitutes a promising target for novel treatments of disorders associated with the control of sleep and wakefulness, such as insomnia, the development of orexin receptor antagonists has emerged as an important focus in drug discovery research. Here, we report the design, synthesis, characterization, and structure-activity relationships (SARs) of novel orexin receptor antagonists. Various modifications made to the core structure of a previously developed compound (-)-5, the lead molecule, resulted in compounds with improved chemical and pharmacological profiles. The investigation afforded a potential therapeutic agent, (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide (E2006), an orally active, potent orexin antagonist. The efficacy was demonstrated in mice in an in vivo study by using sleep parameter measurements.

Synthesis and structures of six closely related N-[3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl]arylamides, together with an isolated reaction intermediate: order versus disorder, molecular conformations and hydrogen bonding in zero, one and two dimensions.

Science.gov (United States)

Sagar, Belakavadi K; Yathirajan, Hemmige S; Rathore, Ravindranath S; Glidewell, Christopher

2018-02-01

Six closely related N-[3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl]arylamides have been synthesized and structurally characterized, together with a representative reaction intermediate. In each of N-[3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl]benzamide, C 20 H 16 ClNO 2 S, (I), N-[3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl]-4-phenylbenzamide, C 26 H 20 ClNO 2 S, (II), and 2-bromo-N-[3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl]benzamide, C 20 H 15 BrClNO 2 S, (III), the molecules are disordered over two sets of atomic sites, with occupancies of 0.894 (8) and 0.106 (8) in (I), 0.832 (5) and 0.168 (5) in (II), and 0.7006 (12) and 0.2994 (12) in (III). In each of N-[3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl]-2-iodobenzamide, C 20 H 15 ClINO 2 S, (IV), and N-[3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl]-2-methoxybenzamide, C 21 H 18 ClNO 3 S, (V), the molecules are fully ordered, but in N-[3-(2-chlorobenzoyl)-5-ethylthiophen-2-yl]-2,6-difluorobenzamide, C 20 H 14 ClF 2 NO 2 S, (VI), which crystallizes with Z' = 2 in the space group C2/c, one of the two independent molecules is fully ordered, while the other is disordered over two sets of atomic sites having occupancies of 0.916 (3) and 0.084 (3). All of the molecules in compounds (I)-(VI) exhibit an intramolecular N-H...O hydrogen bond. The molecules of (I) and (VI) are linked by C-H...O hydrogen bonds to form finite zero-dimensional dimers, which are cyclic in (I) and acyclic in (VI), those of (III) are linked by C-H...π(arene) hydrogen bonds to form simple chains, and those of (IV) and (V) are linked into different types of chains of rings, built in each case from a combination of C-H...O and C-H...π(arene) hydrogen bonds. Two C-H...O hydrogen bonds link the molecules of (II) into sheets containing three types of ring. In benzotriazol-1-yl 3,4-dimethoxybenzoate, C 15 H 13 N 3 O 4 , (VII), the benzoate component is planar and makes a dihedral angle of 84.51 (6)° with the benzotriazole unit. Comparisons are made

SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride], a new nonpeptide antagonist of the bradykinin B1 receptor: biochemical and pharmacological characterization.

Science.gov (United States)

Gougat, Jean; Ferrari, Bernard; Sarran, Lionel; Planchenault, Claudine; Poncelet, Martine; Maruani, Jeanne; Alonso, Richard; Cudennec, Annie; Croci, Tiziano; Guagnini, Fabio; Urban-Szabo, Katalin; Martinolle, Jean-Pierre; Soubrié, Philippe; Finance, Olivier; Le Fur, Gérard

2004-05-01

The biochemical and pharmacological properties of a novel non-peptide antagonist of the bradykinin (BK) B(1) receptor, SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride] were evaluated. SSR240612 inhibited the binding of [(3)H]Lys(0)-des-Arg(9)-BK to the B(1) receptor in human fibroblast MRC5 and to recombinant human B(1) receptor expressed in human embryonic kidney cells with inhibition constants (K(i)) of 0.48 and 0.73 nM, respectively. The compound selectivity for B(1) versus B(2) receptors was in the range of 500- to 1000-fold. SSR240612 inhibited Lys(0)-desAr(9)-BK (10 nM)-induced inositol monophosphate formation in human fibroblast MRC5, with an IC(50) of 1.9 nM. It also antagonized des-Arg(9)-BK-induced contractions of isolated rabbit aorta and mesenteric plexus of rat ileum with a pA(2) of 8.9 and 9.4, respectively. Antagonistic properties of SSR240612 were also demonstrated in vivo. SSR240612 inhibited des-Arg(9)-BK-induced paw edema in mice (3 and 10 mg/kg p.o. and 0.3 and 1 mg/kg i.p.). Moreover, SSR240612 reduced capsaicin-induced ear edema in mice (0.3, 3 and 30 mg/kg p.o.) and tissue destruction and neutrophil accumulation in the rat intestine following splanchnic artery occlusion/reperfusion (0.3 mg/kg i.v.). The compound also inhibited thermal hyperalgesia induced by UV irradiation (1 and 3 mg/kg p.o.) and the late phase of nociceptive response to formalin in rats (10 and 30 mg/kg p.o.). Finally, SSR240612 (20 and 30 mg/kg p.o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat. In conclusion, SSR240612 is a new, potent, and orally active specific non-peptide bradykinin B(1) receptor antagonist.

[Pr2(pdc3(Hpdc(H2O4]n·n(H3hp·8n(H2O, a One-Dimensional Coordination Polymer Containing PrO6N3 Tri-Capped Trigonal Prisms and PrO8N Mono-Capped Square Anti-Prisms (H2pdc = Pyridine 2,6-Dicarboxylic Acid, C7H5NO4; 3hp = 3-Hydroxy Pyridine, C5H5NO

Directory of Open Access Journals (Sweden)

Shahzad Sharif

2012-08-01

Full Text Available The synthesis, structure and some properties of the one-dimensional coordination polymer, [Pr2(pdc3(Hpdc]n·n(H3hp·8n(H2O, (H2pdc = pyridine 2,6-dicarboxylic acid, C7H5NO4; 3hp = 3-hydroxypyridine, C5H5NO are described. One of the Pr3+ ions is coordinated by two O,N,O-tridentate pdc2− ligands and one tridentate Hpdc− anion to generate a fairly regular PrO6N3 tri-capped trigonal prism, with the N atoms acting as the caps. The second Pr3+ ion is coordinated by one tridentate pdc2− dianion, four water molecules and two monodentate bridging pdc2− ligands to result in a PrO8N coordination polyhedron that approximates to a mono-capped square-anti-prism. The ligands bridge the metal-atom nodes into a chain, which extends in the [100] direction. The H3hp+ cation and uncoordinated water molecules occupy the inter-chain regions and an N–HLO and numerous O–HLO hydrogen bonds consolidate the structure. The H3hp+ species appears to intercalate between pendant pdc rings to consolidate the polymeric structure. Crystal data: 1 (C33H43N5O29Pr2, Mr = 1255.54, triclinic,  (No. 2, Z = 2, a = 13.2567(1 Å, b = 13.6304(2 Å, c = 13.6409(2 Å, α = 89.695(1°, β = 63.049(1°, γ = 86.105(1°, V = 2191.16(5 Å3, R(F = 0.033, wR(F2 = 0.084.

Evaluasi Karakteristik XBee Pro dan nRF24L01+ sebagai Transceiver Nirkabel

Directory of Open Access Journals (Sweden)

BURHAN FAJRIANSYAH

2016-01-01

Full Text Available ABSTRAK Pemillihan modul transciever sebagai media transmisi data digital menjadi permasalahan bagi perancang ketika mendesain suatu sistem komunikasi nirkabel. Pada penelitian ini penulis melakukan evaluasi pada dua modul transceiver yaitu XBee Pro dan nRFf24L01+ dengan tujuan untuk menentukan modul transceiver mana yang tepat digunakan untuk kebutuhan perancangan sistem Wireless Sensor Network (WSN. Evaluasi dilakukan dengan mengirimkan data dalam bentuk karakter ASCII/ bytes secara kontinyu maupun sekuensial melalui komunikasi serial UART. Pada pengaturan untuk mode data rate 250 Kbps, XBee Pro memiliki data rate 27 Kbps dan nRF24L01+ 16 Kbps untuk protokol komunikasi serial UART. Modul nRF24L01+ lebih unggul dalam mengirimkan data secara streaming (kontinyu dibandingkan Xbee Pro, dan nRF24L01+ memiliki Round Time Trip (RTT tercepat 0,003 sekon sedangkan XBee Pro hanya 0,036sekon. Pada aplikasi dalam ruangan XBee Pro memiliki performa lebih tinggi karena lebih stabil dalam transmisi dengan hambatan 4 dinding sedangkan nRF24L01+ hanya 2 dinding. Kata kunci: UART, Data Rate, Nirkabel, XBee Pro, nRF24L01+.   ABSTRACT Chosing transciever module as a media for a digital transmission data has becoming a serious problem for a designer to design a wireless communication system. In this research, author do the evaluation for a two transceiver module that are XBee Pro and nRF24L01+, the purpose is to chose which the right transceiver module that designer need to make a Wireless Sensor Network (WSN system. The evaluation was done by sending a data in ASCII character/ bytes as continuous and sequensial method using serial communication UART. When data rate is set to 250 Kbps mode, XBee Pro data rate is 27 Kbps and nRF24L01+ 16Kbps for serial communicaton UART purpose. nRF24L01+ is better at sending a streaming data (continuous than XBee Pro, and also nRF24L01+ has a fastest Round Time Trip (RTT that are 0,003 sec while XBee Pro only 0,036 sec. For

Synthesis of N-(6-Arylbenzo[d]thiazole-2-acetamide Derivatives and Their Biological Activities: An Experimental and Computational Approach.

Science.gov (United States)

Gull, Yasmeen; Rasool, Nasir; Noreen, Mnaza; Altaf, Ataf Ali; Musharraf, Syed Ghulam; Zubair, Muhammad; Nasim, Faiz-Ul-Hassan; Yaqoob, Asma; DeFeo, Vincenzo; Zia-Ul-Haq, Muhammad

2016-02-25

A new series of N-(6-arylbenzo[d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these compounds were found to have moderate to good activities. Among the tested biological activities screened these compounds displayed the most significant activity for urease inhibition. In urease inhibition, all compounds were found more active than the standard used. The compound N-(6-(p-tolyl)benzo[d]thiazol-2-yl)acetamide was found to be the most active. To understand this urease inhibition, molecular docking studies were performed. The in silico studies showed that these acetamide derivatives bind to the non-metallic active site of the urease enzyme. Structure-activity studies revealed that H-bonding of compounds with the enzyme is important for its inhibition.

3-Diazo-N-[(2S-1-hydroxypropan-2-yl]-2-oxopropanamide

Directory of Open Access Journals (Sweden)

Xiao-na Chen

2011-05-01

Full Text Available In the title compound, C6H9N3O3, the 3-diazo-2-oxopropanamide section of the molecule is nearly planar, with a maximum deviation of 0.025 (1 Å from the mean plane of its constituent atoms. The diazo C=N=N angle is 178.0 (3°. In the crystal, pairs of intermolecular O—H...O and N—H...O hydrogen bonds link the molecules into infinite double chains along the [100] direction. The double chains are additionally stabilized by weak C—H...O contacts with C...O distances of 3.039 (3 Å. Neighboring double chains in turn interact with each other through π–π stacking interactions [centroid–centroid distance of the 3-diazo-2-oxopropanamide units = 3.66 (6 Å] to form infinite stacks along the b axis. Molecules from neighboring stacks interdigitate with each other in the c-axis direction, thus leading to an interwoven three-dimensional network held together by O—H...O, N—H...O and C—H...O interactions and π–π stacking.

Canted ferrimagnetism and giant coercivity in the nonstoichiometric double perovskite L a2N i1.19O s0.81O6

Science.gov (United States)

Feng, Hai L.; Reehuis, Manfred; Adler, Peter; Hu, Zhiwei; Nicklas, Michael; Hoser, Andreas; Weng, Shih-Chang; Felser, Claudia; Jansen, Martin

2018-05-01

The nonstoichiometric double perovskite oxide L a2N i1.19O s0.81O6 was synthesized by solid-state reaction and its crystal and magnetic structures were investigated by powder x-ray and neutron diffraction. L a2N i1.19O s0.81O6 crystallizes in the monoclinic double perovskite structure (general formula A2B B'O6 ) with space group P 21/n , where the B site is fully occupied by Ni and the B ' site by 19% Ni and 81% Os atoms. Using x-ray absorption spectroscopy an O s4.5 + oxidation state was established, suggesting the presence of about 50% paramagnetic O s5 + (5 d3 , S =3 /2 ) and 50% nonmagnetic O s4 + (5 d4 , Jeff=0 ) ions at the B ' sites. Magnetization and neutron diffraction measurements on L a2N i1.19O s0.81O6 provide evidence for a ferrimagnetic transition at 125 K. The analysis of the neutron data suggests a canted ferrimagnetic spin structure with collinear N i2 + -spin chains extending along the c axis but a noncollinear spin alignment within the a b plane. The magnetization curve of L a2N i1.19O s0.81O6 features a hysteresis with a very high coercive field, HC=41 kOe , at T =5 K , which is explained in terms of large magnetocrystalline anisotropy due to the presence of Os ions together with atomic disorder. Our results are encouraging to search for rare-earth-free hard magnets in the class of double perovskite oxides.

N-O chemistry for antibiotics: discovery of N-alkyl-N-(pyridin-2-yl)hydroxylamine scaffolds as selective antibacterial agents using nitroso Diels-Alder and ene chemistry.

Science.gov (United States)

Wencewicz, Timothy A; Yang, Baiyuan; Rudloff, James R; Oliver, Allen G; Miller, Marvin J

2011-10-13

The discovery, syntheses, and structure-activity relationships (SAR) of a new family of heterocyclic antibacterial compounds based on N-alkyl-N-(pyridin-2-yl)hydroxylamine scaffolds are described. A structurally diverse library of ∼100 heterocyclic molecules generated from Lewis acid-mediated nucleophilic ring-opening reactions with nitroso Diels-Alder cycloadducts and nitroso ene reactions with substituted alkenes was evaluated in whole cell antibacterial assays. Compounds containing the N-alkyl-N-(pyridin-2-yl)hydroxylamine structure demonstrated selective and potent antibacterial activity against the Gram-positive bacterium Micrococcus luteus ATCC 10240 (MIC(90) = 2.0 μM or 0.41 μg/mL) and moderate activity against other Gram-positive strains including antibiotic resistant strains of Staphylococcus aureus (MRSA) and Enterococcus faecalis (VRE). A new synthetic route to the active core was developed using palladium-catalyzed Buchwald-Hartwig amination reactions of N-alkyl-O-(4-methoxybenzyl)hydroxylamines with 2-halo-pyridines that facilitated SAR studies and revealed the simplest active structural fragment. This work shows the value of using a combination of diversity-oriented synthesis (DOS) and parallel synthesis for identifying new antibacterial scaffolds.

A NEW METHOD FOR PREPARING 6-NITRO-2-(4-BOC-PIPERAZIN-1-YL-3H-QUINAZOLIN-4-ONE

Directory of Open Access Journals (Sweden)

A. Yu. Kornylov

2017-11-01

Full Text Available The 2-amino-3H-quinazolin-4-one scaffold is found in a large number of molecules with physiological significance and pharmaceutical utility. Previously we synthesized a series of potent antagonists of fibrinogen receptor, derivatives of 2-(piperazin-1-yl-3H-quinazolin-4-one. The key building block for preparing the above series of compounds is 6-amino-2-(4-Boc-piperazin-1-yl-3H-quinazolin-4-one, which was synthesized by hydrogenation of 6-nitro-2-(4-Boc-piperazin-1-yl-3H-quinazolin-4-one. In turn, the nitro derivative was obtained starting from isatoic anhydride in four stages, by a method that can be considered classical, but difficult. The purpose of this work is to simplify the preparation of 6-nitro-2-(4-Boc-piperazin-1-yl-3H-quinazolin-4-one. We proposed an effective method for the synthesis of 6-nitro-2-(4-Boc-piperazin-1-yl-3H-quinazolin-4-one based on a sequential process, C-N cross-coupling and intramolecular amidation. As the arylhalogenide, 2-bromo-5-nitrobenzoic acid methyl ester was used, as the N-nucleophile, 4-Boc-piperazine-1-carboxamidine, a guanidine derivative, was used. In the study, we used two types of catalytic systems, which both gave good results. The application of the third generation of Palladacycleprecatalyst –[(4,5-Bis(diphenylphosphino-9,9-dimethylxanthene-2-(2′-amino-1,1′-biphenyl] palladium(II methanesulfonate, leads to the production of the target product in a high yield, in comparison with the use of the catalytic system: precatalyst – Tris(dibenzylideneacetone dipalladium(0 chloroform adduct and Buchwald Ligands – 4,5-Bis(diphenylphosphino-9,9-dimethylxanthene. The structure of the title compound was confirmed by spectroscopy 1H and 13C NMR, and FAB mass spectrometry methods, purity was controlled by HPLC. This method has potential implications for the design of various 2-amino-3H-quinazolin-4-ones.

Experimental and theoretical studies on the structural, spectroscopic and hydrogen bonding on 4-nitro-n-(2,4-dinitrophenyl) benzenamine

Science.gov (United States)

Subhapriya, G.; Kalyanaraman, S.; Jeyachandran, M.; Ragavendran, V.; Krishnakumar, V.

2018-04-01

Synthesized 4-nitro-N-(2,4-dinitrophenyl) benzenamine (NDPBA) molecule was confirmed applying the tool of NMR. Theoretical prediction addressed the NMR chemical shifts and correlated well with the experimental data. The molecule subjected to theoretical DFT at 6-311++G** level unraveled the spectroscopic and structural properties of the NDPBA molecule. Moreover the structural features proved the occurrence of intramolecular Nsbnd H· · O hydrogen bonding in the molecule which was further confirmed with the help of Frontier molecular orbital analysis. Vibrational spectroscopic characterization through FT-IR and Raman experimentally and theoretically gave an account for the vibrational properties. An illustration of the topology of the molecule theoretically helped also in finding the hydrogen bonding energy.

Structure and spectroscopic properties of N,S-coordinating 2-methyl-sulfanyl-N-[(1H-pyrrol-2-yl)methyl-idene]aniline methanol monosolvate.

Science.gov (United States)

Richards, D Douglas; Ang, M Trisha C; McDonald, Robert; Bierenstiel, Matthias

2015-10-01

The reaction of pyrrole-2-carboxaldehyde and 2-(methyl-sulfan-yl)aniline in refluxing methanol gave an olive-green residue in which yellow crystals of the title compound, C12H12N2S·CH3OH, were grown from slow evaporation of methanol at 263 K. In the crystal, hydrogen-bonding inter-actions link the aniline mol-ecule and a nearby methanol solvent mol-ecule. These units are linked by a pair of weak C-H⋯Omethanol interactions, forming inversion dimers consisting of two main molecules and two solvent molecules.

Radiolabelling of isopeptide Nε-(γ-glutamyl)-L-lysine by conjugation with N-succinimidyl-4-[18F]fluorobenzoate

International Nuclear Information System (INIS)

Wuest, F.; Hultsch, C.; Bergmann, R.; Johannsen, B.; Henle, T.

2003-01-01

The isopeptide N ε -(γ-glutamyl)-L-lysine 4 was labelled with 18 F via N-succinimidyl-4-[ 18 F]fluorobenzoate ([ 18 F]SFB). A modified approach for the convenient synthesis of [ 18 F]SFB was used, and [ 18 F]SFB could be obtained in decay-corrected radiochemical yields of 44-53% (n=20) and radiochemical purity >95% within 40 min after EOB. For labelling N ε -(γ-glutamyl)-L-lysine with [ 18 F]SFB the effects of isopeptide concentration, temperature, and pH were studied to determine the optimum reaction conditions. The coupling reaction was shown to be temperature and pH independent while being strongly affected by the isopeptide concentration. Using the optimized labelling conditions, in a typical experiment 1.3 GBq of [ 18 F]SFB could be converted into 447 MBq (46%, decay-corrected) of [ 18 F]fluorobenzoylated isopeptide within 45 min, including HPLC purification

Design, synthesis and biological evaluation of new hybrid anticonvulsants derived from N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide and 2-(2,5-dioxopyrrolidin-1-yl)butanamide derivatives.

Science.gov (United States)

Kamiński, Krzysztof; Rapacz, Anna; Łuszczki, Jarogniew J; Latacz, Gniewomir; Obniska, Jolanta; Kieć-Kononowicz, Katarzyna; Filipek, Barbara

2015-05-15

The purpose of this study was to synthesize the library of 33 new N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamides, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanamides, and 2-(2,5-dioxopyrrolidin-1-yl)butanamides as potential new hybrid anticonvulsant agents. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. The coupling reaction of the 2-(2,5-dioxopyrrolidin-1-yl)propanoic acid, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanoic acid, or 2-(2,5-dioxopyrrolidin-1-yl)butanoic acid with the appropriately substituted benzylamines in the presence of the coupling reagent, N,N-carbonyldiimidazole (CDI) generated the final compounds 4-36. Spectral data acquired via (1)H NMR, (13)C NMR, and LC-MS confirmed the chemical structures of the newly prepared compounds. The initial anticonvulsant screening was performed in mice intraperitoneally (ip), using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The rotarod test determined the acute neurological toxicity (NT). The results of preliminary pharmacological screening revealed that 25 compounds showed protection in half or more of the animals tested in the MES and/or scPTZ seizure models at the fixed dose of 100mg/kg. The broad spectra of activity across the preclinical seizure models displayed compounds 4, 7, 8, 13, 15-18, 24, and 26. The quantitative pharmacological studies in mice demonstrated the highest protection for compounds 4 (ED50 MES=67.65 mg/kg, ED50scPTZ=42.83 mg/kg); 8 (ED50 MES=54.90 mg/kg, ED50scPTZ=50.29 mg/kg); and 20 (ED50scPTZ=47.39 mg/kg). These compounds were distinctly more potent and provided better safety profiles in the rotarod test compared to valproic acid or ethosuximide, which were used as model AEDs. Compound 8 underwent only a slight metabolic change by the human liver microsomes (HLMs), and also did not affect the activity of human cytochrome P450 isoform

A coordination polymer of CdII with benzene-1,3-dicarboxylate and 1,4-bis[1-(2-pyridylmethylbenzimidazol-2-yl]butane

Directory of Open Access Journals (Sweden)

Wei-Ping Zhang

2009-11-01

Full Text Available The title CdII coordination polymer, catena-poly[[{1,4-bis[1-(2-pyridylmethylbenzimidazol-2-yl]butane}cadmium(II]-μ-benzene-1,3-dicarboxylato], [Cd(C8H4O4(C30H28N6]n, was obtained by reaction of CdCO3, benzene-1,3-dicarboxylic acid (H2btc and 1,4-bis[1-(2-pyridylmethylbenzimidazol-2-yl]butane (L. The CdII cation is six-coordinated by an N2O4-donor set. L acts as a bidentate ligand and btc anions link CdII centers into a chain propagating parallel to [010].

Synthesis and characterization of N-hydroxysuccinimide ester chemical affinity derivatives of asialoorosomucoid that covalently cross-link to galactosyl receptors on isolated rat hepatocytes

International Nuclear Information System (INIS)

Herzig, M.C.S.; Weigel, P.H.

1989-01-01

The authors have developed chemical affinity reagents for the hepatic galactosyl receptor. Asialoorosomucoid (ASOR) was derivatized with five homobifunctional N-hydroxysuccinimide (NHS) ester cross-linkers. NHS/ASOR derivatives were synthesized, purified, and applied within 10 min to isolated rat hepatocytes at 4 degree C. Specific binding of these 125 I-labeled derivatives was ∼90% in the presence of either EGTA or excess ASOR. Specific cross-linking assessed by the resistance of specifically bound NHS/ 125 I-ASOR to release by EGTA, was 50-75% of the specifically bound ligand. The extent of specific cross-linking correlated with the average number of NHS groups per ASOR and was controlled by varying the molar ratio of cross-linker to ASOR during the synthesis. After being cross-linked with any of the NHS/ 125 I-ASOR derivatives, cells were washed with EGTA, solubilized in Triton X-100, and analyzed by SDA-PAGE and autoradiography. They conclude that all three receptor subunits can cross-link to ligand. They propose a model in which the native receptor is a heterohexamer composed of four subunits of RHL 1 and two subunits of RHL 2 and/or RHL 3

A two-dimensional bilayered Cd(II) coordination polymer with a three-dimensional supramolecular architecture incorporating 1,2-bis(pyridin-4-yl)ethene and 2,2'-(diazenediyl)dibenzoic acid.

Science.gov (United States)

Liu, Lei-Lei; Zhou, Yan; Li, Ping; Tian, Jiang-Ya

2014-02-01

In poly[[μ2-1,2-bis(pyridin-4-yl)ethene-κ(2)N:N'][μ2-2,2'-(diazenediyl)dibenzoato-κ(3)O,O':O'']cadmium(II)], [Cd(C14H8N2O4)(C12H10N2)]n, the asymmetric unit contains one Cd(II) cation, one 2,2'-(diazenediyl)dibenzoate anion (denoted L(2-)) and one 1,2-bis(pyridin-4-yl)ethene ligand (denoted bpe). Each Cd(II) centre is six-coordinated by four O atoms of bridging/chelating carboxylate groups from three L(2-) ligands and by two N atoms from two bpe ligands, forming a distorted octahedron. The Cd(II) cations are bridged by L(2-) and bpe ligands to give a two-dimensional (4,4) layer. The layers are interlinked through bridging carboxylate O atoms from L(2-) ligands, generating a two-dimensional bilayered structure with a 3(6)4(13)6(2) topology. The bilayered structures are further extended to form a three-dimensional supramolecular architecture via a combination of hydrogen-bonding and aromatic stacking interactions.

Synthesis of Some O-Substituted Derivatives of Natural 6-hydroxymethyl-4-methoxy-2H-pyran-2-one (opuntiol)

International Nuclear Information System (INIS)

Shahzadi, T.; Akhtar, M.; Rehman, A.; Riaz, T.; Ashraf, M.

2013-01-01

This manuscript reports the synthesis of a series of new O-substituted derivatives of opuntiol (1) which is a naturally occurring compound isolated from a plant Opuntia dillenii Haw belonging to family Cactaceae. These derivatives 3a-t, were characterized by FAB-MS, IR, and 1H-NMR and then screened against acetylcholinesterase, butyrylcholinesterase, lipoxygenase and H-chymotrypsin enzymes. The screening results revealed that 6-(acetyloxy) methyl- 4-methoxy-2H-pyran-2-one (3b) and N-(2,5-dimethylphenyl)-2-((4-methoxy-6-oxo-2H-pyran-2-yl) methoxy)acetamide (3p) were found to be the inhibitor of butyrylcholinesterase while 6-(acetyloxy) methyl- 4-methoxy-2H-pyran-2-one (3b), 6-(ethoxymethyl)-4-methoxy-2H-pyran-2-one (3c), 4-methoxy-6-((phenylmethoxy)methyl)-2H-pyran-2-one (3g), 6-((2-bromoethyloxy)methyl)-4-methoxy-2H-pyran-2-one (3j), N-(5-chloro-2-ethoxyphenyl)-2-((4-methoxy-6-oxo-2H-pyran-2-yl)methoxy) acetamide (3r), N-(3,4-dimethylphenyl)-2-((4-methoxy-6-oxo-2H-pyran-2-yl)methoxy)acetamide (3s) N-(3,5-dimethylphenyl)-2-((4-methoxy-6-oxo-2H-pyran-2-yl)methoxy)acetamide (3t) were found to be active against H-chymotrypsin and among these 3s was the good inhibitor of this enzyme having IC50 value of 142.71 +- 0.22 micro moles/L. (author)

Expedient Access to an N -phenylpyrrolidin-2-yl Heterocycle via a ...

African Journals Online (AJOL)

Expedient Access to an N -phenylpyrrolidin-2-yl Heterocycle via a Base-Induced Intramolecular aza -Michael Reaction. ... in good overall yield when employing a stoichiometric amount of base to facilitate the intramolecular aza-Michael reaction. Keywords: aza Michael, intramolecular, catalysed, piperidine, pyrrolidine, base ...

Crystal structure, solvothermal synthesis, thermogravimetric studies and DFT calculations of a five-coordinate cobalt(II) compound based on the N,N-bis-(2-hy-droxy-eth-yl)glycine anion.

Science.gov (United States)

Zhou, Yanling; Liu, Xianrong; Wang, Qijun; Wang, Lisheng; Song, Baoling

2016-10-01

The reaction of CoCl 2 ·6H 2 O, N , N -bis-(2-hy-droxy-eth-yl)glycine and tri-ethyl-amine (Et 3 N) in ethanol solution under solvothermal conditions produced crystals of [ N , N -bis-(2-hy-droxy-eth-yl)glycinato]chloridocobalt(II), [Co(C 6 H 12 NO 4 )Cl]. The Co II ion is coordinated in a slightly distorted trigonal-bipyramidal environment which is defined by three O atoms occupying the equatorial plane and the N and Cl atoms in the apical sites. In the crystal, two types of O-H⋯O hydrogen bonds connect the mol-ecules, forming a two-dimensional network parallel to (001). The mol-ecular structure of the title compound confirms the findings of FTIR, elemental analysis, ESI-MS analysis and TG analysis. By using the density functional theory (DFT) (B3LYP) method with 6-31G(d) basis set, the molecular structure has been calculated and optimized.

(Bipyridine-κ2N,N′chlorido[N-(2-hydroxyethyl-N-isopropyldithiocarbamato-κ2S,S′]zinc(II

Directory of Open Access Journals (Sweden)

Fatin Allia Mohamad

2012-07-01

Full Text Available The ZnII atom in the title compound, [Zn(C6H12NOS2Cl(C10H8N2], is coordinated by a chelating N-2-hydroxyethyl-N-isopropyldithiocarbamate ligand, a 2,2′-bipyridine ligand and a Cl atom. The resulting ClN2S2 donor set defines a distorted square-pyramidal coordination geometry. Helical supramolecular chains sustained by O—H...S hydrogen bonds and propagating along the b axis feature in the crystal packing. A three-dimensional architecture is stabilized by C—H...O, C—H...S and C—H...Cl interactions.

2-(4-Methylpiperazin-1-yl-4-phenyl-6-(thiophen-2-yl-pyridine-3-carbonitrile

Directory of Open Access Journals (Sweden)

Nawal Mishriky

2013-02-01

Full Text Available 2-(4-Methylpiperazin-1-yl-4-phenyl-6-(thiophen-2-yl-pyridine-3-carbonitrile (4 was synthesized via nucleophilic substitution reaction of 1-methylpiperazine with 2-bromo analogue 3. The latter was obtained through bromination (Br2/AcOH of 2-[3-oxo-1-phenyl-3-(thiophen-2-ylpropyl]malononitrile (2.

A new class of anticonvulsants possessing 6 Hz psychomotor seizure test activity: 2-(1H-benzotriazol-1-yl)-N'-[substituted] acetohydrazides.

Science.gov (United States)

Kumar, Praveen; Tripathi, Laxmi

2012-05-01

A series of 2-(1H-Benzotriazol-1-yl)-N'-[substituted]acetohydrazides were designed & synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The new compounds were characterized using FT-IR, 1H NMR, mass spectral data and elemental analysis. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The neurotoxicity was assessed using the rotorod method. The most active compound of the series was N'-[4-(1,3-Benzodioxol-5-yloxy)benzylidene]-2-(1H-benzotriazol-1-yl)acetohydrazide (BTA 9), which showed good activity with 75 % protection (3/4, 0.5 h) at a dose of 100 mg/kg in mice. All the compounds exhibited no neurotoxicity. A computational study was carried out for calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta, GABA (A) alpha-1 receptors and Na/H exchanger, in Lamarckian genetic algorithm based flexible docking studies.

Enhanced bovine serum albumin absorption on the N-hydroxysuccinimide activated graphene oxide and its corresponding cell affinity.

Science.gov (United States)

Xiong, Kun; Fan, Qingbo; Wu, Tingting; Shi, Haishan; Chen, Lin; Yan, Minhao

2017-12-01

By successively reacting with N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), the carboxyl on the graphene oxide (GO) surface was successfully activated into NHS active ester. In this study, bovine serum albumin (BSA) was selected as a model protein, used for studying the protein absorption capacity of the NHS activated GO (GO-EDC-NHS). Approximately 12.75mg of BSA could be covalent bonded onto the GO-EDC-NHS surface (BSA-CB-GO), whereas only 6.83mg of BSA physical absorbed onto the GO surface (BSA-NB-GO). With a 168h of phosphate buffer saline (PBS) soaking, the BSA accumulative desorption ratio, which was accordingly assigned to the BSA-NB-GO and the BSA-CB-GO, was separately 29.91wt% and 2.95wt%. Consequently, it proved GO-EDC-NHS exhibited more stable and stronger BSA absorption capacity. As compared to the mouse bone marrow mesenchymal stem cells (mBMSCs) cultivated on the BSA-NB-GO surface, the immunofluorescence staining images showed that more vinculins and integrin α5 were visible in the mBMSCs cultivated on the BSA-CB-GO surface, they also produced more distinct stress fibers and actin-containing microfilaments. In summary, BSA-CB-GO possesses an excellent cell affinity, which can be considered as a promising functional material used for promoting the bone remodeling. Copyright © 2017 Elsevier B.V. All rights reserved.

Aqua[bis(pyrimidin-2-yl-kappa N)amine](carbonato-kappa 2O,O')copper(II) dihydrate.

Science.gov (United States)

van Albada, Gerard A; Mutikainen, Ilpo; Turpeinen, Urho; Reedijk, Jan

2002-03-01

The title mononuclear complex, [Cu(CO(3))(C(8)H(7)N(5))(H(2)O)] x 2H(2)O, was obtained by fixation of CO(2) by a mixture of copper(II) tetrafluoroborate and the ligand bis(pyrimidin-2-yl)amine in ethanol/water. The Cu(II) ion of the complex has a distorted square-pyramidal environment, with a basal plane formed by two N atoms of the ligand and two chelating O atoms of the carbonate group, while the apical position is occupied by the O atom of the coordinating water molecule. In the solid state, hydrogen-bonding interactions are dominant, the most unusual being the Watson-Crick-type coplanar ligand pairing through two N--H...N bonds. Lattice water molecules also participate in hydrogen bonding.

Energiantuotannon ratkaisut Penttilän Puu Oy:n höyläämön sivuvirrasta

OpenAIRE

Kortelainen, Toni

2017-01-01

Tässä teknistaloudellisessa opinnäytetyössä selvitettiin Penttilän Puu Oy:n Joensuun höyläämölle taloudellisesti kannattavin energiantuotantoratkaisu. Käyttöikänsä päähän tulleen nykyisen ruuvisyötteisen arinakattilan tilalle on harkittu pienen kokoluokan sähkön ja lämmön yhteistuotantoa (pien-CHP), mikäli sellainen osoittautuu kannattavaksi. Muussa tapauksessa arinakattila vaihdetaan uuteen biokattilaan lähivuosina. Opinnäytetyön teknisessä osiossa esitellään korvaavat lämmitysvaih...

Synthesis of carboxylic acids, esters, alcohols and ethers containing a tetrahydropyran ring derived from 6-methyl-5-hepten-2-one.

Science.gov (United States)

Hanzawa, Yohko; Hashimoto, Kahoko; Kasashima, Yoshio; Takahashi, Yoshiko; Mino, Takashi; Sakamoto, Masami; Fujita, Tsutomu

2012-01-01

3-hydroxy acids, 3-hydroxy-3,7-dimethyloct-6-enoic acid (1) and 3-hydroxy-2,2,3,7-tetramethyloct-6-enoic acid (2), were prepared from 6-methyl-5-hepten-2-one, and they were subsequently used to prepare (2,6,6-trimethyltetrahydropyran-2-yl)acetic acid (3) and 2-methyl-2-(2,6,6-trimethyltetrahydropyran-2-yl)propanoic acid (4), respectively, via cyclization with an acidic catalyst such as boron trifluoride diethyl etherate or iodine. The reaction of carboxylic acids 3 and 4 with alcohols, including methanol, ethanol, and 1-propanol, produced the corresponding methyl, ethyl, and propyl esters, which all contained a tetrahydropyran ring. Reduction of carboxylic acids 3 and 4 afforded the corresponding alcohols. Subsequent reactions of these alcohols with several acyl chlorides produced novel esters. The alcohols also reacted with methyl iodide and sodium hydride to provide novel ethers. A one-pot cyclization-esterification of 1 to produce esters containing a tetrahydropyran ring, using iodine as a catalyst, was also investigated.

Aqua{2-(pyridin-2-yl-N-[(pyridin-2-ylmethylidene]ethanamine-κ3N,N′,N′′}(sulfato-κ2O,O′copper(II tetrahydrate

Directory of Open Access Journals (Sweden)

Daniel Tinguiano

2013-01-01

Full Text Available The title complex, [Cu(SO4(C13H13N3(H2O]·4H2O, was obtained by mixing copper sulfate pentahydrate and 2-(pyridin-2-yl-N-(pyridin-2-ylmethylideneethanamine in ethanol under reflux conditions. The CuII ion shows a Jahn–Teller-distorted octahedral geometry, with equatorial positions occupied by three N atoms from the tridentate ligand (average Cu—N = 2.004 Å and one O atom from a bidentate sulfate anion [Cu—O = 1.963 (2 Å]. The axial positions are occupied by one O atom from a coordinating water molecule [Cu—O = 2.230 (3 Å] and one weakly bonded O atom [Cu—O = 2.750 (2 Å] from the bidentate sulfate ion. The complex molecules are connected through O—H...O hydrogen bonds between the coordinating water molecules and sulfate ions from neighboring complexes, forming a double chain parallel to the c axis. The chains are stabilized through additional hydrogen bonds by one of the non-coordinating water molecules bridging between neighboring strands of the double chains. The remaining three water molecules fill the interstitial space between the double chains and are involved in an intricate hydrogen-bonding network that consolidates the structure.

2-Amino­benzoic acid–4-[2-(pyridin-4-yl)eth­yl]pyridine (2/1)

OpenAIRE

Arman, Hadi D.; Tiekink, Edward R. T.

2013-01-01

The asymmetric unit of the title co-crystal, C12H12N2·2C7H7NO2, comprises a centrosymmetric 4-[2-(pyridin-4-yl)ethyl]pyridine molecule and a 2-aminobenzoic acid molecule in a general position. The acid has a small twist between the carboxylic acid residue and the ring [dihedral angle = 7.13 (6)°] despite the presence of an intramolecular N—H...O(carbonyl) hydrogen bond. Three-molecule aggregates are formed via O—H...N(pyridyl) hydrogen bonds, and these are connecte...

The methylcobalt(III) complex of a tetrapodal pentadentate amine ligand, 2,6-bis(1′,3′-diamino-2′-methyl-prop-2′-yl)pyridine

DEFF Research Database (Denmark)

Grohmann, Andreas; Heinemann, Frank W; Kofod, Pauli

1999-01-01

The pentaamine methylcobalt(III) compound [Co(pyN4)(CH3)](NO3)2 (pyN4=2,6-bis(1′,3′-diamino-2′-methyl-prop-2′-yl)pyridine) has been synthesised from [Co(NH3)5(CH3)](NO3)2 and pyN4 by ligand exchange, and characterised by IR, 1H, 13C and 59Co NMR spectroscopy as well as elemental analysis. The str......The pentaamine methylcobalt(III) compound [Co(pyN4)(CH3)](NO3)2 (pyN4=2,6-bis(1′,3′-diamino-2′-methyl-prop-2′-yl)pyridine) has been synthesised from [Co(NH3)5(CH3)](NO3)2 and pyN4 by ligand exchange, and characterised by IR, 1H, 13C and 59Co NMR spectroscopy as well as elemental analysis...... nitrogen atom, while the four equivalent primary amino groups take the equatorial positions. The other axial position, trans to the pyridine ring, is occupied by the methyl group. The Co–Npy bond length of 2.018(2) Å is significantly elongated compared with other cobalt(III) complexes of the pyN4 ligand...

Human dosimetry of carbon-11 labeled N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide extrapolated from whole-body distribution kinetics and radiometabolism in rats

DEFF Research Database (Denmark)

Luoto, Pauliina; Laitinen, Iina; Suilamo, Sami

2010-01-01

Carbon-11 labeled N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide ([11C]PK11195) is a peripheral benzodiazepine receptor (PBR) antagonist that is used as a positron emission tomography (PET) radiopharmaceutical for neuroinflammatory imaging. This study was designed to investigate...

Improved tumor targeting of anti-HER2 nanobody through N-succinimidyl 4-guanidinomethyl-3-iodobenzoate radiolabeling.

Science.gov (United States)

Pruszynski, Marek; Koumarianou, Eftychia; Vaidyanathan, Ganesan; Revets, Hilde; Devoogdt, Nick; Lahoutte, Tony; Lyerly, H Kim; Zalutsky, Michael R

2014-04-01

Nanobodies are approximately 15-kDa proteins based on the smallest functional fragments of naturally occurring heavy chain-only antibodies and represent an attractive platform for the development of molecularly targeted agents for cancer diagnosis and therapy. Because the human epidermal growth factor receptor type 2 (HER2) is overexpressed in breast and ovarian carcinoma, as well as in other malignancies, HER2-specific Nanobodies may be valuable radiodiagnostics and therapeutics for these diseases. The aim of the present study was to evaluate the tumor-targeting potential of anti-HER2 5F7GGC Nanobody after radioiodination with the residualizing agent N-succinimidyl 4-guanidinomethyl 3-(125/131)I-iodobenzoate (*I-SGMIB). The 5F7GGC Nanobody was radiolabeled using *I-SGMIB and, for comparison, with N(ε)-(3-*I-iodobenzoyl)-Lys(5)-N(α)-maleimido-Gly(1)-GEEEK (*I-IB-Mal-d-GEEEK), another residualizing agent, and by direct radioiodination using IODO-GEN ((125)I-Nanobody). The 3 labeled Nanobodies were evaluated in affinity measurements, and paired-label internalization assays were performed on HER2-expressing BT474M1 breast carcinoma cells and in paired-label tissue distribution measurements in mice bearing subcutaneous BT474M1 xenografts. *I-SGMIB-Nanobody was produced in 50.4% ± 3.6% radiochemical yield and exhibited a dissociation constant of 1.5 ± 0.5 nM. Internalization assays demonstrated that intracellular retention of radioactivity was up to 1.5-fold higher for *I-SGMIB-Nanobody than for coincubated (125)I-Nanobody or *I-IB-Mal-d-GEEEK-Nanobody. Peak tumor uptake for *I-SGMIB-Nanobody was 24.50% ± 9.89% injected dose/g at 2 h, 2- to 4-fold higher than observed with other labeling methods, and was reduced by 90% with trastuzumab blocking, confirming the HER2 specificity of localization. Moreover, normal-organ clearance was fastest for *I-SGMIB-Nanobody, such that tumor-to-normal-organ ratios greater than 50:1 were reached by 24 h in all tissues except lungs

Density functional theory investigation of the geometric and electronic structures of [UO2(H2O)m(OH)n](2 - n) (n + m = 5).

Science.gov (United States)

Ingram, Kieran I M; Häller, L Jonas L; Kaltsoyannis, Nikolas

2006-05-28

Gradient corrected density functional theory has been used to calculate the geometric and electronic structures of the family of molecules [UO2(H2O)m(OH)n](2 - n) (n + m = 5). Comparisons are made with previous experimental and theoretical structural and spectroscopic data. r(U-O(yl)) is found to lengthen as water molecules are replaced by hydroxides in the equatorial plane, and the nu(sym) and nu(asym) uranyl vibrational wavenumbers decrease correspondingly. GGA functionals (BP86, PW91 and PBE) are generally found to perform better for the cationic complexes than for the anions. The inclusion of solvent effects using continuum models leads to spurious low frequency imaginary vibrational modes and overall poorer agreement with experimental data for nu(sym) and nu(asym). Analysis of the molecular orbital structure is performed in order to trace the origin of the lengthening and weakening of the U-O(yl) bond as waters are replaced by hydroxides. No evidence is found to support previous suggestions of a competition for U 6d atomic orbitals in U-O(yl) and U-O(hydroxide)pi bonding. Rather, the lengthening and weakening of U-O(yl) is attributed to reduced ionic bonding generated in part by the sigma-donating ability of the hydroxide ligands.

Towards the chiral metabolomics: Liquid chromatography–mass spectrometry based DL-amino acid analysis after labeling with a new chiral reagent, (S)-2,5-dioxopyrrolidin-1-yl-1-(4,6-dimethoxy-1,3,5-triazin-2-yl) pyrrolidine-2-carboxylate, and the application to saliva of healthy volunteers

Energy Technology Data Exchange (ETDEWEB)

Mochizuki, Toshiki; Takayama, Takahiro; Todoroki, Kenichiro; Inoue, Koichi; Min, Jun Zhe; Toyo’oka, Toshimasa, E-mail: toyooka@u-shizuoka-ken.ac.jp

2015-05-22

Highlights: • A novel chiral labeling reagent was synthesized. • Analysis of DL-amino acids was performed by UPLC–ESI-MS/MS. • Efficient enantioseparation and detection of DL-amino acids were performed. • DL-Amino acid in saliva was successfully determined under mild conditions. - Abstract: A novel triazine-type chiral derivatization reagent, i.e., (S)-2,5-dioxopyrrolidin-1-yl-1-(4,6-dimethoxy-1,3,5-triazin-2-yl) pyrrolidine-2-carboxylate (DMT-(S)-Pro-OSu), was developed for the highly sensitive and selective detection of chiral amines and amino acids by UPLC–MS/MS analysis. The enantiomers of amino acids were easily labeled with the reagents at room temperature within 40 min in an alkaline medium containing triethylamine. The diastereomers derived from proteolytic amino acids, except serine, were well separated under isocratic elution conditions by reversed-phase chromatography using an ODS column (R{sub s} = 1.2–9.0). DL-Serine was separated by use of an ADME column which has relatively higher polar surface than the conventional ODS column. The characteristic product ions, i.e., m/z 195.3 and m/z 209.3, were detected from all the diastereomers by the collision-induced dissociation of the protonated molecule. A highly sensitive detection on the amol–fmol level was obtained from the selected reaction monitoring (SRM) chromatogram. The chiral amines (e.g., adrenaline and noradrenaline) labeled with DMT-(S)-Pro-OSu were also well separated and sensitively detected by the present procedure. The method using DMT-(S)-Pro-OSu was used for the determination of DL-amino acids in the human saliva from healthy volunteers. Various L-amino acids were identified in the saliva. Furthermore, D-alanine (D-Ala) and D-proline (D-Pro) were also detected in relatively high concentrations (>5%). The ratio was higher in male saliva than in female saliva. However, the difference in the ratio of D-Ala for one day was not very high and the effect of foods and beverage

Tetraaquatetrakis{μ3-3,3′-[(E,E-ethane-1,2-diylbis(nitrilomethylidyne]benzene-1,2-diolato}octazinc(II N,N-dimethylformamide hexasolvate

Directory of Open Access Journals (Sweden)

Lan-Sun Zheng

2009-12-01

Full Text Available The asymmetric unit of the title compound [Zn8(C16H12N2O44(H2O4]·6C3H7NO, consists of eight ZnII cations, four tetravalent anionic ligands, L4− (L4− = 3,3′-(1E,1′E-(ethane-1,2-diylbis(azan-1-yl-1-ylidenebis(methan-1-yl-1-ylidenedibenzene-1,2-bis(olate, four coordinated water molecules and six N,N-dimethylformamide solvate molecules. The coordination complex comprises an octanuclear ZnII unit with its ZnII centers coordinated in two discrete distorted square-pyramidal geometries. Four ZnII atoms each coordinate to two nitrogen atoms and two phenolate oxygen atoms from an individual L4− ligand and one coordinated water molecule. The other four ZnII atoms each bind to five phenolate oxygen atoms from three different L4− ligands. In the crystal structure, the ZnII complex unit, coordinated water molecules and dimethylformamide solvate molecules are linked via O—H...O and C—H...O hydrogen bonds. Molecules are connected by additional intermolecular O—H...O and C—H...O hydrogen bonds, forming an extensive three dimensional framework.

The Photochemistry of Benzotriazole Derivatives. Part 2: Photolysis of 1-Substituted Benzotriazole Arylhydrazones: New Route to Phenanthridin-6-yl-2-phenyldiazines

Directory of Open Access Journals (Sweden)

Nouria A. Al-Awadi

2011-12-01

Full Text Available Irradiation of 1-substituted benzotriazole arylhydrazones 3a–c, 4a,b and 5a,b with a 16 W low pressure mercury arc-lamp (254 nm for 24 h gave phenanthridin-6-yl-2-phenyldiazines 9a–c, phenanthridin-6(5H-ones 10a–c, 1-anilinobenzimidazoles 11a–c, 2-aryl-1H-benzimidazoles 12a–c, 1-arylamino-1H-benzimidazol-2-carboxylic acid ethyl esters 14a,b, 1-aryl-1H, 9H-benzo [4,5][1,2,3] triazolo[1,2-a]tetrazole-3-carboxylic acid ethyl esters 16a,b, 1-arylamino-2-benzoylbenzimidazoles 18a,b and 2-benzoylbenzoxazole 21.

Marine Inspired 2-(5-Halo-1H-indol-3-yl)-N,N-dimethylethanamines as Modulators of Serotonin Receptors: An Example Illustrating the Power of Bromine as Part of the Uniquely Marine Chemical Space.

Science.gov (United States)

Ibrahim, Mohamed A; El-Alfy, Abir T; Ezel, Kelly; Radwan, Mohamed O; Shilabin, Abbas G; Kochanowska-Karamyan, Anna J; Abd-Alla, Howaida I; Otsuka, Masami; Hamann, Mark T

2017-08-09

In previous studies, we have isolated several marine indole alkaloids and evaluated them in the forced swim test (FST) and locomotor activity test, revealing their potential as antidepressant and sedative drug leads. Amongst the reported metabolites to display such activities was 5-bromo- N , N -dimethyltryptamine. Owing to the importance of the judicious introduction of halogens into drug candidates, we synthesized two series built on a 2-(1 H -indol-3-yl)- N , N -dimethylethanamine scaffold with different halogen substitutions. The synthesized compounds were evaluated for their in vitro and in vivo antidepressant and sedative activities using the mouse forced swim and locomotor activity tests. Receptor binding studies of these compounds to serotonin (5-HT) receptors were conducted. Amongst the prepared compounds, 2-(1 H -indol-3-yl)- N , N -dimethyl-2-oxoacetamide ( 1a ), 2-(5-bromo-1 H -indol-3-yl)- N , N -dimethyl-2-oxoacetamide ( 1d ), 2-(1 H -indol-3-yl)- N , N -dimethylethanamine ( 2a ), 2-(5-chloro-1 H -indol-3-yl)- N , N -dimethylethanamine ( 2c ), 2-(5-bromo-1 H -indol-3-yl)- N , N -dimethylethanamine ( 2d ), and 2-(5-iodo-1 H -indol-3-yl)- N , N -dimethylethanamine ( 2e ) have been shown to possess significant antidepressant-like action, while compounds 2c , 2d , and 2e exhibited potent sedative activity. Compounds 2a , 2c , 2d , and 2e showed nanomolar affinities to serotonin receptors 5-HT 1A and 5-HT₇. The in vitro data indicates that the antidepressant action exerted by these compounds in vivo is mediated, at least in part, via interaction with serotonin receptors. The data presented here shows the valuable role that bromine plays in providing novel chemical space and electrostatic interactions. Bromine is ubiquitous in the marine environment and a common element of marine natural products.

Discovery of (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), a kinesin spindle protein inhibitor and potential anticancer agent.

Science.gov (United States)

Theoclitou, Maria-Elena; Aquila, Brian; Block, Michael H; Brassil, Patrick J; Castriotta, Lillian; Code, Erin; Collins, Michael P; Davies, Audrey M; Deegan, Tracy; Ezhuthachan, Jayachandran; Filla, Sandra; Freed, Ellen; Hu, Haiqing; Huszar, Dennis; Jayaraman, Muthusamy; Lawson, Deborah; Lewis, Paula M; Nadella, Murali V P; Oza, Vibha; Padmanilayam, Maniyan; Pontz, Timothy; Ronco, Lucienne; Russell, Daniel; Whitston, David; Zheng, Xiaolan

2011-10-13

Structure-activity relationship analysis identified (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), from a series of novel kinesin spindle protein (KSP) inhibitors, as exhibiting both excellent biochemical potency and pharmaceutical properties suitable for clinical development. The selected compound arrested cells in mitosis leading to the formation of the monopolar spindle phenotype characteristic of KSP inhibition and induction of cellular death. A favorable pharmacokinetic profile and notable in vivo efficacy supported the selection of this compound as a clinical candidate for the treatment of cancer.

(Z)-N,N-Dimethyl-2-[phen­yl(pyridin-2-yl)methyl­idene]hydrazinecarbothio­amide

Science.gov (United States)

Jayakumar, K.; Sithambaresan, M.; Prathapachandra Kurup, M. R.

2011-01-01

The title compound, C15H16N4S, exists in the Z conformation with the thionyl S atom lying cis to the azomethine N atom. The shortening of the N—N distance [1.3697 (17) Å] is due to extensive delocalization with the pyridine ring. The hydrazine–carbothio­amide unit is almost planar, with a maximum deviation of 0.013 (2) Å for the amide N atom. The stability of this conformation is favoured by the formation of an intra­molecular N—H⋯N hydrogen bond. The packing of the mol­ecules involves no classical inter­molecular hydrogen-bonding inter­actions; however, a C—H⋯π inter­action occurs. PMID:22199715

Electrode Potentials of l-Tryptophan, l-Tyrosine, 3-Nitro-l-tyrosine, 2,3-Difluoro-l-tyrosine, and 2,3,5-Trifluoro-l-tyrosine.

Science.gov (United States)

Mahmoudi, Leila; Kissner, Reinhard; Nauser, Thomas; Koppenol, Willem H

2016-05-24

Electrode potentials for aromatic amino acid radical/amino acid couples were deduced from cyclic voltammograms and pulse radiolysis experiments. The amino acids investigated were l-tryptophan, l-tyrosine, N-acetyl-l-tyrosine methyl ester, N-acetyl-3-nitro-l-tyrosine ethyl ester, N-acetyl-2,3-difluoro-l-tyrosine methyl ester, and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester. Conditional potentials were determined at pH 7.4 for all compounds listed; furthermore, Pourbaix diagrams for l-tryptophan, l-tyrosine, and N-acetyl-3-nitro-l-tyrosine ethyl ester were obtained. Electron transfer accompanied by proton transfer is reversible, as confirmed by detailed analysis of the current waves, and because the slopes of the Pourbaix diagrams obey Nernst's law. E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) at pH 7 are 0.99 ± 0.01 and 0.97 ± 0.01 V, respectively. Pulse radiolysis studies of two dipeptides that contain both amino acids indicate a difference in E°' of approximately 0.06 V. Thus, in small peptides, we recommend values of 1.00 and 0.96 V for E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH), respectively. The electrode potential of N-acetyl-3-nitro-l-tyrosine ethyl ester is higher, while because of mesomeric stabilization of the radical, those of N-acetyl-2,3-difluoro-l-tyrosine methyl ester and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester are lower than that of tyrosine. Given that the electrode potentials at pH 7 of E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) are nearly equal, they would be, in principle, interchangeable. Proton-coupled electron transfer pathways in proteins that use TrpH and TyrOH are thus nearly thermoneutral.

2-(2,3-Dihydro-1H-indol-3-yl)ethanol

DEFF Research Database (Denmark)

Frydenvang, Karla Andrea; Sommer, Michael Bech; Heckmann, Dieter

2004-01-01

The first direct resolution of racemic 2-(2,3-dihydro-lH-indol-3-yl)ethanol-prepared by catalytic hydrogenation of 2-(lH-indol-3-yl)ethanol-has been accomplished by chiral simulated moving bed (SMB) chromatography. The single enantiomers were isolated as their dihydrogen phosphate salts. Single......-crystal X-ray analyses were successful, revealing that the (+)-enantiomer of 2-(2,3-dihydro-lH-indol-3-yl)ethanol has the (S) configuration. Chirality 16:126-130, 2004....

Synthesis of (E-2,4-Dinitro-N-((2E,4E-4-phenyl-5-(pyrrolidin-1-ylpenta-2,4-dienylideneaniline

Directory of Open Access Journals (Sweden)

Mostafa Fesanghari

2009-07-01

Full Text Available (E-2,4-Dinitro-N-((2E,4E-4-phenyl-5-(pyrrolidin-1-ylpenta-2,4-dienylidene aniline dye was prepared in one pot by reaction of premade N-2,4-dinitrophenyl-3-phenylpyridinium chloride (DNPPC and pyrrolidine in absolute MeOH.

Crystal structures of 2-(N,N-dimethylaminoalkyl)ferroceneboronic acids and their diol derivatives. The quest for a B-N intramolecular bond in the solid state

DEFF Research Database (Denmark)

Norrild, Jens Chr.; Søtofte, Inger

2001-01-01

The crystal structures of (S,S)-2-(N,N-dimethyl-1-aminoethyl)ferroceneboronic acid (2), (S,S)-1-(N,N-dimethyl-1-aminoethyl)-2-(4,4,5,5-tetraphenyl-1,3,2-dioxaborolan-2-yl)ferrocene (3), rac-2-(N,N-dimethylaminomethyl)-ferroceneboronic acid (rac-4), (S)-[(1S,2S,3R,5S)-pinane-1,2-diyl] 2-(N...

Crystal structure of 2-hy-droxy-imino-2-(pyridin-2-yl)-N'-[1-(pyridin-2-yl)ethyl-idene]acetohydrazide.

Science.gov (United States)

Plutenko, Maxym O; Lampeka, Rostislav D; Haukka, Matti; Nordlander, Ebbe

2014-12-01

The mol-ecule of the title compound, C14H13N5O2, is approximately planar (r.m.s deviation for all non-H atoms = 0.093 Å), with the planes of the two pyridine rings inclined to one another by 5.51 (7)°. The oxime group is syn to the amide group, probably due to the formation of an intra-molecular N-H⋯N hydrogen bond that forms an S(6) ring motif. In the crystal, mol-ecules are linked by pairs of bifurcated O-H⋯(O,N) hydrogen bonds, forming inversion dimers. The latter are linked via C-H⋯O and C-H⋯N hydrogen bonds, forming sheets lying parallel to (502). The sheets are linked via π-π stacking inter-actions [inter-centroid distance = 3.7588 (9) Å], involving the pyridine rings of inversion-related mol-ecules, forming a three-dimensional structure.

One-electron capture into Li-like autoionising N4+ (1s2ln'l') configurations by metastable N5+ (1s2s3S) multicharged ions in collisions with He and H2, observed by electron spectrometry at 3.4 keV amu-1

International Nuclear Information System (INIS)

Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.

1985-01-01

One-electron capture into N 4+ (1s2ln'l') configurations, with n'=2 to 4, has been observed by electron spectrometry when a N 5+ (1s2s 3 S) multicharged ion beam encounters an He or H 2 target, at low collision velocity (upsilon=0.37 au) within single-collision conditions. Contributions of other 1s2l metastable states and of the 1s 2 ground state may be disregarded. A small indication of two-electron capture by 1s2s 3 S ions into (1s2s 3 S)3l3l' configurations is also seen. (author)

Synthesis and the crystal and molecular structures of (H3L . Cl)[CoCl4] and H2L[CuBr4] (L is 2,4,6-Tri(N,N-dimethylamino)methylphenol)

International Nuclear Information System (INIS)

Kovalchukova, O. V.; Stash, A. I.; Strashnova, S. B.; Romashkina, E. P.; Zaitsev, B. E.

2010-01-01

The complex compounds (H 3 L . Cl)[CoCl 4 ] (I) and H 2 L[CuBr 4 ] (II), where L is 2,4,6-tri(N,N-dimethylamino)methylphenol, were isolated in the crystalline state and studied by X-ray diffraction. The organic cations were found to be outer-sphere ligands. All three nitrogen atoms of the tertiary amino groups are protonated. In compound I, the H 3 L 3+ cation exists as the cis tautomer. In compound II, the H 2 L 2+ dication exists as the trans isomer. In the crystal structure, the dications are arranged in layers via hydrogen bonds.

A two-dimensional ZnII coordination polymer constructed from benzene-1,2,3-tricarboxylic acid and N,N'-bis[(pyridin-4-yl)methylidene]hydrazine.

Science.gov (United States)

Wang, Xiangfei; Yang, Fang; Tang, Meng; Yuan, Limin; Liu, Wenlong

2015-07-01

The hydrothermal synthesis of the novel complex poly[aqua(μ4-benzene-1,2,3-tricarboxylato)[μ2-4,4'-(hydrazine-1,2-diylidenedimethanylylidene)dipyridine](μ3-hydroxido)dizinc(II)], [Zn(C9H3O6)(OH)(C12H10N4)(H2O)]n, is described. The benzene-1,2,3-tricarboxylate ligand connects neighbouring Zn4(OH)2 secondary building units (SBUs) producing an infinite one-dimensional chain. Adjacent one-dimensional chains are connected by the N,N'-bis[(pyridin-4-yl)methylidene]hydrazine ligand, forming a two-dimensional layered structure. Adjacent layers are stacked to generate a three-dimensional supramolecular architecture via O-H...O hydrogen-bond interactions. The thermal stability of this complex is described and the complex also appears to have potential for application as a luminescent material.

4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as potent anti-tumor agents.

Science.gov (United States)

Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

2004-01-19

Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which exhibits selective cytotoxicity against a tumorigenic cell line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)-methanone (18m) was designed and synthesized as a biologically stable derivative containing no ester group. Although the potency of 18m was almost the same as our initial hit compound 1, 18m is expected to last longer in the human body as an anticancer agent.

Bis[tris(1H-pyrazol-1-yl-κN2methane]nickel(II bis{[tris(1H-pyrazol-1-yl-κN2methane]tris(thiocyanato-κNnickelate(II} methanol disolvate

Directory of Open Access Journals (Sweden)

Ganna Lyubartseva

2011-12-01

Full Text Available Attempts to prepare the mononuclear [(tpmNiIIL3]−1 [tpm = tris(1H-pyrazol-1-ylmethane and L = thiocyanate] anion yielded the methanol-solvated salt, [(tpm2NiII][(tpmNiII(NCS3]2·2CH3OH or [Ni(C10H10N62][Ni(NCS3(C10H10N6]2·2CH3OH. The asymmetric unit consists of half a centrosymmetric bis[tris(1H-pyrazol-1-ylmethane]nickel(II cation and an octahedral nickelate(II anion bound to one tpm and three L ligands, and a methanol solvent molecule. One of the L ligands is disordered over two positions with occupancy factors of 0.650 (3 and 0.350 (3. There are O—H...S interactions between the methanol and the disordered thiocyanate anion, and a weak C—H...O hydrogen bond between the cation and the methanol O atom.

Influence of halogen substitution in the ligand sphere on the antitumor and antibacterial activity of half-sandwich ruthenium(II) complexes [RuX(η{sup 6}-arene)(C{sub 5}H{sub 4}N-2-cH=N-Ar)]{sup +}

Energy Technology Data Exchange (ETDEWEB)

Gichumbi, Joel M.; Omondi, Bernard; Friedrich, Holger B. [School of Chemistry, University of KwaZulu-Natal, Durban (South Africa); Lazarus, Geraldine; Singh, Moganavelli; Shaikh, Nazia; Chenia, Hafizah Y. [School of Life Sciences, University of KwaZulu-Natal, Durban (South Africa)

2017-06-01

New complexes [(η{sup 6}-p-cymene)Ru(C{sub 5}H{sub 4}N-2-CH=N-Ar)X]PF{sub 6} [X = Br (1), I (2); Ar = 4-fluorophenyl (a), 4-chlorophenyl (b), 4-bromophenyl (c), 4-iodophenyl (d), 2,5-dichlorophenyl (e)] were prepared, as well as 3a-3e (X = Cl) and the new complexes [(η{sup 6}-arene)RuCl(N-N)]PF{sub 6} [arene = C{sub 6}H{sub 5}OCH{sub 2}CH{sub 2}OH, N-N = 2,2{sup '}-bipyridine (4), 2,6-(dimethylphenyl)-pyridin-2-yl-methylene amine (5), 2,6-(diisopropylphenyl)-pyridin-2-yl-methylene amine (6); arene = p-cymene, N-N = 4-(aminophenyl)-pyridin-2-yl-methylene amine (7)]. X-ray diffraction studies were performed for 1a, 1b, 1c, 1d, 2b, 5, and 7. Cytotoxicities of 1a-1d and 2 were established versus human cancer cells epithelial colorectal adenocarcinoma (Caco-2) (IC{sub 50}: 35.8-631.0 μM), breast adenocarcinoma (MCF7) (IC{sub 50}: 36.3-128.8.0 μM), and hepatocellular carcinoma (HepG2) (IC{sub 50}: 60.6-439.8 μM), 3a-3e were tested against HepG2 and Caco-2, and 4-7 were tested against Caco-2. 1-7 were tested against non-cancerous human epithelial kidney cells. 1 and 2 were more selective towards tumor cells than the anticancer drug 5-fluorouracil (5-FU), but 3a-3e (X = Cl) were not selective. 1 and 2 had good activity against MCF7, some with lower IC{sub 50} than 5-FU. Complexes with X = Br or I had moderate activity against Caco-2 and HepG2, but those with Cl were inactive. Antibacterial activities of 1a, 2b, 3a, and 7 were tested against antibacterial susceptible and resistant Gram-negative and -positive bacteria. 1a, 2b, and 3a showed activity against methicillin-resistant S. aureus (MIC = 31-2000 μg.mL{sup -1}). (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Anti-leishmanial and structure-activity relationship of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives

Directory of Open Access Journals (Sweden)

Asunción Burguete

2008-12-01

Full Text Available A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E-3-(3,4,5-trimethoxy-phenyl-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.

Rational synthesis of high nuclearity Mo/Fe/S clusters: the reductive coupling approach in the convenient synthesis of (Cl(4)-cat)(2)Mo(2)Fe(6)S(8)(PR(3))(6) [R = Et, (n)Pr, (n)Bu] and the new [(Cl(4)-cat)(2)Mo(2)Fe(2)S(3)O(PEt(3))(3)Cl]-1/2(Fe(PEt(3))(2)(MeCN)(4)) and (Cl(4)-cat)(2)Mo(2)Fe(3)S(5)(PEt(3))(5) clusters.

Science.gov (United States)

Han, J; Koutmos, M; Ahmad, S A; Coucouvanis, D

2001-11-05

A general method for the synthesis of high nuclearity Mo/Fe/S clusters is presented and involves the reductive coupling of the (Et(4)N)(2)[(Cl(4)-cat)MoOFeS(2)Cl(2)] (I) and (Et(4)N)(2)[Fe(2)S(2)Cl(4)] (II) clusters. The reaction of I and II with Fe(PR(3))(2)Cl(2) or sodium salts of noncoordinating anions such as NaPF(6) or NaBPh(4) in the presence of PR(3) (R = Et, (n)Pr, or (n)Bu) affords (Cl(4)-cat)(2)Mo(2)Fe(6)S(8)(PR(3))(6) [R = Et (IIIa), (n)Pr (IIIb), (n)Bu (IIIc)], Fe(6)S(6)(PEt(3))(4)Cl(2) (IV) and (PF(6))[Fe(6)S(8)(P(n)Pr(3))(6)] (V) as byproducts. The isolation of (Et(4)N)[Fe(PEt(3))Cl(3)] (VI), NaCl, and SPEt(3) supports a reductive coupling mechanism. Cluster IV and V also have been synthesized by the reductive self-coupling of compound II. The reductive coupling reaction between I and II by PEt(3) and NaPF(6) in a 1:1 ratio produces the (Et(4)N)(2)[(Cl(4)-cat)Mo(L)Fe(3)S(4)Cl(3)] clusters [L = MeCN (VIIa), THF (VIIb)]. The hitherto unknown [(Cl(4)-cat)(2)Mo(2)Fe(2)S(3)O(PEt(3))(3)Cl](+) cluster (VIII) has been isolated as the 2:1 salt of the (Fe(PEt(3))(2)(MeCN)(4))(2+) cation after the reductive self-coupling reaction of I in the presence of Fe(PEt(3))(2)Cl(2). Cluster VIII crystallizes in the monoclinic space group P2(1)/c with a = 11.098(3) A, b = 22.827(6) A, c = 25.855(6) A, beta = 91.680(4) degrees, and Z = 4. The formal oxidation states of metal atoms in VIII have been assigned as Mo(III), Mo(IV), Fe(II), and Fe(III) on the basis of zero-field Mössbauer spectra. The Fe(PEt(3))(2)(MeCN)(4) cation of VIII is also synthesized independently, isolated as the BPh(4)(-) salt (IX), and has been structurally characterized. The reductive coupling of compound I also affords in low yield the new (Cl(4)-cat)(2)Mo(2)Fe(3)S(5)(PEt(3))(5) cluster (X) as a byproduct. Cluster X crystallizes in the monoclinic space group P2(1)/n with a = 14.811(3) A, b = 22.188(4) A, c = 21.864(4) A, beta = 100.124(3) degrees, and Z = 4 and the structure shows very short Mo

N-(N-benzylpiperidin-4-yl)-2-[18F]fluorobenzamide: A potential ligand for PET imaging of σ receptors

International Nuclear Information System (INIS)

Shiue Chyngyann; Shiue, Grace G.; Zhang, Sue X.; Wilder, Susan; Greenberg, Joel H.; Benard, Francois; Wortman, Jeffrey A.; Alavi, Abass A.

1997-01-01

Four nitro- and fluorobenzamides (1-4) have been synthesized in good yields from nitro- and fluoro-substituted benzoyl chloride with 4-amino-1-benzylpiperidine. In vitro studies showed that these compounds have high affinities to σ receptors. N-(N-Benzylpiperidin-4-yl)-2-fluorobenzamide (3), in particular, bound to σ receptors with high affinity (K i = 3.4 nM, guinea pig brain membranes) and high selectivity (σ-2/σ-1 = 120). It was, therefore, labeled with 18 F and evaluated as a σ receptor radioligand. N-(N-Benzylpiperidin-4-yl)-2-[ 18 F]fluorobenzamide (3a) was synthesized in one step by nucleophilic substitution of the 2-nitro precursor (1) with [ 18 F]fluoride in DMSO at 140 deg. C for 20 min followed by purification with HPLC in 4-10% yield (decay corrected). The synthesis time was 90 min and the specific activity was 0.4-1.0 Ci/μmol. Tissue distribution in mice revealed that the uptakes of 3a in the brain, heart, liver, lungs, spleen, kidneys and small intestine were high, and the radioactivity in these organs remained constant from 60 to 120 min post-injection. The radioactivity in the bone did not significantly increase, suggesting in vivo defluorination may not be the major route of metabolism of 3a in mice. Blocking studies with haloperidol in rats indicated that the uptake of compound 3a in the rat brain was selective to haloperidol-sensitive σ sites. These results suggest that compound 3a is a potent σ receptor radioligand and may be a potential ligand for PET imaging of σ receptors in humans

Polymerization of 1,3-butadiene catalyzed by pincer cobalt(II) complexes derived from 2-(1-arylimino)-6-(pyrazol-1-yl)pyridine ligands

KAUST Repository

Gong, Dirong

2013-08-01

A new class of air stable and structurally well-defined cobalt complexes with unsymmetrical pincer type ligands ([2-(ArNCMe)-6-(Py)C5H 3N]CoCl2) (Ar = C6H5, Py = pyrazol-1-yl, 5a; Ar = 2,4,6-Me3C6H2, Py = pyrazol-1-yl, 5b; Ar = 2,6-iPr2C6H3, Py = pyrazol-1-yl, 5c; Ar = C6H5, Py = 3,5-Me 2pyrazol-1-yl, 5d; Ar = 2,4,6-Me3C6H 2, Py = 3,5-Me2pyrazol-1-yl, 5e; Ar = 2,6- iPr2C6H3, Py = 3,5-Me 2pyrazol-1-yl, 5f; Ar = 2,6-iPr2C 6H3, Py = 3,5-iPr2pyrazol-1-yl, 5g and [2-(OCMe)-6-(3,5-diphenylpyrazol-1-yl)C5H3N]CoCl 2 5h) were prepared and the molecular structures of 5a, 5c and 5f were determined by single crystal X-ray crystallography. Upon activation by methylaluminoxane (MAO) in toluene at room temperature, all complexes initiate polymerization of 1,3-butadiene (polymer yields: 65-99%), affording polybutadiene with excellent cis-1,4 regularity (97.5-98.7%). The polymer yields and properties in terms of molecular weight and distribution are well controlled by the substituents on iminoaryl rings and pyrazole rings. Selectivity switch from cis-1,4 to syndio-1,2 was also achievable by adding phosphine as microstructure regulator. © 2013 Elsevier B.V. All rights reserved.

In-vitro DNA binding and cleavage studies with pBR322 of N,N-Bis(3β-acetoxy-5α-cholest-6-yl-idene)hydrazine

International Nuclear Information System (INIS)

Tabassum, Zishan; Muddassir, Mohd; Sulaiman, Othman; Arjmand, Farukh

2012-01-01

The DNA binding studies of the triterpenoid derivative, cholesterol, N,N-Bis(3β-acetoxy-5α-cholest-6-yl-idene)hydrazine (L) with CT DNA were carried out by employing different optical methods viz, UV–vis and fluorescence spectroscopy. The ligand binds to DNA through hydrophobic interaction with K b value found to be 4.7×10 3 M −1 . These observations have been validated also by fluorescence spectroscopy. (L) exhibits a remarkable DNA cleavage activity with pBR322 DNA in the presence of different activators and the DNA is probably cleaved by an other than oxidative mechanism, possibly by a discernable hydrolytic pathway. In the presence of major and minor groove binding agents, (L) prefers major groove binding of the DNA. - Highlights: ► DNA binding studies of the triterpenoid derivative, cholesterol, N,N-Bis(3β-acetoxy-5α-cholest-6-yl-idene)hydrazine. ► The ligand binds to DNA through hydrophobic interaction with K b value found to be 4.7×10 3 M −1 . ► DNA is probably cleaved by an other than oxidative mechanism, possibly by a discernable hydrolytic pathway. ► In the presence of major and minor groove binding agents, the (L) prefers major groove binding of the DNA.

The study of new complex compounds of Ni (II) and Co (II) with N- hydroxy-succinimide and their potential applications as sensors

Science.gov (United States)

Sibiescu, Doina; Tutulea, Mihaela-Dana; Mîţă, Carmen; Stan, Corneliu; Roţca, Ioan; Vizitiu, Mihaela

2010-11-01

In this paper, the study of obtaining new coordination compounds of Ni (II) and Co(II) using as ligand, N-hydroxy-succinimide, was presented. Also, the stability constants of these compounds in aqueous medium were determined. The obtaining conditions and the stability of the new compounds were accomplished in aqueous solutions using characteristic methods for coordination compounds: pH-metry, conductometry and UV-VIS absorption spectroscopy. The combination ratios and the stability constants were determined with methods characteristic for studies in solutions. From experimental data resulted that the combination ratio of central metallic atoms with the ligand N-hydroxy-succinimide was: 1:1 and respectively 1:2. In the experiments were used salts of NiCl2.6H2O and CoCl2.6H2O. The optimal domain of pH stability of the studied compounds is limited between 5.74 - 5.86 for Co- N-hydroxy-succinimide (for molar ratio 1:1 and 1:2) and respectively 5.69 - 5.87 for Ni-N-hydroxysuccinimide( for molar ratio 1:1 and 1:2, too). It is important to mention that these compounds were used with very good results in determination of wastewaters from textile, metallurgical, chemical and food industry. Complexion reactions with this ligand are very sensitive for the cations in this paper mentioned. Therefore it is used most often with success in analytical chemistry and also it is posibil to use as sensors. The new complex compounds has electronics transitions at λ = 517 nm for both complexes Co-N-hydroxy-succinimide at molar ratio 1:1 and 1:2 and also at the same λ = 397nm for Ni-N-hydroxysuccinimide at molar ratio 1:1 and 1:2. These complexes compounds was separated and recrystallized from aqueous solution. From the spectrophotometric data it was determined the type and the nature of the electronics transitions by Dq parameters.

Oxidative degradation of the organometallic iron(II) complex [Fe{bis[3-(pyridin-2-yl)-1H-imidazol-1-yl]methane}(MeCN)(PMe3)](PF6)2: structure of the ligand decomposition product trapped via coordination to iron(II).

Science.gov (United States)

Haslinger, Stefan; Pöthig, Alexander; Cokoja, Mirza; Kühn, Fritz E

2015-12-01

Iron is of interest as a catalyst because of its established use in the Haber-Bosch process and because of its high abundance and low toxicity. Nitrogen-heterocyclic carbenes (NHC) are important ligands in homogeneous catalysis and iron-NHC complexes have attracted increasing attention in recent years but still face problems in terms of stability under oxidative conditions. The structure of the iron(II) complex [1,1'-bis(pyridin-2-yl)-2,2-bi(1H-imidazole)-κN(3)][3,3'-bis(pyridin-2-yl-κN)-1,1'-methanediylbi(1H-imidazol-2-yl-κC(2))](trimethylphosphane-κP)iron(II) bis(hexafluoridophosphate), [Fe(C17H14N6)(C16H12N6)(C3H9P)](PF6)2, features coordination by an organic decomposition product of a tetradentate NHC ligand in an axial position. The decomposition product, a C-C-coupled biimidazole, is trapped by coordination to still-intact iron(II) complexes. Insights into the structural features of the organic decomposition products might help to improve the stability of oxidation catalysts under harsh conditions.

N-(n-benzylpiperidin-4-yl)-2-[18f]fluorobenzamide: a potential ligand for PET imaging of breast cancer

International Nuclear Information System (INIS)

Shiue, Chyng-Yann; Shiue, Grace G.; Benard, Francois; Visonneau, Sophie; Santoli, Daniela; Alavi, Abass A.

2000-01-01

N-(N-Benzylpiperidin-4-yl)-2-[ 18 F]fluorobenzamide (2), a potential ligand for PET imaging of sigma receptor, has been found to be a potential agent for detection of breast cancer. In vivo studies in severe combined immunodeficient (SCID) mice bearing MDA-MB231 tumors showed that the uptake of compound 2 in these tumors was high (3.8%/g); the ratios of tumor/muscle and tumor/blood were 6.2 and 7.0, respectively, at 1 h postinjection. Pretreatment of SCID mice with haldol increased the uptake of compound 2 in blood, muscle, and other well-perfused organs while decreasing its uptake in tumors. The ratios of tumor/muscle and tumor/blood decreased from 6.2 and 7.0 to 1.3 and 1.1, respectively, at 1 h postinjection. At 2 h postinjection, the ratios of tumor/muscle and tumor/blood decreased from 4.9 and 7.8 to 1.4 and 1.4, respectively. The tumor uptake of compound 2 in SCID mice bearing primary tumor explants from a human breast cancer patient was lower than that in MDA-MB231 tumors (1.66%/g versus 3.78%/g), and the ratios of tumor/muscle and tumor/blood were 3.5 and 3.7, respectively, at 1 h postinjection. These results suggest that compound 2 may be a potential ligand for PET imaging of breast cancer

Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4

International Nuclear Information System (INIS)

Zhao Qian; Ma Liying; Jiang Shibo; Lu Hong; Liu Shuwen; He Yuxian; Strick, Nathan; Neamati, Nouri; Debnath, Asim Kumar

2005-01-01

We have identified two N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamide analogs as a novel class of human immunodeficiency virus type 1 (HIV-1) entry inhibitors that block the gp120-CD4 interaction, using database screening techniques. The lead compounds, NBD-556 and NBD-557, are small molecule organic compounds with drug-like properties. These compounds showed potent cell fusion and virus-cell fusion inhibitory activity at low micromolar levels. A systematic study showed that these compounds target viral entry by inhibiting the binding of HIV-1 envelope glycoprotein gp120 to the cellular receptor CD4 but did not inhibit reverse transcriptase, integrase, or protease, indicating that they do not target the later stages of the HIV-1 life cycle to inhibit HIV-1 infection. These compounds were equally potent inhibitors of both X4 and R5 viruses tested in CXCR4 and CCR5 expressing cell lines, respectively, indicating that their anti-HIV-1 activity is not dependent on the coreceptor tropism of the virus. A surface plasmon resonance study, which measures binding affinity, clearly demonstrated that these compounds bind to unliganded HIV-1 gp120 but not to the cellular receptor CD4. NBD-556 and NBD-557 were active against HIV-1 laboratory-adapted strains including an AZT-resistant strain and HIV-1 primary isolates, indicating that these compounds can potentially be further modified to become potent HIV-1 entry inhibitors

Synthesis, structural characterization, superoxide dismutase and antimicrobial activities studies of copper (II) complexes with 2-(E)-(2-(2-aminoethylamino) methyl)-4-bromophenol and (19E, 27E)-N1, N2-bis (phenyl (pyridine-2-yl)-methylene)-ethane-1, 2-diamine as ligands

Science.gov (United States)

Choudhary, Mukesh; Patel, R. N.; Rawat, S. P.

2014-07-01

Three new copper (II) complexes, [Cu(L)(H2O)]ClO4 (1), [Cu(L1)(ClO4)]+ (2) and [Cu(L1)]2+ (3), where HL = 2-(E)-(2-(2-aminoethylamino)methyl)-4-bromophenol, L1 =(19E, 27E)-N1,N2-bis(phenyl(pyridine-2-yl)-methylene)-ethane-1, 2-diamine, have been synthesized and characterized by using various physic-chemical and spectroscopic methods. The solid-state structures of 1 and 2 were determined by single crystal X-ray crystallography. Infrared spectra, ligand field spectra and magnetic susceptibility measurements agree with the observed crystal structures. The molecular structure of copper complexes showed that the ligands occupies the basal plane of square pyramidal geometry with the H2O of 1 or the ClO4 of 2 occupying the remaining apical position. Complexes 1 and 2 crystallize in the monoclinic system of the space group P21/c, a = 10.5948(6)Å, b = 19.6164(11)Å, c = 8.6517(5)Å, α = 90°, β = 108.213(2)°, γ = 90° and Z = 4 for 1, a = 9.5019(3)Å, b = 11.3 801(3)Å, c = 25.3168(14)Å, α = 90°, β = 100.583(4)°, γ = 90°, and Z = 4 for 2. The synthesized Schiff base (HL/L1) was behaves as tetradentate ON3/N4 ligands with donor groups suitable placed for forming 2 or 3 five membered chelate rings. Copper (II) complexes display X-band EPR spectra in 100% DMSO at 77 K giving g|| > g⊥ > 2.0023 indicating dx2-y2 ground state. The half-wave potential values for Cu (II)/Cu (I) redox couple obtained in the reaction of the copper (II) complexes with molecular oxygen and superoxide radical (O2-) electronegated in DMSO are in agreement with the SOD-like activity of the copper (II) complexes. In vitro antimicrobial activities of the complexes against the two bacteria (Escherichia coli, Salmonella typhi) and the two fungi (Penicillium, Aspergillus sp.) have been investigated comparing with the Schiff base ligands.

Experimental and quantum chemical simulations on the corrosion inhibition of mild steel by 3-((5-(3,5-dinitrophenyl)-1,3,4-thiadiazol-2-yl)imino)indolin-2-one

Science.gov (United States)

Al-Azawi, Khalida F.; Mohammed, Iman Mahdi; Al-Baghdadi, Shaimaa B.; Salman, Taghried A.; Issa, Hamsa A.; Al-Amiery, Ahmed A.; Gaaz, Tayser Sumer; Kadhum, Abdul Amir H.

2018-06-01

Iraq has been one of the most extensive oil and natural gas industries in the world. The corrosion of mild steel is costly and insufficiency process. It is responsible for great loss in manufacture and environment. Natural and organic inhibitors have been utilized for a long time to inhibit the corrosion. Selected thiadiazol derivative, namely 3-((5-(3,5-dinitrophenyl)-1,3,4-thiadiazol-2-yl)imino)indolin-2-one (TDIO) was investigated for it inhibitive impacts in 1 M HCl medium on corrosion of mild steel using weight loss and scanning electron microscope techniques. The maximum inhibition efficiency up to 90.7% at the maximum inhibitor concentration 0.5 mM. Surface morphology of results demonstrated that TDIO formed adsorbed film on surface of mild steel in hydrochloric acid solution. Give molecular based clarifications to the inhibitive impacts of the studied. The interactions between mild steel surface and the inhibitor molecules have been undertaken to further corroborate the methodological results.

N,N'-Diethyl-N,N'-diphenylpyridine-2,6-dicarboxamide

Czech Academy of Sciences Publication Activity Database

Klepetářová, Blanka; Makrlík, E.; Babain, V.A.; Kašička, Václav

2012-01-01

Roč. 68, č. 4 (2012), o1099-o1100 ISSN 1600-5368 Grant - others:GA ČZU(CZ) 42900/1312/3114 Institutional research plan: CEZ:AV0Z40550506 Keywords : N,N'-Diethyl-N,N'-diphenylpyridine-2,6-dicarboxamide * crystal structure * amide nitrogen Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.347, year: 2011

Next Generation Hemostatic Materials Based on NHS-Ester Functionalized Poly(2-oxazoline)s.

Science.gov (United States)

Boerman, Marcel A; Roozen, Edwin; Sánchez-Fernández, María José; Keereweer, Abraham R; Félix Lanao, Rosa P; Bender, Johan C M E; Hoogenboom, Richard; Leeuwenburgh, Sander C; Jansen, John A; Van Goor, Harry; Van Hest, Jan C M

2017-08-14

In order to prevent hemorrhage during surgical procedures, a wide range of hemostatic agents have been developed. However, their efficacy is variable; hemostatic devices that use bioactive components to accelerate coagulation are dependent on natural sources, which limits reproducibility. Hybrid devices in which chain-end reactive poly(ethylene glycol) is employed as active component sometimes suffer from irregular cross-linking and dissolution of the polar PEG when blood flow is substantial. Herein, we describe a synthetic, nonbioactive hemostatic product by coating N-hydroxysuccinimide ester (NHS)-functional poly(2-oxazoline)s (POx-NHS) onto gelatin patches, which acts by formation of covalent cross-links between polymer, host blood proteins, gelatin and tissue to seal the wound site and prevent hemorrhage during surgery. We studied different process parameters (including polymer, carrier, and coating technique) in direct comparison with clinical products (Hemopatch and Tachosil) to obtain deeper understanding of this class of hemostatic products. In this work, we successfully prove the hemostatic efficacy of POx-NHS as polymer powders and coated patches both in vitro and in vivo against Hemopatch and Tachosil, demonstrating that POx-NHS are excellent candidate polymers for the development of next generation hemostatic patches.

Alkyne- and 1,6-elimination- succinimidyl carbonate - terminated heterobifunctional poly(ethylene glycol) for reversible "Click" PEGylation.

Science.gov (United States)

Xie, Yumei; Duan, Shaofeng; Forrest, M Laird

2010-01-01

A new heterobifunctional (succinimidyl carbonate, SC)-activated poly(ethylene glycol) (PEG) with a reversible 1,6-elimination linker and a terminal alkyne for "click" chemistry was synthesized with high efficiency and low polydispersity. The α-alkyne-ω-hydroxyl PEG was first prepared using trimethylsilyl-2-propargyl alcohol as an initiator for ring-opening polymerization of ethylene oxide followed by mild deprotection with tetrabutylammonium fluoride. The hydroxy end was then modified with diglycolic anhydride to generate α-alkyne-ω-carboxylic acid PEG. The reversible 1, 6-elimination linker was introduced by conjugation of a hydroxymethyl phenol followed by activation with N,N'-disuccinimidyl carbonate to generate the heterobifunctional α-alkyne-ω-SC PEG. The terminal alkyne is available for "click" conjugation to azido ligands via 1,3-dipolar cycloaddition, and the succinimidyl carbonate will form a reversible conjugate to amines (e.g. in proteins) that can release the unaltered amine after base or enzyme catalyzed cleavage of the 1,6-linker.

Neutral bidentate N-heterocyclic ligands - phase transfer reagents improving the kinetics of solvent extraction of Am(III) and Eu(III) ions with tetradentate 6,6'-bis-(diethyl-1,2,4-triazin-3-yl)-2,2'-bipyridine

International Nuclear Information System (INIS)

Narbutt, J.; Krejzler, J.

2008-01-01

Poor kinetics of solvent extraction of Am(III) and Eu(III) ions from 1 M HNO 3 with 6,6'-bis-(diethyl-1,2,4-triazin-3-yl)-2,2'-bipyridine (etBTBP) has been improved by adding an auxiliary bidentate N-heterocyclic ligand to the extraction system. Two such ligands were studied, derivatives of bis-triazine and pyridine-triazine, which alone poorly extract the metal ions, but together with etBTBP they act as phase transfer reagents, improving the extraction kinetics to a different degree. The ability to transfer the metal ions from aqueous to organic phase depends on lipophilicity and acid/base properties of these auxiliary ligands, as well as on the mode of shaking the two liquid phases - gentle or vigorous. (orig.)

Synthesis, physical-chemical properties, antimicrobial and antifungal activity of some 2-(2-((5-(adamantane-1-yl-4-R-1,2,4-triazole-3-ylthioacetyl-N-R1–hydrazine-carbothioamides

Directory of Open Access Journals (Sweden)

V. M. Odyntsova

2017-12-01

Full Text Available Special attention of pharmaceutical scientists is attracted to the creation of new potential substances. They select natural heterocyclic molecules that exhibit various types of pharmacological activity as basic structures. Adamantane derivatives, as well as a number of other framework compounds, in the vast majority are biologically active substances. This fact causes interest to the given classes of organic compounds as potential sources for the development of new drugs. Due to the high pharmacological action of 1,2,4-triazole derivatives, the combination of adamantane and 1,2,4-triazole in one molecule can lead to the formation of high-level pharmacological substances. The aim of this work is the synthesis of some 2- (2 - ((5- (adamantane-1-yl -4-R-1,2,4-triasole-3-yl thio acetyl -N-R1-hydrazine-carbothioamides, study of their physical and chemical properties, antimicrobial and antifungal activity. Materials and methods. The chemical names of the compounds are given in accordance with the requirements of the IUPAC nomenclature (1979 and the recommendations of the IUPAC (1993. Study of the physical and chemical properties of 2-(2-((5-(adamantane-1-yl-4-R-1,2,4-triazole-3-ylthioacetyl-N-R1-hydrazine-carbothioamides have been carried out on the certified and licensed equipment in the ZSMU physical-chemical laboratories. The melting temperature was determined by an open capillary method on the Opti Melt MPA 100. The elemental composition of the synthesized compounds was determined on the universal analyzer Elementar Vario L cube (CHNS (standard – sulfanilamide. 1H NMR spectra were recorded on a spectrometer Varian Mercury VX-200 (1H, 200 MHz in dimethylsulfoxide-d6solvent (tetramethylsilane - internal standard and are decoded using ADVASP(tmAnalyzer program (Umatek International Inc.. Chromatographic mass spectral studies were performed on a gas-liquid chromatograph Agilent 1260 Infinity HPLC equipped with an Agilent 6120 mass spectrometer

Synthesis and biological activity of a new class of insecticides: the N-(5-aryl-1,3,4-thiadiazol-2-yl)amides.

Science.gov (United States)

Eckelbarger, Joseph D; Parker, Marshall H; Yap, Maurice Ch; Buysse, Ann M; Babcock, Jonathan M; Hunter, Ricky; Adelfinskaya, Yelena; Samaritoni, Jack G; Garizi, Negar; Trullinger, Tony K

2017-04-01

Optimization studies on a high-throughput screening (HTS) hit led to the discovery of a series of N-(6-arylpyridazin-3-yl)amides with insecticidal activity. It was hypothesized that the isosteric replacement of the pyridazine ring with a 1,3,4-thiadiazole ring could lead to more potent biological activity and/or a broader sap-feeding pest spectrum. The resulting N-(5-aryl-1,3,4-thiadiazol-2-yl)amides were explored as a new class of insecticides. Several methods for 2-amino-1,3,4-thiadiazole synthesis were used for the preparation of key synthetic intermediates. Subsequent coupling to variously substituted carboxylic acid building blocks furnished the final targets, which were tested for insecticidal activity against susceptible strains of Aphis gossypii (Glover) (cotton aphid), Myzus persicae (Sulzer) (green peach aphid) and Bemisia tabaci (Gennadius) (sweetpotato whitefly). Structure-activity relationship (SAR) studies on both the amide tail and the aryl A-ring of novel N-(5-aryl-1,3,4-thiadiazol-2-yl)amides led to a new class of insecticidal molecules active against sap-feeding insect pests. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

In-vitro DNA binding and cleavage studies with pBR322 of N,N-Bis(3{beta}-acetoxy-5{alpha}-cholest-6-yl-idene)hydrazine

Energy Technology Data Exchange (ETDEWEB)

Tabassum, Zishan [School of Industrial Technology, Universiti Sains Malaysia, 11800 USM, Penang (Malaysia); Muddassir, Mohd [Department of Chemistry, Aligarh Muslim University, Aligarh 202002, U.P. (India); Sulaiman, Othman [School of Industrial Technology, Universiti Sains Malaysia, 11800 USM, Penang (Malaysia); Arjmand, Farukh [Department of Chemistry, Aligarh Muslim University, Aligarh 202002, U.P. (India)

2012-08-15

The DNA binding studies of the triterpenoid derivative, cholesterol, N,N-Bis(3{beta}-acetoxy-5{alpha}-cholest-6-yl-idene)hydrazine (L) with CT DNA were carried out by employing different optical methods viz, UV-vis and fluorescence spectroscopy. The ligand binds to DNA through hydrophobic interaction with K{sub b} value found to be 4.7 Multiplication-Sign 10{sup 3} M{sup -1}. These observations have been validated also by fluorescence spectroscopy. (L) exhibits a remarkable DNA cleavage activity with pBR322 DNA in the presence of different activators and the DNA is probably cleaved by an other than oxidative mechanism, possibly by a discernable hydrolytic pathway. In the presence of major and minor groove binding agents, (L) prefers major groove binding of the DNA. - Highlights: Black-Right-Pointing-Pointer DNA binding studies of the triterpenoid derivative, cholesterol, N,N-Bis(3{beta}-acetoxy-5{alpha}-cholest-6-yl-idene)hydrazine. Black-Right-Pointing-Pointer The ligand binds to DNA through hydrophobic interaction with K{sub b} value found to be 4.7 Multiplication-Sign 10{sup 3} M{sup -1}. Black-Right-Pointing-Pointer DNA is probably cleaved by an other than oxidative mechanism, possibly by a discernable hydrolytic pathway. Black-Right-Pointing-Pointer In the presence of major and minor groove binding agents, the (L) prefers major groove binding of the DNA.

N-(N-benzylpiperidin-4-yl)-2-[{sup 18}F]fluorobenzamide: A potential ligand for PET imaging of {sigma} receptors

Energy Technology Data Exchange (ETDEWEB)

Chyngyann, Shiue; Shiue, Grace G; Zhang, Sue X; Wilder, Susan; Greenberg, Joel H; Benard, Francois; Wortman, Jeffrey A; Alavi, Abass A

1997-10-01

Four nitro- and fluorobenzamides (1-4) have been synthesized in good yields from nitro- and fluoro-substituted benzoyl chloride with 4-amino-1-benzylpiperidine. In vitro studies showed that these compounds have high affinities to {sigma} receptors. N-(N-Benzylpiperidin-4-yl)-2-fluorobenzamide (3), in particular, bound to {sigma} receptors with high affinity (K{sub i} = 3.4 nM, guinea pig brain membranes) and high selectivity ({sigma}-2/{sigma}-1 = 120). It was, therefore, labeled with {sup 18}F and evaluated as a {sigma} receptor radioligand. N-(N-Benzylpiperidin-4-yl)-2-[{sup 18}F]fluorobenzamide (3a) was synthesized in one step by nucleophilic substitution of the 2-nitro precursor (1) with [{sup 18}F]fluoride in DMSO at 140 deg. C for 20 min followed by purification with HPLC in 4-10% yield (decay corrected). The synthesis time was 90 min and the specific activity was 0.4-1.0 Ci/{mu}mol. Tissue distribution in mice revealed that the uptakes of 3a in the brain, heart, liver, lungs, spleen, kidneys and small intestine were high, and the radioactivity in these organs remained constant from 60 to 120 min post-injection. The radioactivity in the bone did not significantly increase, suggesting in vivo defluorination may not be the major route of metabolism of 3a in mice. Blocking studies with haloperidol in rats indicated that the uptake of compound 3a in the rat brain was selective to haloperidol-sensitive {sigma} sites. These results suggest that compound 3a is a potent {sigma} receptor radioligand and may be a potential ligand for PET imaging of {sigma} receptors in humans.

N-Succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: Influence of isomeric substitution on radiolabeling and target cell residualization

International Nuclear Information System (INIS)

Choi, Jaeyeon; Vaidyanathan, Ganesan; Koumarianou, Eftychia; McDougald, Darryl; Pruszynski, Marek; Osada, Takuya; Lahoutte, Tony; Lyerly, H. Kim; Zalutsky, Michael R.

2014-01-01

Introduction: N-succinimidyl 4-guanidinomethyl-3-[ ⁎ I]iodobenzoate ([ ⁎ I]SGMIB) has shown promise for the radioiodination of monoclonal antibodies (mAbs) and other proteins that undergo extensive internalization after receptor binding, enhancing tumor targeting compared to direct electrophilic radioiodination. However, radiochemical yields for [ 131 I]SGMIB synthesis are low, which we hypothesize is due to steric hindrance from the Boc-protected guanidinomethyl group ortho to the tin moiety. To overcome this, we developed the isomeric compound, N-succinimidyl 3-guanidinomethyl-5-[ 131 I]iodobenzoate (iso-[ 131 I]SGMIB) wherein this bulky group was moved from ortho to meta position. Methods: Boc 2 -iso-SGMIB standard and its tin precursor, N-succinimidyl 3-((1,2-bis(tert-butoxycarbonyl)guanidino)methyl)-5-(trimethylstannyl) benzoate (Boc 2 -iso-SGMTB), were synthesized using two disparate routes, and iso-[*I]SGMIB synthesized from the tin precursor. Two HER2-targeted vectors — trastuzumab (Tras) and a nanobody 5 F7 (Nb) — were labeled using iso-[ ⁎ I]SGMIB and [ ⁎ I]SGMIB. Paired-label internalization assays in vitro with both proteins, and biodistribution in vivo with trastuzumab, labeled using the two isomeric prosthetic agents were performed. Results: When the reactions were performed under identical conditions, radioiodination yields for the synthesis of Boc 2 -iso-[ 131 I]SGMIB were significantly higher than those for Boc 2 -[ 131 I]SGMIB (70.7 ± 2.0% vs 56.5 ± 5.5%). With both Nb and trastuzumab, conjugation efficiency also was higher with iso-[ 131 I]SGMIB than with [ 131 I]SGMIB (Nb, 33.1 ± 7.1% vs 28.9 ± 13.0%; Tras, 45.1 ± 4.5% vs 34.8 ± 10.3%); however, the differences were not statistically significant. Internalization assays performed on BT474 cells with 5 F7 Nb indicated similar residualizing capacity over 6 h; however, at 24 h, radioactivity retained intracellularly for iso-[ 131 I]SGMIB-Nb was lower than for [ 125 I]SGMIB-Nb (46

Polymerization of 1,3-butadiene catalyzed by pincer cobalt(II) complexes derived from 2-(1-arylimino)-6-(pyrazol-1-yl)pyridine ligands

KAUST Repository

Gong, Dirong; Jia, Weiguo; Chen, Tao; Huang, Kuo-Wei

2013-01-01

A new class of air stable and structurally well-defined cobalt complexes with unsymmetrical pincer type ligands ([2-(ArNCMe)-6-(Py)C5H 3N]CoCl2) (Ar = C6H5, Py = pyrazol-1-yl, 5a; Ar = 2,4,6-Me3C6H2, Py = pyrazol-1-yl, 5b; Ar = 2,6-iPr2C6H3, Py

Crystal structure of 5-{4'-[(2-{2-[2-(2-ammonio-eth-oxy)eth-oxy]eth-oxy}eth-yl)carbamo-yl]-4-meth-oxy-[1,1'-biphen-yl]-3-yl}-3-oxo-1,2,5-thia-diazo-lidin-2-ide 1,1-dioxide: a potential inhibitor of the enzyme protein tyrosine phosphatase 1B (PTP1B).

Science.gov (United States)

Ruddraraju, Kasi Viswanatharaju; Hillebrand, Roman; Barnes, Charles L; Gates, Kent S

2015-04-01

The title compound, C24H32N4O8S, (I), crystallizes as a zwitterion. The terminal amine N atom of the [(2-{2-[2-(2-ammonio-eth-oxy)eth-oxy]eth-oxy}eth-yl)carbamo-yl] side chain is protonated, while the 1,2,5-thia-diazo-lidin-3-one 1,1-dioxide N atom is deprotonated. The side chain is turned over on itself with an intra-molecular N-H⋯O hydrogen bond. The 1,2,5-thia-diazo-lidin-3-one 1,1-dioxide ring has an envelope conformation with the aryl-substituted N atom as the flap. Its mean plane is inclined by 62.87 (8)° to the aryl ring to which it is attached, while the aryl rings of the biphenyl unit are inclined to one another by 20.81 (8)°. In the crystal, mol-ecules are linked by N-H⋯O and N-H⋯N hydrogen bonds, forming slabs lying parallel to (010). Within the slabs there are C-H⋯O and C-H⋯N hydrogen bonds and C-H⋯π inter-actions present.

Identification of a new psychoactive substance in seized material: the synthetic opioid N-phenyl-N-[1-(2-phenethyl)piperidin-4-yl]prop-2-enamide (Acrylfentanyl)

DEFF Research Database (Denmark)

Breindahl, Torben; Kimergård, Andreas; Andreasen, Mette Findal

2017-01-01

Among the new psychoactive substances (NPS) that have recently emerged on the market, many of the new synthetic opioids have shown to be particularly harmful. A new synthetic analogue of fentanyl, N-phenyl-N-[1-(2-phenethyl)piperidin-4-yl]prop-2-enamide (acrylfentanyl), was identified in powder...... from a seized capsule found at a forensic psychiatric ward in Denmark. Gas chromatography with mass spectrometry (GC-MS) identified a precursor to synthetic fentanyls, N-phenyl-1-(2-phenylethyl)piperidin-4-amine; however, the precursor 1-(2-phenethyl)piperidin-4-one, was not detected. Analysis...... of the electron impact mass spectrum of the main, unknown chromatographic peak (GC) tentatively identified an acryloyl analogue of fentanyl. Further analyses by quadrupole time-of-flight high resolution mass spectrometry (QTOF-MS), matrix-assisted laser ionization Orbitrap mass spectrometry (MALDI...

Synthesis, structure, luminescent, and magnetic properties of carbonato-bridged Zn(II)2Ln(III)2 complexes [(μ4-CO3)2{Zn(II)L(n)Ln(III)(NO3)}2] (Ln(III) = Gd(III), Tb(III), Dy(III); L(1) = N,N'-bis(3-methoxy-2-oxybenzylidene)-1,3-propanediaminato, L(2) = N,N'-bis(3-ethoxy-2-oxybenzylidene)-1,3-propanediaminato).

Science.gov (United States)

Ehama, Kiyomi; Ohmichi, Yusuke; Sakamoto, Soichiro; Fujinami, Takeshi; Matsumoto, Naohide; Mochida, Naotaka; Ishida, Takayuki; Sunatsuki, Yukinari; Tsuchimoto, Masanobu; Re, Nazzareno

2013-11-04

Carbonato-bridged Zn(II)2Ln(III)2 complexes [(μ4-CO3)2{Zn(II)L(n)Ln(III)(NO3)}2]·solvent were synthesized through atmospheric CO2 fixation reaction of [Zn(II)L(n)(H2O)2]·xH2O, Ln(III)(NO3)3·6H2O, and triethylamine, where Ln(III) = Gd(III), Tb(III), Dy(III); L(1) = N,N'-bis(3-methoxy-2-oxybenzylidene)-1,3-propanediaminato, L(2) = N,N'-bis(3-ethoxy-2-oxybenzylidene)-1,3-propanediaminato. Each Zn(II)2Ln(III)2 structure possessing an inversion center can be described as two di-μ-phenoxo-bridged {Zn(II)L(n)Ln(III)(NO3)} binuclear units bridged by two carbonato CO3(2-) ions. The Zn(II) ion has square pyramidal coordination geometry with N2O2 donor atoms of L(n) and one oxygen atom of a bridging carbonato ion at the axial site. Ln(III) ion is coordinated by nine oxygen atoms consisting of four from the deprotonated Schiff-base L(n), two from a chelating nitrate, and three from two carbonate groups. The temperature-dependent magnetic susceptibilities in the range 1.9-300 K, field-dependent magnetization from 0 to 5 T at 1.9 K, and alternating current magnetic susceptibilities under the direct current bias fields of 0 and 1000 Oe were measured. The magnetic properties of the Zn(II)2Ln(III)2 complexes are analyzed on the basis of the dicarbonato-bridged binuclear Ln(III)-Ln(III) structure, as the Zn(II) ion with d(10) electronic configuration is diamagnetic. ZnGd1 (L(1)) and ZnGd2 (L(2)) show a ferromagnetic Gd(III)-Gd(III) interaction with J(Gd-Gd) = +0.042 and +0.028 cm(-1), respectively, on the basis of the Hamiltonian H = -2J(Gd-Gd)ŜGd1·ŜGd2. The magnetic data of the Zn(II)2Ln(III)2 complexes (Ln(III) = Tb(III), Dy(III)) were analyzed by a spin Hamiltonian including the crystal field effect on the Ln(III) ions and the Ln(III)-Ln(III) magnetic interaction. The Stark splitting of the ground state was so evaluated, and the energy pattern indicates a strong easy axis (Ising type) anisotropy. Luminescence spectra of Zn(II)2Tb(III)2 complexes were observed, while those

Synthesis and characterization of tritium labeled N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide.

Science.gov (United States)

Hong, Yang; Hynes, John; Tian, Yuan; Balasubramanian, Balu; Bonacorsi, Samuel

2015-08-01

N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide is a potent C-C chemokine receptor 1 (CCR1) antagonist. The compound, possessing benzamide functionality, successfully underwent tritium/hydrogen (T/H) exchange with an organoiridium catalyst (Crabtree's catalyst). The labeling pattern in the product was studied with liquid chromatography-mass spectrometry, time-of-flight mass spectrometry, and (3) H-NMR. Overall, multiple labeled species were identified. In addition to the anticipated incorporation of tritium in the benzamide moiety, tritium labeling was observed in the valine portion of the molecule including substitution at its chiral carbon. Using authentic standards, liquid chromatography analysis of the labeled compound showed complete retention of stereochemical configuration. Copyright © 2015 John Wiley & Sons, Ltd.

Matrix-isolation FTIR, theoretical structural analysis and reactivity of amino-saccharins: N-(1,1-dioxo-1,2-benzisothiazol-3-yl)- N-methyl amine and - N,N-dimethyl amine

Science.gov (United States)

Almeida, R.; Gómez-Zavaglia, A.; Kaczor, A.; Ismael, A.; Cristiano, M. L. S.; Fausto, R.

2009-12-01

In this work, two novel amino-substituted derivatives of saccharin, N-(1,1-dioxo-1,2-benzisothiazol-3-yl)- N-methyl amine (MBAD) and N-(1,1-dioxo-1,2-benzisothiazol-3-yl)- N, N-dimethyl amine (DMBAD), were synthesized and characterized, and their molecular structure and vibrational properties were investigated by matrix-isolation FTIR spectroscopy and theoretical calculations undertaken using different levels of approximation. The calculations predicted the existence of two conformers of MBAD. The lowest energy form was predicted to be considerably more stable than the second conformer (Δ E > ca. 20 kJ mol -1) and was the sole form contributing to the infrared spectrum of the compound isolated in solid xenon. Both conformers have planar amine moieties. In the case of DMBAD, only one doubly-degenerated-by-symmetry conformer exists, with the amine nitrogen atom considerably pyramidalized. The effect of the electron-withdrawing saccharyl ring on the C-N bond lengths is discussed. The different structural preferences around the amine nitrogen atom in the two molecules were explained in terms of repulsive interactions involving the additional methyl group of DMBAD. Observed structural features are correlated with the reactivity exhibited by the two compounds towards nucleophiles. The experimentally obtained spectra of the matrix-isolated monomers of MBAD and DMBAD were fully assigned by comparison with the corresponding calculated spectra.

A novel route to radioiodinated [{sup 123}I]-N-succinimidyl-3-iodobenzoate, a reagent for radioiodination of bioactive peptides

Energy Technology Data Exchange (ETDEWEB)

Al-Jammaz, I.; Al-Otaibi, B.; Amartey, J.K. E-mail: amarty@kfshrc.edu.sa

2002-11-01

Radiolabeled peptides continue to emerge as potential radiopharmaceuticals for targeting several diseases such as cancer, infection and inflammation and even tissue and organ rejection. The classical method for labeling these molecules has been the electrophilic route. Evidence suggests that most molecules labeled via this route perturb their biological activity. Moreover, this method is not applicable to peptides lacking a tyrosine moiety in their structure. Hence, there is the need to develop alternate methods such as the prosthetic approach. We have optimized a solid-state radioiodination by exchange to produce [{sup 123}I]-metaiodobenzylguanidine ([{sup 123}I]-mIBG). The mIBG served as a precursor to obtain an activated N-succinimidyl ester for efficient coupling to amine functions in peptides, preferably the lysine group(s). The method was used to label a model chemotactic peptide and evaluated in vivo.

Synthesis of tritium-labelled isopenicillin N, penicillin N and 6-aminopenicillanic acid

International Nuclear Information System (INIS)

Usher, J.J.; Loder, B.; Abraham, E.P.

1975-01-01

1. Phenoxymethylpenicillin sulphoxide 4-methoxybenzyl ester was labelled with 3 H in its 2-β-methyl group. Its specific radioactivity was 362mCi/mmol. 2. Removal of the side chain of this compound yielded the corresponding ester of 6-aminopenicillanic acid sulphoxide and coupling of the latter with the appropriate protected α-aminoadipic acid gave 4-methoxybenzyloxycarbonylisopenicillin N sulphoxide di-4-methoxybenzyl ester or the corresponding derivative of penicillin N. 3. Removal of the protective groups by hydrogenolysis and reduction of the sulphoxide group yielded 3 H-labelled isopenicillin N or penicillin N. 4. 3 H-labelled phenoxymethylpenicillin sulphoxide was obtained by hydrogenolysis from its 4-methoxybenzyl ester. Reducton of its sulphoxide group and subsequent removal of the side chain gave 3 H-labelled 6-aminopenicillanic acid. (author)

N,N-Diethylanilinium 2,4-dioxo-5-(2,4,6-trinitrophenyl-1,2,3,4-tetrahydropyrimidin-6-olate

Directory of Open Access Journals (Sweden)

Manickam Buvaneswari

2011-12-01

Full Text Available In the crystal structure of the title molecular salt, C10H16N+·C10H4N5O9−, the components are linked through a N—H...O hydrogen bonds. R22(8 ring motifs are formed between inversion-related barbiturate residues. Two intramoleculer N—H...O hydrogen bonds are observed in the anion. The dihedral angle between 2,4,6-trinitrophenyl and barbiturate rings is 53.6 (2°. The N,N-diethylamine substituent is disordered and was modeled as two geometrically equivalent conformers with occupancies of 0.737 (2 and 0.273 (2.

A second monoclinic polymorph of 2-(3,5-dimethyl-1H-pyrazol-1-yl)-2-hy­droxy­imino-N′-[1-(pyridin-2-yl)ethyl­idene]acetohydrazide

Science.gov (United States)

Plutenko, Maxym O.; Lampeka, Rostislav D.; Haukka, Matti; Nordlander, Ebbe

2013-01-01

The title compound, C14H16N6O2, is a second monoclinic polymorph of 2-[1-(3,5-dimeth­yl)pyrazol­yl]-2-hy­droxy­imino-N′-[1-(2-pyrid­yl)ethyl­idene] acetohydrazide, with two crystallographically independent mol­ecules per asymmetric unit. The non-planar mol­ecules are chemically equal having similar geometric parameters. The previously reported polymorph [Plutenko et al. (2012 ▶). Acta Cryst. E68, o3281] was described in space group Cc (Z = 4). The oxime group and the O atom of the amide group are anti with respect to the C—C bond. In the crystal, mol­ecules are connected by N—H⋯N hydrogen bonds into zigzag chains extending along the b axis. PMID:23723911

Synthesis and coordination chemistry of 1,1,1-tris-(pyrid-2-yl)ethane.

Science.gov (United States)

Santoro, Amedeo; Sambiagio, Carlo; McGowan, Patrick C; Halcrow, Malcolm A

2015-01-21

A new synthesis of 1,1,1-tris(pyrid-2-yl)ethane (L), and a survey of its coordination chemistry, are reported. The complexes [ML2](n+) (M(n+) = Fe(2+), Co(2+), Co(3+), Cu(2+) and Ag(+)), [PdCl2L] and [CuI(L)] have all been crystallographically characterised. Noteworthy results include an unusual square planar silver(i) complex [Ag(L)2]X (X(-) = NO3(-) and SbF6(-)); the oxidative fixation of aerobic CO2 by [CuI(L)] to yield [Cu2I(L)2(μ-CO3)]2[CuI3] and [Cu(CO3)(L)]; and, water/carbonato tape and water/iodo layer hydrogen bonding networks in hydrate crystals of two of the copper(ii) complexes. Cyclic voltammetric data on [Fe(L)2](2+) and [Co(L)2](2+/3+) imply that the peripheral methyl substituent has a weak influence on the ligand field exerted by L onto a coordinated metal ion.

Synthesis, studies and in-vitro antibacterial activity of N-substituted 5-(furan-2-yl-phenyl pyrazolines

Directory of Open Access Journals (Sweden)

Mamta Rani

2015-03-01

Full Text Available Novel compounds with antibacterial properties: pyrazoline derivatives were synthesized by the cyclization of various -1-[2-(alkoxyphenyl]-3-(furan-2-yl prop-2-en-1-one 1a–1d with N-substituted phenyl hydrazine in the presence of CH3COOH in ethanol. The structures of these compounds were elucidated by, IR, 1H NMR, 13C NMR, ESI-MS spectral data and their purities were confirmed by elemental analyses. The in vitro antibacterial activity of these compounds was evaluated against two Gram-positive and two Gram-negative bacteria Aeromonas hydrophila, Yersinia enterocolitica, Listeria monocytogenes, and Staphylococcus aureus by microdilution method and then the minimum inhibitory concentration (MIC of compounds were determined. The results showed that compounds (5R-5-(furan-2-yl-1-phenyl-3-[2-(benzyloxyphenyl]-4, 5-dihydro-1H-pyrazole (2b and (5R-5-(furan-2-yl-1-phenyl-3-[2-(naphthalen-2-ylmethoxy prop-2-en-1-yloxyphenyl]-4,5-dihydro-1H-pyrazole (2d showing most promising antibacterial activities as compared to Gentamicin and Tetracycline are given.

Tetra­kis[bis­(pyridin-2-yl)amine-κN 2](nitrato-κO)silver(I)

Science.gov (United States)

Parashchenko, Yuliia; Pavlishchuk, Anna; Bokach, Nadezhda A.; Haukka, Matti

2014-01-01

In the title complex, [Ag(NO3)(C10H9N3)4], the nitrate ligand is found to be disordered over two sets of positions, with occupancy factors of 0.473 (5) and 0.527 (5). The AgI ion is located in a square-pyramidal coordination environment formed by four N atoms from four bis­(pyridin-2-yl)amine ligands and one O atom from a nitrate ligand. Weak inter­actions between the AgI ions and the nitrate anions acting in a monodentate mode [Ag⋯O = 2.791 (13) and 2.816 (9) Å for the major component of the nitrate ligand, and 2.865 (8) and 2.837 (8) Å for the minor component] link the complex mol­ecules into a chain along [001]. N—H⋯O hydrogen bonds are observed. PMID:24764824

The molecular structure and vibrational spectra of N-(2,2-diphenylacetyl)- N'-(naphthalen-1yl)-thiourea by Hartree-Fock and density functional methods

Science.gov (United States)

Arslan, Hakan; Mansuroglu, Demet Sezgin; VanDerveer, Don; Binzet, Gun

2009-04-01

N-(2,2-Diphenylacetyl)- N'-(naphthalen-1yl)-thiourea (PANT) has been synthesized and characterized by elemental analysis, IR spectroscopy and 1H NMR spectroscopy. The crystal and molecular structure of the title compound has been determined from single crystal X-ray diffraction data. It crystallizes in the triclinic space group P-1, Z = 2 with a = 10.284(2) Å, b = 10.790(2) Å, c = 11.305(2) Å, α = 64.92(3)°, β = 89.88(3)°, γ = 62.99(3)°, V = 983.7(3) Å 3 and Dcalc = 1.339 Mg/m 3. The molecular structure, vibrational frequencies and infrared intensities of PANT were calculated by the Hartree-Fock and density functional theory methods (BLYP and B3LYP) using the 6-31G* basis set. The calculated geometric parameters were compared to the corresponding X-ray structure of the title compound. We obtained 22 stable conformers for the title compound; however Conformer 1 is approximately 9.53 kcal/mol more stable than Conformer 22. The comparison of the theoretical and experimental geometry of the title compound shows that the X-ray parameters fairly well reproduce the geometry of Conformer 17. The harmonic vibrations computed for this compound by the B3LYP/6-31G* method are in good agreement with the observed IR spectral data. Theoretical vibrational spectra of the title compound were interpreted by means of PEDs using the VEDA 4 program. A general better performance of the investigated methods was calculated by PAVF 1.0 program.

(Z-N-[1-(Aziridin-1-yl-2,2,2-trifluoroethylidene]-4-bromoaniline

Directory of Open Access Journals (Sweden)

Alexander S. Bunev

2014-05-01

Full Text Available The title compound, C10H8BrF3N2, crystallizes with two independent molecules in the asymmetric unit, which can be considered as being related by a pseudo-inversion center, so their conformations are different; the corresponding N=C—N—C torsion angles are 54.6 (5 and −50.5 (5°. In the crystal, molecules related by translation in [001] interact through short intermolecular Br...F contacts [3.276 (2 and 3.284 (2 Å], thus forming two types of crystallographically independent chains.

Synthesis and Spectral Analysis of 3,4,5-trichloro-6-(dibenzo[d,f][1,3]diazepin-5-yl-[1,2]-benzoquinones

Directory of Open Access Journals (Sweden)

Mohsen A. M. Gomaa

2011-01-01

Full Text Available Reaction of N1,N2-di-(4-methoxyphenyl- or N1,N2-di-(4-hydroxyphenyl -amidines (1a-d with 3,4,5,6-tetrachloro-1,2-benzoquinone (2 in ethyl acetate at room temperature led to formation of new 3,4,5-trichloro-6-(2-hydroxy-6-methyldibenzo[d,f][1,3]diazepin-5-yl[1,2]-benzoquinones (3a-d in addition to N-aryl-N'-(6,7,8,9-tetrachloro-4-hydroxydibenzo-[1,4]dioxin-2-ylacetamidines (4a,b. The rational of formation of products 3a-d and 4a,b was discussed and structures were confirmed on the basis of elemental analysis and spectral data.

Crystal structure of 4-fluoro-N-[2-(4-fluoro-benzo-yl)hydra-zine-1-carbono-thio-yl]benzamide.

Science.gov (United States)

Firdausiah, Syadza; Salleh Huddin, Ameera Aqeela; Hasbullah, Siti Aishah; Yamin, Bohari M; Yusoff, Siti Fairus M

2014-09-01

In the title compound, C15H11F2N3O2S, the dihedral angle between the fluoro-benzene rings is 88.43 (10)° and that between the central semithiocarbazide grouping is 47.00 (11)°. The dihedral angle between the amide group and attached fluoro-benzene ring is 50.52 (11)°; the equivalent angle between the carbonyl-thio-amide group and its attached ring is 12.98 (10)°. The major twists in the mol-ecule occur about the C-N-N-C bonds [torsion angle = -138.7 (2)°] and the Car-Car-C-N (ar = aromatic) bonds [-132.0 (2)°]. An intra-molecular N-H⋯O hydrogen bond occurs, which generates an S(6) ring. In the crystal, the mol-ecules are linked by N-H⋯O and N-H⋯S hydrogen bonds, generating (001) sheets. Weak C-H⋯O and C-H⋯F inter-actions are also observed.

Synthesis and Cytotoxic Activity of Some New 2,6-Substituted Purines

Directory of Open Access Journals (Sweden)

Nageswara Rao Kode

2011-07-01

Full Text Available A seriesof twenty four acyclic unsaturated 2,6-substututed purines 5a-20b were synthesized. These compounds were evaluated for cytotoxic activity against NCI-60 DTP human tumor cell line screen at 10µMconcentration. N9-[(Z-4'-chloro-2'-butenyl-1'-yl]-2,6-dichloropurine(5a, N9-[4'-chloro-2'-butynyl-1'-yl]-2,6-dichloropurine(10a, N9-[(E-2',3'-dibromo-4'-chloro-2'-butenyl-1'-yl]-6-methoxypurine(14and N9-[4'-chloro-2'-butynyl-1'-yl]-6-(4-methoxyphenyl-purine(19exhibited highly potent cytotoxic activity with GI50 values in the 1–5 µM range for most human tumor cell lines. Other compounds exhibited moderate activity.

6,6'-(1E,1'E-((1R,2R-1,2-Diphenylethane-1,2-diylbis(azan-1-yl-1-ylidenebis(methan-1-yl-1-ylidenebis(2-tert-butyl-4-((trimethylsilylethynylphenol

Directory of Open Access Journals (Sweden)

David Díaz Díaz

2013-03-01

Full Text Available Functionalizable salen derivative, 6,6'-(1E,1'E-((1R,2R-1,2-diphenylethane-1,2-diylbis(azan-1-yl-1-ylidenebis(methan-1-yl-1-ylidenebis(2-tert-butyl-4-((trimethylsilyl ethyn-ylphenol (3, was synthesized by condensation between (1R,2R-1,2-diphenylethane-1,2-diamine (2 and 3-tert-butyl-2-hydroxy-5-((trimethylsilylethynyl benzaldehyde (1 under refluxing conditions. The title compound was characterized by 1H-NMR, 13C-NMR, FT-IR, high-resolution mass spectrometry, optical rotation and melting point determination.

Synthesis of 1-(2,3-dihydroxypropyl)-2-nitro-1H-imidazole-2-14C and N-(2-hydroxyethyl)-2-(2-nitro-1H-imidazol-1-YL-2-14C)acetamide

International Nuclear Information System (INIS)

Fong, M.T.; Leaffer, M.A.

1986-01-01

We have prepared the 14 C-labeled analogs of NSC 261036, 1-(2,3-dihydroxypropyl)-2-nitro-1H-imidazole-2- 14 C, and NSC 301467, N-(2-hydroxyethyl)-2-(2-nitro-1H-imidazol-1-yl-2- 14 C) acetamide, for pharmacological, drug distribution, and mechanisms of action studies. The latter is an analog designed for lower toxicity and improved properties. The former is a metabolite of, and appears to be less toxic than, misonidazole. (author)

(E-N,N-Diethyl-2,6-diisopropyl-4-[2-(4-nitrophenylethenyl]aniline

Directory of Open Access Journals (Sweden)

Heiner Detert

2013-12-01

Full Text Available The title compound, C24H32N2O2, was prepared by Horner olefination of 4-diethylamino-3,5-diisopropylbenzaldehyde and diethyl p-nitrobenzylphosphonate. There are two independent molecules (A and B in the asymmetric unit. Their main axes, defined by the line connecting the N atoms of the nitro and amino groups, open an angle of 79.42 (3°. Steric hindrance around the amino group is reflected in a long aryl C—N bond [1.434 (3 Å for molecule A and 1.440 (3 Å for molecule B], a pyramidal geometry [angle sum = 350.0 (2° for molecule A and 349.6 (2° for molecule B], and dihedral angles between the phenylene group and the plane defined by the CH2—N—CH2 unit of 86.9 (3° for molecule A and 88.3 (3° for molecule B. This gives structural support for the electronic decoupling of the amino group from the nearly planar nitrostilbene moiety (r.m.s. deviation for C, N and O atoms = 0.097 for molecule A and 0.107 Å for molecule B.

Tris(dibenzoylmethanido-κ2O,O′[(6S,8S-(+-7,7-dimethyl-3-(2-pyridyl-5,6,7,8-tetrahydro-6,8-methanoisoquinoline-κ2N,N′]gadolinium(III

Directory of Open Access Journals (Sweden)

Xi-Li Li

2009-09-01

Full Text Available In the title compound, [Gd(C15H11O23(C17H18N2], the GdIII atom is coordinated by six O atoms from three β-diketonate ligands and two N atoms from a chiral ligand LS,S-(+-7,7-dimethyl-3-(2-pyridyl-5,6,7,8-tetrahydro-6,8-methanoisoquinoline, in a coordination geometry best described as distorted square-antiprismatic.

Synthesis of 6-Substituted 2-Pyrones Starting from Renewable Resources: Total Synthesis of Sibirinone, (E)-6-(Pent-1-en-1-yl)-2H-pyran-2-one, and (E)-6-(Hept-1-en-1-yl)-2H-pyran-2-one.

Science.gov (United States)

Dobler, Daniel; Reiser, Oliver

2016-11-04

An atom-economic reaction sequence to 6-substituted 2-pyrones was developed starting from furfuryl alcohol, a renewable resource made from bran or bagasse, and aldehydes, utilizing a thermal rearrangement of cyclopentadienone epoxides as key step. Derivatives bearing a hydroxyalkyl side chain could be enzymatically resolved, providing access to enantiomerically pure 2-pyrones, or converted to alkenyl-substituted 2-pyrones such as naturally occurring sibirinone, (E)-6-(pent-1-en-1-yl)-2H-pyran-2-one, and (E)-6-(hept-1-en-1-yl)-2H-pyran-2-one.

Progesterone up-regulates vasodilator effects of calcitonin gene-related peptide in N(G)-nitro-L-arginine methyl ester-induced hypertension.

Science.gov (United States)

Gangula, P R; Wimalawansa, S J; Yallampalli, C

1997-04-01

We recently reported that calcitonin gene-related peptide can reverse the hypertension produced by N(G)-nitro-L-arginine methyl ester in pregnant rats. In the current study we investigated whether these vasodilator effects of calcitonin gene-related peptide were progesterone dependent. Calcitonin gene-related peptide or N(G)-nitro-L-arginine methyl ester was infused through osmotic minipumps, either separately or in combination, to groups of five pregnant rats from day 17 of gestation until day 8 post partum or to nonpregnant ovariectomized rats for 8 days. Progesterone was injected during days 1 to 6 post partum and for 6 days after ovariectomy. Systolic blood pressure was measured daily. Animals receiving N(G)-nitro-L-arginine methyl ester exhibited significant elevations of blood pressure during pregnancy and post partum. Coadministration of calcitonin gene-related peptide to these rats reversed the hypertension during pregnancy but not during the postpartum period. At the dose used in this study calcitonin gene-related peptide administered alone was without significant effects on blood pressure. However, it reduced both the mortality and growth restriction of the fetus associated with N(G)-nitro-L-arginine methyl ester in these animals. Calcitonin gene-related peptide reversed the hypertension in N(G)-nitro-L-arginine methyl ester-infused postpartum rats during the periods of progesterone treatment only, and these effects were lost when progesterone treatment was stopped. Neither progesterone nor calcitonin gene-related peptide alone were effective. To further confirm these observations, progesterone effects were tested in ovariectomized adult rats. Similar to the findings in postpartum rats, calcitonin gene-related peptide completely reversed the elevation in blood pressure in N(G)-nitro-L-arginine methyl ester-treated rats receiving progesterone injections. The effects of calcitonin gene-related peptide were apparent only during the progesterone treatment

Design, Synthesis and Biological Evaluation of 2-(2-Amino-5(6-nitro-1H-benzimidazol-1-yl-N-arylacetamides as Antiprotozoal Agents

Directory of Open Access Journals (Sweden)

Emanuel Hernández-Núñez

2017-04-01

Full Text Available Parasitic diseases are a public health problem affecting millions of people worldwide. One of the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole moiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group and is considered a privileged structure in medicinal chemistry. In this study, the benzimidazole core served as a model for the synthesis of a series of 2-(2-amino-5(6-nitro-1H-benzimidazol-1-yl-N-arylacetamides 1–8 as benznidazole analogues. The in silico pharmacological results calculated with PASS platform exhibited chemical structures highly similar to known antiprotozoal drugs. Compounds 1–8 when evaluated in silico for acute toxicity by oral dosing, were less toxic than benznidazole. The synthesis of compounds 1–8 were carried out through reaction of 5(6-nitro-1H-benzimidazol-2-amine (12 with 2-chlroactemides 10a–h, in the presence of K2CO3 and acetonitrile as solvent, showing an inseparable mixture of two regioisomers with the -NO2 group in position 5 or 6 with chemical yields of 60 to 94%. The prediction of the NMR spectra of molecule 1 coincided with the experimental chemical displacements of the regioisomers. Comparisons between the NMR prediction and the experimental data revealed that the regioisomer endo-1,6-NO2 predominated in the reaction. The in vitro antiparasitic activity of these compounds on intestinal unicellular parasites (Giardia intestinalis and Entamoeba histolytica and a urogenital tract parasite (Trichomonas vaginalis were tested. Compound 7 showed an IC50 of 3.95 μM and was 7 time more active against G. intestinalis than benznidazole. Compounds 7 and 8 showed 4 times more activity against T. vaginalis compared with benznidazole.

Design, synthesis and pharmacological evaluation of some novel derivatives of 1-{[3-(furan-2-yl-5-phenyl-4,5-dihydro-1,2-oxazol-4-yl]methyl}-4-methyl piperazine

Directory of Open Access Journals (Sweden)

Jagdish Kumar

2017-01-01

Full Text Available A novel series of 1-{[3-(furan-2-yl-5-substituted phenyl-4,5-dihydro-1,2-oxazol-4-yl]methyl}-4-methyl piperazine, compounds 3a–l have been synthesized. The synthetic work was carried out beginning from 2-acetylfuran through Claisen Schmidt condensation with different types of aromatic aldehyde, affording 1-(furan-2-yl-3-substitutedphenylprop-2-en-1-ones which on cyclization with hydroxylamine hydrochloride resulted in 3-(furan-2-yl-5-substitutedphenyl-4,5-dihydro-1,2-oxazole formation. The isoxazolines were subjected to Mannich’s reaction in the presence of N-methyl piperazine to produce the desired product. The chemical structures of the compounds were proved by IR, 1H NMR, 13C-NMR and Mass spectrometric data. The antidepressant activities of the compounds were investigated by Porsolt’s behavioral despair (forced swimming test on albino mice. Moreover, the antianxiety activity of the newly synthesized compounds was investigated by the plus maze method. Compounds 3a and 3k reduced the duration of immobility times of 152.00–152.33% at 10 mg/kg dose level and compounds 3a and 3k have also shown significant antianxiety activity.

One-pot and one-step novel N-methylation of 2,6-diaminopyridine

Directory of Open Access Journals (Sweden)

Mehdi Nabati

2014-07-01

Full Text Available 2,6-Diaminopyridine is extensively used as a pharmaceutical intermediate and a hair dye coupler. It is soluble in protic solvents. Primary and secondary amines are N-methylated by various me-thods such as direct alkylation of amines with Hofmann mechanism, but in many of these me-thods due to over-alkylations, we earn a mixture of amino products. Consequently, they aren't selective in the case of secondary amines preparation. Also, the synthesis of secondary amines is a problematic field in organic chemistry. In this research, 2,6-diaminopyridine N-methylated-selictivity was done from reaction with sodium azide and orthoformic ester in low time with good yields.

Crystal structure of 4′-allyl-4,5,6,7,2′,7′-hexachlorofluorescein allyl ester unknown solvate

Directory of Open Access Journals (Sweden)

Lili Wang

2018-01-01

Full Text Available In the title compound, 4′-allyl-4,5,6,7,2′,7′-hexachlorofluorescein allyl ester {systematic name: prop-2-en-1-yl 2,3,4,5-tetrachloro-6-[2,7-dichloro-6-hydroxy-3-oxo-4-(prop-2-en-1-yl-3H-xanthen-9-yl]benzoate}, C26H14Cl6O5, accompanied by unknown solvate molecules, the dihedral angle between the xanthene ring system (r.m.s. deviation = 0.046 Å and the pentasubstituted benzene ring is 71.67 (9°. Both allyl groups are disordered over two sets of sites in statistical ratios. The scattering contributions of the disordered solvent molecules (both Ph2O and CHCl3, as identified by NMR were removed with the PLATON SQUEEZE algorithm [Spek (2015. Acta Cryst. C71, 9–18]. In the crystal, tetrameric supramolecular aggregates linked by O—H...O hydrogen bonds occur; these further interact with neighboring aggregates through C—Cl...π interactions arising from the benzene rings, forming infinite two-dimensional sheets. Each C6Cl4 ring shifts in the direction perpendicular to the two-dimensional sheet, exhibiting a helical chain in which every C6Cl4 ring is utilized as both a donor and an acceptor of Cl...π contacts. Thus, these two-dimensional sheets pack in a helical fashion, constructing a three-dimensional network.

N,N-Diethyl-2-[5-(4-methoxybenzylidene-2,4-dioxo-1,3-thiazolidin-3-yl]acetamide

Directory of Open Access Journals (Sweden)

Vijayan Viswanathan

2017-05-01

Full Text Available In the title compound, C17H20N2O4S, the thiazolidine (r.m.s. deviation = 0.022 Å and phenyl rings (major and minor occupancies are inclined to one another by 6.3 (3 and 10.5 (3°, respectively. The molecular conformation is stabilized by an intramolecular C—H...S interaction. In the crystal, molecules are linked by C—H...O hydrogen bonds, which generate R22(18, R22(24 and R21(7 ring motifs. Aromatic π–π stacking interactions are also observed.

One-electron capture into Li-like autoionising N/sup 4 +/ (1s2ln'l') configurations by metastable N/sup 5 +/ (1s2s/sup 3/S) multicharged ions in collisions with He and H/sub 2/, observed by electron spectrometry at 3. 4 keV amu/sup -1/

Energy Technology Data Exchange (ETDEWEB)

Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Dousson, S.; Hitz, D.

1985-04-14

One-electron capture into N/sup 4 +/ (1s2ln'l') configurations, with n'=2 to 4, has been observed by electron spectrometry when a N/sup 5 +/ (1s2s /sup 3/S) multicharged ion beam encounters an He or H/sub 2/ target, at low collision velocity (upsilon=0.37 au) within single-collision conditions. Contributions of other 1s2l metastable states and of the 1s/sup 2/ ground state may be disregarded. A small indication of two-electron capture by 1s2s /sup 3/S ions into (1s2s /sup 3/S)3l3l' configurations is also seen.

Bis[2-(2H-benzotriazol-2-yl-4-methylphenolato]palladium(II

Directory of Open Access Journals (Sweden)

Chen-Yen Tsai

2009-06-01

Full Text Available In the title complex, [Pd(C13H10N3O2], the PdII atom is tetracoordinated by two N atoms and two O atoms from two bidentate 2-(2H-benzotriazol-2-yl-4-methylphenolate ligands, forming a square-planar environment. The asymmetric unit contains one half molecule in which the Pd atom lies on a centre of symmetry.

Poly[bis­[μ4-N-(2-hydroxy­imino­propion­yl)-N′-(2-oxidoimino­propion­yl)propane-1,3-diaminato]dimethano­lcalciumdicopper(II)

Science.gov (United States)

Kalibabchuk, Valentina A.; Usenko, Natalia I.; Golenya, Irina A.; Iskenderov, Turganbay S.; Haukka, Matti

2009-01-01

In the title compound, [CaCu2(C9H13N4O4)2(CH3OH)2]n, the CaII atom lies on an inversion center and is situated in a moderately distorted octa­hedral environment. The CuII atom is in a distorted square-pyramidal geometry, defined by four N atoms belonging to the amide and oxime groups of the triply deprotonated residue of N,N′-bis­(2-hydroxy­imino­propano­yl)propane-1,3-diamine (H4pap) and one oxime O atom from a neighboring Hpap ligand at the apical site, forming a dimeric [Cu2(Hpap)2]2− unit. Each dimeric unit connects four Ca atoms and each Ca atom links four [Cu2(Hpap)2]2− units through Ca—O(amide) bonds, leading to a three-dimensional framework. The crystal structure involves intra- and inter­molecular O—H⋯O hydrogen bonds. PMID:21577475

An Introduction of Zoltán D?rnyei's L2 Motivational Theories%An Introduction of Zoltán Dörnyei's L2 Motivational Theories

Institute of Scientific and Technical Information of China (English)

王晓磊; 周密

2016-01-01

Professor Zoltán D?rnyei is an influential researcher of L2 learning motivation. Since 1990s, he put forward several important L2 learning motivational theories and made special contribution to this field. This paper introduces his four L2 learn-ing motivational theories:1)Three-level framework of L2 motivation;2) Process model of L2 motivation;3)The L2 Motivation-al Self System;4) Directed Motivational Currents (DMC).

Bis(2,3,5,6-tetra-2-pyridylpyrazine-κ3N2,N1,N6iron(II bis(dicyanamidate 4.5-hydrate

Directory of Open Access Journals (Sweden)

R. Cortés

2010-03-01

Full Text Available In the title compound, [Fe(C24H16N62][N(CN2]2·4.5H2O, the central iron(II ion is hexacoordinated by six N atoms of two tridentate 2,3,5,6-tetra-2-pyridylpyrazine (tppz ligands. Two dicyanamide anions [dca or N(CN2−] act as counter-ions, and 4.5 water molecules act as solvation agents. The structure contains isolated cationic iron(II–tppz complexes and the final neutrality is obtained with the two dicyanamide anions. One of the dicyanamide anions and a water molecule are disordered with an occupancy ratio of 0.614 (8:0.386 (8. O—H...O, O—H...N and C—H...O hydrogen bonds involving dca, water and tppz molecules are observed.

DFT Calculation of IR Absorption Spectra for PCE-nH2O, TCE-nH2O, DCE-nH2O, VC-nH2O for Small and Water-Dominated Molecular Clusters

Science.gov (United States)

2017-10-31

VC-nH2O for Small and Water-Dominated Molecular Clusters October 31, 2017 Approved for public release; distribution is unlimited. L. Huang S.g...Calculation of IR Absorption Spectra for PCE-nH2O, TCE-nH2O, DCE-nH2O, VC-nH2O for Small and Water-Dominated Molecular Clusters L. Huang,1 S.G...nH2O molecular clusters using density function theory (DFT). DFT can provide interpretation of absorption spectra with respect to molecular

Crystal structures of N2,N3,N5,N6-tetrakis(pyridin-2-ylmethylpyrazine-2,3,5,6-tetracarboxamide and N2,N3,N5,N6-tetrakis(pyridin-4-ylmethylpyrazine-2,3,5,6-tetracarboxamide

Directory of Open Access Journals (Sweden)

Dilovan S. Cati

2017-02-01

Full Text Available The title compounds, C32H28N10O4· unknown solvent, (I, and C32H28N10O4, (II, are pyrazine-2,3,5,6-tetracarboxamide derivatives. In (I, the substituents are (pyridin-2-ylmethylcarboxamide, while in (II, the substituents are (pyridin-4-ylmethylcarboxamide. Both compounds crystallize in the monoclinic space group P21/n, with Z′ = 1 for (I, and Z′ = 0.5 for (II. The whole molecule of (II is generated by inversion symmetry, the pyrazine ring being situated about a center of inversion. In (I, the four pyridine rings are inclined to the pyrazine ring by 83.9 (2, 82.16 (18, 82.73 (19 and 17.65 (19°. This last dihedral angle involves a pyridine ring that is linked to the adjacent carboxamide O atom by an intramolecular C—H...O hydrogen bond. In compound (II, the unique pyridine rings are inclined to the pyrazine ring by 33.3 (3 and 81.71 (10°. There are two symmetrical intramolecular C—H...O hydrogen bonds present in (II. In the crystal of (I, molecules are linked by N—H...O and N—H...N hydrogen bonds, forming layers parallel to (10-1. The layers are linked by C—H...O and C—H...N hydrogen bonds, forming a three-dimensional framework. In the crystal of (II, molecules are linked by N—H...N hydrogen bonds, forming chains propagating along the [010] direction. The chains are linked by a weaker N—H...N hydrogen bond, forming layers parallel to the (101 plane, which are in turn linked by C—H...O hydrogen bonds, forming a three-dimensional structure. In the crystal of compound (I, a region of disordered electron density was treated with the SQUEEZE routine in PLATON [Spek (2015. Acta Cryst. C71, 9–18]. Their contribution was not taken into account during refinement. In compound (II, one of the pyridine rings is positionally disordered, and the refined occupancy ratio for the disordered Car—Car—Npy atoms is 0.58 (3:0.42 (3.

Practical spectrophotometric assay for the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase, a potential antibiotic target.

Science.gov (United States)

Heath, Tahirah K; Lutz, Marlon R; Reidl, Cory T; Guzman, Estefany R; Herbert, Claire A; Nocek, Boguslaw P; Holz, Richard C; Olsen, Kenneth W; Ballicora, Miguel A; Becker, Daniel P

2018-01-01

A new enzymatic assay for the bacterial enzyme succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18) is described. This assay employs N6-methyl-N2-succinyl-L,L-diaminopimelic acid (N6-methyl-L,L-SDAP) as the substrate with ninhydrin used to detect cleavage of the amide bond of the modified substrate, wherein N6-methylation enables selective detection of the primary amine enzymatic product. Molecular modeling supported preparation of the mono-N6-methylated-L,L-SDAP as an alternate substrate for the assay, given binding in the active site of DapE predicted to be comparable to the endogenous substrate. The alternate substrate for the assay, N6-methyl-L,L-SDAP, was synthesized from the tert-butyl ester of Boc-L-glutamic acid employing a Horner-Wadsworth-Emmons olefination followed by an enantioselective reduction employing Rh(I)(COD)(S,S)-Et-DuPHOS as the chiral catalyst. Validation of the new ninhydrin assay was demonstrated with known inhibitors of DapE from Haemophilus influenza (HiDapE) including captopril (IC50 = 3.4 [± 0.2] μM, 3-mercaptobenzoic acid (IC50 = 21.8 [±2.2] μM, phenylboronic acid (IC50 = 316 [± 23.6] μM, and 2-thiopheneboronic acid (IC50 = 111 [± 16] μM. Based on these data, this assay is simple and robust, and should be amenable to high-throughput screening, which is an important step forward as it opens the door to medicinal chemistry efforts toward the discovery of DapE inhibitors that can function as a new class of antibiotics.

Practical spectrophotometric assay for the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase, a potential antibiotic target.

Directory of Open Access Journals (Sweden)

Tahirah K Heath

Full Text Available A new enzymatic assay for the bacterial enzyme succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18 is described. This assay employs N6-methyl-N2-succinyl-L,L-diaminopimelic acid (N6-methyl-L,L-SDAP as the substrate with ninhydrin used to detect cleavage of the amide bond of the modified substrate, wherein N6-methylation enables selective detection of the primary amine enzymatic product. Molecular modeling supported preparation of the mono-N6-methylated-L,L-SDAP as an alternate substrate for the assay, given binding in the active site of DapE predicted to be comparable to the endogenous substrate. The alternate substrate for the assay, N6-methyl-L,L-SDAP, was synthesized from the tert-butyl ester of Boc-L-glutamic acid employing a Horner-Wadsworth-Emmons olefination followed by an enantioselective reduction employing Rh(I(COD(S,S-Et-DuPHOS as the chiral catalyst. Validation of the new ninhydrin assay was demonstrated with known inhibitors of DapE from Haemophilus influenza (HiDapE including captopril (IC50 = 3.4 [± 0.2] μM, 3-mercaptobenzoic acid (IC50 = 21.8 [±2.2] μM, phenylboronic acid (IC50 = 316 [± 23.6] μM, and 2-thiopheneboronic acid (IC50 = 111 [± 16] μM. Based on these data, this assay is simple and robust, and should be amenable to high-throughput screening, which is an important step forward as it opens the door to medicinal chemistry efforts toward the discovery of DapE inhibitors that can function as a new class of antibiotics.

Automated synthesis of ["1"8F](2S,4R)-4-fluoroglutamine on a GE TRACERlab™ FX-N Pro module

International Nuclear Information System (INIS)

Zhang, Xiang; Basuli, Falguni; Shi, Zhen-Dan; Xu, Biying; Blackman, Burchelle; Choyke, Peter L.; Swenson, Rolf E.

2016-01-01

Glutamine (Gln) and its analogues may serve as imaging agents for tumor diagnosis using positron emission tomography (PET), especially for tumors with negative ["1"8F]FDG scan. We report the first automated synthesis of ["1"8F](2S,4R)-4-fluoroglutamine (["1"8F]FGln) on a GE TRACERlab™ FX-N Pro module. ["1"8F]FGln was obtained in 80±3 min with a radiochemical yield of 21±3% (n=5, uncorrected). The radiochemical purity was >98%, and optical purity 90±5%. The synthesis is highly reproducible with good chemical purity, radiochemical yield, and is suitable for translation to cGMP production. - Highlights: • The radiosynthesis of ["1"8F]fluoroglutamine was optimized with improved yield and purity. • Fully automated synthesis was established on a GE TRACERlab™ FX-N Pro module. • Radiochemical yield of 21±3% (uncorrected, n=5) was obtained with good reproducibility. • The automation could be easily adapted to cGMP production for routine clinical use.

Crystal structures of (Z-5-[2-(benzo[b]thiophen-2-yl-1-(3,5-dimethoxyphenylethenyl]-1H-tetrazole and (Z-5-[2-(benzo[b]thiophen-3-yl-1-(3,4,5-trimethoxyphenylethenyl]-1H-tetrazole

Directory of Open Access Journals (Sweden)

Narsimha Reddy Penthala

2016-05-01

Full Text Available (Z-5-[2-(Benzo[b]thiophen-2-yl-1-(3,5-dimethoxyphenylethenyl]-1H-tetrazole methanol monosolvate, C19H16N4O2S·CH3OH, (I, was prepared by the reaction of (Z-3-(benzo[b]thiophen-2-yl-2-(3,5-dimethoxyphenylacrylonitrile with tributyltin azide via a [3 + 2]cycloaddition azide condensation reaction. The structurally related compound (Z-5-[2-(benzo[b]thiophen-3-yl-1-(3,4,5-trimethoxyphenylethenyl]-1H-tetrazole, C20H18N4O3S, (II, was prepared by the reaction of (Z-3-(benzo[b]thiophen-3-yl-2-(3,4,5-trimethoxyphenylacrylonitrile with tributyltin azide. Crystals of (I have two molecules in the asymmetric unit (Z′ = 2, whereas crystals of (II have Z′ = 1. The benzothiophene rings in (I and (II are almost planar, with r.m.s deviations from the mean plane of 0.0084 and 0.0037 Å in (I and 0.0084 Å in (II. The tetrazole rings of (I and (II make dihedral angles with the mean planes of the benzothiophene rings of 88.81 (13 and 88.92 (13° in (I, and 60.94 (6° in (II. The dimethoxyphenyl and trimethoxyphenyl rings make dihedral angles with the benzothiophene rings of 23.91 (8 and 24.99 (8° in (I and 84.47 (3° in (II. In both structures, molecules are linked into hydrogen-bonded chains. In (I, these chains involve both tetrazole and methanol, and are parallel to the b axis. In (II, molecules are linked into chains parallel to the a axis by N—H...N hydrogen bonds between adjacent tetrazole rings.

Autoionisation of N5+ (nln'l') with n = 2,3,4 and n' >= n measured by electron spectrometry in collisions of N7+ with He and H2, at 4.9 keV amu-1

International Nuclear Information System (INIS)

Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Marrakchi, A.I.; Dousson, S.; Hitz, D.

1984-01-01

a spectroscopic investigation of electrons coming from autoionising states N 5+ (nln'l'), with n=2,3,4 and n' >= n, of the fast ion has been made at 11.6 0 and 4.9 keV amu -1 . Only exothermic reactions are observed. It is shown that the ionisation potential of the target has a strong influence on the more probable values of n and n'. In N 7+ -He collisions, the n=3, n'=3 configurations are the more excited. In N 7+ -H 2 , the capture process is less selective since n=3, n' > 3 and also n=4, n' >= 4 configurations are strongly populated. In all these cases, the residual N 6+ ion is left in an excited state (n=2 or 3). The n=2, n' > 2 excitation probability is found to be much smaller for the two collisional systems. (author)

Crystal structure of a looped-chain CoII coordination polymer: catena-poly[[bis-(nitrato-κO)cobalt(II)]bis-[μ-bis-(pyridin-3-ylmeth-yl)sulfane-κ2N:N'

Science.gov (United States)

Moon, Suk-Hee; Seo, Joobeom; Park, Ki-Min

2017-11-01

The asymmetric unit of the title compound, [Co(NO 3 ) 2 (C 12 H 12 N 2 S) 2 ] n , contains a bis-(pyridin-3-ylmeth-yl)sulfane ( L ) ligand, an NO 3 - anion and half a Co II cation, which lies on an inversion centre. The Co II cation is six-coordinated, being bound to four pyridine N atoms from four symmetry-related L ligands. The remaining coordination sites are occupied by two O atoms from two symmetry-related nitrate anions in a monodentate manner. Thus, the Co II centre adopts a distorted octa-hedral geometry. Two symmetry-related L ligands are connected by two symmetry-related Co II cations, forming a 20-membered cyclic dimer, in which the Co II atoms are separated by 10.2922 (7) Å. The cyclic dimers are connected to each other by sharing Co II atoms, giving rise to the formation of an infinite looped chain propagating along the [101] direction. Inter-molecular C-H⋯π (H⋯ring centroid = 2.89 Å) inter-actions between one pair of corresponding L ligands and C-H⋯O hydrogen bonds between the L ligands and the nitrate anions occur in the looped chain. In the crystal, adjacent looped chains are connected by inter-molecular π-π stacking inter-actions [centroid-to-centroid distance = 3.8859 (14) Å] and C-H⋯π hydrogen bonds (H⋯ring centroid = 2.65 Å), leading to the formation of layers parallel to (101). These layers are further connected through C-H⋯O hydrogen bonds between the layers, resulting in the formation of a three-dimensional supra-molecular architecture.

Growth of methyl 2-(2,4-dinitrophenyl)aminopropanoate single crystals

Science.gov (United States)

Perigaud, A.; Nicolau, Y. F.

1986-12-01

Methyl 2-(2,4-dinitrophenyl)aminopropanoate single crystals, 1 cm in diameter and 7 cm in length have been grown by a travelling-heater-Bridgman method in polyethylene tubes introduced into glass ampoules, at a growth rate of 1.5-6 mm/day. The starting material was synthesised and purified by recrystallization from methanol and by vacuum evaporation to a purity of 99.994%. The period of growth, and hence the length of the crystal, is limited due to melt decomposition and polycondensation. The b-axis of the crystals is always oriented at about 72° to the ampoule axis. Good quality single crystals have been obtained giving a FWHM of the Cu Kα (040) rocking curve of about 1'.

Generation of novel metabolites of dietary linoleic acid (18:2n6) by guinea pig epidermis

Energy Technology Data Exchange (ETDEWEB)

Chapkin, R.S.; Ziboh, V.A.

1986-03-05

Although the authors have demonstrated the inability of rat and guinea pig (GP) skin enzyme preparations to desaturate 18:2n6 into gammalinolenic acid (18:3n6) using an in vitro microsomal system, the fate of this dietary essential fatty acid in the GP epidermis is unknown. To explore the fate of 18:2n6, intact tissue slices from GP epidermis were incubated with (1-/sup 14/C)18:2n6. After incubation, the extracted lipids were transesterified using methanolic-HCL. The fatty acid methyl esters were analyzed using a combination of (i) argentation TLC, scanned using a proportional TLC radioscanner, and (ii) reverse phase HPLC, equipped with a flow through radioscanner. The results indicate that the intact epidermis metabolized /sup 14/C-18:2n6 to a group of novel products more polar than 18:2n6. In subsequent experiments, /sup 14/C-18:2n6 was either incubated with the 800 xg supernatant, the 105,000 xg pellet or supernatant from GP epidermis. Metabolism of 18:2n6 by the high speed supernatant resulted in the generation of polar products with chromatographic properties of not greater than 2 double bonds. These results indicate that although the GP epidermis lacks the capacity to desaturate 18:2n6 to 18:3n6, it can convert dietary 18:2n6 into a group of novel polar metabolites via a cytosolic mediated process. The function of these metabolites in the GP integumentary system remains to be determined.

Generation of novel metabolites of dietary linoleic acid (18:2n6) by guinea pig epidermis

International Nuclear Information System (INIS)

Chapkin, R.S.; Ziboh, V.A.

1986-01-01

Although the authors have demonstrated the inability of rat and guinea pig (GP) skin enzyme preparations to desaturate 18:2n6 into gammalinolenic acid (18:3n6) using an in vitro microsomal system, the fate of this dietary essential fatty acid in the GP epidermis is unknown. To explore the fate of 18:2n6, intact tissue slices from GP epidermis were incubated with [1- 14 C]18:2n6. After incubation, the extracted lipids were transesterified using methanolic-HCL. The fatty acid methyl esters were analyzed using a combination of (i) argentation TLC, scanned using a proportional TLC radioscanner, and (ii) reverse phase HPLC, equipped with a flow through radioscanner. The results indicate that the intact epidermis metabolized 14 C-18:2n6 to a group of novel products more polar than 18:2n6. In subsequent experiments, 14 C-18:2n6 was either incubated with the 800 xg supernatant, the 105,000 xg pellet or supernatant from GP epidermis. Metabolism of 18:2n6 by the high speed supernatant resulted in the generation of polar products with chromatographic properties of not greater than 2 double bonds. These results indicate that although the GP epidermis lacks the capacity to desaturate 18:2n6 to 18:3n6, it can convert dietary 18:2n6 into a group of novel polar metabolites via a cytosolic mediated process. The function of these metabolites in the GP integumentary system remains to be determined

Pr4N2S3 and Pr4N2Se3: two non-isostructural praseodymium(iii) nitride chalcogenides

International Nuclear Information System (INIS)

Lissner, Falk; Schleid, Thomas

2005-01-01

The non-isostructural nitride chalcogenides of praseodymium, Pr 4 N 2 S 3 and Pr 4 N 2 Se 3 , are formed by the reaction of the praseodymium metal with sodium azide (NaN 3 ), praseodymium trihalide (PrX 3 ; X = Cl, Br, I) and the respective chalcogen (sulfur or selenium) at 900 C in evacuated silica ampoules after seven days. Both crystallize monoclinically in space group C2/c (Pr 4 N 2 S 3 : a = 1788.57(9), b = 986.04(5), c = 1266.49(6) pm, β = 134.546(7) , Z = 8; Pr 4 N 2 Se 3 : a = 1311.76(7), b = 1017.03(5), c = 650.42(3) pm, β = 90.114(6) , Z = 4). The crystal structures of both compounds show a layered construction, dominated by N 3- -centred (Pr 3+ ) 4 tetrahedra which share a common edge first. Continuing linkage of the so resulting bitetrahedral [N 2 Pr 6 ] 12+ units via the non-connected vertices to layers according to [stack ∞ 2 ]{[N(Pr) 2/2 e (Pr') 2/2 v ] 3+ } forms different kinds of tetrahedral nets which can be described as layers consisting of ''four- and eight-rings'' for Pr 4 N 2 S 3 and as layers of ''six-rings'' for Pr 4 N 2 Se 3 . Whereas the crystal structure of Pr 4 N 2 S 3 exhibits four different Pr 3+ cations with coordination numbers of six (2 x) and seven (2 x) against N 3- and S 2- , the number of cations in the nitride selenide (Pr 4 N 2 Se 3 ) is reduced to half (Pr1 and Pr2) also having six- and sevenfold anionic coordination spheres. Further motifs for the connection of [NM 4 ] 9+ tetrahedra in crystal structures of nitride chalcogenides and halides of the rare-earth elements with ratios of N: M = 1: 2 are presented and discussed. (Abstract Copyright [2005], Wiley Periodicals, Inc.) [de

Characterisation of (R-2-(2-Fluorobiphenyl-4-yl-N-(3-Methylpyridin-2-ylPropanamide as a Dual Fatty Acid Amide Hydrolase: Cyclooxygenase Inhibitor.

Directory of Open Access Journals (Sweden)

Sandra Gouveia-Figueira

Full Text Available Increased endocannabinoid tonus by dual-action fatty acid amide hydrolase (FAAH and substrate selective cyclooxygenase (COX-2 inhibitors is a promising approach for pain-relief. One such compound with this profile is 2-(2-fluorobiphenyl-4-yl-N-(3-methylpyridin-2-ylpropanamide (Flu-AM1. These activities are shown by Flu-AM1 racemate, but it is not known whether its two single enantiomers behave differently, as is the case towards COX-2 for the parent flurbiprofen enantiomers. Further, the effects of the compound upon COX-2-derived lipids in intact cells are not known.COX inhibition was determined using an oxygraphic method with arachidonic acid and 2-arachidonoylglycerol (2-AG as substrates. FAAH was assayed in mouse brain homogenates using anandamide (AEA as substrate. Lipidomic analysis was conducted in unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Both enantiomers inhibited COX-2 in a substrate-selective and time-dependent manner, with IC50 values in the absence of a preincubation phase of: (R-Flu-AM1, COX-1 (arachidonic acid 6 μM; COX-2 (arachidonic acid 20 μM; COX-2 (2-AG 1 μM; (S-Flu-AM1, COX-1 (arachidonic acid 3 μM; COX-2 (arachidonic acid 10 μM; COX-2 (2-AG 0.7 μM. The compounds showed no enantiomeric selectivity in their FAAH inhibitory properties. (R-Flu-AM1 (10 μM greatly inhibited the production of prostaglandin D2 and E2 in both unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Levels of 2-AG were not affected either by (R-Flu-AM1 or by 10 μM flurbiprofen, either alone or in combination with the FAAH inhibitor URB597 (1 μM.Both enantiomers of Flu-AM1 are more potent inhibitors of 2-AG compared to arachidonic acid oxygenation by COX-2. Inhibition of COX in lipopolysaccharide + interferon γ- stimulated RAW 264.7 cells is insufficient to affect 2-AG levels despite the large induction of COX-2 produced by this treatment.

Conformational states of N-acylalanine dithio esters: correlation of resonance Raman spectra with structures

International Nuclear Information System (INIS)

Lee, H.; Angus, R.H.; Storer, A.C.; Varughese, K.I.; Carey, P.R.

1988-01-01

The conformational states of N-acylalanine dithio esters, involving rotational isomers about the RC(=O)NH-CH(CH 3 ) and NHCH(CH 3 )-C(=S) bonds, are defined and compared to those of N-acylglycine dithio esters. The structure of N-(p-nitrobenzoyl)-DL-alanine ethyl dithio ester has been determined by X-ray crystallographic analysis; it is a B-type conformer with the amide N atom cis to the thiol sulfur. Raman and resonance Raman (RR) measurements on this compound and for the B conformers of solid N-benzoyl-DL-alanine ethyl dithio ester and N-(β-phenylpropionyl)-DL-alanine ethyl dithio ester and its NHCH(CD 3 )C(=S) and NHCH(CH 3 ) 13 C(=S) analogues are used to set up a library of RR data for alanine-based dithio esters in a B-conformer state. RR data for this solid material in its isotopically unsubstituted and CH(C-D 3 )C(=S) and CH(CH 3 ) 13 C(=S) forms provide information on the RR signatures of alanine dithio esters in A-like conformations. RR spectra are compared for the solid compounds, for N-(p-nitrobenzoyl)-DL-alanine, N-(β-phenylpropionyl)-DL-alanine, and (methyloxycarbonyl)-L-phenylalanyl-DL-alanine ethyl dithio ester, and for several 13 C=S- and CD 3 -substituted analogues in CCl 4 or aqueous solutions. The RR data demonstrate that the alanine-based dithio esters take up A, B, and C 5 conformations in solution. The RR spectra of these conformers are clearly distinguishable from those for the same conformers of N-acylglycine dithio esters. However, the crystallographic and spectroscopic results show that the results show that the conformational properties of N-acylglycine and N-acylalanine dithio esters are very similar

2-(2,4-Dichlorophenyl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylacetamide

Directory of Open Access Journals (Sweden)

B. Narayana

2013-01-01

Full Text Available In the crystal structure of the title compound, C19H17Cl2N3O2, the molecules form dimers of the R22(10 type through N—H...O hydrogen bonding. As a result of steric repulsion, the amide group is rotated with respect to both the dichlorophenyl and 2,3-dihydro-1H-pyrazol-4-yl rings, making dihedral angles of 80.70 (13 and 64.82 (12°, respectively. The dihedral angle between the dichlorophenyl and 2,3-dihydro-1H-pyrazol-4-yl rings is 48.45 (5° while that between the 2,3-dihydro-1H-pyrazol-4-yl and phenyl rings is 56.33 (6°.

Bis(μ-bis{[4-(2-pyridylpyrimidin-2-yl]sulfanyl}methanedisilver(I bis(perchlorate

Directory of Open Access Journals (Sweden)

Hai-Bin Zhu

2010-12-01

Full Text Available In the macrocyclic centrosymmetric dinuclear complex, [Ag2(C19H14N6S22](ClO42, the AgI atom, bis{[4-(2-pyridylpyrimidin-2-yl]sulfanyl}methane (2-bppt ligand and perchlorate anion each lie on a twofold rotation axis. The 2-bppt ligand chelates two four-coordinated AgI atoms through its two bipyridine-like arms. The O atoms of the perchlorate anion are disordered each over two positions of equal occupancy. Adjacent complex molecules are linked by π–π interactions between the pyridine and pyrimidine rings [centroid–centroid distance = 3.663 (8 Å].

Assembly of bicyclic or monocyclic clusters from [(η5-C5Me5)2Mo2(μ3-S)4(CuMeCN)2]2+ with tetraphosphine or N,P mixed ligands: syntheses, structures and enhanced third-order NLO performances.

Science.gov (United States)

Ren, Zhi-Gang; Sun, Sha; Dai, Min; Wang, Hui-Fang; Lü, Chun-Ning; Lang, Jian-Ping; Sun, Zhen-Rong

2011-09-07

Reactions of the preformed cluster [(η(5)-C(5)Me(5))(2)Mo(2)(μ(3)-S)(4)Cu(2)(MeCN)(2)](ClO(4))(2) (1) with two tetraphosphine ligands, 1,4-N,N,N',N'-tetra(diphenylphosphanylmethyl)benzene diamine (dpppda) and N,N,N',N'-tetra(diphenylphosphanylmethyl)ethylene diamine (dppeda), produced two bicyclic clusters {[(η(5)-C(5)Me(5))(2)Mo(2)(μ(3)-S)(4)Cu(2)](2)(L)}(ClO(4))(4) (3: L = dpppda; 4: L = dppeda). Analogous reactions of 1 or [(η(5)-C(5)Me(5))(2)Mo(2)(μ(3)-S)(4)Cu(2)(MeCN)(2)](PF(6))(2) (2) with two N,P mixed ligands, N,N-bi(diphenylphosphanylmethyl)-2-aminopyridine (bdppmapy) and N-diphenylphosphanylmethyl-4-aminopyridine (dppmapy), afforded two monocyclic clusters {[(η(5)-C(5)Me(5))(2)Mo(2)(μ(3)-S)(4)Cu(2)](2)(L)(2)}X(4) (5: L = bdppmapy, X = ClO(4); 6: L = dppmapy, X = PF(6)). Compounds 3-6 were fully characterized by elemental analysis, IR spectra, UV-vis spectra, (1)H and (31)P{(1)H} NMR spectra, ESI-MS and single-crystal X-ray crystallography. In the tetracations of 3-6, two cubane-like [Mo(2)(μ(3)-S)(4)Cu(2)] cores are linked either by one dpppda or dppeda bridge to form a bicyclic structure or by a pair of bdppmapy or dppmapy bridges to afford a monocyclic structure. The third-order nonlinear optical (NLO) properties of 1 and 3-6 in MeCN were also investigated by femtosecond degenerate four-wave mixing (DFWM) technique with a 50 fs pulse width at 800 nm. Compounds 3-6 exhibited enhanced third-order NLO performances relative to that of 1. This journal is © The Royal Society of Chemistry 2011

Effect of pH on the charge-assisted hydrogen-bonded assembly of the anionic [Cu(oxalate)2]2- building unit and N,N'-ditopic cations.

Science.gov (United States)

Klongdee, Fatima; Boonmak, Jaursup; Youngme, Sujittra

2018-03-01

By the solvothermal reaction under acidic conditions of Cu(NO 3 ) 2 ·3H 2 O, Na 2 C 2 O 4 and the N,N'-ditopic organic coligands 1-(pyridin-4-yl)piperazine (ppz) and 1,2-bis(pyridin-4-yl)ethane (bpa), two novel anionic copper(II) coordination compounds were obtained, namely the one-dimensional coordination polymer catena-poly[4-(pyridin-1-ium-4-yl)piperazin-1-ium [[(oxalato-κ 2 O 1 ,O 2 )copper(II)]-μ-oxalato-κ 3 O 1 ,O 2 :O 1'

Total scattering cross-sections for the systems nH2 + nH2, pH2 + pH2, nD2 + nD2, oD2 + oD2 and HD + HD for relative energies below ten milli-electron volts

International Nuclear Information System (INIS)

Johnson, D.L.

1979-01-01

Relative total scattering cross sections for nH 2 + nH 2 , pH 2 + pH 2 , nD 2 + nD 2 , oD 2 + oD 2 , and HD + HD were measured with inclined nozzle beams derived from nozzle sources and intersecting at 21 0 . Both nozzles could be varied in temperature from 4.2K to 300K to provide the velocity range for the cross sections. The use of a parahydrogen converter allowed the measurement of the pH 2 + pH 2 and oD 2 + oD 2 cross sections. Cross sections for the H 2 + H 2 were measured over a relative velocity range of 200 m/s to 1450 m/s. The nH 2 + nH 2 results show an undulation in the velocity range between 350 m/s and 400 m/s that corresponds to a l = 3 orbiting resonance. Analysis of the pH 2 + pH 2 cross section indicates a l = 4 orbiting resonance near 586 m/s. This resonance has a peak energy of 1.79 meV and a measured energy width of 1.05 meV, both which agree well with theoretical predictions. The D 2 + D 2 cross sections have been measured in the velocity range between 190 m/s and 1000 m/s. No orbiting resonances have been observed, but in the oD 2 + oD 2 cross section a deep minimum between the l = 4 and the l = 5 resonances at low velocities is clearly suggested. Initial measurements of the HD + HD cross section suggests the presence of the l = 4 orbiting resonance near a relative velocity of 300 m/s. The experimental results for each system were normalized to the total cross sections, which were convoluted to account for experimental velocity and angular dispersions. Three different potentials were considered, but a chi-square fit of the data indicates that the Schaefer and Meyer potential, which has been theoretically obtained from first principles, provides the best overall description of the hydrogen systems in the low collisional energy range

A library synthesis of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as anti-tumor agents.

Science.gov (United States)

Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

2004-09-06

As a result of a hit-to-lead program using a technique of solution-phase parallel synthesis, a highly potent (2,4-dimethoxyphenyl)-[6-(3-fluorophenyl)-4-hydroxy-3-methylbenzofuran-2-yl]methanone (15b) was synthesized as an optimized derivative of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which was discovered as a screening hit from small-molecule libraries and exhibited selective cytotoxicity against a tumorigenic cell line.

catena-Poly[[bromidocopper(I)]-?-?2,?1-3-(2-allyl-2H-tetra?zol-5-yl)pyridine

OpenAIRE

Wang, Wei

2008-01-01

The title compound, [CuBr(C9H9N5)] n , has been prepared by the solvothermal treatment of CuBr with 3-(2-allyl-2H-tetra?zol-5-yl)pyridine. It is a new homometallic CuI olefin coord?ination polymer in which the CuI atoms are linked by the 3-(2-allyl-2H-tetra?zol-5-yl)pyridine ligands and bonded to one terminal Br atom each. The organic ligand acts as a bidentate ligand connecting two neighboring Cu centers through the N atom of the pyridine ring and the double bond of the allyl group. A three-...

1D and 2D assembly structures by imidazole···chloride hydrogen bonds of iron(II) complexes [Fe(II)(HL(n-Pr))3]Cl·Y (HL(n-Pr) = 2-methylimidazol-4-yl-methylideneamino-n-propyl; Y = AsF6, BF4) and their spin states.

Science.gov (United States)

Fujinami, Takeshi; Nishi, Koshiro; Matsumoto, Naohide; Iijima, Seiichiro; Halcrow, Malcolm A; Sunatsuki, Yukinari; Kojima, Masaaki

2011-12-07

Two Fe(II) complexes fac-[Fe(II)(HL(n-Pr))(3)]Cl·Y (Y = AsF(6) (1) and BF(4) (2)) were synthesized, where HL(n-Pr) is 2-methylimidazole-4-yl-methylideneamino-n-propyl. Each complex-cation has the same octahedral N(6) geometry coordinated by three bidentate ligands and assumes facial-isomerism, fac-[Fe(II)(HL(n-Pr))(3)](2+) with Δ- and Λ-enantiomorphs. Three imidazole groups per Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) are hydrogen-bonded to three Cl(-) ions or, from the viewpoint of the Cl(-) ion, one Cl(-) ion is hydrogen-bonded to three neighbouring fac-[Fe(II)(HL(n-Pr))(3)](2+) cations. The 3 : 3 NH···Cl(-) hydrogen bonds between Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) and Cl(-) generate two kinds of assembly structures. The directions of the 3 : 3 NH···Cl(-) hydrogen bonds and hence the resulting assembly structures are determined by the size of the anion Y, though Y is not involved into the network structure and just accommodated in the cavity. Compound 1 has a 1D ladder structure giving a larger cavity, in which the Δ- and Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) enantiomorphs are bridged by two NH···Cl(-) hydrogen bonds. Compound 2 has a 2D network structure with a net unit of a cyclic trimer of {fac-[Fe(II)(HL(n-Pr))(3)](2+)···Cl(-)}(3) giving a smaller cavity, in which Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) species with the same chirality are linked by NH···Cl(-) hydrogen bonds to give a homochiral 2D network structure. Magnetic susceptibility and Mössbauer spectral measurements demonstrated that compound 1 showed an abrupt one-step spin crossover with 4.0 K thermal hysteresis of T(c↓) = 125.5 K and T(c↑) = 129.5 K and compound 2 showed no spin transition and stayed in the high-spin state over the 5-300 K temperature range.

40 CFR 721.4575 - L-aspartic acid, N,N′- [(1E) - 1,2 - ethenediylbis[(3-sulfo-4, 1-phenylene)imino [6-(phenylamino...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-aspartic acid, N,Nâ²- [(1E) - 1,2... Substances § 721.4575 L-aspartic acid, N,N′- [(1E) - 1,2 - ethenediylbis[(3-sulfo-4, 1-phenylene)imino [6... uses subject to reporting. (1) The chemical substance identified as l-aspartic acid, N,N′- [(1E) - 1,2...

Conducting polymers of octanoic acid 2-thiophen-3-yl-ethyl ester and their electrochromic properties

International Nuclear Information System (INIS)

Camurlu, Pinar; Cirpan, Ali; Toppare, Levent

2005-01-01

Octanoic acid 2-thiophen-3-yl-ethyl ester was synthesized via the reaction of 3-thiophene ethanol with octanoyl chloride. The resulting monomer was electrochemically homopolymerized in the presence of tetrabutylammonium tetrafluoroborate as the supporting electrolyte, in the acetonitrile/borontrifluoride ethyl ether solvent system. The resulting polymer was characterized using various experimental techniques. Spectroelectrochemistry analysis of the homopolymer reflects electronic transitions at 434, ∼800 and ∼1100 nm, revealing π-π* transition, polaron and bipolaron band formation, respectively, leading to esthetically pleasing color changes between transmissive yellow and blue, with reasonable switching times

Development of luminol-N-hydroxyphthalimide chemiluminescence system for highly selective and sensitive detection of superoxide dismutase, uric acid and Co2.

Science.gov (United States)

Saqib, Muhammad; Qi, Liming; Hui, Pan; Nsabimana, Anaclet; Halawa, Mohamed Ibrahim; Zhang, Wei; Xu, Guobao

2018-01-15

N-hydroxyphthalimide (NHPI), a well known reagent in organic synthesis and biochemical applications, has been developed as a stable and efficient chemiluminescence coreactant for the first time. It reacts with luminol much faster than N-hydroxysuccinimide, eliminating the need of a prereaction coil used in N-hydroxysuccinimide system. Without using prereaction coil, the chemiluminescence peak intensities of luminol-NHPI system are about 102 and 26 times greater than that of luminol-N-hydroxysuccinimide system and classical luminol-hydrogen peroxide system, respectively. The luminol-NHPI system achieves the highly sensitive detection of luminol (LOD = 70pM) and NHPI (LOD = 910nM). Based on their excellent quenching efficiencies, superoxide dismutase and uric acid are sensitively detected with LODs of 3ng/mL and 10pM, respectively. Co 2+ is also detected a LOD of 30pM by its remarkable enhancing effect. Noteworthily, our method is at least 4 orders of magnitude more sensitive than previously reported uric acid detection methods, and can detect uric acid in human urine and Co 2+ in tap and lake water real samples with excellent recoveries in the range of 96.35-102.70%. This luminol-NHPI system can be an important candidate for biochemical, clinical and environmental analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Structure and stability of small Li2 +(X2Σ+ g )-Xen (n = 1-6) clusters

Science.gov (United States)

Saidi, Sameh; Ghanmi, Chedli; Berriche, Hamid

2014-04-01

We have studied the structure and stability of the Li2 +(X2Σ+ g )Xe n ( n = 1-6) clusters for special symmetry groups. The potential energy surfaces of these clusters, are described using an accurate ab initio approach based on non-empirical pseudopotential, parameterized l-dependent polarization potential and analytic potential forms for the Li+Xe and Xe-Xe interactions. The pseudopotential technique has reduced the number of active electrons of Li2 +(X2Σ+ g )-Xe n ( n = 1-6) clusters to only one electron, the Li valence electron. The core-core interactions for Li+Xe are included using accurate CCSD(T) potential fitted using the analytical form of Tang and Toennies. For the Xe-Xe potential interactions we have used the analytical form of Lennard Jones (LJ6 - 12). The potential energy surfaces of the Li2 +(X2Σ+ g )Xe n ( n = 1-6) clusters are performed for a fixed distance of the Li2 +(X2Σ+ g ) alkali dimer, its equilibrium distance. They are used to extract information on the stability of the Li2 +(X2Σ+ g Xe n ( n = 1-6) clusters. For each n, the stability of the different isomers is examined by comparing their potential energy surfaces. Moreover, we have determined the quantum energies ( D 0), the zero-point-energies (ZPE) and the ZPE%. To our best knowledge, there are neither experimental nor theoretical works realized for the Li2 +(X2Σ+ g Xe n ( n = 1-6) clusters, our results are presented for the first time.

4,2':6',4"- and 3,2':6',3"-Terpyridines: The Conflict between Well-Defined Vectorial Properties and Serendipity in the Assembly of 1D-, 2D- and 3D-Architectures.

Science.gov (United States)

Klein, Y Maximilian; Prescimone, Alessandro; Constable, Edwin C; Housecroft, Catherine E

2017-06-30

A comparative investigation of the coordination assemblies formed between Co(NCS)₂ and two monotopic 4,2':6',4''-terpyridine (4,2':6',4"-tpy) ligands or two related ditopic ligands is reported. Crystals were grown by layering MeOH solutions of Co(NCS)₂ over a CHCl₃ or 1,2-C₆H₄Cl₂ solution of the respective ligand at room temperature. With 4'-(2-methylpyrimidin-5-yl)-4,2':6',4"-terpyridine ( 6 ), the 1D-coordination polymer {[Co₂(NCS)₄(MeOH)₄( 6 )₂]∙2MeOH∙8H₂O} n assembles with 6 coordinating only through the outer N-donors of the 4,2':6',4"-tpy unit; coordination by the MeOH solvent blocks two cobalt coordination sites preventing propagation in a higher-dimensional network. A combination of Co(NCS)₂ and 1-(4,2':6',4"-terpyridin-4'-yl)ferrocene ( 7 ) leads to {[Co(NCS)₂( 7 )₂]∙4CHCl₃} n which contains a (4,4) net; the 2D-sheets associate through π-stacking interactions between ferrocenyl and pyridyl units. A 3D-framework is achieved through use of the ditopic ligand 1,4-bis( n propoxy)-2,5-bis(4,2':6',4"-terpyridin-4'-yl)benzene ( 8 ) which acts as a 4-connecting node in {[Co(NCS)₂( 8 )₂] . 2C₆H₄Cl₂} n ; the combination of metal and ligand planar 4-connecting nodes results in a {6⁵.8} cds net. For a comparison with the coordinating abilities of the previously reported 1,4-bis( n octoxy)-2,5-bis(4,2':6',4"-terpyridin-4'-yl)benzene ( 3 ), a more flexible analogue 9 was prepared. {[Co(NCS)₂( 9 )]∙2CHCl₃} n contains a (4,4) net defined by both metal and ligand planar 4-connecting nodes. The n octoxy tails of 9 protrude from each side of the (4,4) net and thread through adjacent sheets; the arene-attached n octoxy chains associate through a combination of van der Waals and C-H...π interactions.

New entry for synthesis of N-acylhydrazones, pyridazinones, and 1,3,4-oxadiazin-6-ones from alpha-amino acid esters.

Science.gov (United States)

Yasui, Eiko; Wada, Masao; Takamura, Norio

2007-11-01

Versatile electrophiles N-acylhydrazones are synthesized via diazotization, reduction, and acylation of alpha-amino acid esters. Reduction of diazo esters with L-selectride or tributylphosphine affords the corresponding hydrazones in good yields. Both reducing agents give anti-hydrazones as the major product although the reactivity of each reductant is slightly different. The resulting hydrazones are acylated to give N-acylhydrazones, which are subjected to further reactions to give 1,3,4-oxadiazin-6-ones that serve as useful synthetic intermediates for the Diels-Alder reaction.

Polymerization of Methyl Methacrylate Catalyzed by Co(II), Cu(II), and Zn(II) Complexes Bearing N-Methyl-N-((pyridin-2-yl)methyl) cyclohexanamine

Energy Technology Data Exchange (ETDEWEB)

Ahn, Seoung Hyun; Lee, Hyosun [Kyungpook National University, Daegu (Korea, Republic of); Shin, Jongwon [POSTECH, Pohang (Korea, Republic of); Nayab, Saira [Shaheed Benazir Bhutto University, Sheringal (Pakistan)

2016-05-15

We demonstrated the synthesis and characterization of Co(II), Cu(II), and Zn(II) complexes ligated to N-methyl-N-((pyridin-2-yl)methyl)cyclohexanamine. The complex [Co(nmpc)Cl{sub 2}] in the presence of MMAO showed the highest catalytic activity for MMA polymerization at 60 °C compared with its Zn(II) and Cu(II) analogs. The metal center showed an obvious influence on the catalytic activity, although this appeared to have no effect on the stereo-regularity of the resultant PMMA. X-ray diffraction analysis revealed that [Co(nmpc)Cl{sub 2}] and [Zn(nmpc)Cl{sub 2}] crystallized in the monoclinic system with space group P2{sub 1}/c and existed as monomeric and solvent-free complexes.

Synthesis, structural and vibrational investigation on 2-phenyl-N-(pyrazin-2-yl)acetamide combining XRD diffraction, FT-IR and NMR spectroscopies with DFT calculations.

Science.gov (United States)

Lukose, Jilu; Yohannan Panicker, C; Nayak, Prakash S; Narayana, B; Sarojini, B K; Van Alsenoy, C; Al-Saadi, Abdulaziz A

2015-01-25

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 2-phenyl-N-(pyrazin-2-yl)acetamide have been investigated experimentally and theoretically using Gaussian09 software package. The title compound was optimized by using the HF/6-31G(6D,7F) and B3LYP/6-31G(6D,7F) calculations. The geometrical parameters are in agreement with the XRD data. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. Gauge-including atomic orbital (1)H-NMR chemical shifts calculations were carried out and compared with experimental data. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. Molecular electrostatic potential was performed by the DFT method. First hyperpolarizability is calculated in order to find its role in non linear optics. From the XRD data, in the crystal, molecules are held together by strong C-H⋯O and N-H⋯O intermolecular interactions. Copyright © 2014 Elsevier B.V. All rights reserved.

N-(4-Chloro-1,3-benzothiazol-2-yl-2-(3-methylphenylacetamide monohydrate

Directory of Open Access Journals (Sweden)

H. S. Yathirajan

2011-10-01

Full Text Available In the title compound, C16H13ClN2OS·H2O, the dihedral angle between the mean planes of the benzothiazole ring system and the methylphenyl ring is 79.3 (6°. The crystal packing features intermolecular O—H...N, O—H...O and N—H...O hydrogen bonds involving the water molecule and weak C—H...O, C—H...Cg and π–π stacking interactions [centroid–centroid distances = 3.8743 (7, 3.7229 (7 and 3.7076 (8 Å].

Synthesis, in vitro binding, and tissue distribution of radioiodinated 2-[125I]N-(N-benzylpiperidin-4-yl)-2-iodo benzamide, 2-[125I]BP: a potential σ receptor marker for human prostate tumors

International Nuclear Information System (INIS)

John, Christy S.; Gulden, Mary E.; Li, Jinghua; Bowen, Wayne D.; McAfee, John G.; Thakur, Mathew L.

1998-01-01

The preclinical evaluation of a σ receptor-specific radiopharmaceutical that binds to human prostate tumor cells with a high affinity is described. We have synthesized and radioiodinated 2-[ 125 I]-N-(N-benzylpiperidin-4-yl)-2-iodobenzamide (2-[ 125 I]BP) that possesses high affinity for both σ-1 and σ-2 receptor subtypes that are expressed on a variety of tumor cells. 2-IBP was synthesized, purified and characterized by routine spectroscopic and analytical methods. Radioiodination was accomplished using an oxidative iododestannylation reaction in the presence of chloramine T in high yields (76%-93%) with a very high-specific activity (1700-1900 Ci/mmol). The in vitro competition binding studies of 2-[ 125 I]BP with various σ receptor ligands in LnCAP human prostate tumor cells showed a dose-dependent saturable binding. The inhibition constants (K i , nM) for binding of 2-[ 125 I]BP to human prostate tumor cells for 4-IBP, haloperidol and 2-IBP were 4.09, 6.34 and 1.6 nM, respectively. The clearance of 2-[ 125 I]BP, in Sprague-Dawley rats, was rapid from the blood pool, other normal tissues and the total body. Tissue distribution studies in nude mice bearing human prostate tumor (DU-145) also showed a fast clearance from normal organs. The tumor had the highest percentage of injected dose per gram (%ID/g) of all tissues at 4 h as well as 24 h (2.0 ± 0.05 and 0.147 ± 0.038 ID/g, respectively) postinjection. The in vivo receptor binding specificity was demonstrated using haloperidol (a known high-affinity σ receptor ligand). A significant decrease (>50%, p = 0.001) was observed in tumor concentration when haloperidol was used as a blocking agent. The high affinity of 2-[ 125 I]BP for σ receptor-binding sites, its fast in vivo clearance from normal organs and its high uptake and retention in tumor implies that 2-[ 123 I]BP or 2-[ 131 I]BP may be a promising tracer for noninvasive imaging of human prostate tumors

Lax-Phillips scattering theory with perturbations of the type: V(x)=(φ(x))/|x|β, where β=2-(n)/s, φ is an element of Ls(Rn), s > 2 and s ≥ (n)/2

International Nuclear Information System (INIS)

Brambila-Paz, F.; Duong Minh Duc.

1990-12-01

A scattering theory for the wave equation with compactly supported perturbations was developed by Lax-Phillips in 1967. Using Enss approach, Phillips developed a Lax-Phillips scattering theory with short range perturbations of the type: V(x)=o((1)/|x| β ), β > 2. In this paper we develop a scattering theory for more general perturbations, i.e. for V(x)=(φ(x))/|x| β , where β=2-(n)/s, φ is an element of L s (R n ), s > 2 and s ≥ (n)/2. Refs

N-(5-Benzylsulfanyl-1,3,4-thiadiazol-2-yl-2-(piperidin-1-ylacetamide

Directory of Open Access Journals (Sweden)

D. S. Ismailova

2014-03-01

Full Text Available The title compound, C16H20N4OS2, was synthesized by the reaction of 2-benzylsulfanyl-5-chloroacetamido-1,3,4-thiadiazole and piperidine in a 1:2 ratio. The planes of the acetamide and 1,3,4-thiadiazole units are twisted by 10.8 (4°. The thiadiazole S atom and the acetamide O atom are syn-oriented due to a hypervalent S...O interaction of 2.628 (4 Å. In the crystal, molecules form centrosymmetric dimers via N—H...N hydrogen bonds. These dimers are further connected by C—H...O interactions into (100 layers.

Crystal structure, spectral property, antimicrobial activity and DFT calculation of N-(coumarin-3-yl)-N‧-(2-amino-5-phenyl-1,3,4-thiadiazol-2-yl) urea

Science.gov (United States)

Zhang, Hong-Song; Zhang, Kong-Yan; Chen, Li-Chuan; Li, Yao-Xin; Chai, Lan-Qin

2017-10-01

N-(coumarin-3-yl)-N‧-(2-amino-5-phenyl-1,3,4-thiadiazol-2-yl) urea was synthesized and characterized by elemental analysis, IR, 1H NMR, 13C NMR, UV-Vis and emission spectroscopy, as well as by single-crystal X-ray diffraction. X-ray crystallographic analyses have indicated that the crystal structure consists of two dimethyl sulfoxide (DMSO) solvent molecules and the structural geometry of DMSO is a trigonal pyramid in shape. In the crystal structure, a self-assembling two-dimensional (2-D) layer supramolecular architecture is formed through intermolecular hydrogen bonds, Cdbnd O···π (thiadiazole ring) and π···π stacking interactions. The geometry of the compound has been optimized by the DFT method and the results are compared with the X-ray diffraction data. The electronic transitions and spectral features of the compound were carried out by using DFT/B3LYP method. In addition, the antimicrobial activity was also studied, and the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), and HOMO-LUMO gap were also calculated.

Design and synthesis of N-(4-aminopyridin-2-yl)amides as B-Raf(V600E) inhibitors.

Science.gov (United States)

Li, Xiaokai; Shen, Jiayi; Tan, Li; Zhang, Zhang; Gao, Donglin; Luo, Jinfeng; Cheng, Huimin; Zhou, Xiaoping; Ma, Jie; Ding, Ke; Lu, Xiaoyun

2016-06-15

B-Raf(V600E) was an effective target for the treatment of human cancers. Based on a pan-Raf inhibitor TAK-632, a series of N-(4-aminopyridin-2-yl)amide derivatives were designed as novel B-Raf(V600E) inhibitors. Detailed structure-activity studies of the compounds revealed that most of the compounds displayed potent enzymatic activity against B-Raf(V600E), and good selectivity over B-Raf(WT). One of the most promising compound 4l exhibited potent inhibitory activity with an IC50 value of 38nM for B-raf(V600E), and displayed antiproliferative activities against colo205 and HT29 cells with IC50 values of 0.136 and 0.094μM, respectively. It also displayed good selectivity on both enzymatic and cellular assays over B-Raf(WT). These inhibitors may serve as lead compounds for further developing novel B-Raf(V600E) inhibitors as anticancer drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Calculations of long-range three-body interactions for He(n0λS )-He(n0λS )-He(n0'λL )

Science.gov (United States)

Yan, Pei-Gen; Tang, Li-Yan; Yan, Zong-Chao; Babb, James F.

2018-04-01

We theoretically investigate long-range interactions between an excited L -state He atom and two identical S -state He atoms for the cases of the three atoms all in spin-singlet states or all in spin-triplet states, denoted by He(n0λS )-He(n0λS )-He(n0'λL ), with n0 and n0' principal quantum numbers, λ =1 or 3 the spin multiplicity, and L the orbital angular momentum of a He atom. Using degenerate perturbation theory for the energies up to second-order, we evaluate the coefficients C3 of the first-order dipolar interactions and the coefficients C6 and C8 of the second-order additive and nonadditive interactions. Both the dipolar and dispersion interaction coefficients, for these three-body degenerate systems, show dependences on the geometrical configurations of the three atoms. The nonadditive interactions start to appear in second-order. To demonstrate the results and for applications, the obtained coefficients Cn are evaluated with highly accurate variationally generated nonrelativistic wave functions in Hylleraas coordinates for He(1 1S ) -He(1 1S ) -He(2 1S ) , He(1 1S ) -He(1 1S ) -He(2 1P ) , He(2 1S ) -He(2 1S ) -He(2 1P ) , and He(2 3S ) -He(2 3S ) -He(2 3P ) . The calculations are given for three like nuclei for the cases of hypothetical infinite mass He nuclei, and of real finite mass 4He or 3He nuclei. The special cases of the three atoms in equilateral triangle configurations are explored in detail, and for the cases in which one of the atoms is in a P state, we also present results for the atoms in an isosceles right triangle configuration or in an equally spaced collinear configuration. The results can be applied to construct potential energy surfaces for three helium atom systems.

2

Indian Academy of Sciences (India)

N-(3-chloro-2-methyl-4,6-dinitrophenyl)pyridin-2-amine (3a). Yield 80%. Orange solid. Mp: 111−113 oC; 1H NMR (300 MHz, CDCl3): δ (ppm) 8.94 (bs, 1H, NH), 8.60 (s, 1H, Ph-H), 8.19-8.22 (m, 1H, pyridin-6-H), 7.65-7.71 (m, 1H, pyridin-4-H), 6.96−7.00 (m, 1H, pyridin-5-H), 6.90 (d, 1H, J=9.0 Hz, pyridin-3-H), 2.26 (s, 3H, ...

Lepton mixing from Δ(3n2 and Δ(6n2 and CP

Directory of Open Access Journals (Sweden)

Claudia Hagedorn

2015-02-01

Full Text Available We perform a detailed study of lepton mixing patterns arising from a scenario with three Majorana neutrinos in which a discrete flavor group Gf=Δ(3n2 or Gf=Δ(6n2 and a CP symmetry are broken to residual symmetries Ge=Z3 and Gν=Z2×CP in the charged lepton and neutrino sectors, respectively. While we consider all possible Z3 and Z2 generating elements, we focus on a certain set of CP transformations. The resulting lepton mixing depends on group theoretical indices and one continuous parameter. In order to study the mixing patterns comprehensively for all admitted Ge and Gν, it is sufficient to discuss only three types of combinations. One of them requires as flavor group Δ(6n2. Two types of combinations lead to mixing patterns with a trimaximal column, while the third one allows for a much richer structure. For the first type of combinations the Dirac phase as well as one of the Majorana phases are trivial, whereas the other two types of combinations predict in general all CP phases to be non-trivial and also non-maximal. Already for small values of the index n of the group, n≤11, experimental data on lepton mixing can be accommodated well for particular choices of the parameters of the theory. We also comment on the relation of the used CP transformations to the automorphisms of Δ(3n2 and Δ(6n2.

Synthesis and crystal structures of two α-bromoamides, (2'R,1S,2S)-N(2-bromopropanoyl)-2-amino-1-phenylpropane-1,3-diol and (2'S,5S,6S)-N(2-bromopropanoyl)-5-amino-6-phenyl-2-oxo-1,3,2-dioxathiane

International Nuclear Information System (INIS)

English, R.B.; Liddell, R.J.; Whiteley, C.G.

1987-01-01

One pair of diastereomeric bromoamides, (2'R,1S,2S)- and (2'S,1S,2S)-N(2-bromopropanoyl)-2-amino-1-phenylpropane-1,3-diol have been synthesized from ethyl 2-bromopropionate and an optically active amino-diol. The crystal structures of both were determined from single-crystal X-ray analyses. Both compounds are orthorhombic with space group P2 1 2 1 2 1 with Z = 4 in a unit cell of dimensions a 22,124(5),b 12,812(5), and c 4,886(5)A and a 15,510(5), b 9,707(5), and c 9,457(5)A. The proton chemical shifts of the groups attached to the asymmetric centre C(2'), and consequently, the identification of the configuration of the molecules, were resolved with the help of high-resolution nuclear magnetic resonance

Different molecular conformations co-exist in each of three 2-aryl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamides: hydrogen bonding in zero, one and two dimensions.

Science.gov (United States)

Narayana, Badiadka; Yathirajan, Hemmige S; Rathore, Ravindranath S; Glidewell, Christopher

2016-09-01

4-Antipyrine [4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one] and its derivatives exhibit a range of biological activities, including analgesic, antibacterial and anti-inflammatory, and new examples are always of potential interest and value. 2-(4-Chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, C19H18ClN3O2, (I), crystallizes with Z' = 2 in the space group P\\overline{1}, whereas its positional isomer 2-(2-chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, (II), crystallizes with Z' = 1 in the space group C2/c; the molecules of (II) are disordered over two sets of atomic sites having occupancies of 0.6020 (18) and 0.3980 (18). The two independent molecules of (I) adopt different molecular conformations, as do the two disorder components in (II), where the 2-chlorophenyl substituents adopt different orientations. The molecules of (I) are linked by a combination of N-H...O and C-H...O hydrogen bonds to form centrosymmetric four-molecule aggregates, while those of (II) are linked by the same types of hydrogen bonds forming sheets. The related compound N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-(3-methoxyphenyl)acetamide, C20H21N3O3, (III), is isomorphous with (I) but not strictly isostructural; again the two independent molecules adopt different molecular conformations, and the molecules are linked by N-H...O and C-H...O hydrogen bonds to form ribbons. Comparisons are made with some related structures, indicating that a hydrogen-bonded R2(2)(10) ring is the common structural motif.

Poly[diaquadi-μ-hydroxido-κ4O:O-dinitrato-κ4O:O′-bis[3-(pyridin-4-yl-κN-5-(pyridin-3-yl-1,2,4-oxadiazole]dicopper(II

Directory of Open Access Journals (Sweden)

Longfei Wu

2012-04-01

Full Text Available The title compound, [Cu2(NO32(OH2(C12H8N4O2(H2O2]n, consists of a neutral polymeric CuII complex in which each CuII atom has a distorted octahedral geometry defined by a pyridyl N atom from a 3-(pyridin-3-yl-5-(pyridin-4-yl-1,2,4-oxadiazole ligand and five O atoms from a water molecule, two nitrates and two hydroxides. Two CuII ions are bridged by two hydroxide anions resulting in a Cu2O2 loop, located across an inversion center and connected by the nitrate anions into a broad two-dimensional polymeric structure parallel to (100. In the crystal, there are O—H...O hydrogen bonds between the coodinated water molecule and the nitrate and hydroxide, and between the hydroxide and the nitrate. Intermolecular π–π interactions are present between pyridine rings in adjacent two-dimensional structures, with a centroid–centroid distance of 3.582 (2 Å.

Magnetic and Photo-Physical Properties of Lanthanide Dinuclear Complexes Involving the 4,5-Bis(2-Pyridyl-N-Oxidemethylthio-4′,5′-Dicarboxylic Acid-Tetrathiafulvalene-, Dimethyl Ester Ligand

Directory of Open Access Journals (Sweden)

Fabrice Pointillart

2015-12-01

Full Text Available The reaction between the 4,5-bis(2-pyridyl-N-oxidemethylthio-4′,5′-dicarboxylic acid-tetrathiafulvalene-, dimethyl ester ligand (L and the metallo-precursors Ln(hfac3·2H2O leads to the formation of two dinuclear complexes of formula [Ln2(hfac6(L]·(CH2Cl2·(C6H140.5 (LnIII = DyIII (1 and YbIII (2. The X-ray structure reveals a quite regular square anti-prism symmetry for the coordination sphere of the lanthanide ion. UV-visible absorption properties have been experimentally measured and rationalized by TD-DFT calculations. The functionalization of the tetrathiafulvalene (TTF core by two methyl ester moieties induces the appearance of an additional absorption band in the lowest-energy region of the spectrum. The latter has been identified as a HOMO (Highest Occupied Molecular Orbital→LUMO (Lowest Unoccupied Molecular Orbital Intra-Ligand Charge Transfer (ILCT transition in which the HOMO and LUMO are centred on the TTF and methyl ester groups, respectively. Irradiation at 22,222 cm−1 of this ILCT band induces an efficient sensitization of the YbIII-centred emission that can be correlated to the magnetic properties.

Synthetic, XRD, non-covalent interactions and solvent dependent nonlinear optical studies of Sulfadiazine-Ortho-Vanillin Schiff base: (E)-4-((2-hydroxy-3-methoxy- benzylidene) amino)-N-(pyrimidin-2-yl)benzene-sulfonamide

Science.gov (United States)

Shahid, Muhammad; Salim, Muhammad; Khalid, Muhammad; Tahir, Muhammad Nawaz; Khan, Muhammad Usman; Braga, Ataualpa Albert Carmo

2018-06-01

In this study, Sulfadiazine-Ortho-Vanillin Schiff base namely (E)-4-((2-hydroxy-3-methoxybenzylidene)amino)sbnd N-(pyrimidin-2-yl)benzene-sulfonamide (BS) was synthesized. Chemical characterization and computational studies using different techniques like XRD, FT-IR, UV-Vis, NBO, FMO, and MEP have been employed. Density functional theory (DFT) calculations have been performed at M06-2X/6-311 + G(d,p) level of theory to obtain optimized geometry and vibrational wave numbers for (E)-4-((2-hydroxy-3-methoxybenzylidene)amino)sbnd N-(pyrimidin-2-yl)benzene-sulfonamide (BS). The DFT optimized geometry supports the experimental XRD parameters. Frontier molecular orbital (FMO) energies and molecular electrostatic potential (MEP) surfaces have been executed at M06-2X/6-311 + G(d,p) level of theory. NBO analysis has been carried out at M06-2X/6-311 + G(d,p) level which not only discovered the hyper conjugative interactions and stability in title molecule but also reconfirmed the existence of Nsbnd H⋯N hydrogen bonds between the dimer. The findings of small EHOMO-ELUMO gap shows less hardness and larger softness values which suggested the bioactiveness of the title molecule. Finally, the effect of solvent on nonlinear optical (NLO) properties has been executed using M06-2X level of theory and 6-311 + G (d,p) basis set. The solvent polarity enhanced the NLO response from 3.62 × 10-30 esu to 4.66 × 10-30 esu indicating the considerable NLO character hence in general may have potential applications in the development of non-linear optical materials.

Efficient one-pot, four-component synthesis of N,N-dibenzyl-N-{1-[5-(3-aryl-1,3,4-oxadiazol-2-yl]cyclobutyl}amine derivatives from the reaction of (isocyanoiminotriphenylphosphorane, dibenzylamine, an aromatic carboxylic acid and cyclobutanone

Directory of Open Access Journals (Sweden)

Shajari Nahid

2012-01-01

Full Text Available Four-component reaction of cyclobutanone, dibenzylamine and (Nisocyanimino triphenylphosphorane in the presence of aromatic carboxylic acids proceed smoothly at room temperature and under neutral conditions to afford N,N-dibenzyl-N-{1-[5-(3-aryl-1,3,4-oxadiazol-2-yl]cyclobutyl}amine derivatives in high yields.

SYNTHESIS OF NEW TWO DERIVATIVES OF 6-MERCAPTOPURINE (6MP) 6-[5-PYRIDINE-4-YL- 1, 2, 3, 4-OXADIAZOLE-2-YL)DITHIOL]-9H-PURINE (38) AND 9H-PURINE-6-YL-BENYLDITHIOCARBAMATE (45) WITH CYTOTOXICITY RESULTS FROM THE NATIONAL CANCER INSTITUTE'S ANTICANCER DRUG SCREEN

OpenAIRE

Mohammed Hassan Mohammed et al

2012-01-01

6-[(5-pyridine-yl-1, 2, 3, 4-oxadiazole-2-yl)dithiol]-9H-purine (38) and 9H-purine-6yl-benzyldithiocarbamate (45) are synthesized as possible prodrugs for 6-mercaptopurine(6-MP). The generation of the compounds 38, 42, 45 and 48 were accomplished following multistep reaction procedures. The reaction and purity of the products were checked by TLC, the structure of the final compounds and their intermediates were confirmed by their melting points, infra red spectroscopy and whether differences ...

Synthesis, spectroscopic and electrochemical properties of mononuclear and dinuclear bis(bipy)ruthenium(II) complexes containing dimethoxyphenyl(pyridin-2-yl)-1,2,4-triazole ligands

NARCIS (Netherlands)

Passaniti, Paolo; Browne, Wesley R.; Lynch, Fiona C.; Hughes, Donal; Nieuwenhuyzen, Mark; James, Paraic; Maestri, Mauro; Vos, Johannes G.

2002-01-01

The ligands HL1 and H(2)L2 and the complexes [Ru(bipy)(2)L1]PF6.2H(2)O 1, [(Ru(bipy)(2))(2)L2](PF6)(2).7H(2)O 2, {where HL1 = 3-(2', 5'-dimethoxyphenyl)-5-(pyridin-2"-yl)- 1H-1,2,4-triazole, H(2)L2 = 1,4- bis(5'-(pyridin-2"-yl)- 1'H- 1', 2', 4'-triazol-3'-yl)- 2,5-dimethoxybenzene and bipy =

N-(2,6-Dimethyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl-2-hydroxy-2,2-diphenylacetamide

Directory of Open Access Journals (Sweden)

Eser Ihan

2008-10-01

Full Text Available In the title compound, C24H28N2O3S, the pendant methyl C atom bonded to the cyclohexane ring is disordered over two sites in a 0.580 (11:0.420 (11 ratio. The cyclohexane ring adopts a distorted chair conformation while the thiazolidine ring has an envelope conformation. The two phenyl rings make a dihedral angle of 71.8 (2° with each other. The conformation is stabilized by an intramolecular N—H...O hydrogen bond. In the crystal structure, an intermolecular hydrogen bond O—H...O occurs.

First principles prediction of the magnetic properties of Fe-X6 (X = S, C, N, O, F) doped monolayer MoS2

KAUST Repository

Feng, Nan; Mi, Wenbo; Cheng, Yingchun; Guo, Zaibing; Schwingenschlö gl, Udo; Bai, Haili

2014-01-01

Using first-principles calculations, we have investigated the electronic structure and magnetic properties of Fe-X 6 clusters (X = S, C, N, O, and F) incorporated in 4 4 monolayer MoS 2, where a Mo atom is substituted by Fe and its nearest S atoms are substituted by C, N, O, and F. Single Fe and Fe-F 6 substituions make the system display half-metallic properties, Fe-C 6 and Fe-N 6 substitutions lead to a spin gapless semiconducting behavior, and Fe-O 6 doped monolayer MoS 2 is semiconducting. Magnetic moments of 1.93, 1.45, 3.18, 2.08, and 2.21...? B are obtained for X = S, C, N, O, and F, respectively. The different electronic and magnetic characters originate from hybridization between the X and Fe/Mo atoms. Our results suggest that cluster doping can be an efficient strategy for exploring two-dimensional diluted magnetic semiconductors.

First principles prediction of the magnetic properties of Fe-X6 (X = S, C, N, O, F) doped monolayer MoS2

KAUST Repository

Feng, Nan

2014-02-05

Using first-principles calculations, we have investigated the electronic structure and magnetic properties of Fe-X 6 clusters (X = S, C, N, O, and F) incorporated in 4 4 monolayer MoS 2, where a Mo atom is substituted by Fe and its nearest S atoms are substituted by C, N, O, and F. Single Fe and Fe-F 6 substituions make the system display half-metallic properties, Fe-C 6 and Fe-N 6 substitutions lead to a spin gapless semiconducting behavior, and Fe-O 6 doped monolayer MoS 2 is semiconducting. Magnetic moments of 1.93, 1.45, 3.18, 2.08, and 2.21...? B are obtained for X = S, C, N, O, and F, respectively. The different electronic and magnetic characters originate from hybridization between the X and Fe/Mo atoms. Our results suggest that cluster doping can be an efficient strategy for exploring two-dimensional diluted magnetic semiconductors.

Comportamiento Mecánico Estático de los Instrumentos S1, S2, F1 de Protaper Universal® Bajo Torsión y Doblamiento. Análisis por Elementos Finitos

Directory of Open Access Journals (Sweden)

Luisa Fernanda Cartagena

2011-10-01

Full Text Available Propósito: Examinar el comportamiento mecánico estático de los instrumentos ProTaper Universal® S1, S2, F1 bajo torsión y doblamiento teniendo en cuenta las propiedades mecánicas del material, mediante el método de elementos finitos. Metodología: Estudio Observacional descriptivo. Las limas investigadas fueron S1, S2, F1 de ProTaper Universal®, modeladas con el software ANSYS 10 y sometidas a fuerzas de torsión empezando en 0.25N/cm hasta alcanzar el torque máximo recomendado por la casa comercial Maillefer® y doblamiento en un ángulo de 600. Resultados:El máximo esfuerzo ocurre en el núcleo de la sección para todos los instrumentos evaluados;  al incrementar el torque el  esfuerzo  se disipa a la periferia para S1 (D5, D10, D14, S2 (D5, D7, D8, D10, F1 (D2, D3, D5.  La lima S1 al ser sometida a  torsión en D0 y D5 independiente del torque que fuese aplicado el máximo de esfuerzo superaba el límite de deformación plástica en el núcleo de la sección  del instrumento. La lima S2 con torques de  1 ó 1,5 N/cm superó  el límite elástico del material. Lima F1 en D0, D2 con torques de  0.25, 0.5, 1, 1.5, 2 N/cm el esfuerzo máximo no supero el límite de deformación plástica. En la prueba de doblamiento la gran mayoría de la estructura de las limas S1, S2, F1, se encuentra  por debajo del esfuerzo de ruptura (línea neutral es bastante ancha.Conclusion: Las fuerzas de  torsión para todas la limas del estudio mostraron tener mayor riesgo de separación del instrumento en comparación con  las fuerzas de doblamiento. 

Di-?-cyanido-tetra?cyanido(5,5,7,12,12,14-hexa?methyl-1,4,8,11-tetra?aza?cyclo?tetra?decane)[N-(quinolin-8-yl)quinoline-2-carboxamidato]diiron(III)nickel(II) 2.07-hydrate

OpenAIRE

Yang, Yuqi; Zhou, Hongbo; Shen, Xiaoping

2013-01-01

The asymmetric unit of the title complex, [Fe2Ni(C19H12N3O)2(CN)6(C16H36N4)]?2.07H2O, contains one [Fe(qcq)(CN)3]? anion, half a [Ni(teta)]2+ cation and two partially occupied inter?stitial water mol?ecules [qcq? is the N-(quinolin-8-yl)quinoline-2-carboxamidate anion and teta is 5,5,7,12,12,14-hexa?methyl-1,4,8,11-tetra?aza?cyclo?tetra?deca?ne]. In the complex mol?ecule, two [Fe(qcq)(CN)3]? anions additionally coordinate the central [Ni(teta)]2+ cation through cyanide groups in a trans mode,...

(Tris{2-[(5-hydroxypyridin-2-yl-κNmethylideneimino-κN]ethyl}aminezinc dinitrate

Directory of Open Access Journals (Sweden)

Maksym Seredyuk

2011-12-01

Full Text Available In the complex cation of the title compound, [Zn(C24H27N7O3](NO32, the tripodal tris{[2-(5-hydroxypyridin-2-ylmethylideneimino]ethyl}amine ligand is coordinated to the Zn atom through the three pyridine and three imino N atoms. The coordination sphere of the Zn atom is based on an octahedron with a significant distortion towards trigonal prismatic, the twist angle being 45.58 (9°. The crystal packing is formed by L and D antipodes arranged in layers disposed parallel to the b axis. Strong O—H...O hydrogen bonding exists between the hydroxy groups of the ligand and the nitrate anion.

In silico binding affinity studies of N-9 substituted 6-(4-(4-propoxyphenylpiperazin-1-yl-9H-purine derivatives-Target for P70-S6K1 & PI3K-δ kinases

Directory of Open Access Journals (Sweden)

Manjunath G. Sunagar

2018-03-01

Full Text Available P70-S6K1 & PI3K-δ kinases are identified to be involved in many physiological processes associated with cancer, therefore many of the inhibitors being designed to target these kinases are in clinical trials. In the current study we have exploited the N-9 substituted 6-(4-(4-propoxyphenyl piperazin-1-yl-9H-purine derivatives for their inhibitory properties with the above kinases. We have used an in silico docking study with seventeen purine derivatives for their binding affinity calculations. The binding affinities of these small molecules with P70-S6K1 & PI3K-δ were performed using AutoDock Vina. Among all the compounds, PP16 showed highest binding affinity of −14.7 kcal/mol with P70-S6K1 kinase & −17.2 kcal/mol with PI3K-δ kinases as compared to the molecules under clinical trials (PF-4708671 & IC-87114. Docking studies revealed that N-9 coumarine substituted purine derivative could be one of the potential ligands for the inhibition of P70-S6K1 & PI3K-δ kinases. Hence, this compound can be further investigated by in vitro and in vivo experiments for further validation.

Fragrance material review on 1-(2,6,6-trimethyl-2-cyclohexen-1-yl)pent-1-en-3-one.

Science.gov (United States)

Scognamiglio, J; Letizia, C S; Api, A M

2013-12-01

A toxicologic and dermatologic review of 1-(2,6,6-trimethyl-2-cyclohexen-1-yl)pent-1-en-3-one when used as a fragrance ingredient is presented. 1-(2,6,6-Trimethyl-2-cyclohexen-1-yl)pent-1-en-3-one is a member of the fragrance structural group Alkyl Cyclic Ketones. These fragrances can be described as being composed of an alkyl, R1, and various substituted and bicyclic saturated or unsaturated cyclic hydrocarbons, R2, in which one of the rings may include up to 12 carbons. Alternatively, R2 may be a carbon bridge of C2-C4 carbon chain length between the ketone and cyclic hydrocarbon. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 1-(2,6,6-trimethyl-2-cyclohexen-1-yl)pent-1-en-3-one were evaluated then summarized and includes physical properties data. A safety assessment of the entire Alkyl Cyclic Ketones will be published simultaneously with this document; please refer to Belsito et al. (Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2013. A Toxicologic and Dermatologic Assessment of Alkyl Cyclic Ketones when used as fragrance ingredients. Submitted for publication) for an overall assessment of the safe use of this material and all Alkyl Cyclic Ketones in fragrances. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bis(2,2'-bipyridyl-κN,N')(carbonato-κO,O')cobalt(III) bromide trihydrate.

Science.gov (United States)

Ma, Peng-Tao; Wang, Yu-Xia; Zhang, Guo-Qian; Li, Ming-Xue

2007-12-06

The title complex, [Co(CO(3))(C(10)H(8)N(2))(2)]Br·3H(2)O, is isostructural with the chloride analogue. The six-coordinated octahedral [Co(2,2'-bipy)(2)CO(3)](+) cation (2,2'-bipy is 2,2'-bipyrid-yl), bromide ion and water mol-ecules are linked together via O-H⋯Br and O-H⋯O hydrogen bonds, generating a one-dimensional chain.

Biodegradation of buprofezin by Rhodococcus sp. strain YL-1 isolated from rice field soil.

Science.gov (United States)

Li, Chao; Zhang, Ji; Wu, Zhi-Guo; Cao, Li; Yan, Xin; Li, Shun-Peng

2012-03-14

A buprofezin-degrading bacterium, YL-1, was isolated from rice field soil. YL-1 was identified as Rhodococcus sp. on the basis of the comparative analysis of 16S rDNA sequences. The strain could use buprofezin as the sole source of carbon and nitrogen for growth and was able to degrade 92.4% of 50 mg L(-1) buprofezin within 48 h in liquid culture. During the degradation of buprofezin, four possible metabolites, 2-tert-butylimino-3-isopropyl-1,3,5-thiadiazinan-4-one, N-tert-butyl-thioformimidic acid formylaminomethyl ester, 2-isothiocyanato-2-methyl-propane, and 2-isothiocyanato-propane, were identified using gas chromatography-mass spectrometry (GC-MS) analysis. The catechol 2,3-dioxygenase activity was strongly induced during the degradation of buprofezin. A novel microbial biodegradation pathway for buprofezin was proposed on the basis of these metabolites. The inoculation of soils treated with buprofezin with strain YL-1 resulted in a higher degradation rate than that observed in noninoculated soils, indicating that strain YL-1 has the potential to be used in the bioremediation of buprofezin-contaminated environments.

Detection of N-(1-deoxy-d-fructos-1-yl) Fumonisins B2 and B3 in Corn by High-Resolution LC-Orbitrap MS

Science.gov (United States)

Matsuo, Yosuke; Takahara, Kentaro; Sago, Yuki; Kushiro, Masayo; Nagashima, Hitoshi; Nakagawa, Hiroyuki

2015-01-01

The existence of glucose conjugates of fumonisin B2 (FB2) and fumonisin B3 (FB3) in corn powder was confirmed for the first time. These “bound-fumonisins” (FB2 and FB3 bound to glucose) were identified as N-(1-deoxy-d-fructos-1-yl) fumonisin B2 (NDfrc-FB2) and N-(1-deoxy-d-fructos-1-yl) fumonisin B3 (NDfrc-FB3) respectively, based on the accurate mass measurements of characteristic ions and fragmentation patterns using high-resolution liquid chromatography-Orbitrap mass spectrometry (LC-Orbitrap MS) analysis. Treatment on NDfrc-FB2 and NDfrc-FB3 with the o-phthalaldehyde (OPA) reagent also supported that d-glucose binding to FB2 and FB3 molecules occurred to their primary amine residues. PMID:26389955

Homopolymerization of Ethylene, 1-Hexene, Styrene and Copolymerization of Styrene With 1,3-Cyclohexadiene Using (h5-Tetramethylcyclopentadienyldimethylsilyl(N-Ar’amido-TiCl2/MAO (Ar’=6-(2-(Diethylborylphenylpyrid-2-yl, Biphen-3-yl

Directory of Open Access Journals (Sweden)

Michael R. Buchmeiser

2011-01-01

Full Text Available The propensity of a half-sandwich (η5-tetramethylcyclopentadienyl dimethylsilylamido TiIV-based catalyst bearing an auxiliary diethylboryl-protected pyridyl moiety (Ti-8, activated by methylaluminoxane (MAO to homopolymerize α-olefins such as ethylene, 1-hexene and styrene as well as to copolymerize styrene with 1,3-cyclo-hexadiene is described. The reactivity of Ti-8 was investigated in comparison to a 6-(2-(diethylborylphenylpyrid-2-yl-free analogue (Ti-3.

Bis[1-methoxy-2,2,2-tris(pyrazol-1-yl-κN2ethane]nickel(II bis(trifluoromethanesulfonate dihydrate

Directory of Open Access Journals (Sweden)

Ganna Lyubartseva

2013-10-01

Full Text Available In the title salt, [Ni(C12H14N6O2](CF3SO32·2H2O, the NiII cation is located on an inversion centre and is coordinated by six N atoms from two tridentate 1-methoxy-2,2,2-tris(pyrazol-1-ylethane ligands in a distorted octahedral geometry. The Ni—N distances range from 2.0594 (12 to 2.0664 (12 Å, intra-ligand N—Ni—N angles range from 84.59 (5 to 86.06 (5°, and adjacent inter-ligand N—Ni—N angles range between 93.94 (5 and 95.41 (5°. In the crystal, inversion-related pyrazole rings are π–π stacked, with an interplanar spacing of 3.4494 (18 Å, forming chains that propagate parallel to the a-axis direction. Intermolecular O—H...O hydrogen bonds are present between water molecules and trifluoromethanesulfonate anions.

N6-Benzyladenosine Derivatives as Novel N-Donor Ligands of Platinum(II Dichlorido Complexes

Directory of Open Access Journals (Sweden)

Ján Vančo

2013-06-01

Full Text Available The platinum(II complexes trans-[PtCl2(Ln2]∙xSolv 1–13 (Solv = H2O or CH3OH, involving N6-benzyladenosine-based N-donor ligands, were synthesized; Ln stands for N6-(2-methoxybenzyladenosine (L1, involved in complex 1, N6-(4-methoxy-benzyladenosine (L2, 2, N6-(2-chlorobenzyladenosine (L3, 3, N6-(4-chlorobenzyl-adenosine (L4, 4, N6-(2-hydroxybenzyladenosine (L5, 5, N6-(3-hydroxybenzyl-adenosine (L6, 6, N6-(2-hydroxy-3-methoxybenzyladenosine (L7, 7, N6-(4-fluoro-benzyladenosine (L8, 8, N6-(4-methylbenzyladenosine (L9, 9, 2-chloro-N6-(3-hydroxy-benzyladenosine (L10, 10, 2-chloro-N6-(4-hydroxybenzyladenosine (L11, 11, 2-chloro-N6-(2-hydroxy-3-methoxybenzyladenosine (L12, 12 and 2-chloro-N6-(2-hydroxy-5-methylbenzyladenosine (L13, 13. The compounds were characterized by elemental analysis, mass spectrometry, IR and multinuclear (1H-, 13C-, 195Pt- and 15N- and two-dimensional NMR spectroscopy, which proved the N7-coordination mode of the appropriate N6-benzyladenosine derivative and trans-geometry of the title complexes. The complexes 1–13 were found to be non-toxic in vitro against two selected human cancer cell lines (HOS and MCF7; with IC50 > 50.0 µM. However, they were found (by ESI-MS study to be able to interact with the physiological levels of the sulfur-containing biogenic biomolecule L-methionine by a relatively simple 1:1 exchange mechanism (one Ln molecule was replaced by one L-methionine molecule, thus forming a mixed-nitrogen/sulfur-ligand dichlorido-platinum(II coordination species.

Copper-Catalyzed N-Arylation of Amides Using (S-N-Methylpyrrolidine-2-carboxylate as the Ligand

Directory of Open Access Journals (Sweden)

Dong-Sheng Ma

2010-03-01

Full Text Available (S-N-methylpyrrolidine-2-carboxylate, a derivative of natural L-proline, was found to be an efficient ligand for the copper-catalyzed Goldberg-type N-arylation of amides with aryl halides under mild conditions. A variety of N-arylamides were synthesized in good to high yields.

Novel synthesis and antitumor evaluation of polyfunctionally substituted heterocyclic compounds derived from 2-cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide.

Science.gov (United States)

Shams, Hoda Z; Mohareb, Rafat M; Helal, Maher H; Mahmoud, Amira E

2010-12-27

The reaction of 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene with ethyl cyanoacetate gave 2-cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide. The latter was used to synthesize different heterocyclic derivatives comprising thiophene, thiazole, pyrazole, pyridine, pyrimidine, and coumarin rings. The mechanistic and synthetic pathways depended on regioselective attack and/or cyclization by the cyanoacetamido moiety in the key precursor on various chemical reagents. The competition of the reaction pathways including dipolar cyclization, dinucleophilic-bielectrophilic attack, β-attack, Gewald-type attack, and condensation reactions led to the diversity of the synthesized products. The antitumor activities of the synthesized products were studied and evaluated. Most of the compounds revealed high inhibitory effects when screened in vitro for their antiproliferative activity. Three human cancer cell lines, namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) were used in the screening tests. The simplicity of the synthetic procedures which mainly involved one-pot reactions under mild reaction conditions, the convenience of yield production and the diversity of the reactive sites in the produced systems play a valuable role for further heterocyclic transformations and further biological investigations.

Composición Esterólica de la Esponja Marina Xestospongia Muta

Directory of Open Access Journals (Sweden)

Carmenza Duque

2009-10-01

Full Text Available De la esponja marina Xestospongia muta recolectada en la bahía de Santa Marta, Caribe Colombiano, se aislaron por Cromatografía en Columna (CC sobre Silica gel, eluyendo con Benceno: Acetato de Etilo 10:2, dos fracciones esteróiicas; XMl (Rf = 0,28,Si02/Benceno; AcOEt 10:2 y XM2 (Rf = 0,24,SiO2/Benceno : AcOEt 10:2, Los esteróles presentes en estas dos fracciones fueron sometidos a Cromatografía Liquida de Alta Eficiencia (CLAE preparativa y analizados por Cromatografía de Gases (CG y Cromatografía de Gases acoplada en Espectometrla de Masas (CG-EM, Catorce esteróles fueron separados y 13 idenficados. La mayoría de ellos fueron 3n-0H-A^-Esteróles (Aproximadamente el 87% de los esteróles totales incluyendo al (24R + 24S-5,28-Estigmastadien-3i3-24-diol, mezclaepimérica por primera vez asi reportada en la naturaleza. El porcentaje restante correspondió a Estañóles y a un 6,2% de compuestos sin identificar.

Molybdenum-95 nuclear magnetic resonance of a series of phosphine and phosphite substituted molybdenum carbonyls Mo(CO)sub(6-n)Lsub(n)(n = 1,2,3,4,5)

International Nuclear Information System (INIS)

Jaitner, P.; Wohlgenannt, W.

1982-01-01

Molybdenum-95 NMR spectra of a series of phosphine and phosphite substituted molybdenum carbonyls Mo(CO)sub(6-n)Lsub(n)n[L = P(OCH 3 ) 3 n = 1,2,3,4,5, L = P(OC 2 H 5 ) 3 n = 1,2,3, L = P(C 6 H 5 ) 3 n = 1] including isomers (cis, trans, fac, mer) are reported. A large range of chemical shifts is found for the title compounds. The coupling constants 1 J( 95 Mo- 31 P) are derived either from 95 Mo-NMR spectra or 31 P-NMR spectra. Syntheses of the measured compounds were performed by thermal or photochemical ligand sustitution. (Author)

Tetraethylammonium tris(thiocyanato-κN[tris(1H-pyrazol-1-yl-κN2methane]nickelate(II

Directory of Open Access Journals (Sweden)

Ganna Lyubartseva

2012-07-01

Full Text Available The title salt, (C8H20N[Ni(NCS3(C10H10N6], consists of a tetraethylammonium cation and an anion comprising an octahedral NiII atom surrounded by three N atoms from a tripodal tris(pyrazol-1-ylmethane ligand, and three thiocyanate ligands, each bound at the N-atom end. The ligand Ni—N distances range from 2.097 (2 to 2.127 (2 Å for the tripodal ligand and from 2.045 (2 to 2.075 (2 Å for the thiocyanate ligands. The dihedral angles between the three pyrazole rings are 59.03 (12, 53.09 (10 and 67.90 (10°.

[KDy(Hptc3(H3ptc]n·2n(Hbipy·5n(H2O, a Layered Coordination Polymer Containing DyO6N3 Tri-Capped Trigonal Prisms (H3ptc = Pyridine 2,4,6-Tricarboxylic Acid, C8H5NO6; Bipy = 2,2'-Bipyridine, C10H8N2

Directory of Open Access Journals (Sweden)

Shoaib Anwar

2012-08-01

Full Text Available The synthesis, structure and properties of the bimetallic layered coordination polymer, [KDy(C8H3NO63(C8H5NO6]n·2n(C10H9N2·5n(H2O = [KDy(Hptc3(H3ptc]n·2n(Hbipy·5n(H2O, are described. The Dy3+ ion is coordinated by three O,N,O-tridentate doubly-deprotonated pyridine tri-carboxylate (Hptc ligands to generate a fairly regular DyO6N3 tri-capped trigonal prism, with the N atoms acting as the caps. The potassium ion is coordinated by an O,N,O-tridentate H3ptc molecule as well as monodentate and bidentate Hptc ligands to result in an irregular KNO9 coordination geometry. The ligands bridge the metal-atom nodes into a bimetallic, layered, coordination polymer, which extends as corrugated layers in the (010 plane, with the mono-protonated bipyridine cations and water molecules occupying the inter-layer regions: Unlike related structures, there are no dysprosium–water bonds. Many O–HLO and N–HLO hydrogen bonds consolidate the structure. Characterization and bioactivity data are described. Crystal data: C52H42DyKN8O29, Mr = 1444.54, triclinic,  (No. 2, Z = 2, a = 9.188(2 Å, b = 15.7332(17 Å, c = 19.1664(19 Å, α = 92.797(6°, β = 92.319(7°, γ = 91.273(9°, V = 2764.3(7 Å3, R(F = 0.029, wR(F2 = 0.084.

Thermodynamics of complexation of lanthanides with 2,6-bis(5,6-diethyl-1,2,4-triazin-3-yl) pyridine

Energy Technology Data Exchange (ETDEWEB)

Rawat, N.; Bhattacharyya, A.; Tomar, B.S. [Bhabha Atomic Research Centre, Trombay, Mumbai (India). Radiochemistry Div.; Ghosh, S.K.; Gadly, T. [Bhabha Atomic Research Centre, Trombay, Mumbai (India). Bioorganic Div.

2011-07-01

Solvent extraction studies on separation of trivalent actinides from lanthanides using 2,6-bis(5,6-dialkyl-1,2,4-triazin-3-yl) pyridines have shown promising results with respect to separation factor and efficiency in acidic medium. In order to understand their complexation behavior, the stability constant (log {beta}) of trivalent lanthanides (La, Nd, Eu, Tb, Ho, Tm, Lu) with 2,6-bis(5,6-diethyl-1,2,4-triazin-3-yl)pyridine (ethyl-BTP) have been determined in methanol medium (ionic strength 0.01 M) using spectrophotometric titrations. The stoichiometry of the complexes is found to vary with the ionic size of lanthanide ion. The variation in log {beta} across the lanthanide series is attributed to variation in solvation characteristics of the metal ion. Comparison of log {beta} for Ln(III)-ethyl-BTP complexes with other alkyl derivatives showed increase in the stability with increasing length of the alkyl group due to hydrophobic interaction. In the case of Eu(III), the speciation was also corroborated by time resolved fluorescence spectroscopy. The thermodynamic parameters ({delta} G, {delta} H, {delta} S) for complexation of Eu(III) with ethyl-BTP, were determined by microcalorimetry, which revealed strong metal ion-ligand interaction with the reactions driven mainly by enthalpy. (orig.)

Plasmatic levels of N-terminal pro-atrial natriuretic peptide in preeclamptic patients and healthy normotensive pregnant women.

Science.gov (United States)

Reyna-Villasmil, Eduardo; Mejia-Montilla, Jorly; Reyna-Villasmil, Nadia; Mayner-Tresol, Gabriel; Herrera-Moya, Pedro; Fernández-Ramírez, Andreina; Rondón-Tapía, Marta

2018-05-11

To compare plasma N-terminal pro-atrial natriuretic peptide concentrations in preeclamptic patients and healthy normotensive pregnant women. A cases-controls study was done with 180 patients at Hospital Central Dr. Urquinaona, Maracaibo, Venezuela, that included 90 preeclamptic patients (group A; cases) and 90 healthy normotensive pregnant women selected with the same age and body mass index similar to group A (group B; controls). Blood samples were collected one hour after admission and prior to administration of any medication in group A to determine plasma N-terminal pro-atrial natriuretic peptide and other laboratory parameters. Plasma N-terminal pro-atrial natriuretic peptide concentrations in group A (mean 1.01 [0.26] pg/mL) showed a significant difference when compared with patients in group B (mean 0.55 [0.07] pg/mL; P<.001]. There was no significant correlation with systolic and diastolic blood pressure values in preeclamptic patients (P=ns). A cut-off value of 0.66ng/mL had an area under the curve of 0.93, sensitivity of 87.8%, specificity of 83.3%, a positive predictive value of 84.0% and a negative predictive value of 87.2%, with a diagnostic accuracy of 85.6%. Preeclamptic patients have significantly higher concentrations of plasma N-terminal pro-atrial natriuretic peptide compared with healthy normotensive pregnant women, with high predictive values for diagnosis. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Synthesis and enzyme inhibitory studies of some new N-alkylated/aralkylated N-(4-ethoxyphenyl)-2,3-drobenzo-(1,4)-dioxin-6-sulfonamides

International Nuclear Information System (INIS)

Abbasi, M.A.; Islam, M.; Rehman, A.U.; Siddiqui, S.Z.

2016-01-01

The research endeavor was aimed to synthesize N-alkyl/aralkylated-N-(4-ethoxyphenyl)-2,3-dihydrobenzo-(1,4)-dioxine-6 sulfonamides and to evaluate their enzyme inhibitory potential. The target molecules were synthesized in two steps. The first step involved the reaction of 4-ethoxyaniline (1) with N-2,3-dihydrobenzo(1,4)-dioxin-6-sulfonyl chloride (2) under dynamic pH control maintained by 10% aqueous Na/sub 2/CO/sub 3/ to yield N-(4-ethoxyphenyl)-2,3-dihydrobenzo-(1,4)-dioxine-6-sulfonamide (3). In second step parent compound 3 was reacted with various alkyl/aralkyl halides (4a-l) in N,N'-dimethylformamide and catalytic amount of lithium hydride to accomplish some new N-alkyl/aralkylated-N-(4-ethoxyphenyl)-2,3-dihydrobenzo-(1,4)-dioxine-6 sulfonamides (5a-l). Probable structures of the synthesized compounds were characterized by contemporary spectral techniques i.e. IR, 1H-NMR and EIMS and were finally evaluated for enzyme inhibitory potential against a-glucosidase and urease. The synthesized compounds exhibited moderate to weak therapeutic potential throughout the series. (author)

Evaluation of the Effects of S-Allyl-L-cysteine, S-Methyl-L-cysteine, trans-S-1-Propenyl-L-cysteine, and Their N-Acetylated and S-Oxidized Metabolites on Human CYP Activities.

Science.gov (United States)

Amano, Hirotaka; Kazamori, Daichi; Itoh, Kenji

2016-01-01

Three major organosulfur compounds of aged garlic extract, S-allyl-L-cysteine (SAC), S-methyl-L-cysteine (SMC), and trans-S-1-propenyl-L-cysteine (S1PC), were examined for their effects on the activities of five major isoforms of human CYP enzymes: CYP1A2, 2C9, 2C19, 2D6, and 3A4. The metabolite formation from probe substrates for the CYP isoforms was examined in human liver microsomes in the presence of organosulfur compounds at 0.01-1 mM by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Allicin, a major component of garlic, inhibited CYP1A2 and CYP3A4 activity by 21-45% at 0.03 mM. In contrast, a CYP2C9-catalyzed reaction was enhanced by up to 1.9 times in the presence of allicin at 0.003-0.3 mM. SAC, SMC, and S1PC had no effect on the activities of the five isoforms, except that S1PC inhibited CYP3A4-catalyzed midazolam 1'-hydroxylation by 31% at 1 mM. The N-acetylated metabolites of the three compounds inhibited the activities of several isoforms to a varying degree at 1 mM. N-Acetyl-S-allyl-L-cysteine and N-acetyl-S-methyl-L-cysteine inhibited the reactions catalyzed by CYP2D6 and CYP1A2, by 19 and 26%, respectively, whereas trans-N-acetyl-S-1-propenyl-L-cysteine showed weak to moderate inhibition (19-49%) of CYP1A2, 2C19, 2D6, and 3A4 activities. On the other hand, both the N-acetylated and S-oxidized metabolites of SAC, SMC, and S1PC had little effect on the reactions catalyzed by the five isoforms. These results indicated that SAC, SMC, and S1PC have little potential to cause drug-drug interaction due to CYP inhibition or activation in vivo, as judged by their minimal effects (IC 50 >1 mM) on the activities of five major isoforms of human CYP in vitro.

Lactobacillus johnsonii N6.2 Modulates the Host Immune Responses: A Double-Blind, Randomized Trial in Healthy Adults

Directory of Open Access Journals (Sweden)

Guillermo E. Marcial

2017-06-01

Full Text Available Lactobacillus johnsonii N6.2 mitigates the onset of type 1 diabetes (T1D in biobreeding diabetes-prone rats, in part, through changes in kynurenine:tryptophan (K:T ratios. The goal of this pilot study was to determine the safety, tolerance, and general immunological response of L. johnsonii N6.2 in healthy subjects. A double-blind, randomized clinical trial in 42 healthy individuals with no known risk factors for T1D was undertaken to evaluate subject responses to the consumption of L. johnsonii N6.2. Participants received 1 capsule/day containing 108 colony-forming units of L. johnsonii N6.2 or placebo for 8 weeks. Comprehensive metabolic panel (CMP, leukocyte subpopulations by complete blood count (CBC and flow cytometry, serum cytokines, and relevant metabolites in the indoleamine-2,3-dioxygenase pathway were assessed. L. johnsonii N6.2 survival and intestinal microbiota was analyzed. Daily and weekly questionnaires were assessed for potential effects of probiotic treatment on general wellness. The administration of L. johnsonii N6.2 did not modify the CMP or CBC of participants suggesting general safety. In fact, L. johnsonii N6.2 administration significantly decreased the occurrence of abdominal pain, indigestion, and cephalic syndromes. As predicted, increased serum tryptophan levels increased resulting in a decreased K:T ratio was observed in the L. johnsonii N6.2 group. Interestingly, immunophenotyping assays revealed that monocytes and natural killer cell numbers were increased significantly after washout (12 weeks. Moreover, an increase of circulating effector Th1 cells (CD45RO+CD183+CD196− and cytotoxic CD8+ T cells subset was observed in the L. johnsonii N6.2 group. Consumption of L. johnsonii N6.2 is well tolerated in adult control subjects, demonstrates systemic impacts on innate and adaptive immune populations, and results in a decreased K:T ratio. These data provide support for the safety and feasibility of using L

Autocatalytic activity and substrate specificity of the pestivirus N-terminal protease N{sup pro}

Energy Technology Data Exchange (ETDEWEB)

Gottipati, Keerthi; Acholi, Sudheer [Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, TX 77555-0647 (United States); Ruggli, Nicolas [Institute of Virology and Immunology, CH-3147 Mittelhäusern (Switzerland); Choi, Kyung H., E-mail: kychoi@utmb.edu [Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, TX 77555-0647 (United States)

2014-03-15

Pestivirus N{sup pro} is the first protein translated in the viral polypeptide, and cleaves itself off co-translationally generating the N-terminus of the core protein. Once released, N{sup pro} blocks the host's interferon response by inducing degradation of interferon regulatory factor-3. N{sup pro'}s intracellular autocatalytic activity and lack of trans-activity have hampered in vitro cleavage studies to establish its substrate specificity and the roles of individual residues. We constructed N{sup pro}-GFP fusion proteins that carry the authentic cleavage site and determined the autoproteolytic activities of N{sup pro} proteins containing substitutions at the predicted catalytic sites Glu22 and Cys69, at Arg100 that forms a salt bridge with Glu22, and at the cleavage site Cys168. Contrary to previous reports, we show that N{sup pro'}s catalytic activity does not involve Glu22, which may instead be involved in protein stability. Furthermore, N{sup pro} does not have specificity for Cys168 at the cleavage site even though this residue is conserved throughout the pestivirus genus. - Highlights: • N{sup pro'}s autoproteolysis is studied using N{sup pro}-GFP fusion proteins. • N-terminal 17 amino acids are dispensable without loss of protease activity. • The putative catalytic residue Glu22 is not involved in protease catalysis. • No specificity for Cys168 at the cleavage site despite evolutionary conservation. • N{sup pro} prefers small amino acids with non-branched beta carbons at the P1 position.

Tunable regioselectivity in 1,3-butadiene polymerization by using 2,6-bis(dimethyl-2-oxazolin-2-yl)pyridine incorporated transition metal (Cr, Fe and Co) catalysts

KAUST Repository

Gong, Dirong; Liu, Wen; Pan, Weijing; Chen, Tao; Jia, Xiaoyu; Huang, Kuo-Wei; Zhang, Xuequan

2015-01-01

Tridentate complexes Cr(III)Cl3L, [L = 2,6-bis(dimethyl-2-oxazolin-2-yl) pyridine], Fe(III)Cl3L, Fe(II)Cl2L and Co(II)Cl2L have been prepared and fully characterized. The solid structures of Cr(III)Cl3L, Fe(III)Cl3L and Co(II)Cl2L have been revealed by single crystal X-ray diffraction, and the Cr(III)Cl3L and Fe(III)Cl3L complexes both exhibit a distorted octahedral geometry, while the Co(II)Cl2L complex has a trigonal bipyramidal conformation. Four complexes have been examined in regioselective polymerization of butadiene in combination with MAO in toluene at room temperature. The trans-1,4, cis-1,4 enchainment of resultant polybutadiene are controlled by the metal center. Activated by MAO, complex Cr(III)Cl3L produces high level of trans-1,4 selectivity (trans-1,4 up to 93.3%) with moderate polymer yield, complexes Fe(III)Cl3L and Fe(II)Cl2L both show equal cis-1,4 and trans-1,4 with minor 1,2 selectivity (<10%), and Co(II)Cl2L catalyst displays predominated cis-1,4 selectivity, which can be shifted to 1,2 selectivity by adding PPh3 as an additive. Thus, tuning of the cis-1,4, trans-1,4 and 1,2 selectivity in full range via central metal and additive chosen by these 2,6-bis(dimethyl-2-oxazolin-2-yl) pyridine supported catalysts has been achieved. © 2015 Elsevier B.V. All rights reserved.

Tunable regioselectivity in 1,3-butadiene polymerization by using 2,6-bis(dimethyl-2-oxazolin-2-yl)pyridine incorporated transition metal (Cr, Fe and Co) catalysts

KAUST Repository

Gong, Dirong

2015-05-21

Tridentate complexes Cr(III)Cl3L, [L = 2,6-bis(dimethyl-2-oxazolin-2-yl) pyridine], Fe(III)Cl3L, Fe(II)Cl2L and Co(II)Cl2L have been prepared and fully characterized. The solid structures of Cr(III)Cl3L, Fe(III)Cl3L and Co(II)Cl2L have been revealed by single crystal X-ray diffraction, and the Cr(III)Cl3L and Fe(III)Cl3L complexes both exhibit a distorted octahedral geometry, while the Co(II)Cl2L complex has a trigonal bipyramidal conformation. Four complexes have been examined in regioselective polymerization of butadiene in combination with MAO in toluene at room temperature. The trans-1,4, cis-1,4 enchainment of resultant polybutadiene are controlled by the metal center. Activated by MAO, complex Cr(III)Cl3L produces high level of trans-1,4 selectivity (trans-1,4 up to 93.3%) with moderate polymer yield, complexes Fe(III)Cl3L and Fe(II)Cl2L both show equal cis-1,4 and trans-1,4 with minor 1,2 selectivity (<10%), and Co(II)Cl2L catalyst displays predominated cis-1,4 selectivity, which can be shifted to 1,2 selectivity by adding PPh3 as an additive. Thus, tuning of the cis-1,4, trans-1,4 and 1,2 selectivity in full range via central metal and additive chosen by these 2,6-bis(dimethyl-2-oxazolin-2-yl) pyridine supported catalysts has been achieved. © 2015 Elsevier B.V. All rights reserved.

Synthesis, Characterization, and Cytotoxicity of a Novel Gold(III Complex with O,O′-Diethyl Ester of Ethylenediamine-N,N′-Di-2-(4-MethylPentanoic Acid

Directory of Open Access Journals (Sweden)

Nebojša Pantelić

2016-09-01

Full Text Available A novel gold(III complex, [AuCl2{(S,S-Et2eddl}]PF6, ((S,S-Et2eddl = O,O′-diethyl ester of ethylenediamine-N,N′-di-2-(4-methylpentanoic acid was synthesized and characterized by IR, 1D (1H and 13C, and 2D (H,H-COSY and H,H-NOESY NMR spectroscopy, mass spectrometry, and elemental analysis. Density functional theory calculations confirmed that (R,R-N,N′ diastereoisomer was energetically the most stable isomer. In vitro antitumor action of ligand precursor [(S,S-H2Et2eddl]Cl2 and corresponding gold(III complex was determined against tumor cell lines: human adenocarcinoma (HeLa, human colon carcinoma (LS174, human breast cancer (MCF7, non-small cell lung carcinoma cell line (A549, and non-cancerous cell line human embryonic lung fibroblast (MRC-5 using microculture tetrazolium test (MTT assay. The results indicate that both ligand precursor and gold(III complex have showed very good to moderate cytotoxic activity against all tested malignant cell lines. The highest activity was expressed by [AuCl2{(S,S-Et2eddl}]PF6 against the LS174 cells, with IC50 value of 7.4 ± 1.2 µM.

Targeting the D1-N-methyl-D-aspartate receptor complex reduces L-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned Parkinson’s rats

Directory of Open Access Journals (Sweden)

Song L

2016-02-01

Full Text Available Lu Song,1,* Zhanzhao Zhang,2,* Rongguo Hu,1 Jie Cheng,1 Lin Li,1 Qinyi Fan,1 Na Wu,1 Jing Gan,1 Mingzhu Zhou,1 Zhenguo Liu11Department of Neurology, Xinhua Hospital, 2Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: L-3,4-dihydroxyphenylalanine (L-dopa remains the most effective therapy for Parkinson’s disease (PD, but its long-term administration is associated with the development of debilitating motor complications known as L-dopa-induced dyskinesia (LID. Enhanced function of dopamine D1 receptor (D1R and N-methyl-d-aspartate receptor (NMDAR is believed to participate in the pathogenesis of LID. Given the existence of physical and functional interactions between D1R and NMDAR, we explored the effects of uncoupling D1R and NMDA GluN1 (GluN1 interaction on LID by using the Tat-conjugated interfering peptide (Tat-D1-t2. In this study, we demonstrated in 6-hydroxydopamine (6-OHDA-lesioned PD rat model that intrastriatal injection of Tat-D1-t2 alleviated dyskinetic behaviors and downregulated the phosphorylation of DARPP-32 at Thr34 induced by levodopa. Moreover, we also showed intrastriatal administration of Tat-D1-t2 elicited alterations in membranous GluN1 and D1R expression. These findings indicate that D1R/GluN1 complexes may be a molecular target with therapeutic potential for the treatment of dyskinesia in Parkinson’s patients.Keywords: 6-hydroxydopamine, Parkinson’s disease, dyskinesia, L-dopa, D1 receptor, NMDA, protein–protein interaction

N-Acetyl-D- and L-esters of 5'-AMP hydrolyze at different rates

Science.gov (United States)

Wickramasinghe, N. S.; Lacey, J. C. Jr; Lacey JC, J. r. (Principal Investigator)

1993-01-01

Studies of the properties of aminoacyl derivatives of 5'-AMP are aimed at understanding the origin of the process of protein synthesis. Aminoacyl (2',3') esters of 5'-AMP can serve as models of the 3'-terminus of aminoacyl tRNA. We report here on the relative rates of hydrolysis of Ac-D- and L-Phe AMP esters as a function of pH. At all pHs above 3, the rate constant of hydrolysis of the Ac-L-Phe ester is 1.7 to 2.1 times that of Ac-D-Phe ester. The D-isomer seems partially protected from hydrolysis by a stronger association with the adenine ring of the 5'-AMP.

Three PbII coordination polymers based on 2-(pyridin-2-yl)-1H-imidazole-4,5-dicarboxylic acid: Syntheses, crystal structures, and fluorescent properties

International Nuclear Information System (INIS)

Yu, Xiao-Yang; Xin, Rui; Gao, Wei-Ping; Wang, Na; Zhang, Xiao; Yang, Yan-Yan; Qu, Xiao-Shu

2013-01-01

Three lead coordination polymers, [PbCl(C 10 H 6 N 3 O 4 )(H 2 O)·H 2 O] n (1), [Pb(C 10 H 6 N 3 O 4 ) 2 (H 2 O)] n (2) and [Pb 3 (C 10 H 5 N 3 O 4 ) 3 ] n (3) (C 10 H 7 N 3 O 4 =2-(pyridin-2-yl)-1H-imidazole-4,5-dicarboxylic acid), have been hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction. In 1, Cl anions connected neighboring wave-like 2D layers, which are constructed with left- and right-handed helical chains, into a 3D network structure with a (6 3 )(6 5 ·8) topology. In 2, Pb cations are linked into a 3D 6 6 network with left- and right-handed helixes by μ 2 -bridging C 10 H 6 N 3 O 4 − ligands. In 3, C 10 H 5 N 3 O 4 2− ligands link Pb 6 O 12 clusters into a 3D (4 12 ·6 3 ) network. Their fluorescent properties were also investigated. - Graphical abstract: Three 3D lead compounds based on 2-(pyridin-2-yl)-1H-imidazole-4,5-dicarboxylic acid have been hydrothermally synthesized. Four new coordination modes of the organic ligand are first reported. Display Omitted - Highlights: • Three new Pb(II) complexes have been synthesized and characterized. • Left- and right-handed helical chains can be found in the 3D networks of 1 and 2. • Pb 6 O 12 clusters are connected into (4 12 ·6 3 ) network in 3

Morita-Baylis-Hillman Route to Dimethyl 2,3-Dihydrobenzo[b]oxepine-2,4- dicarboxylates and Methyl 2-(2-Carbomethoxybenzo[b]furan-3-yl)propanoates from Salicylaldehydes

International Nuclear Information System (INIS)

Ahn, Sang Hyun; Jang, Seung Soon; Kim, Young Keun; Lee, Kee Jung

2012-01-01

A new synthetic method for dimethyl 2,3-dihydrobenzo[b]oxepine-2,4-dicarboxylates and methyl 2-(2- carbomethoxybenzo[b]furan-3-yl)propanoates by an intramolecular conjugate displacement reaction or an S N 2 reaction of acetates of Morita-Baylis-Hillman adducts of methyl (2-formylphenoxy)acetates has been described

Poly[[{μ3-2-[4-(2-hydroxyethylpiperazin-1-yl]ethanesulfonato}silver(I] trihydrate

Directory of Open Access Journals (Sweden)

Stephanie M. Bilinovich

2011-09-01

Full Text Available Ethanesulfonic acid-based buffers like 2-[4-(2-hydroxyethylpiperazin-1-yl]ethanesulfonic acid (HEPES are commonly used in biological experiments because of their ability to act as non-coordinating ligands towards metal ions. However, recent work has shown that some of these buffers may in fact coordinate metal ions. The title complex, {[Ag(C8H17N2O4S]·3H2O}n, is a metal–organic framework formed from HEPES and a silver(I ion. In this polymeric complex, each Ag atom is primarily coordinated by two N atoms in a distorted linear geometry. Weaker secondary bonding interactions from the hydroxy and sulfate O atoms of HEPES complete a distorted seesaw geometry. The crystal structure is stabilized by O—H...O hydrogen-bonding interactions.

Quantification of the enzyme activities of iduronate-2-sulfatase, N-acetylgalactosamine-6-sulfatase and N-acetylgalactosamine-4-sulfatase using liquid chromatography-tandem mass spectrometry

Directory of Open Access Journals (Sweden)

Ryuichi Mashima

2018-03-01

Full Text Available Mucopolysaccharidosis (MPS is a genetic disorder characterized by the accumulation of glycosaminoglycans in the body. Of the multiple MPS disease subtypes, several are caused by defects in sulfatases. Specifically, a defect in iduronate-2-sulfatase (ID2S leads to MPS II, whereas N-acetylgalactosamine-6-sulfatase (GALN and N-acetylgalactosamine-4-sulfatase (ARSB defects relate to MPS IVA and MPS VI, respectively. A previous study reported a combined assay for these three disorders in a 96-well plate using a liquid chromatography-tandem mass spectrometry (LC-MS/MS-based technique (Kumar et al., Clin Chem 2015 61(11:1363-1371. In our study, we applied this methodology to a Japanese population to examine the assay precision and the separation of populations between disease-affected individuals and controls for these three disorders. Within our assay conditions, the coefficient of variation (CV, % values for an interday assay of ID2S, GALN, and ARSB were 9%, 18%, and 9%, respectively (n = 7. The average enzyme activities of ID2S, GALN, and ARSB in random neonates were 19.6 ± 5.8, 1.7 ± 0.7, and 13.4 ± 5.2 μmol/h/L (mean ± SD, n = 240, respectively. In contrast, the average enzyme activities of ID2S, GALN, and ARSB in disease-affected individuals were 0.5 ± 0.2 (n = 6, 0.3 ± 0.1 (n = 3, and 0.3 (n = 1 μmol/h/L, respectively. The representative analytical range values corresponding to ID2S, GALN, and ARSB were 39, 17, and 168, respectively. These results raise the possibility that the population of disease-affected individuals could be separated from that of healthy individuals using the LC-MS/MS-based technique.

Synthesis of the Novel 4,4?- and 6,6?- Dihydroxamic - 2,2?-Bipyridines and Improved Routes to 4,4?- and 6,6?- Substituted 2,2?-Bipyridines and Mono-N-Oxide-2,2?-Bipyridine

Directory of Open Access Journals (Sweden)

Donnici Claudio Luis

1998-01-01

Full Text Available The preparation of key precursors for many 2,2?-bipyridine derivatives such as 4,4?-dicarboxy- 2,2?-bipyridine (I, 6,6?-dicarboxy-2,2?-bipyridine- acid (II, 4,4?-dinitro-2,2?-bipyridine-N,N-dioxide (III, 6,6?-dicarbothioamide-2,2?-bipyridine (IV and mono-N-oxide-2,2?-bipyridine (VII through more efficient methods is described. The syntheses of the novel ligands 4,4?-dihydroxamic-2,2?-bipyridine (V and 6,6?-dihydroxamic-2,2?-bipyridine (VI are also reported.

Autoionisation of N/sup 5 +/ (nln'l') with n = 2,3,4 and n' >= n measured by electron spectrometry in collisions of N/sup 7 +/ with He and H/sub 2/, at 4. 9 keV amu/sup -1/

Energy Technology Data Exchange (ETDEWEB)

Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Marrakchi, A.I.; Dousson, S.; Hitz, D. (CEA Centre d' Etudes Nucleaires de Grenoble, 38 (France))

1984-03-14

a spectroscopic investigation of electrons coming from autoionising states N/sup 5 +/(nln'l'), with n=2,3,4 and n' >= n, of the fast ion has been made at 11.6/sup 0/ and 4.9 keV amu/sup -1/. Only exothermic reactions are observed. It is shown that the ionisation potential of the target has a strong influence on the more probable values of n and n'. In N/sup 7 +/-He collisions, the n=3, n'=3 configurations are the more excited. In N/sup 7 +/-H/sub 2/, the capture process is less selective since n=3, n' > 3 and also n=4, n' >= 4 configurations are strongly populated. In all these cases, the residual N/sup 6 +/ ion is left in an excited state (n=2 or 3). The n=2, n' > 2 excitation probability is found to be much smaller for the two collisional systems.

Morita-Baylis-Hillman Route to Dimethyl 2,3-Dihydrobenzo[b]oxepine-2,4- dicarboxylates and Methyl 2-(2-Carbomethoxybenzo[b]furan-3-yl)propanoates from Salicylaldehydes

Energy Technology Data Exchange (ETDEWEB)

Ahn, Sang Hyun; Jang, Seung Soon; Kim, Young Keun; Lee, Kee Jung [Hanyang University, Seoul (Korea, Republic of)

2012-01-15

A new synthetic method for dimethyl 2,3-dihydrobenzo[b]oxepine-2,4-dicarboxylates and methyl 2-(2- carbomethoxybenzo[b]furan-3-yl)propanoates by an intramolecular conjugate displacement reaction or an S{sub N}2 reaction of acetates of Morita-Baylis-Hillman adducts of methyl (2-formylphenoxy)acetates has been described.

Diaquabis[5-(2-pyridyltetrazolato-κ2N1,N5]iron(II

Directory of Open Access Journals (Sweden)

Min Hu

2009-04-01

Full Text Available The title complex, [Fe(C6H4N52(H2O2], was synthesized by the reaction of ferrous sulfate with 5-(2-pyridyl-2H-tetrazole (HL. The FeII atom, located on a crystallographic center of inversion, is coordinated by four N-atom donors from two planar trans-related deprotonated L ligands and two O atoms from two axial water molecules in a distorted octahedral geometry. The FeII mononuclear units are further connected by intermolecular O—H...N and C—H...O hydrogen-bonding interactions, forming a three-dimensional framework.

Crystal structure of bis-[N-(2-hy-droxy-eth-yl)-N-methyl-dithio-carbamato-κ2S,S'](pyridine)-zinc(II) pyridine monosolvate and its N-ethyl analogue.

Science.gov (United States)

Poplaukhin, Pavel; Tiekink, Edward R T

2017-07-01

The common structural feature of the title compounds, [Zn(C 4 H 8 NOS 2 ) 2 (C 5 H 5 N)]·C 5 H 5 N (I) and [Zn(C 5 H 10 NOS 2 ) 2 (C 5 H 5 N)]·C 5 H 5 N (II), which differ by having di-thio-carbamate N-bound methyl (I) and ethyl (II) groups, is the coordination of each Zn II atom by two non-symmetrically chelating di-thio-carbamate ligands and by a pyridine ligand; in each case, the non-coordinating pyridine mol-ecule is connected to the Zn-containing mol-ecule via a (hy-droxy)O-H⋯N(pyridine) hydrogen bond. The resulting NS 4 coordination geometry is closer to a square-pyramid than a trigonal bipyramid in the case of (I), but almost inter-mediate between the two extremes in (II). The mol-ecular packing features (hy-droxy)O-H⋯O(hy-droxy) hydrogen bonds, leading to supra-molecular chains with a zigzag arrangement along [10-1] (I) or a helical arrangement along [010] (II). In (I), π-π [inter-centroid distances = 3.4738 (10) and 3.4848 (10) Å] between coordinating and non-coordinating pyridine mol-ecules lead to stacks comprising alternating rings along the a axis. In (II), weaker π-π contacts occur between centrosymmetrically related pairs of coordinating pyridine mol-ecules [inter-centroid separation = 3.9815 (14) Å]. Further inter-actions, including C-H⋯π(chelate) inter-actions in (I), lead to a three-dimensional architecture in each case.

Enrichment of variations in KIR3DL1/S1 and KIR2DL2/L3 among H1N1/09 ICU patients: an exploratory study.

Directory of Open Access Journals (Sweden)

David La

Full Text Available BACKGROUND: Infection by the pandemic influenza A (H1N1/09 virus resulted in significant pathology among specific ethnic groups worldwide. Natural Killer (NK cells are important in early innate immune responses to viral infections. Activation of NK cells, in part, depend on killer-cell immunoglobulin-like receptors (KIR and HLA class I ligand interactions. To study factors involved in NK cell dysfunction in overactive immune responses to H1N1 infection, KIR3DL1/S1 and KIR2DL2/L3 allotypes and cognate HLA ligands of H1N1/09 intensive-care unit (ICU patients were determined. METHODOLOGY AND FINDINGS: KIR3DL1/S1, KIR2DL2/L3, and HLA -B and -C of 51 H1N1/09 ICU patients and 105 H1N1-negative subjects (St. Theresa Point, Manitoba were characterized. We detected an increase of 3DL1 ligand-negative pairs (3DL1/S1(+ Bw6(+ Bw4(-, and a lack of 2DL1 HLA-C2 ligands, among ICU patients. They were also significantly enriched for 2DL2/L3 ligand-positive pairs (PVA, P=0.024, Pc=0.047; Odds Ratio:2.563, CI95%:1.109-5.923, 3DL1*00101 (Ab>VA, PSTh, P=0.034, Pc=0.268, and 3DL1*029 (Ab>STh, P=0.039, Pc=0.301. Aboriginal patients ligand-positive for 3DL1/S1 and 2DL1 had the lowest probabilities of death (R(d (R(d=28%, compared to patients that were 3DL1/S1 ligand-negative (R(d=52% or carried 3DL1*029 (R(d=52%. Relative to Caucasoids (CA, two allotypes were enriched among non-aboriginal ICU patients (NAb: 3DL1*00401 (NAb>CA, P<0.001, Pc<0.001 and 3DL1*01502 (CAS1, 2DL2/L3, and 2DL1 had the lowest probabilities of death (R(d=36%, compared to subjects with 3DL1*01502 (R(d=48% and/or 3DL1*00401 (R(d=58%. CONCLUSIONS: Specific KIR3DL1/S1 allotypes, 3DL1/S1 and 2DL1 ligand-negative pairs, and 2DL2/L3 ligand-positive pairs were enriched among ICU patients. This suggests a possible association with NK cell dysfunction in patients with overactive immune responses to H1N1/09, leading to

Structural modulation and luminescent properties of four CdII coordination architectures based on 3-(pyridin-4-yl)-5-(pyrazin-2-yl)-1H-1,2,4-triazole and flexible/rigid dicarboxylate ligands

Science.gov (United States)

Xia, Liang; Dong, Wen-Wen; Ye, Xiao; Zhao, Jun; Li, Dong-Sheng

2016-10-01

To systematically investigate the influence of the flexible or rigid auxiliary ligands on the structures and properties of transition metal compounds, we synthesized four new d10 coordination polymers (CPs) from 3-(pyridin-4-yl)-5-(pyrazin-2-yl)-1H-1,2,4-triazole (4-Hpzpt) and flexible/rigid dicarboxylate ligands, [Cd(4-pzpt)2]n (1), [Cd3(4-pzpt)2(suc)2]n (2), [Cd2(4-Hpzpt)(nbc)2(H2O)]n (3) and {[Cd2(4-pzpt)2(tfbdc)(H2O)4]·H2O}n (4) (H2suc=1,2-ethanedicarboxylic acid, H2nbc=hthalene-1,4-dicarboxylic acid, H2tfbdc =2,3,5,6-tetrafluoroterephthalic acid). Single crystal X-ray analysis indicates that compound 1 shows a 44-sql layer, which is extended to a 3D network via nonclassical C-H…N hydrogen bonds. Compound 2 possesses a 6-connected pcu-4120.63 net composed of trinuclear CdII-clusters. Compound 3 represents a rare 3D (3,4,4,5)-connected topology with a Schläfli symbol of (4·6·7)(4·53·72)(53·6·7·9)(42·55·6·72). Compound 4 exhibits a 2D+2D→2D parallel interpenetrated 63-hcb network. The adjacent 2D networks are interdigitated with each other to form the resulting 3D supramolecular architecture through classical O-H…N and O-H…O hydrogen bonds. Structural diversities indicate that the nature of flexible/rigid-dicarboxlates plays crucial roles in modulating structures of these compounds. Moreover, the luminescent properties of them have been briefly investigated.

[(4S,5S-2,2-Dimethyl-1,3-dioxolane-4,5-diyl]bis[N-(thiophen-2-ylmethylidenemethanamine

Directory of Open Access Journals (Sweden)

Yan Jiang

2012-02-01

Full Text Available In the title compound, C17H20N2O2S2, the five-membered heterocycle exhibits an envelope conformation and the molecular chirality and configuration are well preserved from l-tartaric acid. The dihedral angle between the two thiophene rings is 17.0 (2°. In the crystal, molecules are linked by C—H...O and C—H...S hydrogen interactions, which are effective in the stabilization of the crystal structure.

Comparison and mechanism of photocatalytic activities of N-ZnO and N-ZrO2 for the degradation of rhodamine 6G.

Science.gov (United States)

Sudrajat, Hanggara; Babel, Sandhya

2016-05-01

N-doped ZnO (N-ZnO) and N-doped ZrO2 (N-ZrO2) are synthesized by novel, simple thermal decomposition methods. The catalysts are evaluated for the degradation of rhodamine 6G (R6G) under visible and UV light. N-ZnO exhibits higher dye degradation under both visible and UV light compared to N-ZrO2 due to possessing higher specific surface area, lower crystalline size, and lower band gap. However, it is less reusable than N-ZrO2 and its photocatalytic activity is also deteriorated at low pH. At the same intensity of 3.5 W/m(2), UVC light is shown to be a better UV source for N-ZnO, while UVA light is more suitable for N-ZrO2. At pH 7 with initial dye concentration of 10 mg/L, catalyst concentration of 1 g/L, and UVC light, 94.3 % of R6G is degraded by N-ZnO within 2 h. Using UVA light under identical experimental conditions, 93.5 % degradation of R6G is obtained by N-ZrO2. Moreover, the type of light source is found to determine the reactive species produced in the R6G degradation by N-ZnO and N-ZrO2. Less oxidative reactive species such as superoxide radical and singlet oxygen play a major role in the degradation of R6G under visible light. On the contrary, highly oxidative hydroxyl radicals are predominant under UVC light. Based on the kinetic study, the adsorption of R6G on the catalyst surface is found to be the controlling step.

New Ru(II)N'NN'-type pincer complexes: synthesis, characterization and the catalytic hydrogenation of CO_2 or bicarbonates to formate salts

International Nuclear Information System (INIS)

Zengjin Dai; Qi Luo; Hengjiang Cong; Jing Zhang; Tianyou Peng

2017-01-01

[RuCl(L1)(MeCN)_2]Cl (1) and [RuCl(L2)(MeCN)_2]Cl (2) complexes were prepared through the reaction of [RuCl2(p-cymene)]_2 with 2,6-bis(benzimidazole-2-yl)-4-hydroxy-pyridine (L1) or 2,6-bis(benzimidazole- 2-yl) pyridine (L2) in acetonitrile, respectively. The treatment of [Ru(OTf)(L2)(MeCN)_2]OTf (3) with 1 equivalent of PPh_3 in ethanol resulted in the formation of [Ru(L2"-"1)(MeCN)(PPh_3)_2]OTf (4), in which one of the N-H moieties of L2 is deprotonated to give an anionic ligand (L2"-"1). It was found that complex 1 can catalyze the hydrogenation of CO_2 to formate salts, producing sodium formate in 34.0% yield with a turnover number (TON) of 407 under the optimized conditions. Further investigations revealed that complexes 1-4 can efficiently catalyze the hydrogenation of sodium bicarbonate to sodium formate, and the catalytic activity follows the order 4 ≥ 1 ≥ 2 ≅ 3. In particular, sodium formate was obtained in good yield (77%) with a high TON (1530) when complex 4 was used as the catalyst. The present results illustrate a new example of Ru(II) complexes bearing a rigid N'NN' framework for the efficient hydrogenation of CO_2 to formate salts in a homogeneous system. (authors)

Discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylthieno[2,3-d]pyrimidines as potent apoptosis inducers.

Science.gov (United States)

Kemnitzer, William; Sirisoma, Nilantha; May, Chris; Tseng, Ben; Drewe, John; Cai, Sui Xiong

2009-07-01

We report the discovery of N-((benzo[d][1,3]dioxol-5-yl)methyl)-6-phenylthieno[3,2-d]pyrimidin-4-amine (2a) as an apoptosis inducer using our proprietary cell- and caspase-based ASAP HTS assay, and SAR study of HTS hit 2a which led to the discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylthieno[2,3-d]pyrimidines as potent apoptosis inducers. Compounds 5d and 5e were the most potent with EC(50) values of 0.008 and 0.004microM in T47D human breast cancer cells, respectively. Compound 5d was found to be highly active in the MX-1 breast cancer model. Functionally, compounds 5d and 5e both induced apoptosis through inhibition of tubulin polymerization.

Discovery of Clinical Candidate 2-((2S,6 S)-2-Phenyl-6-hydroxyadamantan-2-yl)-1-(3'-hydroxyazetidin-1-yl)ethanone [BMS-816336], an Orally Active Novel Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor

Energy Technology Data Exchange (ETDEWEB)

Ye, Xiang-Yang; Chen, Stephanie Y.; Wu, Shung; Yoon, David S.; Wang, Haixia; Hong, Zhenqiu; O’Connor, Stephen P.; Li, Jun; Li, James J.; Kennedy, Lawrence J.; Walker, Steven J.; Nayeem, Akbar; Sheriff, Steven; Camac, Daniel M.; Ramamurthy, Vidyhashankar; Morin, Paul E.; Zebo, Rachel; Taylor, Joseph R.; Morgan, Nathan N.; Ponticiello, Randolph P.; Harrity, Thomas; Apedo, Atsu; Golla, Rajasree; Seethala, Ramakrishna; Wang, Mengmeng; Harper, Timothy W.; Sleczka, Bogdan G.; He, Bin; Kirby, Mark; Leahy, David K.; Li, Jianqing; Hanson, Ronald L.; Guo, Zhiwei; Li, Yi-Xin; DiMarco, John D.; Scaringe, Raymond; Maxwell, Brad; Moulin, Frederick; Barrish, Joel C.; Gordon, David A.; Robl, Jeffrey A.

2017-06-05

BMS-816336 (6n-2), a hydroxy-substituted adamantyl acetamide, has been identified as a novel, potent inhibitor against human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme (IC₅₀ 3.0 nM) with >10000-fold selectivity over human 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). 6n-2 exhibits a robust acute pharmacodynamic effect in cynomolgus monkeys (ED₅₀ 0.12 mg/kg) and in DIO mice. It is orally bioavailable (%F ranges from 20 to 72% in preclinical species) and has a predicted pharmacokinetic profile of a high peak to trough ratio and short half-life in humans. This ADME profile met our selection criteria for once daily administration, targeting robust inhibition of 11β-HSD1 enzyme for the first 12 h period after dosing followed by an “inhibition holiday” so that the potential for hypothalamic–pituitary–adrenal (HPA) axis activation might be mitigated. 6n-2 was found to be well-tolerated in phase 1 clinical studies and represents a potential new treatment for type 2 diabetes, metabolic syndrome, and other human diseases modulated by glucocorticoid control.

Structural studies of lanthanide nitrate-N,N'-dimethyl-N,N'-diphenylpyridine-2,6-dicarboxyamide complexes

International Nuclear Information System (INIS)

Fujiwara, Asako; Nakano, Yoshiharu; Yaita, Tsuyoshi; Okuno, Kenji

2008-01-01

The tridentate ligand N,N'-dimethyl-N,N'-diphenylpyridine-2,6-dicarboxyamide (DMDPhPDA) and the corresponding lanthanum complex [La(NO 3 ) 3 (DMDPhPDA) 2 ] have been prepared and structurally characterised. The crystal structure of DMDPhPDA shows syn-anti conformation. In the lanthanum complex, two DMDPhPDA molecules coordinated to La(III) in a tridentate fashion and to three nitrate ions in a bidentate fashion make the lanthanum atom 12-coordinate. The crystal structure of [La(NO 3 ) 3 (DMDPhPDA) 2 ] has a C 2 symmetry. The stability constants determined by spectrophotometric titration suggest that [Ln(DMDPhPDA) 2 ] 3+ is the primary product in CH 3 CN solution and [Ln(DMDPhPDA) 3 ] 3+ is difficult to form. However, [Ln(DMDPhPDA) 2 ] 3+ could not be distinguished in 1 H NMR spectra. The 1 H NMR titration results imply that a fast ligand exchange process takes place

Preparation of catalytically active, covalent α-polylysine-enzyme conjugates via UV/vis-quantifiable bis-aryl hydrazone bond formation.

Science.gov (United States)

Grotzky, Andrea; Manaka, Yuichi; Kojima, Taisuke; Walde, Peter

2011-01-10

Covalent UV/vis-quantifiable bis-aryl hydrazone bond formation was investigated for the preparation of conjugates between α-poly-d-lysine (PDL) and either α-chymotrypsin (α-CT) or horseradish peroxidase (HRP). PDL and the enzymes were first modified via free amino groups with the linking reagents succinimidyl 6-hydrazinonicotinate acetone hydrazone (S-HyNic, at pH 7.6) and succinimidyl 4-formylbenzoate (S-4FB, at pH 7.2), respectively. The modified PDL and enzymes were then conjugated at pH 4.7, whereby polymer chains carrying several enzymes were obtained. Kinetics of the bis-aryl hydrazone bond formation was investigated spectrophotometrically at 354 nm. Retention of the enzymatic activity after conjugate formation was confirmed by using the substrates N-succinimidyl-l-Ala-l-Ala-l-Pro-l-Phe-p-nitroanilide (for α-CT) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS, for HRP). Thus, not only a mild and efficient preparation and convenient quantification of a conjugate between the polycationic α-polylysine and enzymes could be shown, but also the complete preservation of the enzymatic activity.

Electrochromic properties of multicolored novel polymer synthesized via combination of benzotriazole and N-functionalized 2,5-di(2-thienyl)-1H-pyrrole units

International Nuclear Information System (INIS)

Rende, Eda; Kilic, Cihan E.; Udum, Yasemin Arslan; Toffoli, Daniele; Toppare, Levent

2014-01-01

Synthesis of new conducting polymers is desired since their electrochemical and optical properties enable them to be used as active layers in many device applications. Benzotriazole and N-functionalized 2,5-di(2-thienyl)-1H-pyrrole (SNS Series) containing polymers showed very promising results as electrochromic materials. In order to observe the effect of the combination of these two units, three new monomers; 2-(6-(2,5-bis(5-methylthiophen-2-yl)-1H-pyrrol-1-yl)hexyl)-4,7-di (thiophen-2-yl)-2H benzo[d][1,2,3]triazole (M1), 2-(6-(2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)hexyl)-4,7-di(thiophen-2-yl) -2H-benzo[d][1,2,3]triazole (M2) and 2-(6-(2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)hexyl)-4,7-bis (5-methylthiophen-2-yl)-2H-benzo[d][1,2,3]triazole (M3) were synthesized. To better characterize the electronic and spectroscopic properties of the monomers, density functional theory (DFT) and its time-dependent generalization (TD-DFT) were used to calculate their vertical ionization potentials, vertical electron affinity and to simulate and interpret their infrared and UV-vis spectra. The monomers were electrochemically polymerized and the resultant polymers were characterized with cyclic voltammetry and UV-vis-NIR spectroscopy techniques. An electrochromic device was constructed with electrochemical polymer of M2. The device switched between red and blue colors and showed exceptional optical memory

6d N=(1,0) theories on S{sup 1}/T{sup 2} and class S theories: part II

Energy Technology Data Exchange (ETDEWEB)

Ohmori, Kantaro; Shimizu, Hiroyuki [Department of Physics, Faculty of Science, University of Tokyo,Bunkyo-ku, Tokyo 133-0022 (Japan); Tachikawa, Yuji [Department of Physics, Faculty of Science, University of Tokyo,Bunkyo-ku, Tokyo 133-0022 (Japan); Institute for the Physics and Mathematics of the Universe, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); Yonekura, Kazuya [Institute for the Physics and Mathematics of the Universe, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); School of Natural Sciences, Institute for Advanced Study,Princeton, NJ 08540 (United States)

2015-12-21

We study the T{sup 2} compactification of a class of 6d N=(1,0) theories that is Higgsable to N=(2,0) theories. We show that the resulting 4d N=2 theory at the origin of the Coulomb branch and the parameter space is generically given by two superconformal matter sectors coupled by an infrared-free gauge multiplet and another conformal gauge multiplet. Our analysis utilizes the 5d theories obtained by putting the same class of 6d theories on S{sup 1}. Our class includes, among others, the 6d theories describing multiple M5 branes on an ALE singularity, and we analyze them in detail. The resulting 4d theory has manifestly both the SL(2,ℤ) and the full flavor symmetry. We also discuss in detail the special cases of 6d theories where the infrared-free gauge multiplet is absent. In an appendix, we give a field-theoretical argument for an F-theoretic constraint that forbids a particular 6d anomaly-free matter content, as an application of our analysis.

Isozyme-specific enzyme inhibitors. 14. 5'(R)-C-[(L-homocystein-S-yl)methyl]adenosine 5'-(beta,gamma-imidotriphosphate), a potent inhibitor of rat methionine adenosyltransferases.

Science.gov (United States)

Kappler, F; Vrudhula, V M; Hampton, A

1987-09-01

The title compound is a covalent adduct of L-methionine (Met) and beta,gamma-imido-ATP. In its synthesis the N-Boc derivative of 5'(R)-C-(aminomethyl)-N6-benzoyl-5'-O-tosyl-2',3'-O- isopropylidenadenosine was converted by the successive actions of CF3CO2H and HNO2 into the corresponding 5'(R)-C-hydroxymethyl derivative. Treatment of this with disodium L-homocysteinate led to attack of sulfur at C6', apparently via a 5',6'-epoxide, and to total stereoselective inversion at C5' to furnish, after debenzoylation, 5'(R)-C-(L-homocystein-S-ylmethyl)-2',3'-O-isopropylidene ade nosine. The 5' configuration was established by conversion of this into the known 5'(S)-C-methyl-2',3'-O-isopropylidene adenosine with Raney nickel. The alpha-amino acid residue was protected as an N-Boc methyl ester, after which the 5'-hydroxyl was phosphorylated with benzyl phosphate and dicyclohexylcarbodiimide. The phosphoanhydride bond with inorganic imidodiphosphate was then created by established methods. Finally, blocking groups were removed under conditions that gave the desired adduct with no racemization of its L-methionine residue. It was a potent inhibitor [KM(ATP)/Ki = 1080; KM(Met)/Ki = 7.7] of the M-2 (normal tissue) form of rat methionine adenosyltransferase and of the M-T (hepatoma tissue) form [KM(ATP)/Ki = 670; KM(Met)/Ki = 22]. Inhibitions were competitive with respect to ATP or to L-methionine, indicating a dual substrate site mode of binding to the enzyme forms.

Dibromido(6-methyl-2,2′-bipyridine-κ2N,N′zinc(II