Sample records for n-benzyl 2r-2-acetamido-3-oxysubstituted propionamide

  1. Synthesis and anticonvulsant activities of N-benzyl (2R)-2-acetamido-3-oxysubstituted propionamide derivatives

    PubMed Central

    Morieux, Pierre; Stables, James P.; Kohn, Harold

    2009-01-01

    Lacosamide has been submitted for regulatory approval in the United States and Europe for the treatment of epilepsy. Previous synthetic methods did not permit the elaboration of the structure–activity relationship (SAR) for the 3-oxy site in lacosamide. We report an expedient five-step stereospecific synthesis for N-benzyl (2R)-2-acetamido-3-oxysubstituted propionamide analogs beginning with d-serine methyl ester. The procedure incorporated alkyl (e.g. methyl, primary, secondary, and tertiary) and aryl groups at this position. The SAR for the 3-oxy site showed maximal activity in animal seizure models for small 3-alkoxy substituents. PMID:18789868

  2. The Structure-Activity Relationship of the 3-Oxy Site in the Anticonvulsant (R)-N-Benzyl 2-Acetamido-3-methoxypropionamide

    PubMed Central

    Morieux, Pierre; Salomé, Christophe; Park, Ki Duk; Stables, James P.; Kohn, Harold

    2010-01-01

    Lacosamide ((R)-N-benzyl 2-acetamido-3-methoxypropionamide, (R)-1) is a low molecular weight anticonvulsant recently introduced in the United States and Europe for adjuvant treatment of partial-onset seizures in adults. In this study, we define the structure-activity relationship (SAR) for the compound's 3-oxy site. Placement of small non-polar, non-bulky substituents at the 3-oxy site provided compounds with pronounced seizure protection in the maximal electroshock (MES) seizure test with activities similar to (R)-1. The anticonvulsant activity loss that accompanied introduction of larger moieties at the 3-oxy site in (R)-1 was offset, in part, by including unsaturated groups at this position. Our findings were similar to a recently reported SAR study of the 4′-benzylamide site in (R)-1 (J. Med. Chem.2010, 53, 1288–1305). Together, these results indicate that both the 3-oxy and 4′-benzylamide positions in (R)-1 can accommodate non-bulky, hydrophobic groups and still retain pronounced anticonvulsant activities in rodents in the MES seizure model. PMID:20614888

  3. Primary amino acid derivatives: substitution of the 4'-N'-benzylamide site in (R)-N'-benzyl 2-amino-3-methylbutanamide, (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide, and (R)-N'-benzyl 2-amino-3-methoxypropionamide provides potent anticonvulsants with pain-attenuating properties.

    PubMed

    King, Amber M; Salomé, Christophe; Salomé-Grosjean, Elise; De Ryck, Marc; Kaminski, Rafal; Valade, Anne; Stables, James P; Kohn, Harold

    2011-10-13

    Recently, we reported that select N'-benzyl 2-substituted 2-amino acetamides (primary amino acid derivatives (PAADs)) exhibited pronounced activities in established whole animal anticonvulsant (i.e., maximal electroshock seizure (MES)) and neuropathic pain (i.e., formalin) models. The anticonvulsant activities of C(2)-hydrocarbon N'-benzyl 2-amino acetamides (MES ED(50) = 13-21 mg/kg) exceeded those of phenobarbital (ED(50) = 22 mg/kg). Two additional studies defining the structure-activity relationship of PAADs are presented in this issue of the journal. In this study, we demonstrated that the anticonvulsant activities of (R)-N'-benzyl 2-amino-3-methylbutanamide and (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide were sensitive to substituents at the 4'-N'-benzylamide site; electron-withdrawing groups retained activity, electron-donating groups led to a loss of activity, and incorporating either a 3-fluorobenzyloxy or 3-fluorophenoxymethyl group using a rationally designed multiple ligand approach improved activity. Additionally, we showed that substituents at the 4'-N'-benzylamide site of (R)-N'-benzyl 2-amino-3-methoxypropionamide also improved anticonvulsant activity, with the 3-fluorophenoxymethyl group providing the largest (∼4-fold) increase in activity (ED(50) = 8.9 mg/kg), a value that surpassed phenytoin (ED(50) = 9.5 mg/kg). Collectively, the pharmacological findings provided new information that C(2)-hydrocarbon PAADs represent a novel class of anticonvulsants.

  4. Design synthesis and structure-activity relationship of 5-substituted (tetrahydronaphthalen-2yl)methyl with N-phenyl-N-(piperidin-2-yl)propionamide derivatives as opioid ligands.

    PubMed

    Deekonda, Srinivas; Rankin, David; Davis, Peg; Lai, Josephine; Vanderah, Todd W; Porecca, Frank; Hruby, Victor J

    2016-01-15

    Here, we report the design, synthesis and structure activity relationship of novel small molecule opioid ligands based on 5-amino substituted (tetrahydronaphthalen-2-yl)methyl moiety with N-phenyl-N-(piperidin-2-yl)propionamide derivatives. We synthesized various molecules including amino, amide and hydroxy substitution on the 5th position of the (tetrahydronaphthalen-2-yl)methyl moiety. In our further designs we replaced the (tetrahydronaphthalen-2-yl)methyl moiety with benzyl and phenethyl moiety. These N-phenyl-N-(piperidin-2-yl)propionamide analogues showed moderate to good binding affinities (850-4 nM) and were selective towards the μ opioid receptor over the δ opioid receptors. From the structure activity relationship studies, we found that a hydroxyl substitution at the 5th position of (tetrahydronapthalen-2yl)methyl group, ligands 19 and 20, showed excellent binding affinities 4 and 5 nM, respectively, and 1000 fold selectivity towards the μ opioid relative to the delta opioid receptor. The ligand 19 showed potent agonist activities 75±21 nM, and 190±42 nM in the GPI and MVD assays. Surprisingly the fluoro analogue 20 showed good agonist activities in MVD assays 170±42 nM, in contrast to its binding affinity results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Lacosamide Isothiocyanate-based Agents: Novel Agents to Target and Identify Lacosamide Receptors

    PubMed Central

    Park, Ki Duk; Morieux, Pierre; Salomé, Christophe; Cotten, Steven W.; Reamtong, Onrapak; Eyers, Claire; Gaskell, Simon J.; Stables, James P.; Liu, Rihe; Kohn, Harold

    2009-01-01

    (R)-Lacosamide ((R)-2, (R)-N-benzyl 2-acetamido-3-methoxypropionamide), has recently gained regulatory approval for the treatment of partial-onset seizures in adults. Whole animal pharmacological studies have documented that (R)-2 function is unique. A robust strategy is advanced for the discovery of interacting proteins associated with function and toxicity of (R)-2 through the use of (R)-2 analogs, 3, that contain “affinity bait (AB)” and “chemical reporter (CR)” functional groups. In 3, covalent modification of the interacting proteins proceeds at the AB moiety, and detection or isolation of the selectively captured protein occurs through the bioorthogonal CR group upon reaction with an appropriate probe. We report the synthesis, pharmacological evaluation, and interrogation of the mouse soluble brain proteome using 3 where the AB group is an isothiocyanate moiety. One compound, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-9), exhibited excellent seizure protection in mice and, like (R)-2, anticonvulsant activity principally resided in the (R)-stereoisomer. Several proteins were preferentially labeled by (R)-9 compared with (S)-9, including collapsin response mediator protein 2. PMID:19795888

  6. Biotransformation and pharmacokinetics of the nitrate trans-2-amino-2-methyl-N-(4-nitroxycyclohexyl)-propionamide in dogs.

    PubMed

    Pressmar, F; Neidlein, R; Strein, K

    1992-11-01

    The biotransformation and the pharmacokinetic behavior of the organic nitrate trans-2-Amino-2-methyl-N-(4-nitroxycyclohexyl)-propionamide (BM 12.1179, CAS 129795-96-6) were examined in dogs. BM 12.1179 was predominantly eliminated by urinary excretion, and the unchanged molecule prevailed in urine as well as in plasma. By means of various mass spectroscopic methods, the chemical structures of the metabolites were elucidated. As metabolites trans-2-amino-2-methyl-N-(4-hydroxycyclohexyl)-propionamide and trans-2-amino-2-methyl-N-(4-oxocyclohexyl)-propionamide were formed. Urine levels of the main metabolite were determined by high-pressure liquid chromatography; plasma and urine levels of BM 12.1179 were determined by capillary gas chromatography. The absolute bioavailability of BM 12.1179 was 80-100%. The plasma protein binding was about 34% which is high in comparison to other organic nitrates. BM 12.1179 represents a long-acting organic nitrate in that it shows a slow reductive denitration, and a long elimination half-life of about 10 h.

  7. Substituted N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamides: potent anticonvulsants that affect frequency (use) dependence and slow inactivation of sodium channels.

    PubMed

    Lee, Hyosung; Park, Ki Duk; Torregrosa, Robert; Yang, Xiao-Fang; Dustrude, Erik T; Wang, Yuying; Wilson, Sarah M; Barbosa, Cindy; Xiao, Yucheng; Cummins, Theodore R; Khanna, Rajesh; Kohn, Harold

    2014-07-24

    We prepared 13 derivatives of N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound's whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI=TD50/ED50) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na+ channel slow inactivation and displayed frequency (use) inhibition of Na+ currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed.

  8. Substituted N-(Biphenyl-4′-yl)methyl (R)-2-Acetamido-3-methoxypropionamides: Potent Anticonvulsants That Affect Frequency (Use) Dependence and Slow Inactivation of Sodium Channels

    PubMed Central

    2015-01-01

    We prepared 13 derivatives of N-(biphenyl-4′-yl)methyl (R)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound’s whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI = TD50/ED50) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na+ channel slow inactivation and displayed frequency (use) inhibition of Na+ currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed. PMID:25004277

  9. Some further studies on the synthesis of glycopeptide derivatives: 2-acetamido-2-deoxy-β-d-glucopyranosylamine derivatives

    PubMed Central

    Bolton, C. H.; Hough, L.; Khan, M. Y.

    1966-01-01

    1. The isolation, characterization and properties of two by-products in the preparation of 2-acetamido-3,4,6-tri-O- acetyl-2-deoxy-β-d-glucopyranosylamine are described. They are bis(2-acetamido-2-deoxy-d-glucopyranosyl)amines. 2. An independent synthesis of the bis-glycopyranosylamines is reported and conditions are given for their preparation in high yield. 3. Further improvements are given for the synthesis of 2-acetamido-1-N-(β-l- aspartyl)-2-deoxy-β-d-glucopyranosylamine and the α-l-aspartyl isomer. 4. The synthesis of 2-acetamido-1-N-acetyl-2-deoxy-β-d-glucopyranosylamine is described. PMID:5971780

  10. N-Benzyl­pyridin-2-amine

    PubMed Central

    Wang, Jun; Dai, Chuntao; Nie, Jianhua

    2010-01-01

    In the crystal of the title compound, C12H12N2, inter­molecular N—H⋯N hydrogen bonds form rings of graph-set motif R 2 2(8) and C—H⋯π inter­actions further consolidate the dimers. Neighbouring dimers are further connected into a three-dimensional network by C—H⋯π inter­actions. The benzyl and pyridyl rings form a dihedral angle of 67.2 (1)° PMID:21589385

  11. Crystal structure of benzyl (E)-2-(3,4-di-meth-oxy-benzyl-idene)hydrazine-1-carbodi-thio-ate.

    PubMed

    Tan, Yew-Fung; Break, Mohammed Khaled Bin; Tahir, M Ibrahim M; Khoo, Teng-Jin

    2015-02-01

    The title compound, C17H18N2O2S2, synthesized via a condensation reaction between S-benzyl di-thio-carbazate and 3,4-di-meth-oxy-benzaldehyde, crystallized with two independent mol-ecules (A and B) in the asymmetric unit. Both mol-ecules have an L-shape but differ in the orientation of the benzyl ring with respect to the 3,4-di-meth-oxy-benzyl-idine ring, this dihedral angle is 65.59 (8)° in mol-ecule A and 73.10 (8)° in mol-ecule B. In the crystal, the A and B mol-ecules are linked via pairs of N-H⋯S hydrogen bonds, forming dimers with an R 2 (2)(8) ring motif. The dimers are linked via pairs of C-H⋯O hydrogen bonds, giving inversion dimers of dimers. These units are linked by C-H⋯π inter-actions, forming ribbons propagating in the [100] direction.

  12. Molecular structure and conformation of N-2-[3'-(methoxysalicylideneimino)benzyl]-3″-methoxysalicylideneimine

    NASA Astrophysics Data System (ADS)

    Dey, D. K.; Dey, S. P.; Elmali, A.; Elerman, Y.

    2001-05-01

    The Schiff base, N-2-[3'-(methoxysalicylideneimino)benzyl]-3″-methoxysalicylidene-imine, 1,2-C 6H 4[NCHC 6H 3(OMe-3')OH-2']CH 2NCHC 6H 3(OMe-3″)OH-2″, has been prepared by the reaction of 2-amino-1-benzylamine and 3-methoxysalicylaldehyde ( o-vanillin) in ethanol. The molecular structure has been confirmed by single crystal X-ray crystallography. The crystal is in the monoclinic space group P2 1/ n with a=16.179(5), b=6.715(5), c=18.780(6) Å, β=100.56(3)°, Dcalc=1.293 mg cm -3, V=2006(2) Å 3 and R=0.0357 for 3929 independent reflections. The 1H and 13C NMR spectra in CDCl 3 solution indicate the retention of solid state structure in solution. The title compound is not planar. Intramolecular hydrogen bonds occur between O(1) and N(1) [2.614(2) Å] and between O(2) and N(2) [2.585(2) Å] atoms, the hydrogen atom essentially being bonded to the oxygen atom. Minimum energy conformations from AM1 were calculated as a function of five torsion angles θ1 (C6-C7-N1-C8), θ2 (C14-N2-C15-C16), θ3 (C9-C8-N1-C7), θ4 (C13-C14-N2-C15) and θ5 (C10-C9-C8-N1), varied every 5°. The optimized geometry of the crystal structure corresponding to the non-planar conformation is the most stable conformation in all calculations. The results strongly indicate that the minimum energy conformation is primarily determined by non-bonded hydrogen-hydrogen repulsions.

  13. Benzyl-Functionalized Room Temperature Ionic Liquids for CO2/N2 Separation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mahurin, Shannon Mark; Dai, Thomas N; Yeary, Joshua S

    2011-01-01

    In this work, three classes of room temperature ionic liquids (RTILs), including imidazolium, pyridinium, and pyrrolidinium ionic liquids with a benzyl group appended to the cation, were synthesized and tested for their performance in separating CO{sub 2} and N{sub 2}. All RTILs contained the bis(trifluoromethylsulfonyl)imide anion, permitting us to distinguish the impact of the benzyl moiety attached to the cation on gas separation performance. In general, the attachment of the benzyl group increased the viscosity of the ionic liquid compared with the unfunctionalized analogs and decreased the CO{sub 2} permeability. However, all of the benzyl-modified ionic liquids exhibited enhanced CO{submore » 2}/N{sub 2} selectivities compared with alkyl-based ionic liquids, with values ranging from 22.0 to 33.1. In addition, CO{sub 2} solubilities in the form of Henry's constants were also measured and compared with unfunctionalized analogs. Results of the membrane performance tests and CO{sub 2} solubility measurements demonstrate that the benzyl-functionalized RTILs have significant potential for use in the separation of carbon dioxide from combustion products.« less

  14. Synthesis of P1-(11-phenoxyundecyl)-P2-(2-acetamido-2-deoxy-3-O-α-D-rhamnopyranosyl-α-D-glucopyranosyl) diphosphate and P1-(11-phenoxyundecyl)-P2-(2-acetamido-2-deoxy-3-O-β-D-galactopyranosyl-α-D-galactopyranosyl) diphosphate for the investigation of biosynthesis of O-antigenic polysaccharides in Pseudomonas aeruginosa and Escherichia coli O104.

    PubMed

    Torgov, Vladimir; Danilov, Leonid; Utkina, Natalia; Veselovsky, Vladimir; Brockhausen, Inka

    2017-12-01

    Two new phenoxyundecyl diphosphate sugars were synthesized for the first time: P 1 -(11-phenoxyundecyl)-P 2 - (2-acetamido-2-deoxy-3-O-α-D-rhamnopyranosyl-α-D-glucopyranosyl) diphosphate and P 1 -(11-phenoxyundecyl)-P 2 -(2-acetamido-2-deoxy-3-O-β-D-galactopyranosyl-α-D-galactopyranosyl) diphosphate to study the third step of biosynthesis of the repeating units of O-antigenic polysaccharides in Pseudomonas aeruginosa and E.coli O104 respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Origin of the SN2 benzylic effect.

    PubMed

    Galabov, Boris; Nikolova, Valia; Wilke, Jeremiah J; Schaefer, Henry F; Allen, Wesley D

    2008-07-30

    The S N2 identity exchange reactions of the fluoride ion with benzyl fluoride and 10 para-substituted derivatives (RC6H 4CH 2F, R = CH3, OH, OCH 3, NH2, F, Cl, CCH, CN, COF, and NO2) have been investigated by both rigorous ab initio methods and carefully calibrated density functional theory. Groundbreaking focal-point computations were executed for the C6H5CH 2F + F (-) and C 6H 5CH2Cl + Cl (-) SN2 reactions at the highest possible levels of electronic structure theory, employing complete basis set (CBS) extrapolations of aug-cc-pV XZ (X = 2-5) Hartree-Fock and MP2 energies, and including higher-order electron correlation via CCSD/aug-cc-pVQZ and CCSD(T)/aug-cc-pVTZ coupled cluster wave functions. Strong linear dependences are found between the computed electrostatic potential at the reaction-center carbon atom and the effective SN2 activation energies within the series of para-substituted benzyl fluorides. An activation strain energy decomposition indicates that the SN2 reactivity of these benzylic compounds is governed by the intrinsic electrostatic interaction between the reacting fragments. The delocalization of nucleophilic charge into the aromatic ring in the SN2 transition states is quite limited and should not be considered the origin of benzylic acceleration of SN2 reactions. Our rigorous focal-point computations validate the benzylic effect by establishing SN2 barriers for (F (-), Cl (-)) identity exchange in (C6H5CH2F, C6H 5CH2Cl) that are lower than those of (CH3F, CH3Cl) by (3.8, 1.6) kcal mol (-1), in order.

  16. Synthetic mucin fragments: synthesis of O-sulfo and O-methyl derivatives of allyl O-(beta-D-galactopyranosyl)-(1-->3)-2-acetamido-2-deoxy-alpha-D- galactopyranoside as potential compounds for sulfotransferases.

    PubMed

    Jain, R K; Piskorz, C F; Matta, K L

    1995-10-02

    Allyl 2-acetamido-4,6-O-(4-methoxybenzylidene)-2-deoxy-alpha-D-galact opy ranoside (1) was condensed with either 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide (2) or 2,3,4-tri-O-benzoyl-6-O-bromoacetyl-alpha-D-galactopyranosyl bromide (14) in the presence of mercuric cyanide. Selective substitution with methyl, sulfo or both at desired positions, followed by the removal of protecting groups, afforded allyl O-(beta-D-galactopyranosyl)-(1-->3)-2-acetamido-2-deoxy-6-O-methyl-alpha -D- galactopyranoside (5), allyl O-(6-O-sulfo-beta-D-galactopyranosyl sodium salt)-(1-->3)-2-acetamido-2-deoxy-6- O-methyl-alpha-D-galactopyranoside (10), allyl O-(beta-D-galactopyranosyl)-(1-->3)-2-acetamido-2-deoxy-6-O-sulfo-alpha- D- galactopyranoside sodium salt (13), allyl O-(6-O-sulfo-beta-D-galactopyranosyl sodium salt)-(1-->3)-2-acetamido-2-deoxy- alpha-D-galactopyranoside (17) and allyl O-(3-O-sulfo-beta-D-galactopyranosyl sodium salt)-(1-->3)-2-acetamido-2-deoxy- alpha-D-galactopyranoside (22). The structures of compounds 5, 10, 13, 17 and 22 were established by 13C NMR and FAB mass spectroscopy.

  17. Chimeric Derivatives of Functionalized Amino Acids and α-Aminoamides: Compounds with Anticonvulsant Activity in Seizure Models and Inhibitory Actions on Central, Peripheral, and Cardiac Isoforms of Voltage-gated Sodium Channels

    PubMed Central

    Torregrosa, Robert; Yang, Xiao-Fang; Dustrude, Erik T.; Cummins, Theodore R.

    2015-01-01

    Six novel 3″-substituted (R)-N-(phenoxybenzyl) 2-N-acetamido-3-methoxypropionamides were prepared and then assessed using whole-cell, patch-clamp electrophysiology for their anticonvulsant activities in animal seizure models and for their sodium channel activities. We found compounds with various substituents at the terminal aromatic ring that had excellent anticonvulsant activity. Of these compounds, (R)-N-4′-((3″-chloro)phenoxy)benzyl 2-N-acetamido-3-methoxypropionamide ((R)-5) and (R)-N-4′-((3″-trifluoromethoxy)phenoxy)benzyl 2-N-acetamido-3-methoxypropionamide ((R)-9) exhibited high protective indices (PI = TD50/ED50) comparable with many antiseizure drugs when tested in the maximal electroshock seizure test to mice (intraperitoneally) and rats (intraperitoneally, orally). Most compounds potently transitioned sodium channels to the slow-inactivated state when evaluated in rat embryonic cortical neurons. Treating HEK293 recombinant cells that expressed hNav1.1, rNav1.3, hNav1.5, or hNav1.7 with (R)-9 recapitulated the high levels of sodium channel slow inactivation. PMID:25922183

  18. Studies of a series of [Ni(P(R)2N(Ph)2)2(CH3CN)]2+ complexes as electrocatalysts for H2 production: substituent variation at the phosphorus atom of the P2N2 ligand.

    PubMed

    Kilgore, Uriah J; Stewart, Michael P; Helm, Monte L; Dougherty, William G; Kassel, W Scott; DuBois, Mary Rakowski; DuBois, Daniel L; Bullock, R Morris

    2011-11-07

    A series of [Ni(P(R)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) complexes containing the cyclic diphosphine ligands [P(R)(2)N(Ph)(2) = 1,5-diaza-3,7-diphosphacyclooctane; R = benzyl (Bn), n-butyl (n-Bu), 2-phenylethyl (PE), 2,4,4-trimethylpentyl (TP), and cyclohexyl (Cy)] have been synthesized and characterized. X-ray diffraction studies reveal that the cations of [Ni(P(Bn)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) and [Ni(P(n-Bu)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) have distorted trigonal bipyramidal geometries. The Ni(0) complex [Ni(P(Bn)(2)N(Ph)(2))(2)] was also synthesized and characterized by X-ray diffraction studies and shown to have a distorted tetrahedral structure. These complexes, with the exception of [Ni(P(Cy)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2), all exhibit reversible electron transfer processes for both the Ni(II/I) and Ni(I/0) couples and are electrocatalysts for the production of H(2) in acidic acetonitrile solutions. The heterolytic cleavage of H(2) by [Ni(P(R)(2)N(Ph)(2))(2)(CH(3)CN)](BF(4))(2) complexes in the presence of p-anisidine or p-bromoaniline was used to determine the hydride donor abilities of the corresponding [HNi(P(R)(2)N(Ph)(2))(2)](BF(4)) complexes. However, for the catalysts with the most bulky R groups, the turnover frequencies do not parallel the driving force for elimination of H(2), suggesting that steric interactions between the alkyl substituents on phosphorus and the nitrogen atom of the pendant amines play an important role in determining the overall catalytic rate. © 2011 American Chemical Society

  19. Pharmacokinetics of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide in rats, a non-steroidal selective androgen receptor modulator

    PubMed Central

    KEARBEY, J. D.; WU, D.; GAO, W.; MILLER, D. D.; DALTON, J. T.

    2007-01-01

    1. S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (also known as S-4) is a non-steroidal selective androgen receptor modulator demonstrating tissue-selective androgenic and anabolic effects. The purpose of the present study was to examine the systemic pharmacokinetics, elimination and oral bioavailability of S-4 in rats. 2. Thirty-five male Sprague–Dawley rats weighing approximately 250 g were randomly assigned to one of seven treatment groups. Intravenous doses of 0.5, 1, 10, and 30 mg kg−1 were given via a jugular catheter. Oral doses of 1, 10 and 30 mg kg−1 were administered via gavage. Plasma concentrations were determined using a validated high-performance liquid chromatography or by a high-performance liquid chromatography/mass spectrometry method. 3. Clearances ranged between 1.0 and 2.1 ml min−1 kg−1 and varied with dose. The volume of distribution was approximately 0.448 l kg−1 in all treatment groups. Oral bioavailability was also dose dependent, with the lower doses showing complete oral bioavailability. The half-life of S-4 over the dose range tested was between 2.6 and 5.3 h. 4. It was demonstrated that S-4 is rapidly absorbed, slowly cleared, and has a moderate volume of distribution in rats. The pharmacokinetics and oral bioavailability of S-4 indicate that it is an excellent candidate for clinical development. PMID:15204699

  20. Crystal structure and electrochemical properties of [Ni(bztmpen)(CH3CN)](BF4)2 {bztmpen is N-benzyl-N,N',N'-tris-[(6-methyl-pyridin-2-yl)meth-yl]ethane-1,2-di-amine}.

    PubMed

    Chen, Lin; Ren, Gan; Guo, Yakun; Sang, Ge

    2017-06-01

    The mononuclear nickel title complex (acetonitrile-κ N ){ N -benzyl- N , N ', N '-tris-[(6-methyl-pyridin-2-yl)meth-yl]ethane-1,2-di-amine}-nickel(II) bis-(tetra-fluor-ido-borate), [Ni(C 30 H 35 N 5 )(CH 3 CN)](BF 4 ) 2 , was prepared from the reaction of Ni(BF 4 ) 2 ·6H 2 O with N -benzyl- N , N ', N '-tris-[(6-methyl-pyridin-2-yl)meth-yl]ethane-1,2-di-amine ( bztmpen ) in aceto-nitrile at room temperature. With an open site occupied by the aceto-nitrile mol-ecule, the nickel(II) atom is chelated by five N-atom sites from the ligand and one N atom from the ligand, showing an overall octa-hedral coordination environment. Compared with analogues where the 6-methyl substituent is absent, the bond length around the Ni 2+ cation are evidently longer. Upon reductive dissociation of the acetro-nitrile mol-ecule, the title complex has an open site for a catalytic reaction. The title complex has two redox couples at -1.50 and -1.80 V ( versus F c +/0 ) based on nickel. The F atoms of the two BF 4 - counter-anions are split into two groups and the occupancy ratios refined to 0.611 (18):0.389 (18) and 0.71 (2):0.29 (2).

  1. Discovery of 5-substituted tetrahydronaphthalen-2yl-methyl with N-phenyl-N-(piperidin-4-yl)propionamide derivatives as potent opioid receptor ligands.

    PubMed

    Deekonda, Srinivas; Wugalter, Lauren; Kulkarni, Vinod; Rankin, David; Largent-Milnes, Tally M; Davis, Peg; Bassirirad, Neemah M; Lai, Josephine; Vanderah, Todd W; Porreca, Frank; Hruby, Victor J

    2015-09-15

    A new series of novel opioid ligands have been designed and synthesized based on the 4-anilidopiperidine scaffold containing a 5-substituted tetrahydronaphthalen-2yl)methyl group with different N-phenyl-N-(piperidin-4-yl)propionamide derivatives to study the biological effects of these substituents on μ and δ opioid receptor interactions. Recently our group reported novel 4-anilidopiperidine analogues, in which several aromatic ring-contained amino acids were conjugated with N-phenyl-N-(piperidin-4-yl)propionamide and examined their biological activities at the μ and δ opioid receptors. In continuation of our efforts in these novel 4-anilidopiperidine analogues, we took a peptidomimetic approach in the present design, in which we substituted aromatic amino acids with tetrahydronaphthalen-2yl methyl moiety with amino, amide and hydroxyl substitutions at the 5th position. In in vitro assays these ligands, showed very good binding affinity and highly selective toward the μ opioid receptor. Among these, the lead ligand 20 showed excellent binding affinity (2 nM) and 5000 fold selectivity toward the μ opioid receptor, as well as functional selectivity in GPI assays (55.20 ± 4.30 nM) and weak or no agonist activities in MVD assays. Based on the in vitro bioassay results the lead compound 20 was chosen for in vivo assessment for efficacy in naïve rats after intrathecal administration. Compound 20 was not significantly effective in alleviating acute pain. This discrepancy between high in vitro binding affinity, moderate in vitro activity, and low in vivo activity may reflect differences in pharmacodynamics (i.e., engaging signaling pathways) or pharmacokinetics (i.e., metabolic stability). In sum, our data suggest that further optimization of this compound 20 is required to enhance in vivo activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Dichlorido[N′-(3,5-dichloro-2-hydroxy­benzyl­idene)pyridine-4-carbohydrazide-κN](1,10-phenanthroline-κ2 N,N′)cobalt(II) methanol monosolvate

    PubMed Central

    Wang, Yuan; Liu, Zheng; Liu, Baoyu

    2009-01-01

    In the title compound, [CoCl2(C13H9Cl2N3O2)2(C12H8N2)]·CH3OH, the CoII atom is octahedrally coordinated by two N atoms from the pyridyl rings of the tridentate N′-(3,5-dichloro-2-hydroxy­benzyl­idene)pyridine-4-carbohydrazide (H2 L) ligand, two N atoms from the 1,10-phenanthroline ligand and two chloride ions. The acyl­hydrazone groups are not involved into the coordination of the metal ion. In the crystal packing an extended three-dimensional network formed by N—H⋯Cl, N—H⋯O, O—H⋯N, O—H⋯N and O—H⋯Cl hydrogen bonds is observed. PMID:21578623

  3. Resolution of 2-chloromandelic acid with (R)-(+)-N-benzyl-1-phenylethylamine: chiral discrimination mechanism.

    PubMed

    Peng, Yangfeng; He, Quan; Rohani, Sohrab; Jenkins, Hilary

    2012-05-01

    During the resolution of 2-chloromandelic acid with (R)-(+)-N-benzyl-1-phenylethylamine, the crystals of the less soluble salt were grown, and their structure were determined and presented. The chiral discrimination mechanism was investigated by examining the weak intermolecular interactions (such as hydrogen bond, CH/π, and van der Waals interactions) and molecular packing mode in crystal structure of the less soluble diastereomeric salt. A one-dimensional double-chain hydrogen-bonding network and a "lock-and-key" supramolecular packing mode are disclosed. The investigation demonstrates that hydrophobic layers with corrugated surfaces can fit into the grooves of one another to realize a compact packing, when the molecular structure of resolving agent is much larger than that of the racemate. This "lock-and-key" assembly is recognized to be another characteristic of molecular packing contributing to the chiral discrimination, in addition to the well-known sandwich-like packing by hydrophobic layers with planar boundary surfaces. Copyright © 2012 Wiley Periodicals, Inc.

  4. Synthesis, crystal structures and coordination modes of some triorganotin(IV) complexes with 2-N-propyl and 2-N-benzyl-amino-1-cyclopentene-1-dithiocarboxylates

    NASA Astrophysics Data System (ADS)

    López-Cardoso, Marcela; Vargas-Pineda, Gabriela; Román-Bravo, Perla Patricia; Rodríguez-Narváez, Cristina; Rosas-Valdez, Elena; Cea-Olivares, Raymundo

    2016-07-01

    The syntheses and characterization of six new triorganotin(IV) complexes, Ph3Sn(PrACDA) (1), Bu3Sn(PrACDA) (2), Ph3Sn(BzACDA) (3), Bu3Sn(BzACDA) (4), Me3Sn(BzACDA) (5) and Cy3Sn(BzACDA) (6) (ACDA = 2-amino-1-cyclopentene-1-carbodithioate anion) are reported. Compounds 1-6 were synthesized by the reaction between the sodium salts of 2-N-propyl- or 2-N-benzyl-2-amino-1-cyclopentene-1-carbodithioate and R3SnCl (R = Ph, Bu, Me, Cy) in a 1:1 M ratio. The complexes were characterized by elemental analyses, IR and NMR (1H, 13C and 119Sn) spectroscopy and by FAB+ mass spectrometry. The experimental data reveal that the tin atom is coordinated to the ligand by means of the two sulfur atoms from the carbodithioate group in an anisobidentate mode, while the 119Sn{1H} NMR spectra suggest a pentacoordinate metal center in 1-4 and a tetracoordinate tin atom for 5 and 6. The molecular structures of complexes 1, 3 and 5 were confirmed by single crystal X-ray diffraction analysis showing the presence of N-H···S hydrogen bonding and a distorted trigonal bipyramid geometry for the tin atoms.

  5. Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor.

    PubMed

    Chen, Chen; Wu, Dongpei; Guo, Zhiqiang; Xie, Qiu; Reinhart, Greg J; Madan, Ajay; Wen, Jenny; Chen, Takung; Huang, Charles Q; Chen, Mi; Chen, Yongsheng; Tucci, Fabio C; Rowbottom, Martin; Pontillo, Joseph; Zhu, Yun-Fei; Wade, Warren; Saunders, John; Bozigian, Haig; Struthers, R Scott

    2008-12-11

    The discovery of novel uracil phenylethylamines bearing a butyric acid as potent human gonadotropin-releasing hormone receptor (hGnRH-R) antagonists is described. A major focus of this optimization was to improve the CYP3A4 inhibition liability of these uracils while maintaining their GnRH-R potency. R-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyric acid sodium salt, 10b (elagolix), was identified as a potent and selective hGnRH-R antagonist. Oral administration of 10b suppressed luteinizing hormone in castrated macaques. These efforts led to the identification of 10b as a clinical compound for the treatment of endometriosis.

  6. Cannabinoid receptor type 2 (CB2)-selective N-aryl-oxadiazolyl-propionamides: synthesis, radiolabelling, molecular modelling and biological evaluation

    PubMed Central

    2012-01-01

    Background The endocannabinoid system is involved in many physiological and pathological processes. Two receptors (cannabinoid receptor type 1 (CB1) and type 2 (CB2)) are known so far. Many unwanted psychotic side effects of inhibitors of this system can be addressed to the interaction with CB1. While CB1 is one of the most abundant neuroreceptors, CB2 is expressed in the brain only at very low levels. Thus, highly potent and selective compounds for CB2 are desired. N-aryl-((hetero)aromatic)-oxadiazolyl-propionamides represent a promising class of such selective ligands for the human CB2. Here, a library of various derivatives is studied for suitable routes for labelling with 18F. Such 18F-labelled compounds can then be employed as CB2-selective radiotracers for molecular imaging studies employing positron emission tomography (PET). Results By varying the N-arylamide substructure, we explored the binding pocket of the human CB2 receptor and identified 9-ethyl-9H-carbazole amide as the group with optimal size. Radioligand replacement experiments revealed that the modification of the (hetero)aromatic moiety in 3-position of the 1,2,4-oxadiazoles shows only moderate impact on affinity to CB2 but high impact on selectivity towards CB2 with respect to CB1. Further, we could show by autoradiography studies that the most promising compounds bind selectively on CB2 receptors in mouse spleen tissue. Molecular docking studies based on a novel three-dimensional structural model of the human CB2 receptor in its activated form indicate that the compounds bind with the N-arylamide substructure in the binding pocket. 18F labelling at the (hetero)aromatic moiety at the opposite site of the compounds via radiochemistry was carried out. Conclusions The synthesized CB2-selective compounds have high affinity towards CB2 and good selectivity against CB1. The introduction of labelling groups at the (hetero)aromatic moiety shows only moderate impact on CB2 affinity, indicating the

  7. Optical resolution by preferential crystallization of (RS)-2-benzoylamino-2-benzyl-3-hydroxypropanoic acid and its use in synthesizing optically active 2-amino-2-methyl-3-phenylpropanoic acid.

    PubMed

    Shiraiwa, Tadashi; Suzuki, Masahiro; Sakai, Yoshio; Nagasawa, Hisashi; Takatani, Kazuhiro; Noshi, Daisuke; Yamanashi, Kenji

    2002-10-01

    To synthesize optically active 2-amino-2-methyl-3-phenylpropanoic acid (1), (RS)-2-benzoylamino-2-benzyl-3-hydroxypropanoic acid [(RS)-2] was first optically resolved using cinchonidine as a resolving agent to yield optically pure (S)- and (R)-2 in yields of about 70%, based on half of the starting amount of (RS)-2. Next, the racemic structure of (RS)-2 was examined based on melting point, solubility, IR spectrum, and binary and ternary phase diagrams, with the aim of optical resolution by preferential crystallization of (RS)-2. Results indicated that the (RS)-2 exists as a conglomerate at room temperature, although it forms a racemic compound at the melting point. The optical resolution by preferential crystallization yielded (S)- and (R)-2 with optical purities of about 90%, which were fully purified by recrystallization. After O-tosylation of (S)- and (R)-2, reduction by zinc powder and sodium iodide gave (R)- and (S)-1, respectively.

  8. Synthesis, characterization and cytotoxic activity of substituted benzyl iminoether Pt(II) complexes of the type cis- and trans-[PtCl2{E-N(H)=C(OMe)CH2-C6H4-p-R}2] (R=Me, OMe, F). X-ray structure of trans-[PtCl2{E-N(H)=C(OMe)CH2-C6H4-p-F}2].

    PubMed

    Mazzega Sbovata, Silvia; Bettio, Frazia; Marzano, Christine; Tassan, Augusto; Mozzon, Mirto; Bertani, Roberta; Benetollo, Franco; Michelin, Rino A

    2008-04-01

    New substituted benzyl iminoether derivatives of the type cis- and trans-[PtCl(2){E-N(H)C(OMe)CH(2)-C(6)H(4)-p-R}(2)] (R=Me (1a, 2a), OMe (3a, 4a), F (5a, 6a)) have been synthesized and characterized by elemental analyses, FT-IR spectroscopy and NMR techniques. The iminoether ligands are in the E configuration, which is stable in solution and in the solid state, as confirmed by the (1)H NMR data. Complex trans-[PtCl(2){E-N(H)C(OMe)CH(2)-C(6)H(4)-p-F}(2)] (6a) was also characterized by an X-ray diffraction study. Complexes 1a-6a have been tested against a panel of human tumor cell lines in order to evaluate their cytotoxic activity. cis-Isomers were significant more potent than the corresponding trans-isomers against all tumor cell lines tested; moreover, complexes 1a and 5a showed IC(50) values from about 2-fold to 6-fold lower than those exhibited by cisplatin, used as reference platinum anticancer drug.

  9. Electrocatalytic Oxidation of Formate by [Ni(P R 2N R' 2) 2(CH 3CN)] 2+ Complexes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Galan, Brandon R.; Schöffel, Julia; Linehan, John C.

    2011-08-17

    [Ni(P R 2N R' 2) 2(CH 3CN)] 2+ complexes with R = Ph, R' = 4-MeOPh or R = Cy, R' = Ph , and a mixed-ligand [Ni(P R 2N R' 2)(P R" 2N R' 2)(CH 3CN)] 2+ with R = Cy, R' = Ph, R" = Ph, have been synthesized and characterized by single-crystal X-ray crystallography. These and previously reported complexes are shown to be electrocatalysts for the oxidation of formate in solution to produce CO 2, protons, and electrons, with rates that are first-order in catalyst and formate at formate concentrations below ~0.04 M (34 equiv). At concentrationsmore » above ~0.06 M formate (52 equiv), catalytic rates become nearly independent of formate concentration. For the catalysts studied, maximum observed turnover frequencies vary from <1.1 to 15.8 s –1 at room temperature, which are the highest rates yet reported for formate oxidation by homogeneous catalysts. These catalysts are the only base-metal electrocatalysts as well as the only homogeneous electrocatalysts reported to date for the oxidation of formate. An acetate complex demonstrating an η 1-OC(O)CH 3 binding mode to nickel has also been synthesized and characterized by single-crystal X-ray crystallography. Based on this structure and the electrochemical and spectroscopic data, a mechanistic scheme for electrocatalytic formate oxidation is proposed which involves formate binding followed by a rate-limiting proton and two-electron transfer step accompanied by CO 2 liberation. Finally, the pendant amines have been demonstrated to be essential for electrocatalysis, as no activity toward formate oxidation was observed for the similar [Ni(depe) 2] 2+ (depe = 1,2-bis(diethylphosphino)ethane) complex.« less

  10. Electrocatalytic oxidation of formate by [Ni(P(R)2N(R')2)2(CH3CN)]2+ complexes.

    PubMed

    Galan, Brandon R; Schöffel, Julia; Linehan, John C; Seu, Candace; Appel, Aaron M; Roberts, John A S; Helm, Monte L; Kilgore, Uriah J; Yang, Jenny Y; DuBois, Daniel L; Kubiak, Clifford P

    2011-08-17

    [Ni(P(R)(2)N(R')(2))(2)(CH(3)CN)](2+) complexes with R = Ph, R' = 4-MeOPh or R = Cy, R' = Ph , and a mixed-ligand [Ni(P(R)(2)N(R')(2))(P(R''(2))N(R'(2)))(CH(3)CN)](2+) with R = Cy, R' = Ph, R'' = Ph, have been synthesized and characterized by single-crystal X-ray crystallography. These and previously reported complexes are shown to be electrocatalysts for the oxidation of formate in solution to produce CO(2), protons, and electrons, with rates that are first-order in catalyst and formate at formate concentrations below ∼0.04 M (34 equiv). At concentrations above ∼0.06 M formate (52 equiv), catalytic rates become nearly independent of formate concentration. For the catalysts studied, maximum observed turnover frequencies vary from <1.1 to 15.8 s(-1) at room temperature, which are the highest rates yet reported for formate oxidation by homogeneous catalysts. These catalysts are the only base-metal electrocatalysts as well as the only homogeneous electrocatalysts reported to date for the oxidation of formate. An acetate complex demonstrating an η(1)-OC(O)CH(3) binding mode to nickel has also been synthesized and characterized by single-crystal X-ray crystallography. Based on this structure and the electrochemical and spectroscopic data, a mechanistic scheme for electrocatalytic formate oxidation is proposed which involves formate binding followed by a rate-limiting proton and two-electron transfer step accompanied by CO(2) liberation. The pendant amines have been demonstrated to be essential for electrocatalysis, as no activity toward formate oxidation was observed for the similar [Ni(depe)(2)](2+) (depe = 1,2-bis(diethylphosphino)ethane) complex.

  11. Electrocatalytic Oxidation of Formate by [Ni(P R 2 N R' 2 ) 2 (CH 3 CN)] 2+ Complexes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Galan, Brandon R.; Schöffel, Julia; Linehan, John C.

    2011-08-17

    New [Ni(P R 2N R` 2) 2+(CH 3CN)] 2+ complexes with R = Ph, R` = 4-MeOPh; R = Cy, R` = Ph and a mixed ligand [Ni(P R 2N R` 2)(P R`` 2N R` 2)] 2+ with R = Cy, R` = Ph, R`` = Ph have been synthesized and characterized by single crystal X-ray crystallography. These complexes are shown to be electrocatalysts for the oxidation of formate in solution to produce CO 2, protons, and electrons with rates which are first order in catalyst and in formate at formate concentrations below approximately 0.05 M. For the catalysts studied,more » maximum observed turnover frequencies vary from <1.1 s -1 to 12.5 s -1 at room temperature, which are the highest rates yet reported for formate oxidation by homogeneous catalysts. A mechanistic scheme is proposed which involves an initial nickel complex bound <1-OC(O)H followed by a rate limiting hydride transfer step. An acetate complex demonstrating the η 1-OC(O)CH 3 binding mode to nickel has also been synthesized and characterized by single crystal X-ray crystallography. The pendant amines have been demonstrated to be essential for this electrocatalytic activity as no activity toward formate was found for the similar [Ni(depe) 2][BF 4] 2+ (depe = diethylphosphinoethane) complex. This work was supported by the US Department of Energy Basic Energy Sciences' Chemical Sciences, Geosciences & Biosciences Division. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.« less

  12. Design and synthesis of N-(3,3-diphenylpropenyl)alkanamides as a novel class of high-affinity MT2-selective melatonin receptor ligands.

    PubMed

    Bedini, Annalida; Spadoni, Gilberto; Gatti, Giuseppe; Lucarini, Simone; Tarzia, Giorgio; Rivara, Silvia; Lorenzi, Simone; Lodola, Alessio; Mor, Marco; Lucini, Valeria; Pannacci, Marilou; Scaglione, Francesco

    2006-12-14

    A novel series of melatonin receptor ligands was discovered by opening the cyclic scaffolds of known classes of high affinity melatonin receptor antagonists, while retaining the pharmacophore elements postulated by previously described 3D-QSAR and receptor models. Compounds belonging to the classes of 2,3- and [3,3-diphenylprop(en)yl]alkanamides and of o- or [(m-benzyl)phenyl]ethyl-alkanamides were synthesized and tested on MT(1) and MT(2) receptors. The class of 3,3-diphenyl-propenyl-alkanamides was the most interesting one, with compounds having MT(2) receptor affinity similar to that of MLT, remarkable MT(2) selectivity, and partial agonist or antagonist behavior. In particular, the (E)-m-methoxy cyclobutanecarboxamido derivative 18f and the di-(m-methoxy) acetamido one, 18g, have sub-nM affinity for the MT(2) subtype, with more than 100-fold selectivity over MT(1), 18f being an antagonist and 18g a partial agonist on GTPgammaS test. Docking of 18g into a previously developed MT(2) receptor model showed a binding scheme consistent with that of other antagonists. The MT(2) expected binding affinities of the new compounds were calculated by a previously developed 3D-QSAR CoMFA model, giving satisfactory predictions.

  13. Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists.

    PubMed

    Hansen, Martin; Phonekeo, Karina; Paine, James S; Leth-Petersen, Sebastian; Begtrup, Mikael; Bräuner-Osborne, Hans; Kristensen, Jesper L

    2014-03-19

    N-Benzyl substitution of 5-HT2A receptor agonists of the phenethylamine structural class of psychedelics (such as 4-bromo-2,5-dimethoxyphenethylamine, often referred to as 2C-B) confer a significant increase in binding affinity as well as functional activity of the receptor. We have prepared a series of 48 compounds with structural variations in both the phenethylamine and N-benzyl part of the molecule to determine the effects on receptor binding affinity and functional activity at 5-HT2A and 5-HT2C receptors. The compounds generally had high affinity for the 5-HT2A receptor with 8b having the highest affinity at 0.29 nM but with several other compounds also exhibiting subnanomolar binding affinities. The functional activity of the compounds was distributed over a wider range with 1b being the most potent at 0.074 nM. Most of the compounds exhibited low to moderate selectivity (1- to 40-fold) for the 5-HT2A receptor in the binding assays, although one compound 6b showed an impressive 100-fold selectivity for the 5-HT2A receptor. In the functional assay, selectivity was generally higher with 1b being more than 400-fold selective for the 5-HT2A receptor.

  14. A simple spectrophotometric method for the determination of trace levels of molybdenum using N,N'-bis(2-hydroxy-5-bromo-benzyl)1,2 diaminopropane.

    PubMed

    Kara, Derya; Karadaş, Cennet

    2015-08-05

    The present work describes a selective, rapid and economical spectrophotometric method for the determination of molybdenum using N,N'-bis(2-hydroxy-5-bromo-benzyl)1,2 diaminopropane. Molybdenum(VI) reacts with N,N'-bis(2-hydroxy-5-bromo-benzyl)1,2 diaminopropane to form a stable 1:1 yellow complex with an absorption maximum at 342 nm. The reaction is completed within 10 min and the absorbance of the molybdenum complex remains stable for at least 1 week at room temperature. The effective molar absorption coefficient at 342 nm was 9.6 × 10(3)L mol(-1)cm(-1). Under optimal conditions, the complex obeys Beer's law from 0 to 9.9 μg mL(-1). The relative standard deviation was 0.08% (for 11 samples, each containing 6 μg mL(-1) molybdenum). Under the optimum conditions, the detection limit (3σ) was 17.7 μg L(-1) for molybdenum without any preconcentration. The precision was determined from 30 results obtained for 4.80 μg mL(-1) Mo(VI); the mean value of a molybdenum(VI) was 4.83 μg ml(-1) with a standard derivation of 0.002 μg ml(-1) molybdenum(VI). Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a series of anti-HIV-1 agents of the dihydro-alkoxy-benzyl-oxopyrimidine family with peculiar structure-activity relationship profile.

    PubMed

    Nawrozkij, Maxim B; Rotili, Dante; Tarantino, Domenico; Botta, Giorgia; Eremiychuk, Alexandre S; Musmuca, Ira; Ragno, Rino; Samuele, Alberta; Zanoli, Samantha; Armand-Ugón, Mercedes; Clotet-Codina, Imma; Novakov, Ivan A; Orlinson, Boris S; Maga, Giovanni; Esté, José A; Artico, Marino; Mai, Antonello

    2008-08-14

    A series of dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) bearing a 2-aryl-2-oxoethylsulfanyl chain at pyrimidine C2, an alkyl group at C5, and a 2,6-dichloro-, 2-chloro-6-fluoro-, and 2,6-difluoro-benzyl substitution at C6 (oxophenethyl- S-DABOs, 6-8) is here described. The new compounds showed low micromolar to low nanomolar (in one case subnanomolar) inhibitory activity against wt HIV-1. Against clinically relevant HIV-1 mutants (K103N, Y181C, and Y188L) as well as in enzyme (wt and K103N, Y181I, and L100I mutated RTs) assays, compounds carrying an ethyl/ iso-propyl group at C5 and a 2,6-dichloro-/2-chloro-6-fluoro-benzyl moiety at C6 were the most potent derivatives, also characterized by low fold resistance ratio. Interestingly, the structure-activity relationship (SAR) data drawn from this DABO series are more related to HEPT than to DABO derivatives. These findings were at least in part rationalized by the description of a fair superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in both WT and Y181C RTs.

  16. Synthesis and Structure–Activity Relationships of N-Benzyl Phenethylamines as 5-HT2A/2C Agonists

    PubMed Central

    2014-01-01

    N-Benzyl substitution of 5-HT2A receptor agonists of the phenethylamine structural class of psychedelics (such as 4-bromo-2,5-dimethoxyphenethylamine, often referred to as 2C-B) confer a significant increase in binding affinity as well as functional activity of the receptor. We have prepared a series of 48 compounds with structural variations in both the phenethylamine and N-benzyl part of the molecule to determine the effects on receptor binding affinity and functional activity at 5-HT2A and 5-HT2C receptors. The compounds generally had high affinity for the 5-HT2A receptor with 8b having the highest affinity at 0.29 nM but with several other compounds also exhibiting subnanomolar binding affinities. The functional activity of the compounds was distributed over a wider range with 1b being the most potent at 0.074 nM. Most of the compounds exhibited low to moderate selectivity (1- to 40-fold) for the 5-HT2A receptor in the binding assays, although one compound 6b showed an impressive 100-fold selectivity for the 5-HT2A receptor. In the functional assay, selectivity was generally higher with 1b being more than 400-fold selective for the 5-HT2A receptor. PMID:24397362

  17. X-ray and conformational investigations of a 4:1 mixture of 6-(N-benzyl-N-tert-butoxycarbonylamino)-2,3,6,7-tetradeoxy-alpha- DL-ery thro- and -beta-DL-threo-hept-2-enopyranos-4-uloses.

    PubMed

    Krajewski, J W; Urbańczyk-Lipkowska, Z; Gluziński, P; Jurczak, J; Raczko, J; Gołebiowski, A

    1990-07-01

    The crystals of a 4:1 mixture of 6-(N-benzyl-N-tert-butoxycarbonylamino)-2,3,6,7-tetradeoxy-a-DL-er ythro- and -beta-DL-threo-hept-2-enopyranos-4-ulose were monoclinic, space group P2(1)/c, with cell dimensions: a = 9.490(2), b = 21.516(5), c = 10.279(2) A, beta = 115.31(1) degrees, Z = 4. The ulose ring had a half-chair conformation deformed towards the sofa (envelope) form.

  18. Crystal structures of 3,5-bis-[(E)-3-hy-droxy-benzyl-idene]-1-methyl-piperidin-4-one and 3,5-bis-[(E)-2-chloro-benzyl-idene]-1-methyl-piperidin-4-one.

    PubMed

    Eryanti, Yum; Zamri, Adel; Herlina, Tati; Supratman, Unang; Rosli, Mohd Mustaqim; Fun, Hoong-Kun

    2015-12-01

    The title compounds, C20H19NO3, (1), and C20H17Cl2NO, (2), are the 3-hy-droxy-benzyl-idene and 2-chloro-benzyl-idene derivatives, respectively, of curcumin [systematic name: (1E,6E)-1,7-bis-(4-hy-droxy-3-meth-oxy-phen-yl)-1,6-hepta-diene-3,5-dione]. The dihedral angles between the benzene rings in each compound are 21.07 (6)° for (1) and 13.4 (3)° for (2). In both compounds, the piperidinone rings adopt a sofa confirmation and the methyl group attached to the N atom is in an equatorial position. In the crystal of (1), two pairs of O-H⋯N and O-H⋯O hydrogen bonds link the mol-ecules, forming chains along [10-1]. The chains are linked via C-H⋯O hydrogen bonds, forming undulating sheets parallel to the ac plane. In the crystal of (2), mol-ecules are linked by weak C-H⋯Cl hydrogen bonds, forming chains along the [204] direction. The chains are linked along the a-axis direction by π-π inter-actions [inter-centroid distance = 3.779 (4) Å]. For compound (2), the crystal studied was a non-merohedral twin with the refined ratio of the twin components being 0.116 (6):0.886 (6).

  19. Structures of exocyclic R,R- and S,S-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine adducts induced by 1,2,3,4-diepoxybutane.

    PubMed

    Kowal, Ewa A; Seneviratne, Uthpala; Wickramaratne, Susith; Doherty, Kathleen E; Cao, Xiangkun; Tretyakova, Natalia; Stone, Michael P

    2014-05-19

    1,3-Butadiene (BD) is an industrial and environmental chemical present in urban air and cigarette smoke, and is classified as a human carcinogen. It is oxidized by cytochrome P450 to form 1,2,3,4-diepoxybutane (DEB); DEB bis-alkylates the N(6) position of adenine in DNA. Two enantiomers of bis-N(6)-dA adducts of DEB have been identified: R,R-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (R,R-DHB-dA), and S,S-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (S,S-DHB-dA) [ Seneviratne , U. , Antsypovich , S. , Dorr , D. Q. , Dissanayake , T. , Kotapati , S. , and Tretyakova , N. ( 2010 ) Chem. Res. Toxicol. 23 , 1556 -1567 ]. Herein, the R,R-DHB-dA and S,S-DHB-dA adducts have been incorporated into the 5'-d(C(1)G(2)G(3)A(4)C(5)X(6)A(7)G(8)A(9)A(10)G(11))-3':5'-d(C(12)T(13)T(14)C(15)T(16)T(17)G(18)T(19)C(20)C(21)G(22))-3' duplex [X(6) = R,R-DHB-dA (R(6)) or S,S-DHB-dA (S(6))]. The structures of the duplexes were determined by molecular dynamics calculations, which were restrained by experimental distances obtained from NMR data. Both the R,R- and S,S-DHB-dA adducts are positioned in the major groove of DNA. In both instances, the bulky 3,4-dihydroxypyrrolidine rings are accommodated by an out-of-plane rotation about the C6-N(6) bond of the bis-alkylated adenine. In both instances, the directionality of the dihydroxypyrrolidine ring is evidenced by the pattern of NOEs between the 3,4-dihydroxypyrrolidine protons and DNA. Also in both instances, the anti conformation of the glycosyl bond is maintained, which combined with the out-of-plane rotation about the C6-N(6) bond, allows the complementary thymine, T(17), to remain stacked within the duplex, and form one hydrogen bond with the modified base, between the imine nitrogen of the modified base and the T(17) N3H imino proton. The loss of the second Watson-Crick hydrogen bonding interaction at the lesion sites correlates with the lower thermal stabilities of the R,R- and S,S-DHB-dA duplexes, as

  20. 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.

    PubMed

    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.

  1. Structures of Exocyclic R,R- and S,S-N6,N6-(2,3-Dihydroxybutan-1,4-diyl)-2′-Deoxyadenosine Adducts Induced by 1,2,3,4-Diepoxybutane

    PubMed Central

    2015-01-01

    1,3-Butadiene (BD) is an industrial and environmental chemical present in urban air and cigarette smoke, and is classified as a human carcinogen. It is oxidized by cytochrome P450 to form 1,2,3,4-diepoxybutane (DEB); DEB bis-alkylates the N6 position of adenine in DNA. Two enantiomers of bis-N6-dA adducts of DEB have been identified: R,R-N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (R,R-DHB-dA), and S,S-N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (S,S-DHB-dA) [SeneviratneU., AntsypovichS., DorrD. Q., DissanayakeT., KotapatiS., and TretyakovaN. (2010) Chem. Res. Toxicol.23, 1556−156720873715]. Herein, the R,R-DHB-dA and S,S-DHB-dA adducts have been incorporated into the 5′-d(C1G2G3A4C5X6A7G8A9A10G11)-3′:5′-d(C12T13T14C15T16T17G18T19C20C21G22)-3′ duplex [X6 = R,R-DHB-dA (R6) or S,S-DHB-dA (S6)]. The structures of the duplexes were determined by molecular dynamics calculations, which were restrained by experimental distances obtained from NMR data. Both the R,R- and S,S-DHB-dA adducts are positioned in the major groove of DNA. In both instances, the bulky 3,4-dihydroxypyrrolidine rings are accommodated by an out-of-plane rotation about the C6-N6 bond of the bis-alkylated adenine. In both instances, the directionality of the dihydroxypyrrolidine ring is evidenced by the pattern of NOEs between the 3,4-dihydroxypyrrolidine protons and DNA. Also in both instances, the anti conformation of the glycosyl bond is maintained, which combined with the out-of-plane rotation about the C6-N6 bond, allows the complementary thymine, T17, to remain stacked within the duplex, and form one hydrogen bond with the modified base, between the imine nitrogen of the modified base and the T17 N3H imino proton. The loss of the second Watson–Crick hydrogen bonding interaction at the lesion sites correlates with the lower thermal stabilities of the R,R- and S,S-DHB-dA duplexes, as compared to the corresponding unmodified duplex. The reduced base stacking at the

  2. Pretreatment with 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-D-pyranoside Attenuates Cerebral Ischemia/Reperfusion-Induced Injury In Vitro and In Vivo

    PubMed Central

    Chen, Xia; Deng, Aiqing; Zhou, Tianqiu; Ding, Fei

    2014-01-01

    Salidroside, extracted from the root of Rhodiola rosea L, is known for its pharmacological properties, in particular its neuroprotective effects. 2-(4-Methoxyphenyl) ethyl-2-acetamido-2-deoxy-β-D- pyranoside (GlcNAc-Sal), an analog of salidroside, was recently synthesized and shown to possess neuroprotective properties. The purpose of the current study was to investigate the neuroprotective effects of GlcNAc-Sal against oxygen–glucose deprivation-reperfusion (OGD-R)-induced neurotoxicity in vitro and global cerebral ischemia-reperfusion (GCI-R) injury in vivo. Cell viability tests and Hoechst 33342 staining confirmed that GlcNAc-Sal pretreatment markedly attenuated OGD-R induced apoptotic cell death in immortalized mouse hippocampal HT22 cells. Western blot, immunofluorescence and PCR analyses revealed that GlcNAc-Sal pretreatment restored the balance of pro- and anti-apoptotic proteins and inhibited the activation of caspase-3 and PARP induced by OGD-R treatment. Further analyses showed that GlcNAc-Sal pretreatment antagonized reactive oxygen species (ROS) generation, iNOS-derived NO production and NO-related apoptotic cell death during OGD-R stimulation. GCI-R was induced by bilateral common carotid artery occlusion (BCCAO) and reperfusion in mice in vivo. Western blot analysis showed that GlcNAc-Sal pretreatment decreased the expression of caspase-3 and increased the expression of Bcl-2 (B-cell lymphoma 2)/Bax (Bcl-2-associated X protein) induced by GCI-R treatment. Our findings suggest that GlcNAc-Sal pretreatment prevents brain ischemia reperfusion injury by the direct or indirect suppression of cell apoptosis and GlcNAc-Sal could be developed as a broad-spectrum agent for the prevention and/or treatment of cerebral ischemic injury. PMID:24991917

  3. Tellurium(0) as a ligand: synthesis and characterization of 2-pyridyltellurolates of platinum(II) and structures of [Pt{2-Te-3-(R)C5H3N}2Te(PR'3)] (R = H or Me).

    PubMed

    Chauhan, Rohit Singh; Kedarnath, G; Wadawale, Amey; Muñoz-Castro, Alvaro; Arratia-Perez, Ramiro; Jain, Vimal K; Kaim, Wolfgang

    2010-05-03

    Treatment of toluene solutions of the ditellurides [Te(2){C(5)H(3)N(R)-3}(2)] (R = H or Me) with [Pt(PPh(3))(4)] yielded two types of complexes, [Pt{2-Te-3-(R)C(5)H(3)N}(2)(PPh(3))(2)] (1a-d) as the major products and [Pt{2-Te-3-(R)C(5)H(3)N}(2)Te(PPh(3))] (2a-d) as minor products. The above complexes can also be obtained by the reaction of [PtCl(2)(PR'(3))(2)] (PR'(3) = PPh(3) or PPh(2)(2-C(5)H(4)N)) with 2 equiv of Na(2-Te-C(5)H(3)R). The complexes were characterized by elemental analyses and UV-vis, NMR ((1)H and (31)P), and (in part) XPS spectroscopy. The molecular structures of [Pt(2-Te-C(5)H(4)N)(2)Te(PPh(3))] (2a) and [Pt{2-Te-C(5)H(3)(Me)N}(2)Te(PPh(3))] (2b) were established by single crystal X-ray diffraction. Both complexes exhibit a distorted square-planar configuration at the platinum(II) centers. The two mutually trans positioned 2-pyridinetellurolate ligands [2-Te-C(5)H(3)(R)N] coordinate to the central platinum atom in a monodentate fashion through the tellurium atoms. The tellurium(0) atom adopts a "bent T" configuration as it is bridging the 2-Te- C(5)H(3)(R)N molecules via N-Te-N bonds (166 degrees angle) and coordinates to Pt(II) in the trans position to PPh(3). The novel bis(pyridine)tellurium(0) arrangement resembles the bis(pyridine)iodonium structure. The calculated NICS indices and ELF functions clearly show that the compounds 2a and 2b are aromatic in the region defined by the Te-C-N-Te-Pt five-membered rings.

  4. Photolabeling a Nicotinic Acetylcholine Receptor (nAChR) with an (α4)32)2 nAChR-Selective Positive Allosteric Modulator

    PubMed Central

    Deba, Farah; Wang, Ze-Jun; Cohen, Jonathan B.

    2016-01-01

    Positive allosteric modulators (PAMs) of nicotinic acetylcholine (ACh) receptors (nAChRs) have potential clinical applications in the treatment of nicotine dependence and many neuropsychiatric conditions associated with decreased brain cholinergic activity, and 3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrrazol-4-yl)isoxazole (CMPI) has been identified as a PAM selective for neuronal nAChRs containing the α4 subunit. In this report, we compare CMPI interactions with low-sensitivity (α4)32)2 and high-sensitivity (α4)22)3 nAChRs, and with muscle-type nAChRs. In addition, we use the intrinsic reactivity of [3H]CMPI upon photolysis at 312 nm to identify its binding sites in Torpedo nAChRs. Recording from Xenopus oocytes, we found that CMPI potentiated maximally the responses of (α4)32)2 nAChR to 10 μM ACh (EC10) by 400% and with an EC50 of ∼1 µM. CMPI produced a left shift of the ACh concentration-response curve without altering ACh efficacy. In contrast, CMPI inhibited (∼35% at 10 µM) ACh responses of (α4)22)3 nAChRs and fully inhibited human muscle and Torpedo nAChRs with IC50 values of ∼0.5 µM. Upon irradiation at 312 nm, [3H]CMPI photoincorporated into each Torpedo [(α1)2β1γδ] nAChR subunit. Sequencing of peptide fragments isolated from [3H]CMPI-photolabeled nAChR subunits established photolabeling of amino acids contributing to the ACh binding sites (αTyr190, αTyr198, γTrp55, γTyr111, γTyr117, δTrp57) that was fully inhibitable by agonist and lower-efficiency, state-dependent [3H]CMPI photolabeling within the ion channel. Our results establish that CMPI is a potent potentiator of nAChRs containing an α4:α4 subunit interface, and that its intrinsic photoreactivy makes it of potential use to identify its binding sites in the (α4)32)2 nAChR. PMID:26976945

  5. Ketone isosteres of 2-N-acetamidosugars as substrates for metabolic cell surface engineering

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hang, Howard C.; Bertozzi, Carolyn R.

    2000-08-22

    Novel chemical reactivity can be engendered on cell surfaces by the metabolic incorporation of unnatural sugars into cell surface glycoconjuagtes. 2-N-Acetamido sugars such as GalNAc and GlcNAc are abundant components of cell surface glycoconjugates, and hence attractive targets for metabolic cell surface engineering. Here we report (1) the synthesis of isosteric analogs bearing a ketone group in place of the N-acetamido group, and (2) evaluation of their metabolic incorporation into mammalian cell surface glycans. A ketone isostere of GalNAc was metabolized by CHO cells through the salvage pathway and delivered to O-linked glycoproteins on the cell surface. Its residence atmore » the core position of O-linked glycans is suggested by studies with a-benzyl GalNAc, an inhibitor of O-linked oligosaccharide extension. A mutant CHO cell line lacking endogenous UDP-GalNAc demonstrated enhanced metabolism of the GalNAc analog, suggesting that competition with native intermediates might limits enzymatic transformation in mammalian cells. A ketone isostere of GlcNAc could not be detected on CHO or human cell surfaces after incubation. Thus, the enzymes in the GlcNAc salvage pathway might be less permissive of unnatural substrates than those comprising the GalNAc salvage pathway. Alternatively, high levels of endogenous GlcNAc derivatives might compete with the ketone isostere and prevent its incorporation into oligosaccharides.« less

  6. Efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc) and sp(2)-iminosugar conjugates: Novel hexosaminidase inhibitors with discrimination capabilities between the mature and precursor forms of the enzyme.

    PubMed

    de la Fuente, Alex; Rísquez-Cuadro, Rocío; Verdaguer, Xavier; García Fernández, José M; Nanba, Eiji; Higaki, Katsumi; Ortiz Mellet, Carmen; Riera, Antoni

    2016-10-04

    Due to their capacity to inhibit hexosaminidases, 2-acetamido-1,2-dideoxy-iminosugars have been widely studied as potential therapeutic agents for various diseases. An efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc), the most potent inhibitor of human placenta β-N-acetylglucosaminidase (β-hexosaminidase) among the epimeric series, is here described. This novel procedure can be easily scaled up, providing enough material for structural modifications and further biological tests. Thus, two series of sp(2)-iminosugar conjugates derived from DAJNAc have been prepared, namely monocyclic DAJNAc-thioureas and bicyclic 2-iminothiazolidines, and their glycosidase inhibitory activity evaluated. The data evidence the utmost importance of developing diversity-oriented synthetic strategies allowing optimization of electrostatic and hydrophobic interactions to achieve high inhibitory potencies and selectivities among isoenzymes. Notably, strong differences in the inhibition potency of the compounds towards β-hexosaminidase from human placenta (mature) or cultured fibroblasts (precursor form) were encountered. The ensemble of data suggests that the ratio between them, and not the inhibition potency towards the placenta enzyme, is a good indication of the chaperoning potential of TaySachs disease-associated mutant hexosaminidase. Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  7. Molecular structure studies of (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol

    PubMed Central

    Zhang, Tao; Paluch, Krzysztof; Scalabrino, Gaia; Frankish, Neil; Healy, Anne-Marie; Sheridan, Helen

    2015-01-01

    The single enantiomer (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol (2), has recently been synthesized and isolated from its corresponding diastereoisomer (1). The molecular and crystal structures of this novel compound have been fully analyzed. The relative and absolute configurations have been determined by using a combination of analytical tools including X-ray crystallography, X-ray Powder Diffraction (XRPD) analysis and Nuclear Magnetic Resonance (NMR) spectroscopy. PMID:25750458

  8. Reactions of R(2)P-P(SiMe(3))Li with [(R'(3)P)(2)PtCl(2)]. A general and efficient entry to phosphanylphosphinidene complexes of platinum. Syntheses and structures of [(eta(2)-P=(i)Pr(2))Pt(p-Tol(3)P)(2)], [(eta(2)-P=(t)Bu(2))Pt(p-Tol(3)P)(2)], [{eta(2)-P=(N(i)Pr(2))(2)}Pt(p-Tol(3)P)(2)] and [{(Et(2)PhP)(2)Pt}(2)P(2)].

    PubMed

    Domańska-Babul, Wioleta; Chojnacki, Jaroslaw; Matern, Eberhard; Pikies, Jerzy

    2009-01-07

    The reactions of lithium derivatives of diphosphanes R(2)P-P(SiMe(3))Li (R = (t)Bu, (i)Pr, Et(2)N and (i)Pr(2)N) with [(R'(3)P)(2)PtCl(2)] (R'(3)P = Et(3)P, Et(2)PhP, EtPh(2)P and p-Tol(3)P) proceed in a facile manner to afford side-on bonded phosphanylphosphinidene complexes of platinum [(eta(2)-P=R(2))Pt(PR'(3))(2)]. The related reactions of Ph(2)P-P(SiMe(3))Li with [(R'(3)P)(2)PtCl(2)] did not yield [(eta(2)-P=PPh(2))Pt(PR'(3))(2)] and resulted mainly in the formation of [{(R'(3)P)(2)Pt}(2)P(2)], Ph(2)P-PLi-PPh(2), (Me(3)Si)(2)PLi and (Me(3)Si)(3)P. Crystallographic data are reported for the compounds [(eta(2)-P=R(2))Pt(p-Tol(3)P)(2)] (R = (t)Bu, (i)Pr, ((i)Pr(2)N)(2)P) and for [{(Et(2)PhP)(2)Pt}(2)P(2)].

  9. Selective cyclopalladation of R3P=NCH2Aryl iminophosphoranes. Experimental and computational study.

    PubMed

    Bielsa, Raquel; Navarro, Rafael; Urriolabeitia, Esteban P; Lledós, Agustí

    2007-11-26

    The orientation of the orthopalladation of iminophosphoranes R3P=NCH2Aryl (R=Ph, Aryl=Ph (1a), C6H(4)-2-Br (1b), C6H4-Me-2 (1e), C6H3-(Me)(2)-2,5 (1f); R=p-tolyl, Aryl=Ph (1c); R=m-tolyl, Aryl=Ph (1d); R3P=MePh2P, and Aryl=Ph (1g)) has been studied. 1a reacts with Pd(OAc)2 (OAc=acetate) giving endo-[Pd(micro-Cl){C,N-C6H4(PPh2=NCH2Ph)-2}]2 (3a), while exo-[Pd(micro-Br){C,N-C6H4(CH2N=PPh3)-2}]2 (3b) could only be obtained by the oxidative addition of 1b to Pd2(dba)3. The endo form of the metalated ligand is favored kinetically and thermodynamically, as shown by the conversion of exo-[Pd(micro-OAc){C,N-C6H4(CH2N=PPh3)-2}]2 (2b) into endo-[Pd(micro-OAc){C,N-C6H4(PPh2=NCH2Ph)-2}]2 (2a) in refluxing toluene. The orientation of the reaction is not affected by the introduction of electron-releasing substituents at the Ph rings of the PR3 (1c and 1d) or the benzyl units (1e and 1f), and endo complexes (3c-3f) were obtained in all cases. The palladation of MePh2P=NCH2Ph (1g) can be regioselectively oriented as a function of the solvent. The exo isomer [Pd(micro-Cl){C6H4(CH2N=PPh2Me)-2}]2 (exo-3g) is obtained in refluxing CH2Cl2, while endo-[Pd(micro-Cl){C,N-C6H4(PPh(Me)=NCH2Ph)-2}]2 (endo-3g) can be isolated as a single isomer in refluxing toluene. In this case, the exo metalation is kinetically favored while an endo process occurs under thermodynamic control, as shown through the rearrangement of [Pd(micro-OAc){C6H4(CH2N=PPh2Me)-2}]2 (exo-2g) into [Pd(micro-OAc){C,N-C6H4(P(Ph)Me=NCH2Ph)-2}]2 (endo-2g) in refluxing toluene. The preference for the endo palladation of 1a and the kinetic versus thermodynamic control in 1g has been explained through DFT studies of the reaction mechanism.

  10. New Synthesis, Structure and Analgesic Properties of Methyl 1-R-4-Methyl-2,2-Dioxo-1H-2λ⁶,1-Benzothiazine-3-Carboxylates.

    PubMed

    Azotla-Cruz, Liliana; Lijanova, Irina V; Ukrainets, Igor V; Likhanova, Natalya V; Olivares-Xometl, Octavio; Bereznyakova, Natalya L

    2017-01-12

    According to the principles of the methodology of bioisosteric replacements a series of methyl 1-R-4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylates has been obtained as potential analgesics. In addition, a fundamentally new strategy for the synthesis of compounds of this chemical class involving the introduction of N -alkyl substituent at the final stage in 2,1-benzothiazine nucleus already formed has been proposed. Using nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry and X-ray diffraction analysis it has been proven that in the DMSO/K₂CO₃ system the reaction of methyl 4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylate and alkyl halides leads to formation of N -substituted derivatives with good yields regardless of the structure of the alkylating agent. The peculiarities of NMR (¹Н and 13 С) spectra of the compounds synthesized, their mass spectrometric behavior and the spatial structure are discussed. In N -benzyl derivative the ability to form a monosolvate with methanol has been found. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick it has been determined that replacement of 4-ОН-group in methyl 1-R-4-hydroxy-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylates for the methyl group is actually bioisosteric since all methyl 1-R-4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylates synthesized demonstrated a statistically significant analgesic effect. The majority of the substances can inhibit the thermal pain response much more effective than piroxicam in the same dose. Under the same conditions as an analgesic the N- methyl-substituted analog exceeds not only piroxicam, but more active meloxicam as well. Therefore, it deserves in-depth biological studies on other experimental models.

  11. Computational study of the binding mechanism between farnesoid X receptor α and antagonist N-benzyl-N-(3-(tertbutyl)-4-hydroxyphenyl)-2,6-dichloro-4-(dimethylamino) benzamide.

    PubMed

    Du, Juan; Qiu, Miaoxue; Guo, Lizhong; Yao, Xiaojun

    2018-05-02

    Farnesoid X receptor α (FXRα) is a bile acid-activated transcription factor, which plays important roles in the regulation of multiple metabolic processes. Development of FXR antagonist has revealed great potential for the treatment of metabolic disorders. The compound N-Benzyl-N-(3-(tertbutyl)-4-hydroxyphenyl)-2,6-dichloro-4-(dimethylamino). Benzamide (NDB) was recently determined as a selective antagonist of FXRα, while the detailed interaction mechanism is not well understood. In this study, the combined computational methods including molecular dynamics simulations, binding free energy calculation, and principal component analysis were utilized to investigate the effect of NDB on the dynamics behaviors and dimerization of FXRα The binding free energy calculation indicated that the protein dimerization increases NDB affinity and the binding of NDB also stabilizes the interaction between two subunits of FXRα. Further decomposition of the overall binding free energies into individual residues identifies several residues significant for NDB binding, including Leu291, Met294, Ala295, His298, Met332, Ser336, Ala452, and Leu455. It also suggests that the interactions of L289(A)-W458(B), W458(A)-L289(B), R459(A)-N461(B), and N461(A)-R459(B) are important for the dimer stabilization. This study provides a molecular basis for the understanding of binding mechanism between antagonist NDB and FXRα and valuable information for the novel FXR modulators design for the treatment of metabolic syndrome.

  12. Mercury-Bridged Cobaltacarborane Complexes Containing B-Hg-B Three-Center Bonds. Synthesis and Structure of mu, mu’-((n5-C5R5)Co(CH3)2C2B3H4)Hg, mu-(n(5)-C5R5)Co(CH3)2C2B3H4)HgCl, (R=H, CH3) and Related Compounds.

    DTIC Science & Technology

    1980-11-01

    MERCURY-BRIDGED COBALTACARBORANE COMPLEXES CONTAINING B-HG-B TH--ETC(U) NOV 80 D C FINSTER . R N GRIMES N0 0 0 1 4-75-0305 UNCLASSXFIED TR󈧨 NL ILn...C5R5) Co 3)2C2B3 4 2 5 .- -C5R5 )Co(CH3)2C2B3H4 ]HgCl, (R=H, CH3 ) and Related Compounds, David C./ Finster -- Russell N./Grimes ( Department of Chemistry...Compounds 1 \\David C. Finster And Russell N. Grimes* Abstract. Reactions of the nid~p-cobaltacarborane anions 01CR )(C 3 )C BH and [n (H 1oC ihH~5n 5

  13. Bis(2-{2-[2-(benzyl­carbamo­yl)phen­oxy]acetamido}­eth­yl)ammonium nitrate ethanol disolvate

    PubMed Central

    Liu, Jiaji; Tang, Xiaoliang; Lu, Zhengdan; Zhang, Guolin; Liu, Weisheng

    2011-01-01

    In the title compound, C36H40N5O6 +·NO3 −·2C2H5OH, the nitrate anion is disordered over the two orientations of equal occupancy while the solvent mol­ecule reveals large displacement parameters. The cation is formed by protonation of the N atom of a secondary amine in the middle of the flexible chain and the whole compound has crystallographically imposed C-2 symmetry with the crystallographic b axis. An O atom of the nitrate anion links the acidic H atoms of the cation via N—H⋯O hydrogen bonding. In addition, neighbouring cations are connected by inter­molecular N—H⋯O hydrogen bonds and π–π inter­actions between the benzamide groups of the cations [centroid–centroid distance = 4.000 (3) Å], forming a chain along [001]. The ethanol solvent mol­ecules are arranged on the side of the chain through O—H⋯O hydrogen bonds. PMID:21522705

  14. Diastereoisomers of 2-benzyl-2, 3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol: potential anti-inflammatory agents.

    PubMed

    Sheridan, Helen; Walsh, John J; Cogan, Carina; Jordan, Michael; McCabe, Tom; Passante, Egle; Frankish, Neil H

    2009-10-15

    The synthesis and biological activity of the novel diastereoisomers of 2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol is reported. The 2,2-coupled indane dimers were synthesised by coupling of the silyl enol ether of 1-indanone with the dimethyl ketal of 2-indanone. The coupled product was directly alkylated to give the racemic ketone which was reduced to the diastereoisomeric alcohols. The alcohols were separated and their relative stereochemistry was established by X-ray crystallography. These molecules demonstrate significant anti-inflammatory activity in vivo and in vitro and may represent a new class of anti-inflammatory agent.

  15. High-Field Magnetization Study of R_{2} {Fe}_{17} {N}_{2} R 2 Fe 17 N 2 ( R = {Ho} R = Ho and Er) Nitrides

    NASA Astrophysics Data System (ADS)

    Tereshina, I. S.; Tereshina-Chitrova, E. A.; Pelevin, I. A.; Doerr, M.; Law, J. M.; Verbetski, V. N.; Salamova, A. A.

    2018-03-01

    The structure and magnetic properties of the nitrided compounds R2Fe_{17}N2 (R = Ho and Er) are studied. The type of crystal structure Th2Ni_{17} is preserved upon nitrogenation, and the relative unit cell volume Δ V{/}V increase exceeds 6%. Magnetic studies are performed in fields up to 60 T at 4.2 K on aligned powder samples. Field-induced spin-reorientation (SR) transitions are observed in the M( H) curves of R2Fe_{17}N2. Unlike the parent R2Fe_{17} compounds, where the magnetization increases in steps as the field grows stronger, R2Fe_{17}N2 demonstrate a gradual increase in magnetization. It is indicative of the change of the SR transition from first to the second type. Extrapolation of magnetization curves to the theoretical value of magnetization in the forced ferromagnetic state yields the coefficient of the inter-sublattice R-Fe exchange interaction. The inter-sublattice exchange is found to decrease upon nitrogenation.

  16. Recognition of O6-benzyl-2′-deoxyguanosine by a perimidinone-derived synthetic nucleoside: a DNA interstrand stacking interaction

    PubMed Central

    Kowal, Ewa A.; Lad, Rahul R.; Pallan, Pradeep S.; Dhummakupt, Elizabeth; Wawrzak, Zdzislaw; Egli, Martin; Sturla, Shana J.; Stone, Michael P.

    2013-01-01

    The 2′-deoxynucleoside containing the synthetic base 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-1H-perimidin-2(3H)-one] (dPer) recognizes in DNA the O6-benzyl-2′-deoxyguanosine nucleoside (O6-Bn-dG), formed by exposure to N-benzylmethylnitrosamine. Herein, we show how dPer distinguishes between O6-Bn-dG and dG in DNA. The structure of the modified Dickerson–Drew dodecamer (DDD) in which guanine at position G4 has been replaced by O6-Bn-dG and cytosine C9 has been replaced with dPer to form the modified O6-Bn-dG:dPer (DDD-XY) duplex [5′-d(C1G2C3X4A5A6T7T8Y9G10C11G12)-3′]2 (X = O6-Bn-dG, Y = dPer) reveals that dPer intercalates into the duplex and adopts the syn conformation about the glycosyl bond. This provides a binding pocket that allows the benzyl group of O6-Bn-dG to intercalate between Per and thymine of the 3′-neighbor A:T base pair. Nuclear magnetic resonance data suggest that a similar intercalative recognition mechanism applies in this sequence in solution. However, in solution, the benzyl ring of O6-Bn-dG undergoes rotation on the nuclear magnetic resonance time scale. In contrast, the structure of the modified DDD in which cytosine at position C9 is replaced with dPer to form the dG:dPer (DDD-GY) [5′-d(C1G2C3G4A5A6T7T8Y9G10C11G12)-3′]2 duplex (Y = dPer) reveals that dPer adopts the anti conformation about the glycosyl bond and forms a less stable wobble pairing interaction with guanine. PMID:23748954

  17. Axial zero-field splitting in mononuclear Co(ii) 2-N substituted N-confused porphyrin: Co(2-NC3H5-21-Y-CH2C6H4CH3-NCTPP)Cl (Y = o, m, p) and Co(2-NC3H5-21-CH2C6H5-NCTPP)Cl.

    PubMed

    Lai, Ya-Yuan; Chang, Yu-Chang; Chen, Jyh-Horung; Wang, Shin-Shin; Tung, Jo-Yu

    2016-03-21

    The inner C-benzyl- and C-o-xylyl (or m-xylyl, p-xylyl)-substituted cobalt(ii) complexes of a 2-N-substituted N-confused porphyrin were synthesized from the reaction of 2-NC3H5NCTPPH (1) and CoCl2·6H2O in toluene (or o-xylene, m-xylene, p-xylene). The crystal structures of diamagnetic chloro(2-aza-2-allyl-5,10,15,20-tetraphenyl-21-hydrogen-21-carbaporphyrinato-N,N',N'')zinc(ii) [Zn(2-NC3H5-21-H-NCTPP)Cl; 3 ] and paramagnetic chloro(2-aza-2-allyl-5,10,15,20-tetraphenyl-21-benzyl-21-carbaporphyrinato-N,N',N'')cobalt(ii) [Co(2-NC3H5-21-CH2C6H5NCTPP)Cl; 7], and chloro(2-aza-2-allyl-5,10,15,20-tetraphenyl-21-Y-xylyl-21-carbaporphyrinato-N,N',N'')cobalt(ii) [Co(2-NC3H5-21-Y-CH2C6H4CH3NCTPP)Cl] [Y = o (8), m (9), p (10)] were determined. The coordination sphere around the Zn(2+) (or Co(2+)) ion in 3 (or 7-10) is a distorted tetrahedron (DT). The free energy of activation at the coalescence temperature Tc for the exchange of phenyl ortho protons o-H (26) with o-H (22) in 3 in a CDCl3 solvent is found to be ΔG = 61.4 kJ mol(-1) through (1)H NMR temperature-dependent measurements. The axial zero-field splitting parameter |D| was found to vary from 35.6 cm(-1) in 7 (or 30.7 cm(-1) in 8) to 42.0 cm(-1) in 9 and 46.9 cm(-1) in 10 through paramagnetic susceptibility measurements. The magnitude of |D| can be related to the coordination sphere at the cobalt sites.

  18. Synthesis and blood pressure lowering activity of benzylic ethers of 2-diethylaminoethanol and a related diamine.

    PubMed

    El-Antably, S M; Soine, T O; Shaath, N A; Gupta, P K

    1975-08-01

    Based upon the unpublished finding that 3'-hydroxy-4'-(beta-diethylaminoethoxy)-3',4'-dihydroseselin possessed a potent blood pressure lowering effect in the cat at a dose of 1 mg/kg, the present study examined the activities of several related compounds. These compounds were derived by dissection of the parent compound to give four benzylic ethers of 2-diethylaminoethanol and a diamine, derived by replacing the ether oxygen of the parent compound with an N--CH3 function. The simplest compounds were the benzyl and 2,6-dimethoxybenzyl ethers of the aminoalcohol. Closely related to the benzyl compound was a congener with a hydroxymethyl group on the benzylic carbon. The beta-diethylaminoethyl ether of 4-chromanol was the most complex of the ethers. The blood pressure measurements were carried out on male cats and compared to papaverine hydrochloride as a standard. In all cases, the most potent blood pressure lowering activity resided in the parent compound, which was not greatly superior to the diamine but substantially more active than the other compounds.

  19. 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.

    PubMed

    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.

  20. Resolution of 1-n-butyl-3-methyl-3-phospholene 1-oxide with TADDOL derivatives and calcium salts of O,O'-Dibenzoyl-(2R,3R)- or O,O'-di-p-toluoyl-(2R,3R)-tartaric acid.

    PubMed

    Bagi, Péter; Fekete, András; Kállay, Mihály; Hessz, Dóra; Kubinyi, Miklós; Holczbauer, Tamás; Czugler, Mátyás; Fogassy, Elemér; Keglevich, György

    2014-03-01

    The resolution methods applying (-)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane ("TADDOL"), (-)-(2R,3R)-α,α,α',α'-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol ("spiro-TADDOL"), as well as the acidic and neutral Ca(2+) salts of (-)-O,O'-dibenzoyl- and (-)-O,O'-di-p-toluoyl-(2R,3R)-tartaric acid were extended for the preparation of 1-n-butyl-3-methyl-3-phospholene 1-oxide in optically active form. In one case, the intermediate diastereomeric complex could be identified by single-crystal X-ray analysis. The absolute P-configuration of the enantiomers of the phospholene oxide was also determined by comparing the experimentally obtained and calculated CD spectra. © 2014 Wiley Periodicals, Inc.

  1. (2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

    PubMed Central

    Kozhushkov, Sergei I; Yufit, Dmitrii S; Grosse, Christian; Kaiser, Marcel

    2014-01-01

    Summary Efficient and scalable syntheses of enantiomerically pure (2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-mono(di,tri)fluoromethylcyclopropyl]alanines 9a–c, as well as allo-D-threonine (4) and (2S,3R)-β-methylphenylalanine (3), using the Belokon' approach with (S)- and (R)-2-[(N-benzylprolyl)amino]benzophenone [(S)- and (R)-10] as reusable chiral auxiliaries have been developed. Three new fluoromethyl analogues of the naturally occurring octadepsipeptide hormaomycin (1) with (fluoromethylcyclopropyl)alanine moieties have been synthesized and subjected to preliminary tests of their antibiotic activity. PMID:25550751

  2. Mapping the Reactivity and Selectivity of 2-Azidofucosyl Donors for the Assembly of N-Acetylfucosamine-Containing Bacterial Oligosaccharides.

    PubMed

    Hagen, Bas; Ali, Sara; Overkleeft, Herman S; van der Marel, Gijsbert A; Codée, Jeroen D C

    2017-01-20

    The synthesis of complex oligosaccharides is often hindered by a lack of knowledge on the reactivity and selectivity of their constituent building blocks. We investigated the reactivity and selectivity of 2-azidofucosyl (FucN 3 ) donors, valuable synthons in the synthesis of 2-acetamido-2-deoxyfucose (FucNAc) containing oligosaccharides. Six FucN 3 donors, bearing benzyl, benzoyl, or tert-butyldimethylsilyl protecting groups at the C3-O and C4-O positions, were synthesized, and their reactivity was assessed in a series of glycosylations using acceptors of varying nucleophilicity and size. It was found that more reactive nucleophiles and electron-withdrawing benzoyl groups on the donor favor the formation of β-glycosides, while poorly reactive nucleophiles and electron-donating protecting groups on the donor favor α-glycosidic bond formation. Low-temperature NMR activation studies of Bn- and Bz-protected donors revealed the formation of covalent FucN 3 triflates and oxosulfonium triflates. From these results, a mechanistic explanation is offered in which more reactive acceptors preferentially react via an S N 2-like pathway, while less reactive acceptors react via an S N 1-like pathway. The knowledge obtained in this reactivity study was then applied in the construction of α-FucN 3 linkages relevant to bacterial saccharides. Finally, a modular synthesis of the Staphylococcus aureus type 5 capsular polysaccharide repeating unit, a trisaccharide consisting of two FucNAc units, is described.

  3. Multiple Pathways for Benzyl Alcohol Oxidation by Ru V =O 3+ and Ru IV =O 2+

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Paul, Amit; Hull, Jonathan F.; Norris, Michael R.

    2011-02-21

    Significant rate enhancements are found for benzyl alcohol oxidation by the RuV=O3+ form of the water oxidation catalyst [Ru(Mebimpy)(bpy)(OH2)]2+ [Mebimpy = 2,6-bis(1-methylbenzimidazol-2-yl)pyridine; bpy = 2,2'-bipyridine] compared to RuIV=O2+ and for the RuIV=O2+ form with added bases due to a new pathway, concerted hydride proton transfer (HPT).

  4. Multiple Pathways for Benzyl Alcohol Oxidation by Ru V=O 3+ and Ru IV=O 2+

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Paul, Amit; Hull, Jonathan F.; Norris, Michael R.

    2011-01-20

    Significant rate enhancements are found for benzyl alcohol oxidation by the Ru V=O 3+ form of the water oxidation catalyst [Ru(Mebimpy)(bpy)(OH 2)] 2+ [Mebimpy = 2,6-bis(1-methylbenzimidazol-2-yl)pyridine; bpy = 2,2'-bipyridine] compared to Ru IV=O 2+ and for the Ru IV=O 2+ form with added bases due to a new pathway, concerted hydride proton transfer (HPT).

  5. Syntheses and characterization of phosphonates and diphosphonates of molybdenum, A4[(MoO3)5(O3PR)2]·xH2O, A2[Mo2O5(O3PR)2] and A2[Mo2O5(O3P-R-PO3)] (A = K, Rb, Cs, Tl, NH4).

    PubMed

    Elias Jesu Packiam, D; Vidyasagar, Kanamaluru

    2017-11-28

    Twenty new molybdenum phosphonates and diphosphonates have been synthesized and structurally characterized by single crystal and powder X-ray diffraction, CHN analyses, spectroscopic and thermal studies. Four of them are molecular phenyl- and benzyl-phosphonates containing discrete [(MoO 3 ) 5 (O 3 PR) 2 ] 4- (R = Ph or CH 2 Ph) cyclic anions. The sixteen non-molecular compounds are layered isostructural phenylphosphonates, A 2 [Mo 2 O 5 (O 3 PPh) 2 ] (A = NH 4 , Tl, Rb, Cs) and K 1.5 (H 3 O) 0.5 [Mo 2 O 5 (O 3 PPh) 2 ] and the corresponding diphosphonate compounds with pillared anionic layers, A 2 [Mo 2 O 5 (O 3 P(CH 2 ) 3 PO 3 )], A 2 [Mo 2 O 5 (O 3 P(CH 2 ) 4 PO 3 )] and A 2 [Mo 2 O 5 (O 3 P(C 6 H 4 )PO 3 )]. The A + ions reside in the interlayer region as well as in the cavities within the anionic layers.

  6. A tandem conjugate addition/cyclization protocol for the asymmetric synthesis of 2-aryl-4-aminotetrahydroquinoline-3-carboxylic acid derivatives.

    PubMed

    Davies, Stephen G; Mujtaba, Nadeam; Roberts, Paul M; Smith, Andrew D; Thomson, James E

    2009-05-07

    Condensation of tert-butyl (E)-3-(2'-aminophenyl)propenoate with a range of aromatic and heteroaromatic aldehydes gives the corresponding imines as single diastereoisomers (>98% de). Addition of lithium (R)-N-benzyl-N-(alpha-methylbenzyl)amide initiates a tandem conjugate addition/cyclization reaction to generate 2-aryl-4-aminotetrahydroquinoline-3-carboxylic acid derivatives in >98% de, >98% ee and high isolated yield. Hydrogenolysis of an N(1)-Boc protected derivative allows selective cleavage of the N-benzyl-N-alpha-methylbenzyl protecting groups without compromise of the diastereo- or enantiopurity.

  7. Multiple Pathways for Benzyl Alcohol Oxidation by Ru V=O 3+ and Ru IV=O 2+

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Paul, Amit; Hull, Jonathan F.; Norris, Michael R.

    2011-01-20

    Significant rate enhancements are found for benzyl alcohol oxidation by the Ru V=O 3+ form of the water oxidation catalyst [Ru(Mebimpy)(bpy)(OH 2)] 2+ [Mebimpy = 2,6-bis(1-methylbenzimidazol-2-yl)pyridine; bpy = 2,2'-bipyridine] compared to Ru IV=O 2+ and for the Ru IV=O 2+ form with added bases due to a new pathway involving concerted hydride proton transfer (HPT).

  8. Unusual hafnium-pyridylamido/ER(n) heterobimetallic adducts (ER(n) = ZnR2 or AlR3).

    PubMed

    Rocchigiani, Luca; Busico, Vincenzo; Pastore, Antonello; Talarico, Giovanni; Macchioni, Alceo

    2014-02-17

    NMR spectroscopy and DFT studies indicate that the Symyx/Dow Hf(IV)-pyridylamido catalytic system for olefin polymerization, [{N(-),N,CNph(-)}HfMe][B(C6F5)4] (1, Nph = naphthyl), interacts with ER(n) (E = Al or Zn, R = alkyl group) to afford unusual heterobimetallic adducts [{N(-),N}HfMe(μ-CNph)(μ-R)ER(n-1)][B(C6F5)4 in which the cyclometalated Nph acts as a bridge between Hf and E. (1)H VT (variable-temperature) EXSY NMR spectroscopy provides direct evidence of reversible alkyl exchanges in heterobimetallic adducts, with ZnR2 showing a higher tendency to participate in this exchange than AlR3. 1-Hexene/ERn competitive reactions with 1 at 240 K reveal that the formation of adducts is strongly favored over 1-hexene polymerization. Nevertheless, a slight increase in the temperature (to >265 K) initiates 1-hexene polymerization. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Synthesis of methyl 2-O- and 3-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside.

    PubMed

    Rana, S S; Matta, K L

    1986-09-01

    Methyl 3,4,6-tri-O-benzyl-2-O-[6-O-(tert-butyldiphenylsilyl)-alpha-D- mannopyranosyl]-alpha-D-mannopyranoside (2) was synthesized by treatment of methyl 3,4,6-tri-O-benzyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside with tert-butylchlorodiphenylsilane in the presence of imidazole. Isopropylidenation, followed by oxidation with pyridinium chlorochromate, and stereoselective reduction with sodium borohydride, converted 2 into methyl 3,4,6-tri-O-benzyl-2-O-[6-O-(tert-butyldiphenylsilyl)-2,3-O-isopro pylidene- alpha-D-talopyranosyl]-alpha-D-mannopyranoside (5). Treatment of 5 with a molar solution of tetrabutylammonium fluoride in dry oxolane produced a diol which, on O-de-isopropylidenation followed by catalytic hydrogenolysis, afforded the disaccharide glycoside methyl 2-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside. Synthesis of methyl 3-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside was accomplished by a similar reaction-sequence. The structures of the final disaccharides, and of various other intermediates, were established by 1H- and 13C-n.m.r. spectroscopy.

  10. N,N′-Bis(3-chloro-2-fluoro­benzyl­idene)ethane-1,2-diamine

    PubMed Central

    Fun, Hoong-Kun; Kia, Reza

    2008-01-01

    The mol­ecule of the title centrosymmetric Schiff base compound, C16H12Cl2F2N2, adopts an E configuration with respect to the azomethine C=N bond. The imino groups are coplanar with the aromatic rings. Within the mol­ecule, the planar units are parallel, but extend in opposite directions from the dimethyl­ene bridge. An inter­esting feature of the crystal structure is the short inter­molecular Cl⋯F [3.1747 (5) Å] inter­actions, which are shorter than the sum of the van der Waals radii of these atoms. These inter­actions link neighbouring mol­ecules along the b axis. The crystal structure is further stabilized by π–π inter­actions, with a centroid–centroid distance of 3.5244 (4) Å. PMID:21201124

  11. Synthesis, characterization, structural and biological aspects of copper(II) dithiocarbamate complexes - Part II, [Cu{S2CN(Me)(R1)}2], [Cu{S2CN(Me)(R2)}2] and [Cu{S2CN(R3)(R4)}2] {R1 = CH2CH(OMe)2, R2 = 2-methyl-1,3-dioxolane, R3 = CH2(CH2)2NCHPhOCH2Ph and R4 = CH2CH2OH}

    NASA Astrophysics Data System (ADS)

    Ferreira, Isabella P.; de Lima, Geraldo M.; Paniago, Eucler B.; Takahashi, Jacqueline A.; Krambrock, Klaus; Pinheiro, Carlos B.; Wardell, James L.; Visentin, Lorenzo C.

    2013-09-01

    Three new copper(II) dithiocarbamates (DTC), [Cu{S2CN(Me)(R1)}2] (1), [Cu{S2CN(Me)(R2)}2] (2) and [Cu{S2CN(R3)(R4)}2] (3) with R1 = CH2CH(OMe)2, R2 = 2-methyl-1,3-dioxolane, R3 = CH2(CH2)2NCHPhOCH2Ph and R4 = CH2CH2OH, have been synthesized and characterized by different spectroscopic techniques. Complexes (1) and (2) display typical EPR spectra for separated Cu(II) centers, and the spectrum of (3) is characteristic of two magnetically coupled Cu(II) ions with S = 1. The X-ray crystallographic determination has shown that complexes (1) and (2) crystallise in the triclinic and monoclinic systems. In addition both complexes are monomers in which the geometry at each Cu(II) is square planar. The in vitro antimicrobial activity of the sodium salts of ligands, and of the Cu(II)-DTC complexes have been screened against Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus, Penicillium citrinum and Curvularia senegalensis, as well as Gram positive and Gram negative bacteria. Finally, the toxic effects of complexes (1)-(3) were performed using Chlorella vulgaris.

  12. Aminoacid N-substituted 1,4,7-triazacyclononane and 1,4,7,10-tetraazacyclododecane Zn2+, Cd2+ and Cu2+ complexes. A preparative, potentiometric titration and NMR spectroscopic study.

    PubMed

    Plush, Sally E; Lincoln, Stephen F; Wainwright, Kevin P

    2004-05-07

    The pK(a)s and Zn2+, Cd2+ and Cu2+ complexation constants (K) for 1,4,7-tris[(2''S)-acetamido-2''-(methyl-3''-phenylpropionate)]-1,4,7-triazacyclononane, 1, 1,4,7-tris[(2''S)-acetamido-2''-(1''-carboxy-3''-phenylpropane)]-1,4,7-triazacyclononane, H(3)2, 1,4,7-tris[(2''S)-acetamido-2''-(methyl-3''-(1H-3-indolyl)propionate)]-1,4,7-triazacyclononane, 3, and 1,4,7,10-tetrakis[(2''S)-acetamido-2''-(methyl-3''-phenylpropionate)]-1,4,7,10-tetraazacyclododecane, 4, 1,4,7,10-tetrakis[(2''S)-acetamido-2''-(1''-carboxy-3''-phenylpropane)]-1,4,7,10-tetraazacyclododecane, H(4)5, in 20 : 80 v/v water-methanol solution are reported. The pK(a)s within the potentiometric detection range for H(3)1(3+) = 8.69 and 3.59, for H(6)2(3+) = 9.06, 6.13, 4.93 and 4.52, H(3)3(3+) = 8.79 and 3.67, H(4)4(4+) = 8.50, 5.62 and 3.77 and for H(8)5(4+) = 9.89, 7.06, 5.53, 5.46, 4.44 and 4.26 where each tertiary amine nitrogen is protonated. The complexes of 1: [Zn(1)]2+(9.00), [Cd(1)]2+ (6.49), [Cd(H1)]3+ (4.54) and [Cu(1)]2+ (10.01) are characterized by the log(K/dm3 mol(-1)) values shown in parentheses. Analogous complexes are formed by 3 and 4: [Zn(3)]2+ (10.19), [Cd(3)]2+ (8.54), [Cu(3)]2+ (10.77), [Zn(4)]2+ (11.41) [Cd(4)]2+ (9.16), [Cd(H4)]3+ (6.16) and [Cu(4)]2+ (11.71). The tricarboxylic acid H(3)2 generates a greater variety of complexes as exemplified by: [Zn(2)-] (10.68) [Zn(H2)] (6.60) [Zn(H(2)2)+] (5.15), [Cd(2)](-) (4.99), [Cd(H2)] (4.64), [Cd(H2(2))]+ (3.99), [Cd(H(3)2)]2+ (3.55), [Cu(2)](-) (12.55) [Cu(H2)] (7.66), [Cu(H(2)2)]+ (5.54) and [Cu(2)2](4-) (3.23). The complexes of H(4)5 were insufficiently soluble to study in this way. The 1H and 13C NMR spectra of the ligands are consistent with formation of a predominant Zn2+ and Cd2+ Delta or Lambda diastereomer. The preparations of the new pendant arm macrocycles H(3)2, 3, 4 and H(4)5 are reported.

  13. μ3-Carbonato-κ3 O:O′:O′′-tris­{(η6-ben­zene)[(R)-1-(1-amino­ethyl)naphthyl-κ2 C 2,N]ruthenium(II)} hexa­fluorido­phosphate dichloro­methane solvate

    PubMed Central

    Sortais, Jean-Baptiste; Brelot, Lydia; Pfeffer, Michel; Barloy, Laurent

    2008-01-01

    The title compound, [Ru3(C12H12N)3(CO3)(C6H6)3]PF6·CH2Cl2, was obtained unintentionally as the product of an attempted deprotonation of the monomeric parent ruthenium complex [Ru(C12H12N)(C6H6)(C2H3N)]PF6. The carbonate ligand bridges three half-sandwich cyclo­ruthenated fragments, each of them exhibiting a pseudo-tetra­hedral geometry. The configuration of the Ru atoms is S. The naphthyl groups of the enanti­opure cyclo­ruthenated benzylic amine ligands point in the same direction, adopting a propeller shape. PMID:21201869

  14. 40 CFR 721.10457 - 1,2-Benzenedicarboxylic acid, mixed esters with benzyl alc., cyclohexanol, 2-ethyl-1-hexanol...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 1,2-Benzenedicarboxylic acid, mixed... Substances § 721.10457 1,2-Benzenedicarboxylic acid, mixed esters with benzyl alc., cyclohexanol, 2-ethyl-1... reporting. (1) The chemical substance identified as 1,2-benzenedicarboxylic acid, mixed esters with benzyl...

  15. 40 CFR 721.10457 - 1,2-Benzenedicarboxylic acid, mixed esters with benzyl alc., cyclohexanol, 2-ethyl-1-hexanol...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 1,2-Benzenedicarboxylic acid, mixed... Substances § 721.10457 1,2-Benzenedicarboxylic acid, mixed esters with benzyl alc., cyclohexanol, 2-ethyl-1... reporting. (1) The chemical substance identified as 1,2-benzenedicarboxylic acid, mixed esters with benzyl...

  16. Free metal ion depletion by "Good's" buffers. III. N-(2-acetamido)iminodiacetic acid, 2:1 complexes with zinc(II), cobalt(II), nickel(II), and copper(II); amide deprotonation by Zn(II), Co(II), and Cu(II).

    PubMed

    Lance, E A; Rhodes, C W; Nakon, R

    1983-09-01

    Potentiometric, visible, infrared, electron spin, and nuclear magnetic resonance studies of the complexation of N-(2-acetamido)iminodiacetic acid (H2ADA) by Ca(II), Mg(II), Mn(II), Zn(II), Co(II), Ni(II), and Cu(II) are reported. Ca(II) and Mg(II) were found not to form 2:1 ADA2- to M(II) complexes, while Mn(II), Cu(II), Ni(II), Zn(II), and Co(II) did form 2:1 metal chelates at or below physiological pH values. Co(II) and Zn(II), but not Cu(II), were found to induce stepwise deprotonation of the amide groups to form [M(H-1ADA)4-(2)]. Formation (affinity) constants for the various metal complexes are reported, and the probable structures of the various metal chelates in solution are discussed on the basis of various spectral data.

  17. Synthesis of methyl 2-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside and methyl 2-O-alpha-D-talopyranosyl-alpha-D-talopyranoside.

    PubMed

    Jain, R K; Dubey, R; Abbas, S A; Matta, K L

    1987-03-15

    Treatment of methyl 3-O-benzyl-2-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-alpha-D- mannopyranoside (1) with tert-butyldiphenylsilyl chloride in N,N-dimethylformamide afforded methyl 3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-mannopyranoside (2). Oxidation of 2 with pyridinium chlorochromate, followed by reduction of the carbonyl group, and subsequent O-deacetylation afforded methyl 3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-alpha-D-mannopyranosyl- alpha-D- talopyranoside (5). Cleavage of the tert-butyldiphenylsilyl group of 5 with tetrabutylammonium fluoride in oxolane, followed by hydrogenolysis, gave methyl 2-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside (7). O-Deacetylation of 1 gave methyl 3-O-benzyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (8). Treatment of 8 with tert-butyldiphenylsilyl chloride afforded a 6,6'-disilyl derivative, which was converted into a 2',3'-O-isopropylidene derivative, and then further oxidized with pyridinium chlorochromate. The resulting diketone was reduced and removal of the protecting groups gave methyl 2-O-alpha-D-talopyranosyl-alpha-D-talopyranoside (15). The structures of both 7 and 15 were established by 13C-n.m.r. spectroscopy.

  18. Cloning and expression of a novel UDP-GlcNAc:alpha-D-mannoside beta1,2-N-acetylglucosaminyltransferase homologous to UDP-GlcNAc:alpha-3-D-mannoside beta1,2-N-acetylglucosaminyltransferase I.

    PubMed Central

    Zhang, Wenli; Betel, Doron; Schachter, Harry

    2002-01-01

    A TBLASTN search with human UDP-GlcNAc:alpha-3-d-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GnT I; EC 2.4.1.101) as a probe identified human and mouse Unigenes encoding a protein similar to human GnT I (34% identity over 340 amino acids). The recombinant protein converted Man(alpha1-6)[Man(alpha1-3)]Man(beta1-)O-octyl to Man(alpha1-6)[GlcNAc(beta1-2)Man(alpha1-3)]Man(beta1-)O-octyl, the reaction catalysed by GnT I. The enzyme also added GlcNAc to Man(alpha1-6)[GlcNAc(beta1-2)Man(alpha1-3)]Man(beta1-)O-octyl (the substrate for beta-1,2-N-acetylglucosaminyltransferase II), Man(alpha1-)O-benzyl [with K(m) values of approximately 0.3 and >30 mM for UDP-GlcNAc and Man(alpha1-)O-benzyl respectively] and the glycopeptide CYA[Man(alpha1-)O-T]AV (K(m) approximately 12 mM). The product formed with Man(alpha1-)O-benzyl was identified as GlcNAc(beta1-2)Man(alpha1-)O-benzyl by proton NMR spectroscopy. The enzyme was named UDP-GlcNAc:alpha-d-mannoside beta-1,2-N-acetylglucosaminyltransferase I.2 (GnT I.2). The human gene mapped to chromosome 1. Northern-blot analysis showed a 3.3 kb message with a wide tissue distribution. The cDNA has a 1980 bp open reading frame encoding a 660 amino acid protein with a type-2 domain structure typical of glycosyltransferases. Man(beta1-)O-octyl, Man(beta1-)O-p-nitrophenyl and GlcNAc(beta1-2)Man(alpha1-6)[GlcNAc(beta1-2)Man(alpha1-3)]Man(beta1-4)GlcNAc(beta1-4)GlcNAc(beta1-)O-Asn were not acceptors, indicating that GnT I.2 is specific for alpha-linked terminal Man and does not have N-acetylglucosaminyltransferase III, IV, V, VII or VIII activities. CYA[Man(alpha1-)O-T]AV was between three and seven times more effective as an acceptor than the other substrates, suggesting that GnT I.2 may be responsible for the synthesis of the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety on alpha-dystroglycan and other O-mannosylated proteins. PMID:11742540

  19. Selective liquid phase oxidation of benzyl alcohol to benzaldehyde by tert-butyl hydroperoxide over γ-Al2O3 supported copper and gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Ndolomingo, Matumuene Joe; Meijboom, Reinout

    2017-03-01

    Benzyl alcohol oxidation to benzaldehyde was performed by tert-butyl hydroperoxide (TBHP) in the absence of any solvent using γ-Al2O3 supported copper and gold nanoparticles. Li2O and ionic liquids were used as additive and stabilizers for the synthesis of the catalysts. The physico-chemical properties of the catalysts were characterized by atomic absorption spectroscopy (AAS), X-ray diffraction spectroscopy (XRD), N2 absorption/desorption (BET), transmission electron microscopy (TEM), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and temperature programmed reduction (TPR), whereas, the oxidation reaction was followed by gas chromatography with a flame ionization detector (GC-FID). The as prepared catalysts exhibited good catalytic performance in terms of conversion and selectivity towards benzaldehyde. The performance of the Au-based catalysts is significantly higher than that of the Cu-based catalysts. For both Cu and Au catalysts, the conversion of benzyl alcohol increased as the reaction proceeds, while the selectivity for benzaldehyde decreased. Moreover, the catalysts can be easily recycled and reused with neither significant loss of activity nor selectivity. A kinetic study for the Cu and Au-catalyzed oxidation of benzyl alcohol to benzyldehyde is reported. The rate at which the oxidation of benzyl alcohol is occurring as a function of catalyst and oxidant amounts was investigated, with the apparent rate constant, kapp being proportional to the amount of nano catalyst and oxygen present in the system.

  20. Oxidation of benzyl alcohol by K2FeO4 to benzaldehyde over zeolites

    NASA Astrophysics Data System (ADS)

    Wang, Yuan-Yuan; Song, Hua; Song, Hua-Lin; Jin, Zai-Shun

    2016-10-01

    A novel and green procedure for benzaldehyde synthesis by potassium ferrate oxidation of benzyl alcohol employing zeolite catalysts was studied. The prepared oxidant was characterized by SEM and XRD. The catalytic activity of various solid catalysts was studied using benzyl alcohol as a model compound. USY was found to be a very efficient catalyst for this particular oxidation process. Benzaldehyde yields up to 96.0% could be obtained at the following optimal conditions: 0.2 mL of benzyl alcohol, 4 mmol of K2FeO4, 0.5 g of USY zeolite; 20 mL of cyclohexene, 0.3 mL of acetic acid (36 wt %), 30°C temperature, 4 h reaction time.

  1. Fabrication of novel ternary Au/CeO2@g-C3N4 nanocomposite: kinetics and mechanism investigation of 4-nitrophenol reduction, and benzyl alcohol oxidation

    NASA Astrophysics Data System (ADS)

    Kohantorabi, Mona; Gholami, Mohammad Reza

    2018-06-01

    Au nanoparticles supported on cerium oxide/graphitic carbon nitride (CeO2@g-C3N4) was synthesized and used as heterogeneous catalyst in redox reaction. The catalyst was characterized by different techniques such as FT-IR, XRD, FE-SEM, EDS, TEM, BET, TGA, and ICP. The as-prepared ternary nanocomposite was used as an effective catalyst for the reduction of toxic 4-nitrophenol to useful 4-aminophenol by NaBH4. The rate constant value of reduction reaction reached up to 0.106 s-1 by Au/CeO2@g-C3N4, which was 3.8, and 8.8 times higher than that of Au@CeO2 (0.028 s-1), and Au@g-C3N4 (0.012 s-1) nanocomposites, respectively. The superior catalytic performance of as-prepared catalyst in 4-NP reduction can be attributed to synergistic effect between Au nanoparticles and CeO2@g-C3N4 support, and efficient electron transfer. The reduction reaction was carried out at different temperatures, and the energy of activation ({Ea}), and thermodynamic parameters including, activation of entropy (Δ S^ ≠), enthalpy (Δ H^ ≠), and Gibbs free energy (Δ G^ ≠) were determined. Additionally, the mechanism of reaction was studied in details, and equilibrium constants of 4-NP ( K 4-NP), and {BH}4^{ - } ({K_{{BH}4^{{ - }} }}) were calculated using Langmuir-Hinshelwood model. Furthermore, this nanocomposite exhibited excellent catalytic activity in oxidation of benzyl alcohol by molecular oxygen as a green oxidant. This study revealed that the ternary Au/CeO2@g-C3N4 nanocomposite is an attractive candidate for catalytic applications.

  2. 5-Acetamido-3,5-dideoxy-L-glycero-L-manno-non-2-ulosonic acid-containing O-polysaccharide from marine bacterium Pseudomonas glareae KMM 9500T.

    PubMed

    Kokoulin, Maxim S; Kalinovsky, Anatoly I; Romanenko, Lyudmila A; Mikhailov, Valery V

    2018-05-22

    The O-polysaccharide was isolated from the lipopolysaccharide of a marine bacterium Pseudomonas glareae KMM 9500 T and studied by chemical methods along with 1D and 2D 1 H and 13 C NMR spectroscopy including 1 H, 1 H-TOCSY, 1 H, 1 H-COSY, 1 H, 1 H-ROESY, 1 H, 13 C-HSQC and 1 H, 13 C-HMBC experiments. The O-polysaccharide was found to consist of linear tetrasaccharide repeating units constituted by D-glucuronic acid (D-GlcA), L-rhamnose (L-Rha), D-glucose (D-Glc) and 5-acetamido-7,9-O-[(S)-1-carboxyethylidene]-3,5-dideoxy-L-glycero-L-manno-non-2-ulosonic acid (Sug7,9(S-Pyr)), partially O-acetylated at position 8 (∼70%): →4)-α-D-GlcpA-(1→3)-β-L-Rhap-(1→4)-β-D-Glcp-(1→4)-β-Sugp8Ac(∼70%)7,9(S-Pyr)-(2→. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Enhancement by O6-benzyl-N2-acetylguanosine of N'-[2-chloroethyl]-N-[2-(methylsulphonyl)ethyl]-N'-nitrosourea therapeutic index on nude mice bearing resistant human melanoma.

    PubMed Central

    Debiton, E.; Cussac-Buchdhal, C.; Mounetou, E.; Rapp, M.; Dupuy, J. M.; Maurizis, J. C.; Veyre, A.; Madelmont, J. C.

    1997-01-01

    The exposure of cells to O6-benzyl-N2-acetylguanosine (BNAG) and several guanine derivatives is known to reduce the activity of O6-alkylguanine-DNA alkyltransferase (MGMT) and to enhance the sensitivity of Mer+ (methyl enzyme repair positive) tumour cells to chloroethylnitrosoureas (CENUs) in vitro and in vivo. High water solubility and the pharmacokinetic properties of BNAG make it a candidate for simultaneous administration with CENUs by the i.v. route in human clinical use. In vivo we have shown previously that BNAG significantly increases the efficiency of N'-[2-chloroethyl]-N-[2-(methylsulphonyl)ethyl]-N'-nitrosourea (cystemustine) against M4Beu melanoma cells (Mer+) through its cytostatic activity by the i.p. route, but also increases its toxicity. To investigate the toxicity of BNAG and cystemustine when administered simultaneously in mice, we compared the maximum tolerated dose and LD50 doses of cystemustine alone or in combination with 40 mg kg(-1) BNAG by the i.p. route. The toxicity of cystemustine was enhanced by a factor of almost 1.44 when combined with BNAG. To compare the therapeutic index of cystemustine alone and the cystemustine/BNAG combination, pharmacological tests were carried out in nude mice bearing Mer+ M4Beu human melanoma cells. Isotoxic doses were calculated using the 1.44 ratio. The treatments were administered three times by the i.v. route on days 1, 5 and 9 after s.c. inoculation of tumour cells. Although the toxicities of the treatments were equal, BNAG strongly enhanced tumour growth inhibition. These results demonstrate the increase of the therapeutic index of cystemustine by BNAG and justify the use of BNAG to enhance nitrosourea efficiency in vivo by i.v. co-injection. PMID:9365163

  4. The First Molybdenum(VI) and Tungsten(VI) Oxoazides MO2(N3)2, MO2(N3)22 CH3CN, (bipy)MO2(N3)2, and [MO2(N3)4](2-) (M=Mo, W).

    PubMed

    Haiges, Ralf; Skotnitzki, Juri; Fang, Zongtang; Dixon, David A; Christe, Karl O

    2015-08-10

    Molybdenum(VI) and tungsten(VI) dioxodiazide, MO2(N3)2 (M=Mo, W), were prepared through fluoride-azide exchange reactions between MO2F2 and Me3SiN3 in SO2 solution. In acetonitrile solution, the fluoride-azide exchange resulted in the isolation of the adducts MO2(N3)22 CH3CN. The subsequent reaction of MO2(N3)2 with 2,2'-bipyridine (bipy) gave the bipyridine adducts (bipy)MO2(N3)2. The hydrolysis of (bipy)MoO2(N3)2 resulted in the formation and isolation of [(bipy)MoO2N3]2O. The tetraazido anions [MO2(N3)4](2-) were obtained by the reaction of MO2(N3)2 with two equivalents of ionic azide. Most molybdenum(VI) and tungsten(VI) dioxoazides were fully characterized by their vibrational spectra, impact, friction, and thermal sensitivity data and, in the case of (bipy)MoO2(N3)2, (bipy)WO2(N3)2, [PPh4]2[MoO2(N3)4], [PPh4]2[WO2(N3)4], and [(bipy)MoO2N3]2O by their X-ray crystal structures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Intramolecular addition of benzylic radicals onto ketenimines. Synthesis of 2-alkylindoles.

    PubMed

    Alajarín, Mateo; Vidal, Angel; Ortín, María-Mar

    2003-12-07

    The inter- and intramolecular addition of free radicals onto ketenimines is studied. All the attempts to add intermolecularly several silicon, oxygen or carbon centered radicals to N-(4-methylphenyl)-C,C-diphenyl ketenimine were unsuccessful. In contrast, the intramolecular addition of benzylic radicals, generated from xanthates, onto the central carbon of a ketenimine function with its N atom linked to the ortho position of the aromatic ring occurred under a variety of reaction conditions. These intramolecular cyclizations provide a novel radical-mediated synthesis of 2-alkylindoles.

  6. Structure-property relationship of 3-(4-substituted benzyl)-1,3-diazaspiro[4.4]nonane-2,4-diones as new potentional anticonvulsant agents. An experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Lazić, Anita M.; Božić, Bojan Đ.; Vitnik, Vesna D.; Vitnik, Željko J.; Rogan, Jelena R.; Radovanović, Lidija D.; Valentić, Nataša V.; Ušćumlić, Gordana S.

    2017-01-01

    The structure-property relationship of newly synthesized 3-(4-substituted benzyl)-1,3-diazaspiro [4.4]nonane-2,4-diones was studied by experimental and calculated methods. The prepared compounds were characterized by UV-Vis, FT-IR, 1H NMR and 13C NMR spectroscopy and elemental analysis. The crystal structure was elucidated by single-crystal X-ray diffraction. The 3-benzyl-1,3-diazaspiro[4.4]nonane-2,4-dione crystallizes in triclinic P-1 space group, with two crystallographically independent molecules in the asymmetric unit. Cyclopentane ring adopts an envelope conformation. A three-dimensional crystal packing is governed by hydrogen N-H⋯O bonds, numerous C-H⋯O/N and C-H … π interactions between neighboring molecules. Density functional theory (DFT) calculations with B3LYP and M06-2X methods using 6-311++G(d,p) basis set were performed to provide structural and spectroscopic information. Comparisons between experimental and calculated UV-Vis spectral properties suggest that the monomeric form of the investigated spirohydantoins is dominant in all used solvents. The effects of substituents on the absorption spectra of spirohydantoins are interpreted by correlation of absorption frequencies with Hammett equation. The lipophilicities of the investigated molecules were estimated by calculation of their log P values. Some of the spirohydantoins synthesized in this work, exhibit the lipophilicities comparable to the standard medicine anticonvulsant drug Phenytoin. The results obtained in this investigation afford guidelines for the preparation of new derivatives of spirohydantoin as potential anticonvulsant agents and for better understanding the structure-activity relationship.

  7. The Synthesis of "N"-Benzyl-2-Azanorbornene via Aqueous Hetero Diels-Alder Reaction: An Undergraduate Project in Organic Synthesis and Structural Analysis

    ERIC Educational Resources Information Center

    Sauvage, Xavier; Delaude, Lionel

    2008-01-01

    The synthesis of "N"-benzyl-2-azanorbornene via aqueous hetero Diels-Alder reaction of cyclopentadiene and benzyliminium chloride formed in situ from benzylamine hydrochloride and formaldehyde is described. Characterization of the product was achieved by IR and NMR spectroscopies. The spectral data acquired are thoroughly discussed. Numerous…

  8. Microbial Routes to (2R,3R)-2,3-Butanediol: Recent Advances and Future Prospects.

    PubMed

    Xie, Neng-Zhong; Chen, Xian-Rui; Wang, Qing-Yan; Chen, Dong; Du, Qi-Shi; Zhou, Guo-Ping; Huang, Ri-Bo

    2017-01-01

    (2R,3R)-2,3-Butanediol has many industrial applications, such as it is used as an antifreeze agent and low freezing point fuel. In addition, it is particularly important to provide chiral groups in drugs. In recent years, this valuable bio-based chemical has attracted increasing attention, and significant progress has been made in the development of microbial cell factories for (2R,3R)-2,3-butanediol production. This article reviews recent advances and challenges in microbial routes to (2R,3R)-2,3- butanediol production, and highlights the metabolic engineering and synthetic biological approaches used to improve titers, yields, productivities, and optical purities. Finally, a systematic and integrative strategy for developing high-performance microbial cell factories is proposed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. (2E,5E)-2,5-Bis(4-hy-droxy-3-meth-oxy-benzyl-idene)cyclo-penta-none ethanol monosolvate.

    PubMed

    Da'i, Muhammad; Yanuar, Arry; Meiyanto, Edy; Jenie, Umar Anggara; Supardjan, Amir Margono

    2013-04-01

    In the title structure, C21H20O5·C2H5OH, the curcumine-type mol-ecule has a double E conformation for the two benzyl-idene double bonds [C=C = 1.342 (4) and 1.349 (4) Å] and is nearly planar with respect to the non-H atoms (r.m.s. deviation from planarity = 0.069 Å). The two phenolic OH groups form bifurcated hydrogen bonds with intra-molecular branches to adjacent meth-oxy O atoms and inter-molecular branches to either a neighbouring mol-ecule or an ethanol solvent mol-ecule. The ethanol O atom donates a hydrogen bond to the keto O atom. These hydrogen bonds link the constituents into layers parallel to (101) in the crystal structure.

  10. Molecular Structure of WlbB, a Bacterial N-Acetyltransferase Involved in the Biosynthesis of 2,3-Diacetamido-2,3-dideoxy-d-mannuronic Acid

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Thoden, James B.; Holden, Hazel M.

    2010-09-08

    The pathogenic bacteria Pseudomonas aeruginosa and Bordetella pertussis contain in their outer membranes the rare sugar 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid. Five enzymes are required for the biosynthesis of this sugar starting from UDP-N-acetylglucosamine. One of these, referred to as WlbB, is an N-acetyltransferase that converts UDP-2-acetamido-3-amino-2,3-dideoxy-D-glucuronic acid (UDP-GlcNAc3NA) to UDP-2,3-diacetamido-2,3-dideoxy-D-glucuronic acid (UDP-GlcNAc3NAcA). Here we report the three-dimensional structure of WlbB from Bordetella petrii. For this analysis, two ternary structures were determined to 1.43 {angstrom} resolution: one in which the protein was complexed with acetyl-CoA and UDP and the second in which the protein contained bound CoA and UDP-GlcNAc3NA. WlbB adopts a trimericmore » quaternary structure and belongs to the L{beta}H superfamily of N-acyltransferases. Each subunit contains 27 {beta}-strands, 23 of which form the canonical left-handed {beta}-helix. There are only two hydrogen bonds that occur between the protein and the GlcNAc3NA moiety, one between O{sup {delta}1} of Asn 84 and the sugar C-3{prime} amino group and the second between the backbone amide group of Arg 94 and the sugar C-5{prime} carboxylate. The sugar C-3{prime} amino group is ideally positioned in the active site to attack the si face of acetyl-CoA. Given that there are no protein side chains that can function as general bases within the GlcNAc3NA binding pocket, a reaction mechanism is proposed for WlbB whereby the sulfur of CoA ultimately functions as the proton acceptor required for catalysis.« less

  11. 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.

    PubMed

    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

  12. Synthesis of specifically deuterated S-benzylcysteines and of oxytocin and related diastereomers deuterated in the half-cystine positions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Upson, D.A.; Hruby, V.J.

    1976-04-16

    S-Benzylcysteine derivatives specifically deuterated at the ..cap alpha.. carbon only, the ..beta.. carbon only, and at both the ..cap alpha.. and ..beta.. carbons have been synthesized. These labeled compounds have been enzymatically resolved and the enantiomers and reacemates have been converted to the N-tert-butyloxycarbonyl derivatives. The deuterium labels were not exchanged under the conditions of the syntheses. Condensation of the sodium salt of diethyl ..cap alpha..-acetami-domalonate with benzyl chloromethyl sulfide followed by hydrolysis with DCl afforded S-benzyl-DL-(..cap alpha..-/sup 2/H/sub 1/) cysteine. Acetylation followed by treatment with hog renal acylase separated the stereoisomers. A Mannich reaction with (/sup 2/H/sub 2/) methylenemore » diacetate, diethyl ..cap alpha..-acetamido-..cap alpha..-dimethylamino(/sup 2/H/sub 2/)methylmalonate methiodide (15). Treatment of 15 with sodium benzylmercaptide gave diethyl ..cap alpha..-acetamido-..cap alpha..-benzylthio(/sup 2/H/sub 2/)methylmalonate, which was hydrolyzed with HCl to yield S-benzyl-DL-(..beta..,..beta..-/sup 2/H/sub 2/)cysteine or with DCl to afford S-benzyl-DL-(..cap alpha..,..beta..,..beta..,-/sup 2/H/sub 3/)cysteine. These compounds were resolved as before. The preparation of S-benzyl-DL-(..cap alpha..,..beta..,..beta..-/sup 2/H/sub 3/)cysteine required an efficient source of ethanol-d. This deuterated solvent was prepared in quantitative yield in 2 h from tetraethoxysilane, D/sub 2/O, and a catalytic amount of thionyl chloride. The protected deuterated amino acids were used in the preparation of several oxytocin analogues in which the specific deuteration appears in either the 1-hemicystine or the 6-hemicystine residues.« less

  13. R3 Index for Four-Dimensional N =2 Field Theories

    NASA Astrophysics Data System (ADS)

    Alexandrov, Sergei; Moore, Gregory W.; Neitzke, Andrew; Pioline, Boris

    2015-03-01

    In theories with N =2 supersymmetry on R3 ,1, supersymmetric bound states can decay across walls of marginal stability in the space of Coulomb branch parameters, leading to discontinuities in the BPS indices Ω (γ ,u ) . We consider a supersymmetric index I which receives contributions from 1 /2 -BPS states, generalizing the familiar Witten index Tr (-1 )Fe-β H . We expect I to be smooth away from loci where massless particles appear, thanks to contributions from the continuum of multiparticle states. Taking inspiration from a similar phenomenon in the hypermultiplet moduli space of N =2 string vacua, we conjecture a formula expressing I in terms of the BPS indices Ω (γ ,u ), which is continuous across the walls and exhibits the expected contributions from single particle states at large β . This gives a universal prediction for the contributions of multiparticle states to the index I . This index is naturally a function on the moduli space after reduction on a circle, closely related to the canonical hyperkähler metric and hyperholomorphic connection on this space.

  14. R^{3} index for four-dimensional (N)=2 field theories.

    PubMed

    Alexandrov, Sergei; Moore, Gregory W; Neitzke, Andrew; Pioline, Boris

    2015-03-27

    In theories with N=2 supersymmetry on R^{3,1}, supersymmetric bound states can decay across walls of marginal stability in the space of Coulomb branch parameters, leading to discontinuities in the BPS indices Ω(γ,u). We consider a supersymmetric index I which receives contributions from 1/2-BPS states, generalizing the familiar Witten index Tr(-1)^{F}e^{-βH}. We expect I to be smooth away from loci where massless particles appear, thanks to contributions from the continuum of multiparticle states. Taking inspiration from a similar phenomenon in the hypermultiplet moduli space of N=2 string vacua, we conjecture a formula expressing I in terms of the BPS indices Ω(γ,u), which is continuous across the walls and exhibits the expected contributions from single particle states at large β. This gives a universal prediction for the contributions of multiparticle states to the index I. This index is naturally a function on the moduli space after reduction on a circle, closely related to the canonical hyperkähler metric and hyperholomorphic connection on this space.

  15. The synthesis and crystal structure of 2-[4(S)-4,5-dihydro-4-phenyl-2-oxazolinyl]-benzenamine, and 2-[4(S)-4,5-dihydro-4-benzyl-2-oxazolinyl]-benzenamine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mei Luo, E-mail: Lmhh5523385@yahoo.cn; Hai Zhangjia; Hao Yin

    2010-12-15

    Two oxazolines compound 1a and 1b, 2-[4(S)-4,5-dihydro-4-phenyl-2-ozazolinyl-benzenamine, and (C{sub 15}H{sub 14}N{sub 2}O), 2-[4(S)-4,5-dihydro-4-benzyl-2-ozazolinyl-benzenamine (C{sub 16}H{sub 16}N{sub 2}O) were obtained in moderate yield from the reactions of 2-aminobenzonitrile with optically active L-(+)-Phenylglycinol and L-(+)-Phenylalaninol, respectively, in chlorobenzene under dry, anaerobic conditions. ZnCl{sub 2} was dried under vacuum and acted as a Lewis acid catalyst in this reaction. The structures of 1a and 1b were determined by X-ray diffraction and NMR. There exist intra- and intermolecular N-H-N hydrogen bonds in the crystal structure.

  16. Condensed tannins: A proposed route to 2R,3R-(2,3-cis)-proanthocyanidins

    Treesearch

    Richard W. Hemingway; Peter E. Laks

    1985-01-01

    Roux,1 Haslam,2-4 and Stafford5-8 have proposed differing biogenetic schemes for the formation of proanthocyanidins (condensed tannins) in plants. All three schemes suffer from difficulties in explaining the formation of the 2R,3R-(2,3-cis)-proanthocyanidins that predominate in...

  17. Analytical characterization of bioactive N-benzyl-substituted phenethylamines and 5-methoxytryptamines.

    PubMed

    Brandt, Simon D; Elliott, Simon P; Kavanagh, Pierce V; Dempster, Nicola M; Meyer, Markus R; Maurer, Hans H; Nichols, David E

    2015-04-15

    Substances based on the N-(2-methoxybenzyl)phenethylamine template ('NBOMe' derivatives) play an important role in medicinal research but some of these derivatives have also appeared as 'research chemicals' for recreational use which has attracted attention worldwide. A major challenge associated with newly emerging substances includes the lack of analytical data and the ability to correctly identify positional isomers. Six N-benzylphenethylamines based on the 2,5-dimethoxy-4-iodophenethylamine structure ('25I') and twelve substituted N-benzyl-5-methoxytryptamines ('5MT') have been prepared and extensively characterized. Techniques used for characterization were gas chromatography/ion trap mass spectrometry in electron and chemical ionization mode, liquid chromatography/diode array detection (DAD), infrared spectroscopy, electrospray high mass accuracy quadrupole time-of-flight tandem mass spectrometry, and triple quadrupole tandem mass spectrometry. The characterization of 18 'NBOMe' compounds provided a comprehensive collection of chromatographic and spectral data. Four groups of three positional isomers, i.e. 25I-NB2OMe, 25I-NB3OMe, 25I-NB4OMe, 25I-NB2B, 25I-NB3B, 25I-NB4B and their 5-methoxytryptamine counterparts, were included and assessed for ability to obtain differentiation. Six meta-substituted N-benzyl derivatives of 5-methoxytryptamine (CF3, F, CH3, Cl, I, SCH3) were also studied. The implementation of mass spectral techniques was helpful for the differentiation between isomers, for example, when considering the difference in a number of ion ratios. This was considered beneficial in cases where chromatographic separation was only partially achieved under liquid chromatography (LC) conditions. The use of LC/DAD analysis was also found to be valuable for this particular purpose, which confirmed the integrative value of complementary techniques used in areas related to forensic toxicology. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Asymmetric synthesis of [2,3-(13)C(2),(15)N]-4-benzyloxy-5,6-diphenyl-2,3,5,6-tetrahydro-4H-oxazine-2-one via lipase TL-mediated kinetic resolution of benzoin: general procedure for the synthesis of [2,3-(13)C(2),(15)N]-L-alanine.

    PubMed

    Aoyagi, Y; Iijima, A; Williams, R M

    2001-11-30

    Lipase TL-mediated kinetic resolution of benzoin proceeded to give the corresponding optically pure (R)-benzoin (R)-1. On the other hand, (S)-benzoin O-acetate (S)-7 could be hydrolyzed without epimerization to give (S)-benzoin (S)-1 under alkaline conditions. Furthermore, both enantiomers of benzoin (1) were converted to [(15)N]-(1R,2S)- and (1S,2R)- 2-amino-1,2-diphenylethanol (3a and 3b), respectively, according to the procedure reported previously. [2,3-(13)C(2),(15)N]-(5S,6R)-4-benzyloxy-5,6-diphenyl-2,3,5,6-tetrahydro-4H-oxazine-2-one (10) was synthesized from ethyl [1,2-(13)C(2)]bromoacetate and (1R,2S)-2-amino-1,2-diphenylethanol (3b) in three steps. Finally, [2,3-(13)C(2),(15)N]-L-alanine (12) was prepared via alkylation of the lactone 10 and hydrogenation of the alkylated product 11.

  19. Structure-activity relationship study and optimisation of 2-aminopyrrole-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitrile as a broad spectrum metallo-β-lactamase inhibitor.

    PubMed

    McGeary, Ross P; Tan, Daniel T C; Selleck, Christopher; Monteiro Pedroso, Marcelo; Sidjabat, Hanna E; Schenk, Gerhard

    2017-09-08

    A SAR study on derivatives of 2-amino-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitrile 5a revealed that the 3-carbonitrile group, vicinal 4,5-diphenyl and N-benzyl side chains of the pyrrole are important for the inhibitory potencies of these compounds against members representing the three main subclasses of metallo-β-lactamases (MBLs), i.e. IMP-1 (representing the B1 subgroup), CphA (B2) and AIM-1 (B3). Coupling of 5a with a series of acyl chlorides and anhydrides led to the discovery of two N-acylamide derivatives, 10 and 11, as the two most potent IMP-1 inhibitors in this series. However, these compounds are less effective towards CphA and AIM-1. The N-benzoyl derivative of 5a retained potent in vitro activity against each of MBLs tested (with inhibition constants in the low μM range). Importantly, this compound also significantly enhanced the sensitivity of IMP-1, CphA- or AIM-1-producing cell cultures towards meropenem. This compound presents a promising starting point for the development of a universal MBL inhibitor, targeting members of each of the major subgroups of this family of enzymes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Novel 99mTc(III)-azide complexes [99mTc(N3)(CDO)(CDOH)2B-R] (CDOH2=cyclohexanedione dioxime) as potential radiotracers for heart imaging.

    PubMed

    Liu, Min; Zheng, Yumin; Avcibasi, Ugur; Liu, Shuang

    2016-11-01

    In this study, novel 99m Tc(III)-azide complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R] ( 99m Tc-ISboroxime-N 3 : R=IS; 99m Tc-MPboroxime-N 3 : R=MP; 99m Tc-PAboroxime-N 3 : R=PA; 99m Tc-PYboroxime-N 3 : R=PY; and 99m Tc-Uboroxime-N 3 : R=5U) were evaluated as heart imaging agents. Complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R] (R=IS, MP, PA, PY and 5U) were prepared by ligand exchange between NaN 3 and [ 99m TcCl(CDO)(CDOH) 2 B-R]. Biodistribution and imaging studies were carried out in Sprague-Dawley rats. Image quantification was performed to compare their initial heart uptake and myocardial retention. 99m Tc-ISboroxime-N 3 , 99m Tc-PYboroxime-N 3 and 99m Tc-Uboroxime-N 3 were prepared with high RCP (93-98%) while the RCP of 99m Tc-MPboroxime-N 3 and 99m Tc-PAboroxime-N 3 was 80-85%. The myocardial retention curves of 99m Tc-ISboroxime-N 3 , 99m Tc-PYboroxime-N 3 and 99m Tc-Uboroxime-N 3 were best fitted to the bi-exponential decay function. The half-time of the fast component was 1.6±0.4min for 99m Tc-ISboroxime-N 3 , 0.7±0.1min for 99m Tc-PYboroxime-N 3 and 0.9±0.4min for 99m Tc-Uboroxime-N 3 . The 2-min heart uptake from biodistribution studies followed the ranking order of 99m Tc-ISboroxime-N 3 (3.60±0.68%ID/g)> 99m Tc-PYboroxime-N 3 (2.35±0.37%ID/g)≫ 99m Tc-Uboroxime-N 3 (1.29±0.06%ID/g). 99m Tc-ISboroxime-N 3 had the highest 2-min heart uptake among 99m Tc radiotracers revaluated in SD rats. High quality SPECT images were obtained with the right and left ventricular walls being clearly delineated. The best image acquisition window was 0-5min for 99m Tc-ISboroxime-N 3 . Both azide coligand and boronate caps had significant impact on the heart uptake and myocardial retention of complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R]. Among the radiotracers evaluated in SD rats, 99m Tc-ISboroxime-N 3 has the highest initial heart uptake with the heart retention comparable to that of 99m Tc-Teboroxime. 99m Tc-ISboroxime-N 3 is a promising alternative to 99m Tc-Teboroxime for

  1. Decoy receptor 3 (DcR3) overexpression predicts the prognosis and pN2 in pancreatic head carcinoma.

    PubMed

    Zhou, Jian; Song, Shiduo; Li, Dechun; He, Songbing; Zhang, Bing; Wang, Zhenxin; Zhu, Xinguo

    2014-03-05

    This study was carried out to examine decoy receptor 3 (DcR3) expression and investigate its clinical and prognostic significance in patients with pancreatic head carcinoma. Tissue samples were obtained from 50 patients with pancreatic head carcinoma. DcR3 protein expression in tissues and sera was assessed by immunohistochemistry and ELISA. Correlations between DcR3 and clinicopathologic features and prognoses were analyzed statistically. Serum DcR3 levels were significantly elevated in patients with pancreatic head carcinoma compared with patients with cystadenoma and healthy individuals (P < 0.01 and P < 0.01, respectively). DcR3 overexpression correlated with lymph node metastases and TNM stages (P < 0.05 and P < 0.05, respectively). Median overall survival for the high DcR3 group was 16.3 months, compared to 21.6 months for the low DcR3 group (P < 0.05). In the low DcR3 group, no significant difference was found in the overall survival between patients who underwent standard pancreatoduodenectomy (SPD) and those who had radical pancreatoduodenectomy (RPD) (P > 0.05). In the high DcR3 group, the median overall survival rates were 16.8 months in the RPD group and 13.5 months in the SPD group (P < 0.05). We found that DcR3 was overexpressed in pancreatic head carcinoma. The patients with high DcR3 levels had higher pN2 stages than those with low DcR3 levels. Detecting serum DcR3 level preoperatively might be an additional approach for evaluating pN2 stage and guiding the range of lymphadenectomy.

  2. Prevention of posttraumatic axon sprouting by blocking CRMP2-mediated neurite outgrowth and tubulin polymerization

    PubMed Central

    Wilson, Sarah M.; Xiong, Wenhui; Wang, Yuying; Ping, Xingjie; Head, Jessica D.; Brittain, Joel M.; Gagare, Pravin D.; Ramachandran, P. Veeraraghavan; Jin, Xiaoming; Khanna, Rajesh

    2012-01-01

    Epileptogenesis following traumatic brain injury (TBI) is likely due to a combination of increased excitability, disinhibition, and increased excitatory connectivity via aberrant axon sprouting. Targeting these pathways could be beneficial in the prevention and treatment of posttraumatic epilepsy. Here, we tested this possibility using the novel anticonvulsant (R)-N-benzyl 2-acetamido-3-methoxypropionamide ((R)-lacosamide (LCM) which acts on both voltage-gated sodium channels and collapsin response mediator protein 2 (CRMP2), an axonal growth/guidance protein. LCM inhibited CRMP2-mediated neurite outgrowth, an effect phenocopied by CRMP2 knockdown. Mutation of LCM binding sites in CRMP2 reduced the neurite inhibitory effect of LCM by ~8-fold. LCM also reduced CRMP2-mediated tubulin polymerization. Thus, LCM selectively impairs CRMP2-mediated microtubule polymerization which underlies its neurite outgrowth and branching. To determine whether LCM inhibits axon sprouting in vivo, LCM was injected into rats subjected to partial cortical isolation, an animal model of posttraumatic epileptogenesis that exhibits axon sprouting in cortical pyramidal neurons. Two weeks following injury, excitatory synaptic connectivity of cortical layer V pyramidal neurons was mapped using patch clamp recordings and laser scanning photostimulation of caged glutamate. In comparison to injured control animals, there was a significant decrease in the map size of excitatory synaptic connectivity in LCM-treated rats, suggesting that LCM treatment prevented enhanced excitatory synaptic connectivity due to posttraumatic axon sprouting. These findings suggest, for the first time, that LCM’s mode of action involves interactions with CRMP2 to inhibit posttraumatic axon sprouting. PMID:22433297

  3. Structures, molecular orbitals and UV-vis spectra investigations on methyl 1-benzyl-1H-1,2,3-triazole-4-carboxylate: a computational study.

    PubMed

    Wang, Tsang-Hsiu; Chu, Hsing-Yu; Wang, I-Teng

    2014-10-15

    The methyl 1-benzyl-1H-1,2,3-triazole-4-carboxylate (C11H11N3O2) has been studied by theoretically methods. The structure of this compound is optimized by density functional theory (DFT), the second-order Møller-Plesset perturbation theory (MP2) and G3 theory (G3(MP2)) levels. Our calculation results are in very good agreement with experimental values. Compared to a perfect pentagonal structure, the geometrical structures of C11H11N3O2 show a little distortion of 1,2,3-triazole ring due to the highly electronegativity of substitution groups. In addition, dipole moment and frontier molecular orbitals (FMOs) of the C11H11N3O2 are calculated as well. Because of solvent effect, the HOMO-LUMO energy gap in methanol is predicted to be smaller than in gas phase by 0.367eV. The simulated UV-vis spectra are investigated by time-dependent density functional theory (TD-DFT), and two obviously absorption features have been predicted. These two absorption features are located between 170nm and 210nm, which is in ultraviolet C range. Moreover, the UV absorption features in methanol are predicted to be more intense than in gas phase; besides, the red shift is predicted in methanol as well. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Strong intramolecular Si-N interactions in the chlorosilanes Cl3-nHnSiOCH2CH2NMe2 (n = 1-3).

    PubMed

    Hagemann, Michael; Mix, Andreas; Berger, Raphael J F; Pape, Tania; Mitzel, Norbert W

    2008-11-17

    The compounds Cl 3SiOCH 2CH 2NMe 2 ( 1) and Cl 2HSiOCH 2CH 2NMe 2 ( 2) were prepared by reactions of lithium 2-(dimethylamino)ethanolate with SiCl 4 and HSiCl 3. The analogous reaction with H 2SiCl 2 gave ClH 2SiOCH 2CH 2NMe 2 ( 3), but only in a mixture with Cl 2HSiOCH 2CH 2NMe 2 ( 2), from which it could not be separated. All compounds were characterized by IR and NMR ( (1)H, (13)C, (29)Si) spectroscopy, 1 and 2 by elemental analyses and by determination of their crystal structures. Cl 3SiOCH 2CH 2NMe 2 ( 1) and Cl 2HSiOCH 2CH 2NMe 2 ( 2) crystallize as monomeric ring compounds with pentacoordinate silicon atoms participating in intramolecular Si-N bonds [2.060(2) A ( 1), 2.037(2) A ( 2)]. The dative bonds in 1 and 2 between the silicon and nitrogen atoms could also be proven to exist at low temperatures in solution in (1)H, (29)Si-HMBC-NMR experiments by detection of the scalar coupling between the (29)Si and the protons of the NCH 2 and NCH 3 groups. A function describing the chemical shift delta exp (29)Si dependent on the chemical shifts of the individual equilibrium components, the temperature, and the free enthalpy of reaction was worked out and fitted to the experimental VT-NMR data of 1 and 2. This provided values of the free reaction enthalpies of Delta G = -28.8 +/- 3.9 kJ x mol (-1) for 1 and Delta G = -22.3 +/- 0.4 kJ x mol (-1) for 2 and estimates for the chemical shifts of open-chain (index o) and ring conformers (index r) for 1 of delta r = -94 +/- 2 ppm and delta o = -36 +/- 5 ppm and for 2 of delta r = -82 +/- 1 ppm and delta o = -33 +/- 4 ppm. The value of delta r for 1 is very close to that obtained from a solid-state (29)Si MAS NMR spectrum. Quantumchemical calculations (up to MP2/TZVPP) gave largely differing geometries for 1 (with a Si...N distance of 3.072 A), but well reproduced the geometry of 2. These differences are due to Cl...H and Cl...C repulsions and solid state effects, which can be modeled by conductor-like screening model

  5. Alignment effect of N2(A3Σu+) in the energy transfer reaction of aligned N2(A3Σu+) + NO(X2Π) → NO(A2Σ+) + N2(X1Σg+).

    PubMed

    Ohoyama, H; Maruyama, S

    2012-06-28

    Steric effect in the energy transfer reaction of N(2)(A(3)Σ(u)(+)) + NO(X(2)Π) → NO(A(2)Σ(+)) + N(2)(X(1)Σ(g)(+)) has been studied under crossed beam conditions at a collision energy of ~0.07 eV by using an aligned N(2)(A(3)Σ(u)(+)) beam prepared by a magnetic hexapole. The emission intensity of NO(A(2)Σ(+)) has been measured as a function of the magnetic orientation field direction (i.e., alignment of N(2)(A(3)Σ(u)(+))) in the collision frame. A significant alignment effect on the energy transfer probability is observed. The shape of the steric opacity function turns out to be most reactive at the oblique configuration of N(2)(A(3)Σ(u)(+)) with an orientation angle of γ(v(R)) ~ 45° with respect to the relative velocity vector (v(R)), which has a good correlation with the spatial distribution of the 2pπ(g)* molecular orbital of N(2)(A(3)Σ(u)(+)). We propose the electron exchange mechanism in which the energy transfer probability is dominantly controlled by the orbital overlap between N(2)(2pπ(g)*) and NO(6σ).

  6. Synthesis, structure, photoluminescence and antitumour activity of zinc complex based on 2-(2-(1H-benzo-[d]imidazol-2-yl)benzyl)-1H-benzo-[d]imidazole

    NASA Astrophysics Data System (ADS)

    Che, Zhijian; Wang, Shaoxiang; Liu, Shenggui; Li, Guobi; Wu, Qiting; Lin, Chunyu; Kong, Linglang; Wang, Sheng

    2015-01-01

    A new complex [Zn(bbb)Cl2]·DMF, where bbb is 2-(2-(1H-benzo[d]imidazol-2-yl)benzyl)-1H-benzo[d]imidazole, was synthesized and characterized by element analysis, 1H NMR and X-ray single crystal structure analyses. For complex: crystal system, triclinic, space group, P-1, a = 9.4661(13), b = 10.3534(14), c = 13.0025(18) Å, α = 73.477(2), β = 80.743(2), γ = 88.658(2)°, V = 1205.5(3) Å3, Z = 2. In this complex, the Zn2+ distorted tetrahedron geometry is coordinated by two nitrogen atoms from 2-(2-(1H-benzo[d]imidazol-2-yl)benzyl)-1H-benzo[d]imidazole and two Cl-. The complex emits yellow green luminescence with the maximal emission peak at 550 nm in DMF solution. The complex exhibits inhibition on the growth of Eca109 cancer cell with IC50 value of 8.9 ± 1.1 μM, which was lower than that of cisplatin (14.3 ± 1.4 μM). This complex has potential application in treatment of esophageal cancer.

  7. Reappraising the structures and distribution of metabolites from black aspergilli containing uncommon 2-benzyl-4H-pyran-4-one and 2-benzylpyridin-4(1H)-one systems

    PubMed Central

    Henrikson, Jon C.; Ellis, Trevor K.; King, Jarrod B.; Cichewicz, Robert H.

    2011-01-01

    To date, natural products containing 2-benzyl-4H-pyran-4-one and 2-benzylpyridin-4(1H)-one substructures have been encountered in relatively few fungi outside of the black aspergilli clade. While exploring the occurrence of these compounds among Aspergillus spp., it was determined that the structures of the unusual furopyrrols tensidols A and B (5 and 6) and JBIR-86 and JBIR-87 (9 and 10) were incorrect and should be reassigned as 2-benzyl-4H-pyran-4-ones (7, 8, 11e, and 12, respectively). The origin of the unique N-phenyl groups in the 2-benzylpyridin-4(1H)-ones nygerones A and B (1 and 2) was also examined and it was established that N-phenylamides added to the culture medium were suitable substrates for generating these metabolites; however, this phenomenon remained limited to a single fungus in our collection (Aspergillus niger ATCC 1015). A variety of 2-benzyl-4H-pyran-4-ones and 2-benzylpyridin-4(1H)-ones were detected among the black aspergilli, but only pestalamide B (13) was found in all eleven of the tested strains. These metabolites, as well as a group of synthetic analogues demonstrated weak antifungal activity against several Candida strains, Aspergillus flavus, and Aspergillus fumigatus. PMID:21854017

  8. Synthesis, Characterization, and Bioactivity of Schiff Bases and Their Cd2+, Zn2+, Cu2+, and Ni2+ Complexes Derived from Chloroacetophenone Isomers with S-Benzyldithiocarbazate and the X-Ray Crystal Structure of S-Benzyl-β-N-(4-chlorophenyl)methylenedithiocarbazate

    PubMed Central

    Break, Mohammed Khaled bin; Tahir, M. Ibrahim M.; Crouse, Karen A.; Khoo, Teng-Jin

    2013-01-01

    Two bidentate Schiff base ligands having nitrogen sulphur donor sequence were derived from the condensation of S-benzyldithiocarbazate (SBDTC) with 2-chloroacetophenone and 4-chloroacetophenone to give S-benzyl-β-N-(2-chlorophenyl)methylenedithiocarbazate (NS2) and S-benzyl-β-N-(4-chlorophenyl)methylenedithiocarbazate (NS4) isomers. Each of the ligands was then chelated with Cd2+, Zn2+, Cu2+, and Ni2+. The compounds were characterized via IR spectroscopy and melting point while the structure of NS4 was revealed via X-ray crystallography. Finally, the compounds were screened for antimicrobial activity to investigate the effect that is brought by the introduction of the chlorine atom to the benzene ring. X-ray crystallographic analysis showed that the structure of NS4 is planar with a phenyl ring that is nearly perpendicular to the rest of the molecules. The qualitative antimicrobial assay results showed that NS4 and its complexes lacked antifungal activity while Gram-positive bacteria were generally inhibited more strongly than Gram-negative bacteria. Furthermore, NS4 metal complexes were inhibited more strongly than the ligand while the opposite was seen with NS2 ligand and its complexes due to the partial solubility in dimethyl sulfoxide (DMSO). It was concluded that generally NS2 derivatives have higher bioactivity than that of NS4 derivatives and that the Cd complexes of both ligands have pronounced activity specifically on K. rhizophila. PMID:24319401

  9. 1-(substituted benzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidones: a series with stimulant and depressant activities.

    PubMed

    Ellis, K O; Schwan, T J; Wessels, F L; Miles, N J

    1980-10-01

    A series of 1-(substituted benzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidones was synthesized primarily by catalytic hydrogenation of the corresponding 1-(substituted benzyl)-2(1H)-pyrimidone. The pharmacological evaluation of these compounds in mice revealed a unique profile that included evidence of CNS stimulation and depression within the series and in the same compounds. Some members of this series induced signs of only CNS stimulation, some compounds caused signs of only CNS depression and skeletal muscle relaxation, and some caused signs of both stimulation and depression in the same animal. This apparent dual activity was assessed further in mice with antidepressant tests based on tetrabenazine antagonism and with antianxiety/anticonvulsant tests on the antagonism of a number of convulsants. The 4-chloro-, 4-fluoro-, 4-bromo-, and 3,4-dichlorobenzyl compounds exhibited antidepressant and antianxiety activities in the same dose range. Among these four compounds, the 3,4-dichlorobenzyl compound possessed the lowest antitetrabenazine (17 mg/kg po) and antipentylenetetrazol (23 mg/kg po) ED50 values. The 4-fluoro compound antagonized tetrabenazine-, pentylenetetrazol-, and isoniazid-induced tonic convulsions in the same dose range (congruent to 50 mg/kg po).

  10. Crystal structure of bis-(benzyl-amine-κN)[5,10,15,20-tetra-kis-(4-chloro-phen-yl)porphyrinato-κ(4) N]iron(II) n-hexane monosolvate.

    PubMed

    Dhifaoui, Selma; Harhouri, Wafa; Bujacz, Anna; Nasri, Habib

    2016-01-01

    In the title compound, [Fe(II)(C44H24Cl4N4)(C6H5CH2NH2)2]·C6H14 or [Fe(II)(TPP-Cl)(BzNH2)2n-hexane [where TPP-Cl and BzNH2 are 5,10,15,20-tetra-kis-(4-chloro-phen-yl)porphyrinate and benzyl-amine ligands, respectively], the Fe(II) cation lies on an inversion centre and is octa-hedrally coordinated by the four pyrrole N atoms of the porphyrin ligand in the equatorial plane and by two amine N atoms of the benzyl-amine ligand in the axial sites. The crystal structure also contains one inversion-symmetric n-hexane solvent mol-ecule per complex mol-ecule. The average Fe-Npyrrole bond length [1.994 (3) Å] indicates a low-spin complex. The crystal packing is sustained by N-H⋯Cl and C-H⋯Cl hydrogen-bonding inter-actions and by C-H⋯π inter-molecular inter-actions, leading to a three-dimensional network structure.

  11. Asymmetric Benzylic Allylic Alkylation Reaction of 3-Furfural Derivatives by Dearomatizative Dienamine Activation.

    PubMed

    He, Xiao-Long; Zhao, Hui-Ru; Duan, Chuan-Qi; Han, Xu; Du, Wei; Chen, Ying-Chun

    2018-04-20

    The dearomatizative dienamine-type ortho-quinodimethane species are smoothly generated between 2-alkyl-3-furfurals and chiral secondary amine catalysts, which undergo asymmetric benzylic allylic alkylation reactions with 2-nitroallylic acetates efficiently. A spectrum of densely functionalized 3-furfural derivatives are delivered in moderate to high yields with good to excellent diastereo- and enantioselectivity (up to 98 % yield, >19:1 d.r., >99 % ee). The latent transformations allow the facile production of some enantioenriched architectures, such as 1,1,2,2-tetraarylethanes and triarylmethanes, which are not easily available from other protocols. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Crystallization and preliminary X-ray study of a (2R,3R)-2,3-butanediol dehydrogenase from Bacillus coagulans 2-6.

    PubMed

    Miao, Xiangzhi; Huang, Xianhui; Zhang, Guofang; Zhao, Xiufang; Zhu, Xianming; Dong, Hui

    2013-10-01

    (2R,3R)-2,3-Butanediol dehydrogenase (R,R-BDH) from Bacillus coagulans 2-6 is a zinc-dependent medium-chain alcohol dehydrogenase. Recombinant R,R-BDH with a His6 tag at the C-terminus was expressed in Escherichia coli BL21 (DE3) cells and purified by Ni2+-chelating affinity and size-exclusion chromatography. Crystals were grown by the hanging-drop vapour-diffusion method at 289 K. The crystallization condition consisted of 8%(v/v) Tacsimate pH 4.6, 18%(w/v) polyethylene glycol 3350. The crystal diffracted to 2.8 Å resolution in the orthorhombic space group P222₁, with unit-cell parameters a=88.35, b=128.73, c=131.03 Å.

  13. Evaluation of electron population terms for <r-3Se>4p, <r-3S>3p, and <r-3O>(2p): how do HOMO and LUMO shrink or expand depending on nuclear charges?

    PubMed

    Nakanishi, Waro; Hayashi, Satoko; Narahara, Kenji; Yamaki, Daisuke; Hada, Masahiko

    2008-01-01

    Electron population terms <r(-3)N> are evaluated for N=Se, S, and O. Calculations are performed on HOMO and LUMO constructed by pure atomic 4p(Se), 3p(S), and 2p(O) orbitals, employing the 6-311+G(3d) and/or 6-311(++)G(3df,3pd) basis sets at the HF, MP2, and DFT (B3 LYP) levels. Se(4+), Se(2+), Se(0), and Se(2-) with the O(h) symmetry are called G(A: Se) and HSe(+), H(2)Se, and HSe(-) with the C(infinityh) or C(2v) symmetry are named G(B: Se), here [G(A+B: Se) in all]. HOMO and LUMO in G(A+B: N) (N=Se, S, and O) satisfy the conditions of the calculations for <r(-3)N>. The <r(-3)Se>(4p), <r(-3)S>(3p), and <r(-3)O>(2p) values correlate well with the corresponding MO energies (epsilon(N)) for all calculation levels employed. Plots of <r(-3)N>(HOMO) and <r(-3)N>(LUMO) versus Q(N) (N=Se, S, and O) at the HF and MP2 levels are analyzed as two correlations. However, the plots at the DFT level can be analyzed as single correlation. A regression curve is assumed for the analysis. Behaviors of <r(-3)N> clarify how valence orbitals shrink or expand depending on Q(N). The applicability of <r(-3)N> is examined to establish a new method that enables us to analyze chemical shifts with the charge effect separately from others. A utility program derived from the Gaussian 03 (NMRANAL-NH03G) is applied to evaluate <r(-3)N> and examine the applicability to the NMR analysis.

  14. A new window towards multidimensional sensing of transition metal cations through dual mode sensing ability of N-benzyl-(3-hydoxy-2-naphthalene): Emission enhancement coupled remarkable spectral shift

    NASA Astrophysics Data System (ADS)

    Paul, Bijan Kumar; Mahanta, Subrata; Singh, Rupashree Balia; Guchhait, Nikhil

    2011-06-01

    A structurally simple Schiff base N-benzyl-(3-hydroxy-2-naphthalene) (NBHN32) has been synthesized and characterized by 1H NMR, 13C NMR, and DEPT spectroscopy. The photophysical behaviour of NBHN32 in response to the presence of various transition metal cations has been explored by means of steady-state absorption, emission and time-resolved emission spectroscopy techniques. Efficient through space intramolecular photoinduced electron transfer (PET) between the naphthalene fluorophore and the imine group has been argued for extremely low fluorescence yield of NBHN32 compared to the parent molecule 3-hydroxy-2-naphthaldehyde (HN32) containing the same fluorophore but lacking the receptor moiety. Transition metal ion-induced emission enhancement is thus addressed on the lexicon of perturbation of the PET by the metal ions. Apart from fluorescence enhancement, transition metal ion imparts remarkable shift of the emission maxima of NBHN32, which is another unique aspect on the proposed ability of NBHN32 to function as a fluorescence chemosensor.

  15. Spectroscopic and structural studies of a new para-iodo-N-benzyl amide of salinomycin

    NASA Astrophysics Data System (ADS)

    Antoszczak, Michał; Janczak, Jan; Rutkowski, Jacek; Brzezinski, Bogumił; Huczyński, Adam

    2017-11-01

    A new para-iodo-N-benzyl amide of salinomycin was synthesized and characterized by NMR, FT-IR, DFT, single crystal X-ray diffraction and theoretical methods. The results obtained for the crystal, in solution and in gas phase provided evidence of pseudo-cyclic structure of this compound stabilized by intramolecular hydrogen bonds. It was shown that the compound studied forms stable 1:1 complexes with monovalent (Li+, Na+, K+, Rb+ and Cs+) and divalent (Mg2+, Ca2+, Sr2+ and Ba2+) cations demonstrating that the chemical modification of salinomycin carboxyl group considerably changes the ionophoretic properties of this antibiotic. For the first time, the ESI MS fragmentations of the complex of para-iodo-N-benzyl amide of salinomycin with Na+ are also discussed in details.

  16. Vector correlation between the alignment of reactant N2 (A 3Σu+) and the alignment of product NO (A 2Σ+) rotation in the energy transfer reaction of aligned N2 (A 3Σu+) + NO (X 2Π) → NO (A 2Σ+) + N2 (X 1Σg+).

    PubMed

    Ohoyama, H

    2013-12-21

    The vector correlation between the alignment of reactant N2 (A (3)Σu(+)) and the alignment of product NO (A (2)Σ(+)) rotation has been studied in the energy transfer reaction of aligned N2 (A (3)Σu(+)) + NO (X (2)Π) → NO (A (2)Σ(+)) + N2 (X (1)Σg(+)) under the crossed beam condition at a collision energy of ~0.07 eV. NO (A (2)Σ(+)) emission in the two linear polarization directions (i.e., parallel and perpendicular with respect to the relative velocity vector v(R)) has been measured as a function of the alignment of N2 (A (3)Σu(+)) along its molecular axis in the collision frame. The degree of polarization of NO (A (2)Σ(+)) emission is found to depend on the alignment angle (θ(v(R))) of N2 (A (3)Σu(+)) in the collision frame. The shape of the steric opacity function at the two polarization conditions turns out to be extremely different from each other: The steric opacity function at the parallel polarization condition is more favorable for the oblique configuration of N2 (A (3)Σu(+)) at an alignment angle of θ(v(R)) ~ 45° as compared with that at the perpendicular polarization condition. The alignment of N2 (A (3)Σu(+)) is found to give a significant effect on the alignment of NO (A (2)Σ(+)) rotation in the collision frame: The N2 (A (3)Σu(+)) configuration at an oblique alignment angle θ(v(R)) ~ 45° leads to a parallel alignment of NO (A (2)Σ(+)) rotation (J-vector) with respect to v(R), while the axial and sideways configurations of N2 (A (3)Σu(+)) lead to a perpendicular alignment of NO (A (2)Σ(+)) rotation with respect to vR. These stereocorrelated alignments of the product rotation have a good correlation with the stereocorrelated reactivity observed in the multi-dimensional steric opacity function [H. Ohoyama and S. Maruyama, J. Chem. Phys. 137, 064311 (2012)].

  17. Local metric dimension of circulant graph c i r c (n :1 ,2 ,…,n/+1 2 )

    NASA Astrophysics Data System (ADS)

    Rimadhany, Ruzika; Darmaji

    2017-08-01

    Let G be a connected graph with two vertices u and v. The distance between u and v, denoted by d(u, v), is defined as length of the shortest path from u to v in G. For an ordered set W = {w1, w2, w3, … , wk} of k distinct vertices in a nontrivial connected graph G, the representation of a vertex v of V(G) respect to W is r(v|W) = (d(v, w1), d(v, w2), … , d(v, wk)). The set W is a resolving set of G if r(v|W) for each vertex v ∈ V(G) is distinct. A resolving set of minimum cardinality is a metric dimension and denoted by dim(G). The set W is a local resolving set of G if r(v|W) for every two adjacent vertices of V(G) is distinct. The minimum cardinality of local resolving set of G is a local metric dimension and denoted by ldim(G). In this research, we determine local metric dimension of circulant graph c i r c (n :1 ,2 ,3 ,…,n/+1 2 ) .

  18. Crystallization and preliminary X-ray study of a (2R,3R)-2,3-butanediol dehydrogenase from Bacillus coagulans 2-6

    PubMed Central

    Miao, Xiangzhi; Huang, Xianhui; Zhang, Guofang; Zhao, Xiufang; Zhu, Xianming; Dong, Hui

    2013-01-01

    (2R,3R)-2,3-Butanediol dehydrogenase (R,R-BDH) from Bacillus coagulans 2-6 is a zinc-dependent medium-chain alcohol dehydrogenase. Recombinant R,R-BDH with a His6 tag at the C-terminus was expressed in Escherichia coli BL21 (DE3) cells and purified by Ni2+-chelating affinity and size-exclusion chromatography. Crystals were grown by the hanging-drop vapour-diffusion method at 289 K. The crystallization condition consisted of 8%(v/v) Tacsimate pH 4.6, 18%(w/v) polyethylene glycol 3350. The crystal diffracted to 2.8 Å resolution in the orthorhombic space group P212121, with unit-cell parameters a = 88.35, b = 128.73, c = 131.03 Å. PMID:24100567

  19. Phase relations in the pseudobinary systems RAO3-R2Ti2O7 (R: rare earth element and Y, A: Fe, Ga, Al, Cr and Mn) and syntheses of new compounds R(A1-xTix)O3+x/2 (2/3≤x≤3/4) at elevated temperatures in air

    NASA Astrophysics Data System (ADS)

    Brown, Francisco; Jacobo-Herrera, Ivan; Alvarez-Montaño, Victor; Kimizuka, Noboru; Kurashina, Keiji; Michiue, Yuichi; Matsuo, Yoji; Mori, Shigeo; Ikeda, Naoshi; Medrano, Felipe

    2017-07-01

    Phase relations in the pseudo-binary systems RFeO3-R2Ti2O7 (R: Lu, Ho and Dy), RGaO3-R2Ti2O7 (R: Lu and Er), LuAlO3-Lu2Ti2O7 and RAO3-R2Ti2O7 (R: Lu and Yb. A: Cr and Mn) at elevated temperatures in air were determined by means of a classic quenching method. There exist Lu(Fe1-xTix)O3+x/2, R(Ga1-xTix)O3+x/2 (R: Lu and Er) and Lu(Al1-xTix)O3+x/2 (2/3≤ x≤3/4) having the Yb(Fe1-xTix)O3+x/2-type of crystal structure (x=0.72, space group: R3m, a(Å)=17.9773 and c(Å)=16.978 as a hexagonal setting) in these pseudo binary systems. Eighteen compounds R(A1-xTix)O3+x/2 (R: Lu-Sm and Y, A: Fe, Ga and Al) were newly synthesized and their lattice constants as a hexagonal setting were measured by means of the X-ray powder diffraction method. The R occupies the octahedral site and both A and Ti does the trigonalbipyramidal one in these compounds. Relation between lattice constants for the rhombic R(A1-xTix)O3+x/2 and the monoclinic In(A1-xTix)O3+x/2 are as follows, ah≈5 x bm, ch≈3 x cm x sin β and am=31/2 x bm, where ah and ch are the lattice constants as a hexagonal setting for R(A1-xTix)O3+x/2 and am, bm, cm and β are those of the monoclinic In(A1-xTix)O3+x/2. Crystal structural relationships among α-InGaO3 (hexagonal, high pressure form, space group: P63/mmc), InGaO3 (rhombic, hypothetical), (RAO3)n(BO)m and RAO3(ZnO)m (R: Lu-Ho, Y and In, A: Fe, Ga, and Al, B: divalent cation element, m, n: natural number), the orthorhombic-and monoclinic In(A1-xTix)O3+x/2 (A: Fe, Ga, Al, Cr and Mn) and the hexagonal-and rhombic R(A1-xTix)O3+x/2 (R: Lu-Sm and Y, A: Fe, Ga and Al) are schematically presented. We concluded that the crystal structures of both the α-InGaO3 (high pressure form, hexagonal, space group: P63/mmc) and the hypothetical InGaO3 (rhombic) are the key structures for constructing the crystal structures of these compounds having the cations with CN=5.

  20. [(S)-1-Carbamoylethyl]bis(dimethylglyoximato-kappa2N,N')[(S)-1-phenylethylamine]cobalt(III) and bis(dimethylglyoximato-kappa2N,N')[(R)-1-(N-methylcarbamoyl)ethyl][(R)-1-phenylethylamine]cobalt(III) monohydrate.

    PubMed

    Orisaku, Keiko Komori; Hagiwara, Mieko; Ohgo, Yoshiki; Arai, Yoshifusa; Ohgo, Yoshiaki

    2005-04-01

    The title complexes, [Co(C3H6NO)(C4H7N2O2)2(C8H11N)] and [Co(C4H8NO)(C4H7N2O2)2(C8H11N)].H2O, were resolved from [(RS)-1-carbamoylethyl]bis(dimethylglyoximato)[(S)-1-phenylethylamine]cobalt(III) and bis(dimethylglyoximato)[(RS)-1-(N-methylcarbamoyl)ethyl][(R)-1-phenylethylamine]cobalt(III), respectively, and their crystal structures were determined in order to reveal the absolute configuration of the major enantiomer produced in the photoisomerization of each series of 2-carbamoylethyl and 2-(N-methylcarbamoyl)ethyl cobaloxime complexes.

  1. Synthesis, characterization, computational studies and biological evaluation of S-benzyl-β-N-[3-(4-hydroxy-3-methoxy-phenylallylidene)]dithiocarbazate

    NASA Astrophysics Data System (ADS)

    Bhat, Rayees A.; Kumar, D.; Malla, Manzoor A.; Bhat, Sami U.; Khan, Md Shahzad; Manzoor, Ovais; Srivastava, Anurag; Naikoo, Rawoof A.; Mohsin, Mohd; Mir, Muzzaffar A.

    2018-03-01

    S-Benzyl-β-N-[3-(4-hydroxy-3-methoxy-phenylallylidene)]dithiocarbazate (HL1), Schiff base of S-benzyl dithiocarbazate, was synthesized by 1:1 condensation between S-benzyl dithiocarbazate and 4-hydroxy-3-methoxy cinnamaldehyde. The nitrogen-sulfur Schiff base (HL1) was characterized by Mass, FT-IR, H1-NMR, Raman, and UV-VIS spectroscopic techniques. Theoretical quantum chemical calculations were performed using DFT in combination with B3LYP exchange correlation functional and 6-311++ G (d, p) basis sets level. The calculated values of chemical potential (μ), HOMO-LUMO energy gap, chemical hardness, softness (S), ionization energy (IE), electron affinity (EA), dipole moment (D) and relative stabilization energy of the compound were 0.14881 eV, 0.12542 eV, 0.06271 eV, 3.37299 eV, -0.21152 eV, -0.08610 eV, 4.4090 Debye and -1753.350 eV respectively. Theoretically calculated parameters like H1-NMR, FT-IR, UV-VIS, Raman, electrostatic potential and HOMO-LUMO energy gap are in good agreement with experimental results. Also, in-vitro cytotoxicity studies were done against two habitually infection causing bacteria strains including gram-positive (S. aureus) and gram-negative (E. coli) for antibacterial activity. The results showed appreciable biological activity and the activity increased with increase in dose.

  2. Fragrance material review on benzyl alcohol.

    PubMed

    Scognamiglio, J; Jones, L; Vitale, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of benzyl alcohol when used as a fragrance ingredient is presented. Benzyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for benzyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, photoallergy, toxicokinetics, repeated dose, reproductive toxicity, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Ultraviolet photodissociation dynamics of the benzyl radical.

    PubMed

    Song, Yu; Zheng, Xianfeng; Lucas, Michael; Zhang, Jingsong

    2011-05-14

    Ultraviolet (UV) photodissociation dynamics of jet-cooled benzyl radical via the 4(2)B(2) electronically excited state is studied in the photolysis wavelength region of 228 to 270 nm using high-n Rydberg atom time-of-flight (HRTOF) and resonance enhanced multiphoton ionization (REMPI) techniques. In this wavelength region, H-atom photofragment yield (PFY) spectra are obtained using ethylbenzene and benzyl chloride as the precursors of benzyl radical, and they have a broad peak centered around 254 nm and are in a good agreement with the previous UV absorption spectra of benzyl. The H + C(7)H(6) product translational energy distributions, P(E(T))s, are derived from the H-atom TOF spectra. The P(E(T)) distributions peak near 5.5 kcal mol(-1), and the fraction of average translational energy in the total excess energy, , is ∼0.3. The P(E(T))s indicate the production of fulvenallene + H, which was suggested by recent theoretical studies. The H-atom product angular distribution is isotropic, with the anisotropy parameter β ≈ 0. The H/D product ratios from isotope labeling studies using C(6)H(5)CD(2) and C(6)D(5)CH(2) are reasonably close to the statistical H/D ratios, suggesting that the H/D atoms are scrambled in the photodissociation of benzyl. The dissociation mechanism is consistent with internal conversion of the electronically excited benzyl followed by unimolecular decomposition of the hot benzyl radical on the ground state.

  4. 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.

    PubMed

    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

  5. Structure-activity relationships of substituted N-benzyl piperidines in the GBR series: Synthesis of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl)piperidine, an allosteric modulator of the serotonin transporter.

    PubMed

    Boos, Terrence L; Greiner, Elisabeth; Calhoun, W Jason; Prisinzano, Thomas E; Nightingale, Barbara; Dersch, Christina M; Rothman, Richard B; Jacobson, Arthur E; Rice, Kenner C

    2006-06-01

    A series of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-(substituted benzyl) piperidines with substituents at the ortho and meta positions in the aromatic ring of the N-benzyl side chain were synthesized and their affinities and selectivities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined. One analogue, 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl)piperidine (the C(2)-trifluoromethyl substituted compound), has been found to act as an allosteric modulator of hSERT binding and function. It had little affinity for any of the transporters. Several compounds showed affinity for the DAT in the low nanomolar range and displayed a broad range of SERT/DAT selectivity ratios and very little affinity for the NET. The pharmacological tools provided by the availability of compounds with varying transporter affinity and selectivity could be used to obtain additional information about the properties a compound should have to act as a useful pharmacotherapeutic agent for cocaine addiction and help unravel the pharmacological mechanisms relevant to stimulant abuse.

  6. Environmentally benign Friedel-Crafts benzylation over nano-TiO2/SO4 2-

    NASA Astrophysics Data System (ADS)

    Devi, Kalathiparambil RPS; Sreeja, Puthenveetil B.; Sugunan, Sankaran

    2013-05-01

    During the past decade, much attention has been paid to the replacement of homogeneous catalysts by solid acid catalysts. Friedel-Crafts benzylation of toluene with benzyl chloride (BC) in liquid phase was carried out over highly active, nano-crystalline sulfated titania systems. These catalysts were prepared using the sol gel method. Modification was done by loading 3% of transition metal oxides over sulfated titania. Reaction parameters such as catalyst mass, molar ratio, temperature, and time have been studied. More than 80% conversion of benzyl chloride and 100% selectivity are shown by all the catalysts under optimum conditions. Catalytic activity is correlated with Lewis acidity obtained from perylene adsorption studies. The reaction appears to proceed by an electrophile, which involves the reaction of BC with the acidic titania catalyst. The catalyst was regenerated and reused up to four reaction cycles with equal efficiency as in the first run. The prepared systems are environmentally friendly and are easy to handle.

  7. 3-O-Benzyl-6-O-benzoyl-1,2-O-isopropil-idene-5-C-nitro-methyl-a-d-glucofuran-ose.

    PubMed

    Pampín, Begoña; Valencia, Laura; Estévez, Juan C; Estévez, Ramón J

    2009-01-17

    The title compound, C(24)H(27)NO(9), is one of the epimers of the Henry reaction of 3-O-benzyl-6-O-benzoyl-2-O-isopropyl-idene-a-d-glucofuran-5-one with nitro-methane. The conformation of the five membered rings is as expected from the precursor compound and the mol-ecule is folded with a dihedral angle of 51.4 (2)° between the aromatic rings. One O-H⋯O hydrogen bond and some intra-molecular and inter-molecular C-H⋯O inter-actions are observed in the structure.

  8. Pathogenicity and Transmission in Pigs of the Novel A(H3N2)v Influenza Virus Isolated from Humans and Characterization of Swine H3N2 Viruses Isolated in 2010-2011

    PubMed Central

    Kitikoon, Pravina; Gauger, Phillip C.; Schlink, Sarah N.; Bayles, Darrell O.; Gramer, Marie R.; Darnell, Daniel; Webby, Richard J.; Lager, Kelly M.; Swenson, Sabrina L.; Klimov, Alexander

    2012-01-01

    Swine influenza virus (SIV) H3N2 with triple reassorted internal genes (TRIG) has been enzootic in Unites States since 1998. Transmission of the 2009 pandemic H1N1 (pH1N1) virus to pigs in the United States was followed by reassortment with endemic SIV, resulting in reassorted viruses that include novel H3N2 genotypes (rH3N2p). Between July and December 2011, 12 cases of human infections with swine-lineage H3N2 viruses containing the pandemic matrix (pM) gene [A(H3N2)v] were detected. Whole-genome analysis of H3N2 viruses isolated from pigs from 2009 to 2011 sequenced in this study and other available H3N2 sequences showed six different rH3N2p genotypes present in the U.S. swine population since 2009. The presence of the pM gene was a common feature among all rH3N2p genotypes, but no specific genotype appeared to predominate in the swine population. We compared the pathogenic, transmission, genetic, and antigenic properties of a human A(H3N2)v isolate and two swine H3N2 isolates, H3N2-TRIG and rH3N2p. Our in vivo study detected no increased virulence in A(H3N2)v or rH3N2p viruses compared to endemic H3N2-TRIG virus. Antibodies to cluster IV H3N2-TRIG and rH3N2p viruses had reduced cross-reactivity to A(H3N2)v compared to other cluster IV H3N2-TRIG and rH3N2p viruses. Genetic analysis of the hemagglutinin gene indicated that although rH3N2p and A(H3N2)v are related to cluster IV of H3N2-TRIG, some recent rH3N2p isolates appeared to be forming a separate cluster along with the human isolates of A(H3N2)v. Continued monitoring of these H3N2 viruses is necessary to evaluate the evolution and potential loss of population immunity in swine and humans. PMID:22491461

  9. Pathogenicity and transmission in pigs of the novel A(H3N2)v influenza virus isolated from humans and characterization of swine H3N2 viruses isolated in 2010-2011.

    PubMed

    Kitikoon, Pravina; Vincent, Amy L; Gauger, Phillip C; Schlink, Sarah N; Bayles, Darrell O; Gramer, Marie R; Darnell, Daniel; Webby, Richard J; Lager, Kelly M; Swenson, Sabrina L; Klimov, Alexander

    2012-06-01

    Swine influenza virus (SIV) H3N2 with triple reassorted internal genes (TRIG) has been enzootic in Unites States since 1998. Transmission of the 2009 pandemic H1N1 (pH1N1) virus to pigs in the United States was followed by reassortment with endemic SIV, resulting in reassorted viruses that include novel H3N2 genotypes (rH3N2p). Between July and December 2011, 12 cases of human infections with swine-lineage H3N2 viruses containing the pandemic matrix (pM) gene [A(H3N2)v] were detected. Whole-genome analysis of H3N2 viruses isolated from pigs from 2009 to 2011 sequenced in this study and other available H3N2 sequences showed six different rH3N2p genotypes present in the U.S. swine population since 2009. The presence of the pM gene was a common feature among all rH3N2p genotypes, but no specific genotype appeared to predominate in the swine population. We compared the pathogenic, transmission, genetic, and antigenic properties of a human A(H3N2)v isolate and two swine H3N2 isolates, H3N2-TRIG and rH3N2p. Our in vivo study detected no increased virulence in A(H3N2)v or rH3N2p viruses compared to endemic H3N2-TRIG virus. Antibodies to cluster IV H3N2-TRIG and rH3N2p viruses had reduced cross-reactivity to A(H3N2)v compared to other cluster IV H3N2-TRIG and rH3N2p viruses. Genetic analysis of the hemagglutinin gene indicated that although rH3N2p and A(H3N2)v are related to cluster IV of H3N2-TRIG, some recent rH3N2p isolates appeared to be forming a separate cluster along with the human isolates of A(H3N2)v. Continued monitoring of these H3N2 viruses is necessary to evaluate the evolution and potential loss of population immunity in swine and humans.

  10. Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual binding site acetylcholinesterase inhibitors.

    PubMed

    Alipour, Masoumeh; Khoobi, Mehdi; Foroumadi, Alireza; Nadri, Hamid; Moradi, Alireza; Sakhteman, Amirhossein; Ghandi, Mehdi; Shafiee, Abbas

    2012-12-15

    A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC(50) in which compound 3r (IC(50) = 0.11 nM) was the most active compound against acetylcholinesterase enzyme. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. A new window towards multidimensional sensing of transition metal cations through dual mode sensing ability of N-benzyl-(3-hydoxy-2-naphthalene): emission enhancement coupled remarkable spectral shift.

    PubMed

    Paul, Bijan Kumar; Mahanta, Subrata; Singh, Rupashree Balia; Guchhait, Nikhil

    2011-06-01

    A structurally simple Schiff base N-benzyl-(3-hydroxy-2-naphthalene) (NBHN32) has been synthesized and characterized by (1)H NMR, (13)C NMR, and DEPT spectroscopy. The photophysical behaviour of NBHN32 in response to the presence of various transition metal cations has been explored by means of steady-state absorption, emission and time-resolved emission spectroscopy techniques. Efficient through space intramolecular photoinduced electron transfer (PET) between the naphthalene fluorophore and the imine group has been argued for extremely low fluorescence yield of NBHN32 compared to the parent molecule 3-hydroxy-2-naphthaldehyde (HN32) containing the same fluorophore but lacking the receptor moiety. Transition metal ion-induced emission enhancement is thus addressed on the lexicon of perturbation of the PET by the metal ions. Apart from fluorescence enhancement, transition metal ion imparts remarkable shift of the emission maxima of NBHN32, which is another unique aspect on the proposed ability of NBHN32 to function as a fluorescence chemosensor. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Triggering N2 Uptake via Redox Induced Expulsion of Coordinated NH3 and N2 Silylation at Trigonal Bipyramidal Iron

    PubMed Central

    Lee, Yunho; Mankad, Neal P.

    2010-01-01

    The biological reduction of nitrogen to ammonia may occur via one of two predominant pathways in which nitrogenous NxHy intermediates including hydrazine (N2H4), diazene (N2H2), nitride (N3-) and imide (NH2-) may be involved. To test the validity of hypotheses concerning iron’s direct role in the stepwise reduction of N2, iron model systems are needed. Such systems can test the chemical compatibility of iron with various proposed NxHy intermediates, and the reactivity patterns of such species. Here we describe a TBP (SiPR3)Fe-L scaffold (SiPR3 represents [Si(o-C6H4PR2)3]−; R = Ph and iPr) where the apical site is occupied by nitrogenous ligands such as N2, N2H4, NH3 and N2R. The system accommodates terminally bound N2 in the three formal oxidation states (iron(0), +1, and +2). N2 uptake is demonstrated via displacement of its reduction partners NH3 and N2H4, and N2 functionalizaton is illustrated via electrophilic silylation. PMID:20571574

  13. Synthesis and conformational studies of carrabiose and its 4'-sulphate and 2,4'-disulphate.

    PubMed

    Parra, E; Caro, H N; Jiménez-Barbero, J; Martín-Lomas, M; Bernabé, M

    1990-12-15

    Methyl alpha-carrabioside (13), and its 4-sulphate (19) and 2,4-disulphate (20) have been synthesised via glycosylation of methyl 3,6-anhydro-2-O-benzyl-alpha-D-galactopyranoside with 2,3,6-tri-O-acetyl-4-O-benzyl-beta-D-galactopyranosyl bromide and subsequent partial or complete debenzylation, sulphation, and deprotection of the resulting disaccharide derivatives. Conformational studies have been carried out on 13, 19, and 20 on the basis of 1D and 2D 1H-n.m.r. spectroscopy and molecular mechanics calculations.

  14. Substituent effect of N-benzylated gramine derivatives that prevent the PP2A inhibition and dissipate the neuronal Ca2+ overload, as a multitarget strategy for the treatment of Alzheimer's disease.

    PubMed

    Gonzalez, Dorleta; Arribas, Raquel L; Viejo, Lucia; Lajarin-Cuesta, Rocio; de Los Rios, Cristobal

    2018-05-15

    Following the premises of the multitarget-directed ligands approach for the drug R&D against neurodegenerative diseases, where Alzheimer's disease (AD) outstands, we have synthesized and evaluated analogues of the gramine derivative ITH12657 (1-benzyl-5-methyl-3-(piperidin-1-ylmethyl-1H-indole, 2), which had shown important neuroprotective properties, such as blocking effect of voltage-gated Ca 2+ channels (VGCC), and prevention of phosphoprotein phosphatase 2A (PP2A) inhibition. The new analogues present different substitutions at the pending phenyl ring, what slightly modified their pharmacological characteristics. The VGCC blockade was enhanced in derivatives possessing nitro groups, while the pro-PP2A feature was ameliorated by the presence of fluorine. Chlorine atoms supplied good activities over the two biological targets aimed; nevertheless that substitution provoked loss of viability at 100-fold higher concentrations (10 μM), what discards them for a deeper pharmacological study. Overall, the para-fluorine derivative of ITH12657 was the most promising candidate for further preclinical assays. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Crystal structure of N′′-benzyl-N′′-[3-(benzyl­dimethyl­aza­nium­yl)prop­yl]-N,N,N′,N′-tetra­methyl­guanidinium bis­(tetra­phenyl­borate)

    PubMed Central

    Tiritiris, Ioannis; Kantlehner, Willi

    2015-01-01

    In the crystal structure of the title salt, C24H38N4 22C24H20B−, the C—N bond lengths in the central CN3 unit of the guanidinium ion are 1.3364 (13), 1.3407 (13) and 1.3539 (13) Å, indicating partial double-bond character. The central C atom is bonded to the three N atoms in a nearly ideal trigonal–planar geometry and the positive charge is delocalized in the CN3 plane. The bonds between the N atoms and the terminal methyl groups of the guanidinium moiety and the four C—N bonds to the central N atom of the (benzyl­dimethyl­aza­nium­yl)propyl group have single-bond character. In the crystal, C—H⋯π inter­actions between the guanidin­ium H atoms and the phenyl C atoms of the tetra­phenyl­borate ions are present, leading to the formation of a two-dimensional supra­molecular pattern parallel to the ac plane. PMID:26870511

  16. NKG2D and CD94 bind to multimeric alpha2,3-linked N-acetylneuraminic acid.

    PubMed

    Imaizumi, Yuzo; Higai, Koji; Suzuki, Chiho; Azuma, Yutaro; Matsumoto, Kojiro

    2009-05-08

    Killer lectin-like receptors on natural killer cells mediate cytotoxicity through glycans on target cells including the sialyl Lewis X antigen (sLeX). We investigated whether NK group 2D (NKG2D) and CD94 can bind to sialylated N-linked glycans, using recombinant glutathione S-transferase-fused extracellular lectin-like domains of NKG2D (rNKG2Dlec) and CD94 (rCD94lec). Both rNKG2Dlec and rCD94lec bound to plates coated with high-sLeX-expressing transferrin secreted by HepG2 cells (HepTF). The binding of rNKG2Dlec and rCD94lec to HepTF was markedly suppressed by treatment of HepTF with neuraminidase and in the presence of N-acetylneuraminic acid. Moreover, rNKG2Dlec and rCD94lec bound to alpha2,3-sialylated human alpha(1)-acid glycoprotein (AGP) but not to alpha2,6-sialylated AGP. Mutagenesis revealed that (152)Y of NKG2D and (144)F and (160)N of CD94 were critical for HepTF binding. This is the first report that NKG2D and CD94 bind to alpha2,3-sialylated but not to alpha2,6-sialylated multi-antennary N-glycans.

  17. The C- and N-Terminal Residues of Synthetic Heptapeptide Ion Channels Influence Transport Efficacy Through Phospholipid Bilayers

    PubMed Central

    Djedovič, Natasha; Ferdani, Riccardo; Harder, Egan; Pajewska, Jolanta; Pajewski, Robert; Weber, Michelle E.; Schlesinger, Paul H.; Gokel, George W.

    2008-01-01

    The synthetic peptide, R2N-COCH2OCH2CO-Gly-Gly-Gly-Pro-Gly-Gly-Gly-OR’, was shown to be selective for Cl- over K+ when R is n-octadecyl and R’ is benzyl. Nineteen heptapeptides have now been prepared in which the N-terminal and C-terminal residues have been varied. All of the N-terminal residues are dialkyl but the C-terminal chains are esters, 2° amides, or 3° amides. The compounds having varied N-terminal anchors and C-terminal benzyl groups are as follows: 1, R = n-propyl; 2, R = n-hexyl; 3, R = n-octyl; 4, R = n-decyl; 5, R = n-dodecyl; 6, R = n-tetradecyl; 7, R = n-hexadecyl; 8, R = n-octadecyl. Compounds 9-19 have R = n-octadecyl and C-terminal residues as follows: 9, OR’ = OCH2CH3; 10, OR’ = OCH(CH3)2; 11, OR’ = O(CH2)6CH3; 12, OR’ = OCH2-c-C6H11; 13, OR’ = O(CH2)9CH3; 14, OR’ = O (CH2)17CH3; 15, NR’2 = N[(CH2)6CH3]2; 16, NHR’ = NH(CH2)9CH3; 17, NR’2 = N[(CH2)9CH3]2; 18, NHR’ = NH(CH2)17CH3; 19, NR’2 = N[(CH2)17CH3]2. The highest anion transport activities were observed as follows. For the benzyl esters whose N-terminal residues were varied, i.e. 1-8, compound 3 was most active. For the C18 anchored esters 10-14, n-heptyl ester 11 was most active. For the C18 anchored, C-terminal amides 15-19, di-n-decylamide 17 was most active. It was concluded that both the C- and N-terminal anchors were important for channel function in the bilayer but that activity was lost unless only one of the two anchoring groups was dominant. PMID:19633728

  18. Synthesis of the (N2)3- radical from Y2+ and its protonolysis reactivity to form (N2H2)2- via the Y[N(SiMe3)2]3/KC8 reduction system.

    PubMed

    Fang, Ming; Lee, David S; Ziller, Joseph W; Doedens, Robert J; Bates, Jefferson E; Furche, Filipp; Evans, William J

    2011-03-23

    Examination of the Y[N(SiMe(3))(2)](3)/KC(8) reduction system that allowed isolation of the (N(2))(3-) radical has led to the first evidence of Y(2+) in solution. The deep-blue solutions obtained from Y[N(SiMe(3))(2)](3) and KC(8) in THF at -35 °C under argon have EPR spectra containing a doublet at g(iso) = 1.976 with a 110 G hyperfine coupling constant. The solutions react with N(2) to generate (N(2))(2-) and (N(2))(3-) complexes {[(Me(3)Si)(2)N](2)(THF)Y}(2)(μ-η(2):η(2)-N(2)) (1) and {[(Me(3)Si)(2)N](2)(THF)Y}(2)(μ-η(2):η(2)-N(2))[K(THF)(6)] (2), respectively, and demonstrate that the Y[N(SiMe(3))(2)](3)/KC(8) reaction can proceed through an Y(2+) intermediate. The reactivity of (N(2))(3-) radical with proton sources was probed for the first time for comparison with the (N(2))(2-) and (N(2))(4-) chemistry. Complex 2 reacts with [Et(3)NH][BPh(4)] to form {[(Me(3)Si)(2)N](2)(THF)Y}(2)(μ-N(2)H(2)), the first lanthanide (N(2)H(2))(2-) complex derived from dinitrogen, as well as 1 as a byproduct, consistent with radical disproportionation reactivity.

  19. Graphite-supported gold nanoparticles as efficient catalyst for aerobic oxidation of benzylic amines to imines and N-substituted 1,2,3,4-tetrahydroisoquinolines to amides: synthetic applications and mechanistic study.

    PubMed

    So, Man-Ho; Liu, Yungen; Ho, Chi-Ming; Che, Chi-Ming

    2009-10-05

    Selective oxidation of amines using oxygen as terminal oxidant is an important area in green chemistry. In this work, we describe the use of graphite-supported gold nanoparticles (AuNPs/C) to catalyze aerobic oxidation of cyclic and acyclic benzylic amines to the corresponding imines with moderate-to-excellent substrate conversions (43-100%) and product yields (66-99%) (19 examples). Oxidation of N-substituted 1,2,3,4-tetrahydroisoquinolines in the presence of aqueous NaHCO3 solution gave the corresponding amides in good yields (83-93%) with high selectivity (up to amide/enamide=93:4) (6 examples). The same protocol can be applied to the synthesis of benzimidazoles from the reaction of o-phenylenediamines with benzaldehydes under aerobic conditions (8 examples). By simple centrifugation, AuNPs/C can be recovered and reused for ten consecutive runs for the oxidation of dibenzylamine to N-benzylidene(phenyl)methanamine without significant loss of catalytic activity and selectivity. This protocol "AuNPs/C+O2" can be scaled to the gram scale, and 8.9 g (84 % isolated yield) of 3,4-dihydroisoquinoline can be obtained from the oxidation of 10 g 1,2,3,4-tetrahydroisoquinoline in a one-pot reaction. Based on the results of kinetic studies, radical traps experiment, and Hammett plot, a mechanism involving the hydrogen-transfer reaction from amine to metal and oxidation of M-H is proposed.

  20. Solution Synthesis, Structure, and CO2 Reduction Reactivity of a Scandium(II) Complex, {Sc[N(SiMe3 )2 ]3 }.

    PubMed

    Woen, David H; Chen, Guo P; Ziller, Joseph W; Boyle, Timothy J; Furche, Filipp; Evans, William J

    2017-02-13

    The first crystallographically characterizable complex of Sc 2+ , [Sc(NR 2 ) 3 ] - (R=SiMe 3 ), has been obtained by LnA 3 /M reactions (Ln=rare earth metal; A=anionic ligand; M=alkali metal) involving reduction of Sc(NR 2 ) 3 with K in the presence of 2.2.2-cryptand (crypt) and 18-crown-6 (18-c-6) and with Cs in the presence of crypt. Dark maroon [K(crypt)] + , [K(18-c-6)] + , and [Cs(crypt)] + salts of the [Sc(NR 2 ) 3 ] - anion are formed, respectively. The formation of this oxidation state of Sc is also indicated by the eight-line EPR spectra arising from the I=7/2 45 Sc nucleus. The Sc(NR 2 ) 3 reduction differs from Ln(NR 2 ) 3 reactions (Ln=Y and lanthanides) in that it occurs under N 2 without formation of isolable reduced dinitrogen species. [K(18-c-6)][Sc(NR 2 ) 3 ] reacts with CO 2 to produce an oxalate complex, {K 2 (18-c-6) 3 }{[(R 2 N) 3 Sc] 2 (μ-C 2 O 4 -κ 1 O:κ 1 O'')}, and a CO 2 - radical anion complex, [(R 2 N) 3 Sc(μ-OCO-κ 1 O:κ 1 O')K(18-c-6)] n . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Effects of the [OC6F5] moiety upon structural geometry: crystal structures of half-sandwich tantalum(V) aryloxide complexes from reaction of Cp*Ta(N(t)Bu)(CH2R)2 with pentafluorophenol.

    PubMed

    Cole, Jacqueline M; Chan, Michael C W; Gibson, Vernon C; Howard, Judith A K

    2011-10-01

    The synthesis, chemical and structural characterization of a series of pentamethylcyclopentadienyl (Cp*) tantalum imido complexes and aryloxide derivatives are presented. Specifically, the imido complexes Cp*Ta(N(t)Bu)(CH(2)R)(2), where R = Ph [dibenzyl(tert-butylamido) (η(5)-pentamethylcyclopentadienyl)tantalum(IV) (1)], Me(2)Ph [tert-butylamido)bis(2-methyl-2-phenylpropyl) (η(5)-pentamethylcyclopentadienyl)tantalum(IV) (2)], CMe(3) [(tert-butylamido)bis(2,2-dimethylpropyl) (η(5)-pentamethylcyclopentadienyl)tantalum(IV) (3)], are reported. The crystal structure of (3) reveals α-agostic interactions with the Ta atom. The resulting increase in the tantalum core coordination improves electronic stability. As such it does not react with pentafluorophenol, in contrast to the other two reported imido complexes [(1) and (2)]. Addition of C(6)F(5)OH to (1) yields a dimeric aryl-oxide derivative, [Cp*Ta(CH(2)Ph)(OC(6)H(5))(μ-O)](2) [di-μ-oxido-bis[benzyl(pentafluorophenolato) (η(5)-pentamethylcyclopentadienyl)tantalum(V)] (4)]. Its crystal structure reveals long Ta-O(C(6)H(5)) bonds but short oxo-bridging Ta-O bonds. This is explained by accounting for the fierce electronic competition for the vacant d(π) orbitals of the electrophilic Ta(V) centre. Steric congestion around each metal is alleviated by a large twist angle (77.1°) between the benzyl and pentafluorophenyl ligands and the ordering of each of these groups into stacked pairs. The imido complex (2) reacts with C(6)F(5)OH to produce a mixture of Cp*Ta(OC(6)F(5))(4) [tetrakis(pentafluorophenolato)(η(5)-pentamethylcyclopentadienyl)tantalum(V) (5)] and [Cp*Ta(OC(6)F(5))(2)(μ-O)](2) [di-μ-oxido-bis[bis(pentafluorophenolato)(η(5)-pentamethylcyclopentadienyl)tantalum(V)] (6)]. Steric congestion is offset in both cases by the twisting of its pentafluorophenyl ligands. Particularly strong electronic competition for the empty d(π) metal orbitals in (6) is reflected in its bond geometry, and owes itself to the

  2. Ab initio studies of Th3N4, Th2N3 and Th2N2(NH)

    NASA Astrophysics Data System (ADS)

    Obodo, K. O.; Chetty, N.

    2014-09-01

    Using density functional theory within the Perdew-Burke-Ernzerhof generalized gradient approximation [GGA (PBE)] implemented in the VASP codes, we investigate the structural, elastic and electronic properties of Th3N4, Th2N3 and Th2N2(NH). The calculated structural properties of these thorium-based nitrides are in good agreement with experimental data. We observe that all the Th-N based compounds that we considered are energetically favorable and elastically stable. We find that Th3N4 is semiconducting with a band gap of 1.59 eV, which compares well with the experimental band gap of 1.7 eV and we find Th2N3 to be metallic. Th2N2(NH), which is crystallographically equivalent to Th2N3, is insulating with a band gap of 2.12 eV. This is due to the -(NH) group that effects a shifting of the energy bands that results in the opening of a gap at the Fermi-level. The Th-N based compounds that we considered are predominantly ionic.

  3. (E)-1-(2,4-Di-nitro-phen-yl)-2-(3-eth-oxy-4-hy-droxy-benzyl-idene)hydrazine.

    PubMed

    Fun, Hoong-Kun; Chantrapromma, Suchada; Ruanwas, Pumsak; Kobkeatthawin, Thawanrat; Chidan Kumar, C S

    2014-01-01

    The mol-ecule of the title hydrazine derivative, C15H14N4O6, is essentially planar, the dihedral angle between the substituted benzene rings being 2.25 (9)°. The eth-oxy and hy-droxy groups are almost coplanar with their bound benzene ring [r.m.s. deviation = 0.0153 (2) Å for the ten non-H atoms]. Intra-molecular N-H⋯O and O-H⋯Oeth-oxy hydrogen bonds generate S(6) and S(5) ring motifs, respectively. In the crystal, mol-ecules are linked by O-H⋯Onitro hydrogen bonds into chains propagating in [010]. Weak aromatic π-π inter-actions, with centroid-centroid distances of 3.8192 (19) and 4.0491 (19) Å, are also observed.

  4. Synthesis, Spatial Structure and Analgesic Activity of Sodium 3-Benzylaminocarbonyl-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazin-4-olate Solvates

    PubMed Central

    Ukrainets, Igor V.; Petrushova, Lidiya A.; Shishkina, Svitlana V.; Grinevich, Lina A.; Sim, Galina

    2016-01-01

    In order to obtain and then test pharmocologically any possible conformers of the new feasible analgesic N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide, its 4-O-sodium salt was synthesized using two methods. X-ray diffraction study made possible to determine that, depending on the chosen synthesis conditions, the above-mentioned compound forms either monosolvate with methanol or monohydrate, where organic anion exists in the form of three different conformers. Pharmacological testing of the two known pseudo-enantiomeric forms of the original N-benzylamide and of the two solvates of its sodium salt was performed simultaneously under the same conditions and in equimolar doses. Comparison of the results obtained while studying the peculiarities of the synthesized compounds spatial structure and biological properties revealed an important structure-action relationship. In particular, it was shown that the intensity of analgesic effect of different conformational isomers of N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide may change considerably: while low active conformers are comparable with piroxicam, highly active conformers are more than twice as effective as meloxicam. PMID:27775559

  5. Gold(I) Complexes with N-Donor Ligands. 2.(1) Reactions of Ammonium Salts with [Au(acac-kappaC(2))(PR(3))] To Give [Au(NH(3))L](+), [(AuL)(2)(&mgr;(2)-NH(2))](+), [(AuL)(4)(&mgr;(4)-N)](+), or [(AuL)(3)(&mgr;(3)-O)](+). A New and Facile Synthesis of [Au(NH(3))(2)](+) Salts. Crystal Structure of [{AuP(C(6)H(4)OMe-4)(3)}(3)(&mgr;(3)-O)]CF(3)SO(3).

    PubMed

    Vicente, José; Chicote, María-Teresa; Guerrero, Rita; Jones, Peter G.; Ramírez De Arellano, M. Carmen

    1997-09-24

    The complexes [Au(acac-kappaC(2))(PR(3))] (acac = acetylacetonate, R = Ph, C(6)H(4)OMe-4) react with (NH(4))ClO(4) to give amminegold(I), [Au(NH(3))(PR(3))]ClO(4), amidogold(I), [(AuPR(3))(2)(&mgr;(2)-NH(2))]ClO(4), or nitridogold(I), [(AuPR(3))(4)(&mgr;(4)-N)]ClO(4), complexes, depending on the reaction conditions. Similarly, [Au(acac-kappaC(2))(PPh(3))] reacts with (NH(3)R')OTf (OTf = CF(3)SO(3)) (1:1) or with [H(3)N(CH(2))(2)NH(2)]OTf (1:1) to give (amine)gold(I) complexes [Au(NH(2)R')(PPh(3))]OTf (R' = Me, C(6)H(4)NO(2)-4) or [(AuPPh(3))(2){&mgr;(2)-H(2)N(CH(2))(2)NH(2)}](OTf)(2), respectively. The ammonium salts (NH(2)R'(2))OTf (R' = Et, Ph) react with [Au(acac-kappaC(2))(PR(3))] (R = Ph, C(6)H(4)OMe-4) (1:2) to give, after hydrolysis, the oxonium salts [(AuPR(3))(3)(&mgr;(3)-O)]OTf (R = Ph, C(6)H(4)OMe-4). When NH(3) is bubbled through a solution of [AuCl(tht)] (tht = tetrahydrothiophene), the complex [Au(NH(3))(2)]Cl precipitates. Addition of [Au(NH(3))(2)]Cl to a solution of AgClO(4) or TlOTf leads to the isolation of [Au(NH(3))(2)]ClO(4) or [Au(NH(3))(2)]OTf, respectively. The crystal structure of [(AuPR(3))(3)(&mgr;(3)-O)]OTf.Me(2)CO (R = C(6)H(4)OMe-4) has been determined: triclinic, space group P&onemacr;, a = 14.884(3) Å, b = 15.828(3) Å, c = 16.061(3) Å, alpha = 83.39(3) degrees, beta = 86.28(3) degrees, gamma = 65.54(3) degrees, R1 (wR2) = 0.0370 (0.0788). The [(AuPR(3))(3)(&mgr;(3)-O)](+) cation shows an essentially trigonal pyramidal array of three gold atoms and one oxygen atom with O-Au-P bond angles of ca. 175 degrees and Au.Au contacts in the range 2.9585(7)-3.0505(14) Å. These cations are linked into centrosymmetric dimers through two short Au.Au [2.9585(7), 3.0919(9) Å] contacts. The gold atoms of the dimer form a six-membered ring with a chair conformation.

  6. Discovery of Lacosamide Affinity Bait Agents That Exhibit Potent Voltage-Gated Sodium Channel Blocking Properties

    PubMed Central

    2012-01-01

    Lacosamide ((R)-1) is a recently marketed, first-in-class, antiepileptic drug. Patch-clamp electrophysiology studies are consistent with the notion that (R)-1 modulates voltage-gated Na+ channel function by increasing and stabilizing the slow inactivation state without affecting fast inactivation. The molecular pathway(s) that regulate slow inactivation are poorly understood. Affinity baits are chemical reactive units, which when appended to a ligand (drug) can lead to irreversible, covalent modification of the receptor thus permitting drug binding site identification including, possibly, the site of ligand function. We describe, herein, the synthesis of four (R)-1 affinity baits, (R)-N-(4″-isothiocyanatobiphenyl-4′-yl)methyl 2-acetamido-3-methoxypropionamide ((R)-8), (S)-N-(4″-isothiocyanatobiphenyl-4′-yl)methyl 2-acetamido-3-methoxypropionamide ((S)-8), (R)-N-(3″-isothiocyanatobiphenyl-4′-yl)methyl 2-acetamido-3-methoxypropionamide ((R)-9), and (R)-N-(3″-acrylamidobiphenyl-4′-yl)methyl 2-acetamido-3-methoxypropionamide ((R)-10). The affinity bait compounds were designed to interact with the receptor(s) responsible for (R)-1-mediated slow inactivation. We show that (R)-8 and (R)-9 are potent inhibitors of Na+ channel function and function by a pathway similar to that observed for (R)-1. We further demonstrate that (R)-8 function is stereospecific. The calculated IC50 values determined for Na+ channel slow inactivation for (R)-1, (R)-8, and (R)-9 were 85.1, 0.1, and 0.2 μM, respectively. Incubating (R)-9 with the neuronal-like CAD cells led to appreciable levels of Na+ channel slow inactivation after cellular wash, and the level of slow inactivation only modestly decreased with further incubation and washing. Collectively, these findings have identified a promising structural template to investigate the voltage-gated Na+ channel slow inactivation process. PMID:23509982

  7. Structure–Activity Relationships for a Novel Series of Dopamine D2-like Receptor Ligands Based on N-Substituted 3-Aryl-8-azabicyclo[3.2.1]octan-3-ol

    PubMed Central

    Paul, Noel M.; Taylor, Michelle; Kumar, Rakesh; Deschamps, Jeffrey R.; Luedtke, Robert R.; Newman, Amy Hauck

    2011-01-01

    Discovering dopamine D2-like receptor subtype-selective ligands has been a focus of significant investigation. The D2R-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole (1, L741,626; Ki(D2R/D3R) = 11.2:163 nM) has previously provided a lead template for chemical modification. Herein, analogues have been synthesized where the piperidine was replaced by a tropane ring that reversed the selectivity seen in the parent compound, in human hD2LR- or hD3R-transfected HEK 293 cells (31, Ki(D2R/D3R) = 33.4: 15.5 nM). Further exploration of both N-substituted and aryl ring-substituted analogues resulted in the discovery of several high affinity D2R/D3R ligands with 3-benzofurylmethyl-substituents (e.g., 45, Ki(D2R/D3R) = 1.7:0.34 nM) that induced high affinity not achieved in similarly N-substituted piperidine analogues and significantly (470-fold) improved D3R binding affinity compared to the parent ligand 1. X-ray crystallographic data revealed a distinctive spatial arrangement of pharmacophoric elements in the piperidinol vs tropine analogues, providing clues for the diversity in SAR at the D2 and D3 receptor subtypes. PMID:18774793

  8. Expanding the Chemistry of Actinide Metallocene Bromides. Synthesis, Properties and Molecular Structures of the Tetravalent and Trivalent Uranium Bromide Complexes: (C 5Me 4R) 2UBr 2, (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(Br), and [K(THF)][(C 5Me 4R) 2UBr 2] (R = Me, Et)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lichtscheidl, Alejandro Gaston; Pagano, Justin K.; Scott, Brian Lindley

    The organometallic uranium species (C 5Me 4R) 2UBr 2 (R = Me, Et) were obtained by treating their chloride analogues (C 5Me 4R) 2UCl 2 (R = Me, Et) with Me 3SiBr. Treatment of (C 5Me 4R) 2UCl 2 and (C 5Me 4R) 2UBr 2 (R = Me, Et) with K(O-2,6- iPr 2C 6H 3) afforded the halide aryloxide mixed-ligand complexes (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(X) (R = Me, Et; X = Cl, Br). Complexes (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(Br) (R = Me, Et) can also be synthesized by treating (C 5Me 4R) 2U(O-2,6-more » iPr 2C 6H 3)(Cl) (R = Me, Et) with Me 3SiBr, respectively. Reduction of (C 5Me 4R) 2UCl 2 and (C 5Me 4R) 2UBr 2 (R = Me, Et) with KC 8 led to isolation of uranium(III) “ate” species [K(THF)][(C 5Me 5) 2UX 2] (X = Cl, Br) and [K(THF) 0.5][(C 5Me 4Et) 2UX 2] (X = Cl, Br), which can be converted to the neutral complexes (C 5Me 4R) 2U[N(SiMe 3) 2] (R = Me, Et). Analyses by nuclear magnetic resonance spectroscopy, X-ray crystallography, and elemental analysis are also presented.« less

  9. Expanding the Chemistry of Actinide Metallocene Bromides. Synthesis, Properties and Molecular Structures of the Tetravalent and Trivalent Uranium Bromide Complexes: (C 5Me 4R) 2UBr 2, (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(Br), and [K(THF)][(C 5Me 4R) 2UBr 2] (R = Me, Et)

    DOE PAGES

    Lichtscheidl, Alejandro Gaston; Pagano, Justin K.; Scott, Brian Lindley; ...

    2016-01-06

    The organometallic uranium species (C 5Me 4R) 2UBr 2 (R = Me, Et) were obtained by treating their chloride analogues (C 5Me 4R) 2UCl 2 (R = Me, Et) with Me 3SiBr. Treatment of (C 5Me 4R) 2UCl 2 and (C 5Me 4R) 2UBr 2 (R = Me, Et) with K(O-2,6- iPr 2C 6H 3) afforded the halide aryloxide mixed-ligand complexes (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(X) (R = Me, Et; X = Cl, Br). Complexes (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(Br) (R = Me, Et) can also be synthesized by treating (C 5Me 4R) 2U(O-2,6-more » iPr 2C 6H 3)(Cl) (R = Me, Et) with Me 3SiBr, respectively. Reduction of (C 5Me 4R) 2UCl 2 and (C 5Me 4R) 2UBr 2 (R = Me, Et) with KC 8 led to isolation of uranium(III) “ate” species [K(THF)][(C 5Me 5) 2UX 2] (X = Cl, Br) and [K(THF) 0.5][(C 5Me 4Et) 2UX 2] (X = Cl, Br), which can be converted to the neutral complexes (C 5Me 4R) 2U[N(SiMe 3) 2] (R = Me, Et). Analyses by nuclear magnetic resonance spectroscopy, X-ray crystallography, and elemental analysis are also presented.« less

  10. Synthesis and biological characterization of (3R,4R)-4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol and its stereoisomers for activity toward monoamine transporters.

    PubMed

    Kharkar, Prashant S; Batman, Angela M; Zhen, Juan; Beardsley, Patrick M; Reith, Maarten E A; Dutta, Aloke K

    2009-07-01

    A novel series of optically active molecules based on a 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol template were developed. Depending on stereochemistry, the compounds exhibit various degrees of affinity for three dopamine, serotonin, and norepinephrine transporters. These molecules have the potential for treating several neurological disorders such as drug abuse, depression, and attention deficit hyperactivity disorder.Herein we describe the synthesis and biological evaluation of a series of asymmetric 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol-based dihydroxy compounds in which the hydroxy groups are located on both the piperidine ring and the N-phenylethyl side chain. In vitro uptake inhibition data of these molecules indicate high affinity for the dopamine transporter (DAT) in addition to moderate to high affinity for the norepinephrine transporter (NET). Interestingly, compounds 9 b and 9 d exhibit affinities for all three monoamine transporters, with highest potency at DAT and NET, and moderate potency at the serotonin transporter (SERT) (K(i): 2.29, 78.4, and 155 nM for 9 b and 1.55, 14.1, and 259 nM for 9 d, respectively). Selected compounds 9 a, 9 d, and 9 d' were tested for their locomotor activity effects in mice and for their ability to occasion the cocaine-discriminative stimulus in rats. These test compounds generally exhibit a much longer duration of action than cocaine for elevating locomotor activity, and completely generalize the cocaine-discriminative stimulus in a dose-dependent manner.

  11. Crystal and molecular structure of the first dibino non-geminal macrocyclic dicyclophosphazene, & {;N 3P 3Cl 4[HN(CH 2) 3O(CH 2) 2O(CH 2) 3NH]&}; 2

    NASA Astrophysics Data System (ADS)

    Enjalbert, Renée; Galy, Jean; Sournies, François; Labarre, Jean-François

    1990-04-01

    Reaction of N 3P 3Cl 6 with the 4,7-dioxadecane-1,10-diamine (coded as 3O2O3) using an Et 2O/Na 2CO 3 water interface process leads to the DIBINO non-geminal 30-membered macrocyclic dicyclophosphazene &{;N 3P 3Cl 4[HN(CH 2) 3O(CH 2) 2O(CH 2) 3NH]&}; 2. This 30-crown-ether-like architecture crystallizes in the triclinic system, P1, a=9.019(6), b=9.224(5), c=11.542(8) Å, α=94.87(4), β=95.97(4), γ=99.68(3)°, V=936(1) Å 3, Dx=1.599 Mg m -3, R=0.049 for 2862 unique reflections and 199 variable parameters. The structure exhibits a spatial arrangement of two N 3P 3Cl 4 with two [HN(CH 2) 3O(CH 2) 3O(CH 2) 3NH] as bridges on different P atoms of N 3P 3 rings. Moreover, the two N 3P 3 rings are trans to the average plane of the 30-membered macrocycle ("chair" conformation).

  12. Four N(7)-benzyl-substituted 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine-5-spiro-1'-cyclohexane-2',6'-diones as ethanol hemisolvates: similar molecular constitutions but different crystal structures.

    PubMed

    Cruz, Silvia; Trilleras, Jorge; Cobo, Justo; Low, John N; Glidewell, Christopher

    2008-12-01

    3-tert-Butyl-7-(4-chlorobenzyl)-4',4'-dimethyl-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine-5-spiro-1'-cyclohexane-2',6'-dione ethanol hemisolvate, C(30)H(34)ClN(3)O(2) x 0.5C(2)H(6)O, (I), its 7-(4-bromobenzyl)- analogue, C(30)H(34)BrN(3)O(2) x 0.5C(2)H(6)O, (II), and its 7-(4-methylbenzyl)- analogue, C(31)H(37)N(3)O(2) x 0.5C(2)H(6)O, (III), are isomorphous, with the ethanol component disordered across a twofold rotation axis in the space group C2/c. In the corresponding 7-[4-(trifluoromethyl)benzyl]- compound, C(31)H(34)F(3)N(3)O(2) x 0.5C(2)H(6)O, (IV), the ethanol component is disordered across a centre of inversion in the space group P\\overline{1}. In each of (I)-(IV), the reduced pyridine ring adopts a half-chair conformation. The heterocyclic components in (I)-(III) are linked into centrosymmetric dimers by a single C-H...pi interaction, with the half-occupancy ethanol component linked to the dimer by a combination of C-H...O and O-H...pi(arene) hydrogen bonds. The heterocyclic molecules in (IV) are linked into chains of centrosymmetric rings by C-H...O and C-H...pi hydrogen bonds, again with the half-occupancy ethanol component pendent from the chain. The significance of this study lies in the isomorphism of the related derivatives (I)-(III), in the stoichiometric hemisolvation by ethanol, where the disordered solvent molecule is linked to the heterocyclic component by a two-point linkage, and in the differences between the crystal structures of (I)-(III) and that of (IV).

  13. cfa-miR-143 Promotes Apoptosis via the p53 Pathway in Canine Influenza Virus H3N2-Infected Cells.

    PubMed

    Zhou, Pei; Tu, Liqing; Lin, Xi; Hao, Xiangqi; Zheng, Qingxu; Zeng, Weijie; Zhang, Xin; Zheng, Yun; Wang, Lifang; Li, Shoujun

    2017-11-25

    MicroRNAs regulate multiple aspects of the host response to viral infection. This study verified that the expression of cfa-miR-143 was upregulated in vivo and in vitro by canine influenza virus (CIV) H3N2 infection. To understand the role of cfa-miR-143 in CIV-infected cells, the target gene of cfa-miR-143 was identified and assessed for correlations with proteins involved in the apoptosis pathway. A dual luciferase reporter assay showed that cfa-miR-143 targets insulin-like growth factor binding protein 5 (Igfbp5). Furthermore, a miRNA agomir and antagomir of cfa-miR-143 caused the downregulation and upregulation of Igfbp5, respectively, in CIV-infected madin-darby canine kidney (MDCK) cells. This study demonstrated that cfa-miR-143 stimulated p53 and caspase3 activation and induced apoptosis via the p53 pathway in CIV H3N2-infected cells. In conclusion, CIV H3N2 induced the upregulation of cfa-miR-143, which contributes to apoptosis via indirectly activating the p53-caspase3 pathway.

  14. The 3R polymorph of CaSi{sub 2}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nedumkandathil, Reji; Benson, Daryn E.; Grins, Jekabs

    The Zintl phase CaSi{sub 2} commonly occurs in the 6R structure where puckered hexagon layers of Si atoms are stacked in an AA′BB′CC′ fashion. In this study we show that sintering of CaSi{sub 2} in a hydrogen atmosphere (30 bar) at temperatures between 200 and 700 °C transforms 6R-CaSi{sub 2} quantitatively into 3R-CaSi{sub 2}. In the 3R polymorph (space group R-3m (no. 166), a=3.8284(1), c=15.8966(4), Z=3) puckered hexagon layers are stacked in an ABC fashion. The volume per formula unit is about 3% larger compared to 6R-CaSi{sub 2}. First principles density functional calculations reveal that 6R and 3R-CaSi{sub 2} aremore » energetically degenerate at zero Kelvin. With increasing temperature 6R-CaSi{sub 2} stabilizes over 3R because of its higher entropy. This suggests that 3R-CaSi{sub 2} should revert to 6R at elevated temperatures, which however is not observed up to 800 °C. 3R-CaSi{sub 2} may be stabilized by small amounts of incorporated hydrogen and/or defects. - Graphical abstract: The common 6R form of CaSi{sub 2} can be transformed quantitatively into 3R-CaSi{sub 2} upon sintering in a hydrogen atmosphere. - Highlights: • Quantitative and reproducible bulk synthesis of the rare 3R polymorph of CaSi{sub 2}. • Clarification of the energetic relation between 3R and conventional 6R form. • 3R-CaSi{sub 2} is presumably stabilized by small amounts of incorporated hydrogen and/or defects.« less

  15. Secondary benzylation with benzyl alcohols catalyzed by a high-valent heterobimetallic Ir-Sn complex.

    PubMed

    Podder, Susmita; Choudhury, Joyanta; Roy, Sujit

    2007-04-13

    A highly efficient secondary benzylation procedure has been demonstrated using a high-valent heterobimetallic complex [Ir2(COD)2(SnCl3)2(Cl)2(mu-Cl)2] 1 as the catalyst in 1,2-dichloroethane to afford the corresponding benzylated products in moderate to excellent yields. The reaction was performed not only with carbon nucleophiles (arenes and heteroarenes) but also with oxygen (alcohol), nitrogen (amide and sulfonamide), and sulfur (thiol) nucleophiles. Mechanistic investigation showed the intermediacy of the ether in this reaction. An electrophilic mechanism is proposed from Hammett correlation.

  16. 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl as a model organic redox active compound for nonaqueous flow batteries

    NASA Astrophysics Data System (ADS)

    Milshtein, Jarrod D.; Barton, John L.; Darling, Robert M.; Brushett, Fikile R.

    2016-09-01

    Nonaqueous redox flow batteries (NAqRFBs) that utilize redox active organic molecules are an emerging energy storage concept with the possibility of meeting grid storage requirements. Sporadic and uneven advances in molecular discovery and development, however, have stymied efforts to quantify the performance characteristics of nonaqueous redox electrolytes and flow cells. A need exists for archetypal redox couples, with well-defined electrochemical properties, high solubility in relevant electrolytes, and broad availability, to serve as probe molecules. This work investigates the 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl (AcNH-TEMPO) redox pair for such an application. We report the physicochemical and electrochemical properties of the reduced and oxidized compounds at dilute concentrations for electroanalysis, as well as moderate-to-high concentrations for RFB applications. Changes in conductivity, viscosity, and UV-vis absorbance as a function of state-of-charge are quantified. Cyclic voltammetry investigates the redox potential, reversibility, and diffusion coefficients of dilute solutions, while symmetric flow cell cycling determines the stability of the AcNH-TEMPO redox pair over long experiment times. Finally, single electrolyte flow cell studies demonstrate the utility of this redox couple as a platform chemistry for benchmarking NAqRFB performance.

  17. Synthesis and structure of R{sub 2}[UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}] (R = Rb or Cs)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Serezhkin, V. N., E-mail: lserezh@samsu.ru; Peresypkina, E. V.; Grigor’eva, V. A.

    2015-01-15

    Crystals Rb{sub 2}[UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}] (I) and Cs{sub 2}[UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}] (II) have been synthesized and studied by IR spectroscopy and X-ray diffraction. Crystals I are monoclinic, with the following parameters: a = 12.2118(5) Å, b = 10.2545(3) Å, c = 11.8754(4) Å, β = 110.287(1)°, sp. gr. C2/c, Z = 4, and R = 0.0523. Crystals II are orthorhombic, with a = 13.7309(3) Å, b = 10.5749(2) Å, c = 10.1891(2) Å, sp. gr. Pnma, Z = 4, and R = 0.0411. The basic structural units of crystals I and II are one-core complexes [UO{submore » 2}(NO{sub 3}){sub 2}(NCS){sub 2}]{sup 2−}, which belong to the crystallochemical group cis-AB{sub 2}{sup 01}M{sub 2}{sup 1} (A = UO{sub 2}{sup 2+}, B{sup 01} = NO{sub 3}{sup −}, M{sup 1} = NCS{sup −}), which are combined into a framework via electrostatic interactions with ions of alkaline metals R (R = Rb or Cs). The structural features of crystals I and II, which condition the formation of [UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}]{sup 2−} complexes with a cis rather than a trans position of isothiocyanate ions in the coordination sphere of uranyl ions, are discussed.« less

  18. Characteristics of the Li+-Ion Conductivity of Li3R2(PO4)3 Crystals (R = Fe, Sc) in the Superionic State

    NASA Astrophysics Data System (ADS)

    Sorokin, N. I.

    2018-05-01

    The characteristics of Li+-ion conductivity σdc of structural γ modifications of Li3R2(PO4)3 compounds (R = Fe, Sc) existing in the superionic state have been investigated by impedance spectroscopy. The type of structural framework [R2P3O12]∞ 3- affects the σdc value and the σdc activation enthalpy in these compounds. The ion transport activation enthalpy in γ-Li3R2(PO4)3 (Δ H σ = 0.31 ± 0.03 eV) is lower than in γ-Li3Fe2(PO4)3 (Δ H σ = 0.36 ± 0.03 eV). The conductivity of γ-Li3Fe2(PO4)3 (σdc = 0.02 S/cm at 573 K) is twice as high as that of γ-Li3R2(PO4)3. A decrease in temperature causes a structural transformation of Li3R2(PO4)3 from the superionic γ modification (space group Pcan) through the intermediate metastable β modification (space group P21/ n) into the "dielectric" α modification (space group P21/ n). Upon cooling, σdc for both phosphates decreases by a factor of about 100 at the superionic TSIC transition. In Li3Fe2(PO4)3 σdc gradually decreases in the temperature range T SIC = 430-540 K, whereas in Li3R2(PO4)3 σdc undergoes a jump at T SIC = 540 ± 25 K. Possible crystallochemical factors responsible for the difference in the σdc and Δ H σ values and the thermodynamics and kinetics of the superionic transition for Li3R2(PO4)3 are discussed.

  19. Role of CYP2B6 and CYP3A4 in the in vitro N-dechloroethylation of (R)- and (S)-ifosfamide in human liver microsomes.

    PubMed

    Granvil, C P; Madan, A; Sharkawi, M; Parkinson, A; Wainer, I W

    1999-04-01

    The central nervous system toxicity of ifosfamide (IFF), a chiral antineoplastic agent, is thought to be dependent on its N-dechloroethylation by hepatic cytochrome P-450 (CYP) enzymes. The purpose of this study was to identify the human CYPs responsible for IFF-N-dechloroethylation and their corresponding regio- and enantioselectivities. IFF exists in two enantiomeric forms, (R) - and (S)-IFF, which can be dechloroethylated at either the N2 or N3 positions, producing the corresponding (R,S)-2-dechloroethyl-IFF [(R, S)-2-DCE-IFF] and (R,S)-3-dechloroethyl-IFF [(R,S)-3-DCE-IFF]. The results of the present study suggest that the production of (R)-2-DCE-IFF and (S)-3-DCE-IFF from (R)-IFF is catalyzed by different CYPs as is the production of (S)-2-DCE-IFF and (R)-3-DCE-IFF from (S)-IFF. In vitro studies with a bank of human liver microsomes revealed that the sample-to-sample variation in the production of (S)-3-DCE-IFF from (R)-IFF and (S)-2-DCE-IFF from (S)-IFF was highly correlated with the levels of (S)-mephenytoin N-demethylation (CYP2B6), whereas (R)-2-DCE-IFF production from (R)-IFF and (R)-3-DCE-IFF production from (S)-IFF were both correlated with the activity of testosterone 6beta-hydroxylation (CYP3A4/5). Experiments with cDNA-expressed P-450 and antibody and chemical inhibition studies supported the conclusion that the formation of (S)-3-DCE-IFF and (S)-2-DCE-IFF is catalyzed primarily by CYP2B6, whereas (R)-2-DCE-IFF and (R)-3-DCE-IFF are primarily the result of CYP3A4/5 activity.

  20. Synthesis, anticancer and antibacterial activity of salinomycin N-benzyl amides.

    PubMed

    Antoszczak, Michał; Maj, Ewa; Napiórkowska, Agnieszka; Stefańska, Joanna; Augustynowicz-Kopeć, Ewa; Wietrzyk, Joanna; Janczak, Jan; Brzezinski, Bogumil; Huczyński, Adam

    2014-11-25

    A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at -ortho position and the least anticancer active derivatives were those substituted at the -para position.

  1. Complexes possessing rare "tertiary" sulfonamide nitrogen-to-metal bonds of normal length: fac-[Re(CO)3(N(SO2R)dien)]PF6 complexes with hydrophilic sulfonamide ligands.

    PubMed

    Abhayawardhana, Pramuditha L; Marzilli, Patricia A; Fronczek, Frank R; Marzilli, Luigi G

    2014-01-21

    Tertiary sulfonamide nitrogen-to-metal bonds of normal length are very rare. We recently discovered such a bond in one class of fac-[Re(CO)3(N(SO2R)(CH2Z)2)](n) complexes (Z = 2-pyridyl) with N(SO2R)dpa ligands derived from di-(2-picolyl)amine (N(H)dpa). fac-[M(CO)3(N(SO2R)(CH2Z)2)](n) agents (M = (186/188)Re, (99m)Tc) could find use as radiopharmaceutical bioconjugates when R is a targeting moiety. However, the planar, electron-withdrawing 2-pyridyl groups of N(SO2R)dpa destabilize the ligand to base and create relatively rigid chelate rings, raising the possibility that the rare M-N(sulfonamide) bond is an artifact of a restricted geometry. Also, the hydrophobic 2-pyridyl groups could cause undesirable accumulation in the liver, limiting future use in radiopharmaceuticals. Our goal is to identify a robust, hydrophilic, and flexible N(CH2Z)2 chelate framework. New C2-symmetric ligands, N(SO2R)(CH2Z)2 with (Z = CH2NH2; R = Me, dmb, or tol), were prepared by treating N(H)dien(Boc)2, a protected diethylenetriamine (N(H)dien) derivative, with methanesulfonyl chloride (MeSO2Cl), 3,5-dimethylbenzenesulfonyl chloride (dmbSO2Cl), and 4-methylbenzenesulfonyl chloride (tolSO2Cl). Treatment of fac-[Re(CO)3(H2O)3](+) with these ligands, designated as N(SO2R)dien, afforded new fac-[Re(CO)3(N(SO2R)dien)]PF6 complexes. Comparing the fac-[Re(CO)3(N(SO2Me)dien)]PF6 and fac-[Re(CO)3(N(SO2Me)dpa)]PF6 complexes, we find that the Re(I)-N(sulfonamide) bonds are normal in length and statistically identical and that the methyl (13)C NMR signal has an unusually upfield shift compared to that in the free ligand. We attribute this unusual upfield shift to the fact that the sulfonamide N undergoes an sp(2)-to-sp(3) rehybridization upon coordination to Re(I) in both complexes. Thus, the sulfonamide N of N(SO2R)dien ligands is a good donor, even though the chelate rings are conformationally flexible. Addition of the strongly basic and potentially monodentate ligand, 4-dimethylaminopyridine

  2. The mGlu(2/3) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate, is anti- and proconvulsant in DBA/2 mice.

    PubMed

    Moldrich, R X; Talebi, A; Beart, P M; Chapman, A G; Meldrum, B S

    2001-02-16

    The anticonvulsant activity of the selective group II metabotropic glutamate receptor (mGlu) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) has been evaluated in chemoconvulsant and sound-induced models of epileptic seizures in DBA/2 mice. 2R,4R-APDC (> or =10 nmol, intracerebroventricularly (i.c.v.), -15 min) transiently reduced sound-induced seizure activity including clonic seizures to 40% of vehicle at 20 nmol (i.c.v.) and 30% of vehicle at 100 mg/kg (intraperitoneally (i.p.), -15 min). 2R,4R-APDC inhibited clonic seizures induced by the group III mGlu antagonist (R,S)-alpha-methylserine-O-phosphate (2.5 micromol, i.c.v.) when co-injected at 20-40 nmol and inhibited limbic seizure activity induced by the mGlu(1/5) agonist (R,S)-3,5-dihydroxyphenylglycine (1.5 micromol, i.c.v.) when co-injected at 10-40 nmol. A reversal of the anticonvulsant activity of 2R,4R-APDC was observed at (>20 nmol) in each of the chemoconvulsant and sound-induced models of epileptic seizures. 2R,4R-APDC (0.1-1 micromol, i.c.v.) induced stimulus-independent, rapid and dose-dependent clonic seizures. Selective mGlu(2/3) agonists represent a novel class of potential anti-epileptic drugs, however due to the proconvulsant activity observed here, 2R,4R-APDC is obviously limited in this regard.

  3. Reduced 3,4'-bipyrazoles from a simple pyrazole precursor: synthetic sequence, molecular structures and supramolecular assembly.

    PubMed

    Cuartas, Viviana; Insuasty, Braulio; Cobo, Justo; Glidewell, Christopher

    2017-10-01

    The reaction of 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde and N-benzylmethylamine under microwave irradiation gives 5-[benzyl(methyl)amino]-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, C 19 H 19 N 3 O, (I). Subsequent reactions under basic conditions, between (I) and a range of acetophenones, yield the corresponding chalcones. These undergo cyclocondensation reactions with hydrazine to produce reduced bipyrazoles which can be N-formylated with formic acid or N-acetylated with acetic anhydride. The structures of (I) and of representative examples from this reaction sequence are reported, namely the chalcone (E)-3-{5-[benzyl(methyl)amino]-3-methyl-1-phenyl-1H-pyrazol-4-yl}-1-(4-bromophenyl)prop-2-en-1-one, C 27 H 24 BrN 3 O, (II), the N-formyl derivative (3RS)-5'-[benzyl(methyl)amino]-3'-methyl-1',5-diphenyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazole]-2-carbaldehyde, C 28 H 27 N 5 O, (III), and the N-acetyl derivative (3RS)-2-acetyl-5'-[benzyl(methyl)amino]-5-(4-methoxyphenyl)-3'-methyl-1'-phenyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazole], which crystallizes as the ethanol 0.945-solvate, C 30 H 31 N 5 O 2 ·0.945C 2 H 6 O, (IV). There is significant delocalization of charge from the benzyl(methyl)amino substituent onto the carbonyl group in (I), but not in (II). In each of (III) and (IV), the reduced pyrazole ring is modestly puckered into an envelope conformation. The molecules of (I) are linked by a combination of C-H...N and C-H...π(arene) hydrogen bonds to form a simple chain of rings; those of (III) are linked by a combination of C-H...O and C-H...N hydrogen bonds to form sheets of R 2 2 (8) and R 6 6 (42) rings, and those of (IV) are linked by a combination of O-H...N and C-H...O hydrogen bonds to form a ribbon of edge-fused R 2 4 (16) and R 4 4 (24) rings.

  4. (2R,3S,4R)-3,4-Isopropyl­idenedi­oxy-2-(phenyl­sulfonyl­meth­yl)pyrrolidin-1-ol

    PubMed Central

    Flores, Mari Fe; Garcia, Pilar; M. Garrido, Narciso; Sanz, Francisca; Diez, David

    2012-01-01

    The title compound, C14H19NO5S, was prepared by nucleophilic addition of the lithium derivative of methyl­phenyl­sulfone to (3S,4R)-3,4-isopropyl­idene­dioxy­pyrroline 1-oxide. There are four mol­ecules in the asymmetric unit. The crystal structure determination confirms the configuration of the chiral centres as 2R,3S,4R. In the crystal, pairs of O—H⋯N hydrogen bonds link the mol­ecules into dimers. PMID:22904989

  5. Visible Light Assisted Photocatalytic Hydrogen Generation by Ta 2O 5/Bi 2O 3, TaON/Bi 2O 3, and Ta 3N 5/Bi 2O 3 Composites

    DOE PAGES

    Adhikari, Shiba; Hood, Zachary D.; More, Karren Leslie; ...

    2015-06-15

    Composites comprised of two semiconducting materials with suitable band gaps and band positions have been reported to be effective at enhancing photocatalytic activity in the visible light region of the electromagnetic spectrum. Here, we report the synthesis, complete structural and physical characterizations, and photocatalytic performance of a series of semiconducting oxide composites. UV light active tantalum oxide (Ta2O5) and visible light active tantalum oxynitride (TaON) and tantalum nitride (Ta 3N 5) were synthesized, and their composites with Bi 2O 3 were prepared in situ using benzyl alcohol as solvent. The composite prepared using equimolar amounts of Bi 2O 3 andmore » Ta 2O 5 leads to the formation of the ternary oxide, bismuth tantalate (BiTaO 4) upon calcination at 1000 °C. The composites and single phase bismuth tantalate formed were characterized by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), Brunauer–Emmett–Teller (BET) surface area measurement, scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV–Vis diffuse reflectance spectroscopy, and photoluminescence. The photocatalytic activities of the catalysts were evaluated for generation of hydrogen using aqueous methanol solution under visible light irradiation (λ ≥ 420 nm). The results show that as-prepared composite photocatalysts extend the light absorption range and restrict photogenerated charge-carrier recombination, resulting in enhanced photocatalytic activity compared to individual phases. The mechanism for the enhanced photocatalytic activity for the heterostructured composites is elucidated based on observed activity, band positions calculations, and photoluminescence data.« less

  6. Synthesis, spectroscopic characterization and quantum chemical computational studies of (S)-N-benzyl-1-phenyl-5-(pyridin-2-yl)-pent-4-yn-2-amine

    NASA Astrophysics Data System (ADS)

    Kose, Etem; Atac, Ahmet; Karabacak, Mehmet; Karaca, Caglar; Eskici, Mustafa; Karanfil, Abdullah

    2012-11-01

    The synthesis and characterization of a novel compound (S)-N-benzyl-1-phenyl-5-(pyridin-2-yl)-pent-4-yn-2-amine (abbreviated as BPPPYA) was presented in this study. The spectroscopic properties of the compound were investigated by FT-IR, NMR and UV spectroscopy experimentally and theoretically. The molecular geometry and vibrational frequencies of the BPPPYA in the ground state were calculated by using density functional theory (DFT) B3LYP method invoking 6-311++G(d,p) basis set. The geometry of the BPPPYA was fully optimized, vibrational spectra were calculated and fundamental vibrations were assigned on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method and PQS program. The results of the energy and oscillator strength calculated by time-dependent density functional theory (TD-DFT) and CIS approach complement with the experimental findings. Total and partial density of state (TDOS and PDOS) and also overlap population density of state (COOP or OPDOS) diagrams analysis were presented. The theoretical NMR chemical shifts (1H and 13C) complement with experimentally measured ones. The dipole moment, linear polarizability and first hyperpolarizability values were also computed. The linear polarizabilities and first hyper polarizabilities of the studied molecule indicate that the compound is a good candidate of nonlinear optical materials. The calculated vibrational wavenumbers, absorption wavelengths and chemical shifts showed the best agreement with the experimental results.

  7. NTP Toxicology and Carcinogenesis Studies of Benzyl Acetate (CAS No. 140-11-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    PubMed

    1986-08-01

    Benzyl acetate, a water-white liquid with a pear-like odor, is a natural constituent of several essential oils and flower absolutes extracted from jasmine, hyacinth, gardenia, tuberose, ylang-ylang, cananga, and neroli. Commercial benzyl acetate, a liquid prepared synthetically from benzyl chloride, acetic acid, and triethylamine is used primarily as a component of perfumes for soaps and as a flavoring ingredient. This compound is practically insoluble in water but is miscible in alcohol and ether and soluble in benzene and chloroform. Toxicology and carcinogenesis studies of benzyl acetate (>99% pure) were conducted by administering benzyl acetate in corn oil gavage to groups of 50 male and 50 female F344/N rats at doses of 0, 250, or 500 mg/kg body weight and to groups of 50 male and 50 female B6C3F1 mice at doses of 0, 500, or 1,000 mg/kg once daily five days per week for 103 weeks. Dose selection for the 2-year study was based on mean body weight gain depression and decreased survival observed at higher doses in 13 week studies. The absence of any observable adverse effect of benzyl acetate on the survival or mean body weight gains of the rats or mice in the 2-year studies suggests that both the rats and the mice of each sex could have tolerated higher doses. An infection in the genital tract was probably responsible for the deaths of 26/35 control, 14/32 low-dose, and 8/20 high-dose female mice before the end of the study. Acinar-cell adenomas in the pancreas of male rats occurred with a positive trend (P<0.01), and the incidence in the high-dose group (37/49, 76%) was significantly (P<0.01) higher than in the vehicle controls (22/50, 40%). The incidence of these tumors in the low-dose group (27/50, 54%) was comparable to that in the gavage controls. Acinar-cell hyperplasia of the pancreas was observed in 37/50 control, 34/50 low-dose, and 36/49 high-dose male rats. No acinar-cell hyperplasia or adenoma of the pancreas was observed in female rats. The

  8. Reaction of singlet-excited 2,3-diazabicyclo[2.2.2]oct-2-ene and tert-butoxyl radicals with aryl-substituted benzofuranones.

    PubMed

    Lundgren, Cecilia Vannesjö; Koner, Apurba L; Tinkl, Michael; Pischel, Uwe; Nau, Werner M

    2006-03-03

    5,7-Di-tert-butyl-3-aryl-3H-benzofuran-2-ones are lactones with potential antioxidant activity, owing to their abstractable benzylic C-H hydrogens. The fluorescence quenching of the azoalkane 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO), an established probe for the hydrogen-donor propensity of chain-breaking antioxidants, was investigated for 16 aryl-substituted benzofuranone derivatives [m,m-(CF3)2, p-CN, m-CN, p-CF3, p-COOCH3, m-CF3, p-Cl, p-F, H, m-CH3, p-CH3, m,p-(CH3)2, p-OCH3, o-CH3, o-CF3, o,m-(CH3)2]. Analysis of the rate data in terms of a linear free energy relationship yielded a reaction constant of rho = +0.35. This implies that n,pi*-excited DBO acts as nucleophilic species. In contrast, hydrogen abstraction of tert-butoxyl radicals from the benzofuranones was accelerated by electron-donating substituents (rho = -0.23), in conformity with the electrophilic character of oxygen-centered alkoxyl radicals. Possible implications for the optimization of the hydrogen-donor propensity of antioxidants through structural variation are discussed.

  9. C-H bond functionalization via hydride transfer: formation of α-arylated piperidines and 1,2,3,4-tetrahydroisoquinolines via stereoselective intramolecular amination of benzylic C-H bonds.

    PubMed

    Vadola, Paul A; Carrera, Ignacio; Sames, Dalibor

    2012-08-17

    We here report a study of the intramolecular amination of sp(3) C-H bonds via the hydride transfer cyclization of N-tosylimines (HT-amination). In this transformation, 5-aryl aldehydes are subjected to N-toluenesulfonamide in the presence of BF(3)·OEt(2) to effect imine formation and HT-cyclization, leading to 2-arylpiperidines and 3-aryl-1,2,3,4-tetrahydroisoquinolines in a one-pot procedure. We examined the reactivity of a range of aldehyde substrates as a function of their conformational flexibility. Substrates of higher conformational rigidity were more reactive, giving higher yields of the desired products. However, a single substituent on the alkyl chain linking the N-tosylimine and the benzylic sp(3) C-H bonds was sufficient for HT-cyclization to occur. In addition, an examination of various arenes revealed that the electronic character of the hydridic C-H bonds dramatically affects the efficiency of the reaction. We also found that this transformation is highly stereoselective; 2-substituted aldehydes yield cis-2,5-disubstituted piperidines, while 3-substituted aldehydes afford trans-2,4-disubstituted piperidines. The stereoselectivity is a consequence of thermodynamic control. The pseudoallylic strain between the arene and tosyl group on the piperidine ring is proposed to rationalize the greater stability of the isomer with the aryl ring in the axial position. This preferential placement of the arene is proposed to affect the observed stereoselectivity.

  10. C-H Bond Functionalization via Hydride Transfer: Formation of α-Arylated Piperidines and 1,2,3,4-Tetrahydroisoquinolines via Stereoselective Intramolecular Amination of Benzylic C-H Bonds

    PubMed Central

    Vadola, Paul A.; Carrera, Ignacio; Sames, Dalibor

    2012-01-01

    We here report a study of the intramolecular amination of sp3 C-H bonds via the hydride transfer cyclization of N-tosylimines (HT-amination). In this transformation, 5-aryl-aldehydes are subjected to N-toluenesulfonamide in the presence of BF3•OEt2 to effect imine formation and HT-cyclization, leading to 2-aryl-piperidines and 3-aryl-1,2,3,4-tetrahydroisoquinolines in a one-pot procedure. We examined the reactivity of a range of aldehyde substrates as a function of their conformational flexibility. Substrates of higher conformational rigidity were more reactive, giving higher yields of the desired products. However, a single substituent on the alkyl chain linking the N-tosylimine and the benzylic sp3 C-H bonds was sufficient for HT-cyclization to occur. In addition, an examination of various arenes revealed that the electronic character of the hydridic C-H bonds dramatically affects the efficiency of the reaction. We also found that this transformation is highly stereoselective; 2-substituted aldehydes yield cis-2,5-disubstituted piperidines, while 3-substituted aldehydes afford trans-2,4-disubstituted piperidines. The stereoselectivity is a consequence of thermodynamic control. The pseudo-allylic strain between the arene and tosyl group on the piperidine ring is proposed to rationalize the greater stability of the isomer with the aryl ring in the axial position. This preferential placement of the arene is proposed to affect the observed stereoselectivity. PMID:22672002

  11. Crystal structures of HIV-1 nonnucleoside reverse transcriptase inhibitors: N-benzyl-4-methyl-benzimidazoles

    NASA Astrophysics Data System (ADS)

    Ziółkowska, Natasza E.; Michejda, Christopher J.; Bujacz, Grzegorz D.

    2009-07-01

    HIV-1 nonnucleoside reverse transcriptase inhibitors are potentially specific and effective drugs in AIDS therapy. The presence of two aromatic systems with an angled orientation in the molecule of the inhibitor is crucial for interactions with HIV-1 RT. The inhibitor drives like a wedge into the cluster of aromatic residues of RT HIV-1 and restrains the enzyme in a conformation that blocks the chemical step of nucleotide incorporation. Structural studies provide useful information for designing new, more active inhibitors. The crystal structures of four NNRTIs are presented here. The investigated compounds are derivatives of N-benzyl-4-methyl-benzimidazole with various aliphatic and aromatic substituents at carbon 2 positions and a 2,6-dihalogeno-substituted N-benzyl moiety. Structural data reported here show that the conformation of the investigated compounds is relatively rigid. Such feature is important for the nonnucleoside inhibitor binding to HIV-1 reverse transcriptase.

  12. Merging the Structural Motifs of Functionalized Amino Acids and α-Aminoamides: Compounds with Significant Anticonvulsant Activities

    PubMed Central

    Salomé, Christophe; Salomé-Grosjean, Elise; Stables, James P.; Kohn, Harold

    2010-01-01

    Functional amino acids (FAAs) and α-aminoamides (AAAs) are two classes of antiepileptic drugs (AEDs) that exhibit pronounced anticonvulsant activities. We combined key structural pharmacophores present in FAAs and AAAs to generate a new series of compounds and document that select compounds exhibit activity superior to either the prototypical FAA (lacosamide) or the prototypical AAA (safinamide) in the maximal electroshock (MES) seizure model in rats. A representative compound, (R)-N-4′-((3″-fluoro)benzyloxy)benzyl 2-acetamido-3-methoxypropionamide ((R)-10), was tested in the MES (mice, ip), MES (rat, po), psychomotor 6 Hz (32 mA) (mice, ip), and hippocampal kindled (rat, ip) seizure tests providing excellent protection with ED50 values of 13, 14, ~10 mg/kg, and 12 mg/kg, respectively. In the rat sciatic nerve ligation model (ip), (R)-10 (12 mg/kg) provided an 11.2-fold attenuation of mechanical allodynia. In the mouse biphasic formalin pain model (ip), (R)-10 (15 mg/kg) reduced pain responses in the acute and the chronic inflammatory phases. PMID:20394379

  13. Merging the structural motifs of functionalized amino acids and alpha-aminoamides: compounds with significant anticonvulsant activities.

    PubMed

    Salomé, Christophe; Salomé-Grosjean, Elise; Stables, James P; Kohn, Harold

    2010-05-13

    Functional amino acids (FAAs) and alpha-aminoamides (AAAs) are two classes of antiepileptic drugs (AEDs) that exhibit pronounced anticonvulsant activities. We combined key structural pharmacophores present in FAAs and AAAs to generate a new series of compounds and document that select compounds exhibit activity superior to either the prototypical FAA (lacosamide) or the prototypical AAA (safinamide) in the maximal electroshock (MES) seizure model in rats. A representative compound, (R)-N-4'-((3''-fluoro)benzyloxy)benzyl 2-acetamido-3-methoxypropionamide ((R)-10), was tested in the MES (mice, ip), MES (rat, po), psychomotor 6 Hz (32 mA) (mice, ip), and hippocampal kindled (rat, ip) seizure tests providing excellent protection with ED(50) values of 13, 14, approximately 10 mg/kg, and 12 mg/kg, respectively. In the rat sciatic nerve ligation model (ip), (R)-10 (12 mg/kg) provided an 11.2-fold attenuation of mechanical allodynia. In the mouse biphasic formalin pain model (ip), (R)-10 (15 mg/kg) reduced pain responses in the acute and the chronic inflammatory phases.

  14. Synthesis, crystal structure determination, biological screening and docking studies of N1-substituted derivatives of 2,3-dihydroquinazolin-4(1H)-one as inhibitors of cholinesterases.

    PubMed

    Sultana, Nargis; Sarfraz, Muhammad; Tanoli, Saba Tahir; Akram, Muhammad Safwan; Sadiq, Abdul; Rashid, Umer; Tariq, Muhammad Ilyas

    2017-06-01

    Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry out the N 1 -substitution of 2,3-dihydroquinazolin-4(1H)-one core. A set of 32 N-alkylated/benzylated quinazoline derivatives were synthesized, characterized and evaluated for their inhibition against cholinesterases. N-alkylation of the series of the compounds reported previously (N-unsubstituted) resulted in improved activity. All the compounds showed inhibition of both enzymes in the micromolar to submicromolar range. Structure activity relationship (SAR) of the 32 derivatives showed that N-benzylated compounds possess good activity than N-alkylated compounds. N-benzylated compounds 2ad and 2af were found very active with their IC 50 values toward AChE in submicromolar range (0.8µM and 0.6µM respectively). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational predictions of ADMET studies reveal that all the compounds have good pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover, all the compounds are predicted to be absorbed in human intestine and also have the ability to cross blood brain barrier. Overall, the synthesized compounds have established a structural foundation for the design of new inhibitors of cholinesterase. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Design and synthesis of highly potent benzodiazepine gamma-secretase inhibitors: preparation of (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-4- hydroxy-N-((3S)-1-methyl-2-oxo-5- phenyl-2,3-dihydro-1H-benzo[e][1,4]-diazepin-3-yl)butyramide by use of an asymmetric Ireland-Claisen rearrangement.

    PubMed

    Churcher, Ian; Williams, Susie; Kerrad, Sonia; Harrison, Timothy; Castro, José L; Shearman, Mark S; Lewis, Huw D; Clarke, Earl E; Wrigley, Jonathan D J; Beher, Dirk; Tang, Yui S; Liu, Wensheng

    2003-06-05

    Novel benzodiazepine-containing gamma-secretase inhibitors for potential use in Alzheimer's disease have been designed that incorporate a substituted hydrocinnamide C-3 side chain. A syn combination of alpha-alkyl or aryl and beta-hydroxy or hydroxymethyl substituents was shown to give highly potent compounds. In particular, (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N-((3S)-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)butyramide (34) demonstrated excellent in vitro potency (IC(50) = 0.06 nM). 34 could also be selectively methylated to give [(3)H]-28, which is of use in radioligand binding assays.

  16. Genome-wide identification, functional prediction, and evolutionary analysis of the R2R3-MYB superfamily in Brassica napus.

    PubMed

    Hajiebrahimi, Ali; Owji, Hajar; Hemmati, Shiva

    2017-10-01

    R2R3-MYB transcription factors (TFs) have been shown to play important roles in plants, including in development and in various stress conditions. Phylogenetic analysis showed the presence of 249 R2R3-MYB TFs in Brassica napus, called BnaR2R3-MYB TFs, clustered into 38 clades. BnaR2R3-MYB TFs were distributed on 19 chromosomes of B. napus. Sixteen gene clusters were identified. BnaR2R3-MYB TFs were characterized by motif prediction, gene structure analysis, and gene ontology. Evolutionary analysis revealed that BnaR2R3-MYB TFs are mainly formed as a result of whole-genome duplication. Orthologs and paralogs of BnaR2R3-MYB TFs were identified in B. napus, B. rapa, B. oleracea, and Arabidopsis thaliana using synteny-based methods. Purifying selection was pervasive within R2R3-MYB TFs. K n /K s values lower than 0.3 indicated that BnaR2R3-MYB TFs are being functionally converged. The role of gene conversion in the formation of BnaR2R3-MYB TFs was significant. Cis-regulatory elements in the upstream regions of BnaR2R3-MYB genes, miRNA targeting BnaR2R3MYB TFs, and post translational modifications were identified. Digital expression data revealed that BnaR2R3-MYB genes were highly expressed in the roots and under high salinity treatment after 24 h. BnaMYB21, BnaMYB141, and BnaMYB148 have been suggested for improving salt-tolerant B. napus. BnaR2R3-MYB genes were mostly up regulated on the 14th day post inoculation with Leptosphaeria biglobosa and L. maculan. BnaMYB150 is a candidate for increased tolerance to Leptospheria in B. napus.

  17. (2E,5E)-2,5-Bis(4-hy­droxy-3-meth­oxy­benzyl­idene)cyclo­penta­none ethanol monosolvate

    PubMed Central

    Da’i, Muhammad; Yanuar, Arry; Meiyanto, Edy; Jenie, Umar Anggara; Supardjan, Amir Margono

    2013-01-01

    In the title structure, C21H20O5·C2H5OH, the curcumine-type mol­ecule has a double E conformation for the two benzyl­idene double bonds [C=C = 1.342 (4) and 1.349 (4) Å] and is nearly planar with respect to the non-H atoms (r.m.s. deviation from planarity = 0.069 Å). The two phenolic OH groups form bifurcated hydrogen bonds with intra­molecular branches to adjacent meth­oxy O atoms and inter­molecular branches to either a neighbouring mol­ecule or an ethanol solvent mol­ecule. The ethanol O atom donates a hydrogen bond to the keto O atom. These hydrogen bonds link the constituents into layers parallel to (101) in the crystal structure. PMID:23634071

  18. Homoleptic organolanthanide compounds supported by the bis(dimethylsilyl)benzyl ligand

    DOE PAGES

    Boteju, Kasuni C.; Ellern, Arkady; Sadow, Aaron D.

    2016-12-19

    Here, a β-SiH functionalized benzyl anion [C(SiHMe 2) 2Ph]$-$s obtained by deprotonation of HC(SiHMe 2) 2Ph with KCH 2Ph or by reaction of KOtBu and (Me 2HSi) 3CPh; LnI 3(THF)n and three equivalents of this carbanion combine to provide homoleptic tris(alkyl)lanthanide compounds Ln{C(SiHMe 2) 2Ph} 3 (Ln = La, Ce, Pr, Nd) containing secondary metal–ligand interactions.

  19. Synthesis and biological characterization of (3R,4R)-4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol and its stereoisomers for monoamine transporters

    PubMed Central

    Kharkar, Prashant S.; Batman, Angela M.; Zhen, Juan; Beardsley, Patrick M.; Reith, Maarten E. A.

    2012-01-01

    In this report we describe synthesis and biological evaluation of a series of asymmetric 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol based dihydroxy compounds where the hydroxy groups are located both on the piperidine ring and also on the N-phenylethyl side chain exo-cyclically. In vitro uptake inhibition data indicates high affinity of these molecules for the dopamine transporter (DAT) in addition to their moderate to high affinity for the norepinephrine transporter (NET). Interestingly, compounds 9b and 9d exhibited affinities for all three monoamine transporters with highest potency at DAT and NET and moderate potency at the serotonin transporter (SERT) (Ki 2.29, 78.4 and 155 nM for 9b and 1.55, 14.1 and 259 nM for 9d, respectively). Selected compounds, 9a, 9d and 9d’ were tested for their locomotor activity effects in mice, and for their ability to occasion the cocaine discriminative stimulus in rats. These test compounds generally exhibited a much longer duration of action than cocaine for elevating locomotor activity, and dose-dependently completely generalized the cocaine discriminative stimulus. PMID:19449323

  20. Synthesis, characterization stereochemistry and anti-bacterial evaluation of certain N-acyl-c-3,t-3-dimethyl-r-2,c-6-diphenylpiperidin-4-ones

    NASA Astrophysics Data System (ADS)

    Ponnuswamy, S.; Kayalvizhi, R.; Jamesh, M.; Uma Maheswari, J.; Thenmozhi, M.; Ponnuswamy, M. N.

    2016-09-01

    A new series of N-acyl-c-3,t-3-dimethyl-r-2,c-6-diphenylpiperidin-4-ones 2-6 has been synthesized and characterized using IR, mass, 1H, 13C, DEPT and 2D (COSY and HSQC) NMR spectral techniques. The NMR spectral data indicate that the N-acylpiperidin-4-ones 2-6 prefer to exist in a distorted boat conformation B1 with coplanar orientation of N-C=O moiety. The stereodynamics of these systems have been studied by recording the dynamic 1H NMR spectra of compound 4, and the energy barrier for N-CO rotation is determined to be 52.75 kJ/mol. Furthermore the compounds 1-5 show significant antibacterial activity.

  1. CoMoS2/rGO/C3N4 ternary heterojunctions catalysts with high photocatalytic activity and stability for hydrogen evolution under visible light irradiation

    NASA Astrophysics Data System (ADS)

    Xu, Xuejun; Si, Zhichun; Liu, Liping; Wang, Zehao; Chen, Ze; Ran, Rui; He, Yonghong; Weng, Duan

    2018-03-01

    Noble metal free MoS2/g-C3N4 catalyst has attracted intense attentions for visible light photocatalytic hydrogen evolution as a result of its earth abundance, low cost and unique heterojunctions stacked with two dimensional sheets. However, the low charge separation efficiency resulted from the poor conductivity of g-C3N4 and MoS2, and lack of abundant active sites from coordinative unsaturated atoms in MoS2, restricts the photocatalytic hydrogen evolution activity and stability enhancement of MoS2/C3N4 composite catalysts. Herein, CoMoS2/rGO/g-C3N4 catalysts with ternary heterojunctions are prepared by facile solvothermal method, which exhibit high visible light photocatalytic activity and stability for hydrogen evolution. The optimal hydrogen evolution rate of CoMoS2/rGO/g-C3N4 catalysts is 684 μmol g-1 h-1 when the content of CoMoS2 is 2% and the content of rGO is 0.5%. The stability of CoMoS2/rGO/C3N4 catalysts just decrease about 3% after 4 cycling runs for 16 h. The good catalytic performances of catalysts are attributed to the synergistic effect among the g-C3N4 nanosheets, rGO nanosheets and CoMoS2 nanosheets. The high conductivity of rGO nanosheets enhances the electron-hole separation and charge transfer, and Co doping increases the active sites for hydrogen evolution due to the increase of unsaturated atoms in CoMoS2 nanosheets.

  2. (S)-N-[1-(5-Benzyl-sulfan-yl-1,3,4-oxa-diazol-2-yl)-2-phenyl-eth-yl]-4-methyl-benzene-sulfonamide.

    PubMed

    Syed, Tayyaba; Hameed, Shahid; Jones, Peter G

    2011-11-01

    The title compound, C(24)H(23)N(3)O(3)S(2), crystallizes with two independent mol-ecules in the asymmetric unit. They differ essentially in the orientation of the tolyl rings, between which there is π-π stacking (centroid-centroid distance = 3.01 Å). The absolute configuration was confirmed by the determination of the Flack parameter [x = 0.008 (9)]. In the crystal, mol-ecules are connected by two classical N-H⋯N hydrogen bonds and two weak but very short C-H⋯O(sulfon-yl) inter-actions, forming layers lying parallel to the bc plane.

  3. Strong CO+ and {{\\rm{N}}}_{2}^{+} Emission in Comet C/2016 R2 (Pan-STARRS)

    NASA Astrophysics Data System (ADS)

    Cochran, Anita L.; McKay, Adam J.

    2018-02-01

    We report on imaging and spectroscopic observations of comet C/2016 R2 (Pan-STARRS) obtained with the 0.8 m and 2.7 m telescopes of McDonald Observatory in 2017 November and December, respectively. The comet was at a heliocentric distance greater than 3 au during both sets of observations. The images showed a well-developed tail with properties that suggested it was an ion tail. The spectra confirmed that we were observing well-developed bands of CO+ and {{{N}}}2+. The {{{N}}}2+ detection was unequivocally cometary and was one of the strongest bands of {{{N}}}2+ detected in a comet spectrum. We derived the ratio of these two ions and from that we were able to derive that N2/CO = 0.15. This is the highest such ratio reported for a comet. This Letter includes data taken at The McDonald Observatory of The University of Texas at Austin.

  4. Immunocytochemical localization of metabotropic (mGluR2/3 and mGluR4a) and ionotropic (GluR2/3) glutamate receptors in adrenal medullary ganglion cells.

    PubMed

    Sarría, R; Díez, J; Losada, J; Doñate-Oliver, F; Kuhn, R; Grandes, P

    2006-02-01

    The localization of metabotropic glutamate receptors of groups II (mGluR2/3) and III (mGluR4a) and the subunits 2 and 3 of alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) ionotropic glutamate receptors (GluR2/3) was investigated with immunocytochemical methods in the rat adrenal gland. MGluR2/3, mGluR4a and GluR2/3 immunoreactivities were observed in large-sized, centrally located type I adrenal medullary ganglion neurons. Furthermore, the small-sized type II adrenal ganglion neurons identified by their immunoreactivity to brain nitric oxide synthase (bNOS), also expressed mGluR2/3, mGluR4a and GluR2/3. These cells were disposed in the peripheral portion of the adrenal medulla. None of the type I neurons were positively labeled for bNOS. These morphological observations suggest that activation of glutamate receptors in ganglion neurons may be instrumental in the control of adrenal endocrine systems as well as blood regulation.

  5. Pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol following a single induction dose administered intravenously in cats.

    PubMed

    Griffenhagen, Gregg M; Rezende, Marlis L; Gustafson, Daniel L; Hansen, Ryan J; Lunghofer, Paul J; Mama, Khursheed R

    2015-09-01

    To compare the pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol administered intravenously (IV) as a single induction dose in cats. Prospective experimental study. Six healthy adult cats, three female intact, three male castrated, weighing 4.8 ± 1.8 kg. Cats received 8 mg kg(-1) IV of propofol (P) or propofol with 2% benzyl alcohol (P28) using a randomized crossover design. Venous blood samples were collected at predetermined time points to 24 hours after drug administration to determine drug plasma concentrations. Physiologic and behavioral variables were also recorded. Propofol and benzyl alcohol concentrations were determined using high pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were described using a 2-compartment model. Pharmacokinetic and pharmacodynamic parameters were analyzed using repeated measures anova (p < 0.05). Plasma concentrations of benzyl alcohol were below the lower limits of quantification (LLOQ) at all time points for two of the six cats (33%), and by 30 minutes for the remaining four cats. Propofol pharmacokinetics, with or without 2% benzyl alcohol, were characterized by rapid distribution, a long elimination phase, and a large volume of distribution. No differences were noted between treatments with the exception of clearance from the second compartment (CLD2), which was 23.6 and 38.8 mL kg(-1)  minute(-1) in the P and P28 treatments, respectively. Physiologic and behavioral variables were not different between treatments with the exception of heart rate at 4 hours post administration. The addition of 2% benzyl alcohol as a preservative minimally altered the pharmacokinetics and pharmacodynamics of propofol 1% emulsion when administered as a single IV bolus in this group of cats. These data support the cautious use of propofol with 2% benzyl alcohol for induction of anesthesia in healthy cats. © 2014 Association of Veterinary Anaesthetists and the

  6. High performance unipolar MoTe2 field effect transistors enabled by doping and Al2O3 capping

    NASA Astrophysics Data System (ADS)

    Qu, Deshun; Liu, Xiaochi; Ahmed, Faisal; Yoo, Won Jong

    We carry out the first systematic experiment on carrier type modulation of MoTe2 FET in this work. unipolar p- and n-type MoTe2 FETs with 105 and 106 on-off ratios are achieved through rapid thermal annealing (RTA) and Benzyl Viologen (BV) doping respectively. By varying the vacuum level in RTA chamber before annealing and BV dopant concentration, annealing condition, both hole and electron doping concentration can be modulated in a wide range from slight doping to degenerate like doping. Furthermore, Al2O3 is deposited onto the device surfaces for the mobility engineering. Hole and electron mobilities are improved to 62 cm2/Vs and 82 cm2/Vs respectively after Al2O3 capping; they are among the highest carrier mobilities of MoTe2 transistors ever obtained. A lateral homogeneous MoTe2 p-n diode is fabricated combining the electron and hole doping techniques, the device displays excellent diode properties with a high rectification ratio of 104 at 0 gate bias and an ideality factor of 1.2. This work was supported by the Global Research Laboratory and Global Frontier R&D Programs at the Center for Hybrid Interface Materials, both funded by the Ministry of Science, ICT & Future Planning via the National Research Foundation of Korea (NRF).

  7. 3-O-Benzyl-6-O-benzoyl-1,2-O-isopropil­idene-5-C-nitro­methyl-a-d-glucofuran­ose

    PubMed Central

    Pampín, Begoña; Valencia, Laura; Estévez, Juan C.; Estévez, Ramón J.

    2009-01-01

    The title compound, C24H27NO9, is one of the epimers of the Henry reaction of 3-O-benzyl-6-O-benzoyl-2-O-isopropyl­idene-a-d-glucofuran-5-one with nitro­methane. The conformation of the five membered rings is as expected from the precursor compound and the mol­ecule is folded with a dihedral angle of 51.4 (2)° between the aromatic rings. One O—H⋯O hydrogen bond and some intra­molecular and inter­molecular C—H⋯O inter­actions are observed in the structure. PMID:21581936

  8. Synthesis and Pharmacological Characterization of C4-(Thiotriazolyl)-substituted-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of (1R,2S,4R,5R,6R)-2-Amino-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2812223), a Highly Potent, Functionally Selective mGlu2 Receptor Agonist.

    PubMed

    Monn, James A; Prieto, Lourdes; Taboada, Lorena; Hao, Junliang; Reinhard, Matthew R; Henry, Steven S; Beadle, Christopher D; Walton, Lesley; Man, Teresa; Rudyk, Helene; Clark, Barry; Tupper, David; Baker, S Richard; Lamas, Carlos; Montero, Carlos; Marcos, Alicia; Blanco, Jaime; Bures, Mark; Clawson, David K; Atwell, Shane; Lu, Frances; Wang, Jing; Russell, Marijane; Heinz, Beverly A; Wang, Xushan; Carter, Joan H; Getman, Brian G; Catlow, John T; Swanson, Steven; Johnson, Bryan G; Shaw, David B; McKinzie, David L

    2015-09-24

    Identification of orthosteric mGlu(2/3) receptor agonists capable of discriminating between individual mGlu2 and mGlu3 subtypes has been highly challenging owing to the glutamate-site sequence homology between these proteins. Herein we detail the preparation and characterization of a series of molecules related to (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate 1 (LY354740) bearing C4-thiotriazole substituents. On the basis of second messenger responses in cells expressing other recombinant human mGlu2/3 subtypes, a number of high potency and efficacy mGlu2 receptor agonists exhibiting low potency mGlu3 partial agonist/antagonist activity were identified. From this, (1R,2S,4R,5R,6R)-2-amino-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 14a (LY2812223) was further characterized. Cocrystallization of 14a with the amino terminal domains of hmGlu2 and hmGlu3 combined with site-directed mutation studies has clarified the underlying molecular basis of this unique pharmacology. Evaluation of 14a in a rat model responsive to mGlu2 receptor activation coupled with a measure of central drug disposition provides evidence that this molecule engages and activates central mGlu2 receptors in vivo.

  9. Experimental study and detailed modeling of toluene degradation in a low-pressure stoichiometric premixed CH4/O2/N2 flame.

    PubMed

    Bakali, A El; Dupont, L; Lefort, B; Lamoureux, N; Pauwels, J F; Montero, M

    2007-05-17

    Temperature and mole fraction profiles have been measured in laminar stoichiometric premixed CH4/O2/N2 and CH4/1.5%C6H5CH3/O2/N2 flames at low pressure (0.0519 bar) by using thermocouple, molecular beam/mass spectrometry (MB/MS), and gas chromatography/mass spectrometry (GC/MS) techniques. The present study completes our previous work performed on the thermal degradation of benzene in CH4/O2/N2 operating at similar conditions. Mole fraction profiles of reactants, final products, and reactive and stable intermediate species have been analyzed. The main intermediate aromatic species analyzed in the methane-toluene flame were benzene, phenol, ethylbenzene, benzylalcohol, styrene, and benzaldehyde. These new experimental results have been modeled with our previous model including submechanisms for aromatics (benzene up to p-xylene) and aliphatic (C1 up to C7) oxidation. Good agreement has been observed for the main species analyzed. The main reaction paths governing the degradation of toluene in the methane flame were identified, and it occurs mainly via the formation of benzene (C6H5CH3 + H = C6H6 + CH3) and benzyl radical (C6H5CH3 + H = C6H5CH2 + H2). Due to the abundance of methyl radicals, it was observed that recombination of benzyl and methyl is responsible for main monosubstitute aromatic species analyzed in the methane-toluene flame. The oxidation of these substitute species led to cyclopentadienyl radical as observed in a methane-benzene flame.

  10. Thieno[3,2-b]- and thieno[2,3-b]pyrrole bioisosteric analogues of the hallucinogen and serotonin agonist N,N-dimethyltryptamine.

    PubMed

    Blair, J B; Marona-Lewicka, D; Kanthasamy, A; Lucaites, V L; Nelson, D L; Nichols, D E

    1999-03-25

    The synthesis and biological activity of 6-[2-(N, N-dimethylamino)ethyl]-4H-thieno[3,2-b]pyrrole (3a) and 4-[2-(N, N-dimethylamino)ethyl]-6H-thieno[2,3-b]pyrrole (3b), thienopyrroles as potential bioisosteres of N,N-dimethyltryptamine (1a), are reported. Hallucinogen-like activity was evaluated in the two-lever drug discrimination paradigm using LSD- and DOI-trained rats. Neither 3a nor 3b substituted for LSD or DOI up to doses of 50 micromol/kg. By comparison, 1a fully substituted in LSD-trained rats. However, 3a and 3b fully substituted for the 5-HT1A agonist LY293284 ((-)-(4R)-6-acetyl-4-(di-n-propylamino)-1,3,4, 5-tetrahydrobenz[c,d]indole). Both 3a and 3b induced a brief "serotonin syndrome" and salivation, an indication of 5-HT1A receptor activation. At the cloned human 5-HT2A receptor 3b had about twice the affinity of 3a. At the cloned human 5-HT2B and 5-HT2C receptors, however, 3a had about twice the affinity of 3b. Therefore, thiophene lacks equivalence as a replacement for the phenyl ring in the indole nucleus of tryptamines that bind to 5-HT2 receptor subtypes and possess LSD-like behavioral effects. Whereas both of the thienopyrroles had lower affinity than the corresponding 1a at 5-HT2 receptors, 3a and 3b had significantly greater affinity than 1a at the 5-HT1A receptor. Thus, thienopyrrole does appear to serve as a potent bioisostere for the indole nucleus in compounds that bind to the serotonin 5-HT1A receptor. These differences in biological activity suggest that serotonin receptor isoforms are very sensitive to subtle changes in the electronic character of the aromatic systems of indole compounds.

  11. Reusable ionic liquid-catalyzed oxidative coupling of azoles and benzylic compounds via sp(3) C-N bond formation under metal-free conditions.

    PubMed

    Liu, Wenbo; Liu, Chenjiang; Zhang, Yonghong; Sun, Yadong; Abdukadera, Ablimit; Wang, Bin; Li, He; Ma, Xuecheng; Zhang, Zengpeng

    2015-07-14

    The heterocyclic ionic liquid-catalyzed direct oxidative amination of benzylic sp(3) C-H bonds via intermolecular sp(3) C-N bond formation for the synthesis of N-alkylated azoles under metal-free conditions is reported for the first time. The catalyst 1-butylpyridinium iodide can be recycled and reused with similar efficacies for at least eight cycles.

  12. 2.2 A resolution structure analysis of two refined N-acetylneuraminyl-lactose--wheat germ agglutinin isolectin complexes.

    PubMed

    Wright, C S

    1990-10-20

    The crystal structures of complexes of isolectins 1 and 2 of wheat germ agglutinin (WGA1 and WGA2) with N-acetylneuraminyl-lactose (NeuNAc-alpha(2-3)-Gal-beta(1-4)-Glc) have been refined on the basis of data in the 8 to 2.2 A resolution range to final crystallographic R-factors of 17.2% and 15.3% (Fo greater than 1 sigma), respectively. Specific binding interactions and water association, as well as changes in conformation and mobility of the structure upon ligand binding, were compared in the two complexes. The temperature factors (B = 16.3 A2 and 18.4 A2) were found to be much lower compared with those of their respective native structures (19 to 22 A2). Residues involved in sugar binding, dimerization and in lattice contacts exhibit the largest decreases in B-value, suggesting that sugar binding reduces the overall mobility of the protein molecules in the crystal lattice. The binding mode of this sialyl-trisaccharide, an important cell receptor analogue, has been compared in the two isolectins. Only one of the two unique binding sites (4 per dimer), located in the subunit/subunit interface, is occupied in the crystals. This site, termed the "primary" binding site, contains one of the five amino acid substitutions that differentiate WGA1 and WGA2. Superposition of the refined models in each of the independent crystallographic environments indicates a close match only of the terminal non-reducing NeuNAc residue (root-mean-square delta r of 0.5 to 0.6 A). The Gal-Glc portion was found to superimpose poorly, lack electron density, and possess high atomic thermal factors. In both complexes NeuNAc is stabilized through contact with six amino acid side-chains (Ser114 and Glu115 of subunit 1 and Ser62, Tyr64, Tyr(His)66 and Tyr73 of subunit 2), involving all NeuNAc ring substituents. Refinement has allowed accurate assessment of the contact distances for four hydrogen bonds, a strong buried non-polar contact with the acetamido CH3 group and a large number of van der

  13. Energy difference between the (v = 0, R = 1) and the (v = 0, R = 3) states of H2(+), measured with interseries microwave spectroscopy of H2 Rydberg states

    NASA Astrophysics Data System (ADS)

    Arcuni, P. W.; Fu, Z. W.; Lundeen, S. R.

    1990-12-01

    Several transitions between specific Rydberg levels in the nearly degenerate (v = 0, R = 1) n = 28 and (v = 0, R = 3) n = 16 Rydberg manifolds of H2 with microwave spectroscopy. These measurements can be combined with calculations of the Rydberg fine structure to deduce the energy difference between the two states of the free H2(+) core. The result, E(v = 0, R = 3) - E(v = 0, R = 1) = 288.85900(8)/cm, represents the most precise determination to date of any spectral property of the hydrogen molecular ion.

  14. Synthesis of G-N2-(CH2)3-N2-G Trimethylene DNA interstrand cross-links

    PubMed Central

    Gruppi, Francesca; Salyard, Tracy L. Johnson; Rizzo, Carmelo J.

    2014-01-01

    The synthesis of G-N2-(CH2)3-N2-G trimethylene DNA interstrand cross-links (ICLs) in a 5′-CG-3′ and 5′-GC-3′ sequence from oligodeoxynucleotides containing N2-(3-aminopropyl)-2′-deoxyguanosine and 2-fluoro-O6-(trimethylsilylethyl)inosine is presented. Automated solid-phase DNA synthesis was used for unmodified bases and modified nucleotides were incorporated via their corresponding phosphoramidite reagent by a manual coupling protocol. The preparation of the phosphoramidite reagents for incorporation of N2-(3-aminopropyl)-2′-deoxyguanosine is reported. The high-purity trimethylene DNA interstrand cross-link product is obtained through a nucleophilic aromatic substitution reaction between the N2-(3-aminopropyl)-2′-deoxyguanosine and 2-fluoro-O6-(trimethylsilylethyl)inosine containing oligodeoxynucleotides. PMID:25431636

  15. (2R,3S,2R,3R)-manniflavanone, a new gastrointestinal smooth muscle L-type calcium channel inhibitor, which underlies the spasmolytic properties of Garcinia buchananii stem bark extract

    PubMed Central

    Balemba, Onesmo B.; Stark, Timo D.; Lösch, Sofie; Patterson, Savannah; McMillan, John S.; Mawe, Gary M.; Hofmann, Thomas

    2014-01-01

    Garcinia buchananii Baker stem bark extract (GBB) is a traditional medication of diarrhea and dysentery in sub-Saharan Africa. It is believed that GBB causes gastrointestinal smooth muscle relaxation. The aim of this study was to determine whether GBB has spasmolytic actions and identify compounds underlying these actions. Calcium (Ca2+) imaging was used to analyze the effect of GBB on Ca2+ flashes and Ca2+ waves in guinea pig gallbladder and distal colon smooth muscle. Intracellular microelectrode recording was used to determine the effect of GBB, six fractions of GBB, M1–5 and M7, and (2R,3S,2R,3R)-manniflavanone, a compound isolated from M3 on action potentials in gallbladder smooth muscle. The technique was also used to analyze the effect of GBB, M3, and (2R,3S,2R,3R)-manniflavanone on action potentials in the circular muscle of mouse and guinea pig distal colons, and the effect of GBB and (2R,3S,2R,3R)-manniflavanone on slow waves in porcine ileum. GBB inhibited Ca2+ flashes and Ca2+ waves. GBB, M3 and (2R,3S,2R,3R)-manniflavanone inhibited action potentials. L-type Ca2+ channel activator Bay K 8644 increased the discharge of action potentials in mouse colon but did not trigger or increase action potentials in the presence of GBB and (2R,3S,2R,3R)-manniflavanone. GBB and (2R,3S,2R,3R)-manniflavanone inhibited action potentials in the presence of Bay K 8644. GBB and (2R,3S,2R,3R)-manniflavanone reduced the amplitude but did not alter the frequency of slow waves in the porcine ileum. In conclusion, GBB and (2R,3S,2R,3R)-manniflavanone relax smooth muscle by inhibiting L-type Ca2+ channels, thus have potential for use as therapies of gastrointestinal smooth muscle spasms, and arrhythmias. PMID:26081368

  16. Titanium isopropoxide complexes of a series of sterically demanding aryloxo based [N2O2]2- ligands as precatalysts for ethylene polymerization.

    PubMed

    Panda, Manas K; Kaur, Sukhdeep; Reddy, Annapureddy Rajasekhar; Shaikh, Mobin M; Butcher, Ray J; Gupta, Virendrakumar; Ghosh, Prasenjit

    2010-12-07

    Several titanium isopropoxide complexes [N,N'-bis(2-oxo-3-R(1)-5-R(2)-phenylmethyl)-N,N'-bis(methylene-p-R(3)-C(6)H(4))-ethylenediamine]Ti(O(i)Pr)(2) [R(1) = t-Bu, R(2) = Me, R(3) = H (1b); R(1) = R(2) = t-Bu, R(3) = H, (2b); R(1) = R(2) = Cl, R(3) = H, (3b), R(1) = t-Bu, R(2) = Me, R(3) = Cl (4b); R(1) = R(2) = t-Bu, R(3) = Cl, (5b); R(1) = R(2) = R(3) = Cl, (6b)] supported over sterically demanding aryloxy based [N(2)O(2)]H(2) ligands have been designed as precatalysts for the ethylene polymerization. Specifically, the 1b-6b complexes, when treated with methylaluminoxane (MAO) under 88 ± 0.5 psi of ethylene at 30 °C for 3 h, produced polyethylene polymers of high molecular weight (M(w) = ca. 7.2-8.3 × 10(5) g mol(-1)) having broad molecular weight distribution (PDI = ca. 13.1-14.6). The 1b-6b complexes were conveniently synthesized from the direct reaction of the [N(2)O(2)]H(2) ligands, 1a-6a, with Ti(O(i)Pr)(4) in 69-86% yield.

  17. The delta-opioid receptor agonist SNC80 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N,N-diethylbenzamide] synergistically enhances the locomotor-activating effects of some psychomotor stimulants, but not direct dopamine agonists, in rats.

    PubMed

    Jutkiewicz, Emily M; Baladi, Michelle G; Folk, John E; Rice, Kenner C; Woods, James H

    2008-02-01

    The nonpeptidic delta-opioid agonist SNC80 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N,N-diethylbenzamide] produces many stimulant-like behavioral effects in rodents and monkeys, such as locomotor stimulation, generalization to cocaine in discrimination procedures, and antiparkinsonian effects. Tolerance to the locomotor-stimulating effects of SNC80 develops after a single administration of SNC80 in rats; it is not known whether cross-tolerance develops to the effects of other stimulant compounds. In the initial studies to determine whether SNC80 produced cross-tolerance to other stimulant compounds, it was discovered that amphetamine-stimulated locomotor activity was greatly enhanced in SNC80-pretreated rats. This study evaluated acute cross-tolerance between delta-opioid agonists and other locomotor-stimulating drugs. Locomotor activity was measured in male Sprague-Dawley rats implanted with radiotransmitters, and activity levels were recorded in the home cage environment. Three-hour SNC80 pretreatment produced tolerance to further delta-opioid receptor stimulation but also augmented greatly amphetamine-stimulated locomotor activity in a dose-dependent manner. Pretreatments with other delta-opioid agonists, (+)BW373U86 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-hydroxybenzyl]-N,N-diethylbenzamide] and oxymorphindole (17-methyl-6,7-dehydro-4,5-epoxy-3,14-dihydroxy-6,7,2',3'-indolomorphinan), also modified amphetamine-induced activity levels. SNC80 pretreatment enhanced the stimulatory effects of the dopamine/norepinephrine transporter ligands cocaine and nomifensine (1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-isoquinolinanmine maleate salt), but not the direct dopamine receptor agonists SKF81297 [R-(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] and quinpirole [trans-(-)-(4alphaR)-4,4a, 5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo[3,4-g] quinoline

  18. Intramolecular ketenimine-ketenimine [2 + 2] and [4 + 2] cycloadditions.

    PubMed

    Alajarín, Mateo; Bonillo, Baltasar; Sanchez-Andrada, Pilar; Vidal, Angel; Bautista, Delia

    2007-07-20

    Bis(ketenimines), in which the two heterocumulenic functions are placed in close proximity on a carbon skeleton to allow their mutual interaction, show a rich and not easily predictable chemistry. Intramolecular [2 + 2] or [4 + 2] cycloadditions are, respectively, observed when both ketenimine functions are supported on either ortho-benzylic or 2,2'-biphenylenic scaffolds. In addition, nitrogen-to-carbon [1,3] and [1,5] shifts of arylmethyl groups in N-arylmethyl-C,C-diphenyl ketenimines are also disclosed.

  19. DFT study of benzyl alcohol/TiO2 interfacial surface complex: reaction pathway and mechanism of visible light absorption.

    PubMed

    Zhao, Lei; Gu, Feng Long; Kim, Minjae; Miao, Maosheng; Zhang, Rui-Qin

    2017-09-24

    We propose a new pathway for the adsorption of benzyl alcohol on the surface of TiO 2 and the formation of interfacial surface complex (ISC). The reaction free energies and reaction kinetics were thoroughly investigated by density functional calculations. The TiO 2 surfaces were modeled by clusters consisting of 4 Ti atoms and 18 O atoms passivated by H, OH group and H 2 O molecules. Compared with solid-state calculations utilizing the periodicity of the materials, such cluster modeling allows inclusion of the high-order correlation effects that seem to be essential for the adsorption of organic molecules onto solid surfaces. The effects of both acidity and solvation are included in our calculations, which demonstrate that the new pathway is competitive with a previous pathway. The electronic structure calculations based on the relaxed ISC structures reveal that the chemisorption of benzyl alcohol on the TiO 2 surface greatly alters the nature of the frontier molecular orbitals. The resulted reduced energy gap in ISC matches the energy of visible light, showing how the adsorption of benzyl alcohol sensitizes the TiO 2 surface. Graphical Abstract The chemisorption of benzyl alcohol on TiO 2 surface greatly alters the nature of the frontier molecular orbitals and the formed interfacial surface complex can be sensitized by visible light.

  20. Chanabayaite, Cu2(N3C2H2)Cl(NH3,Cl,H2O,□)4, a new mineral containing triazolate anion

    NASA Astrophysics Data System (ADS)

    Chukanov, N. V.; Zubkova, N. V.; Möhn, G.; Pekov, I. V.; Pushcharovsky, D. Yu.; Zadov, A. E.

    2015-12-01

    A new mineral, chanabayaite, has been discovered at a guano deposit located at Mt. Pabellón de Pica near the village of Chanabaya, Iquique Province, Tarapacá region, Chile. It is associated with salammoniac, halite, joanneumite, nitratine and earlier chalcopyrite. Chanabayaite occurs as blue translucent imperfect prismatic crystals, up to 0.05 × 0.1 × 0.5 mm in size, and their radial aggregates. Chanabayaite is brittle, with a Mohs' hardness of 2. The cleavage is perfect on (001) and imperfect on (100) and (010). D meas = 1.48(2) g/cm3, D calc = 1.464 g/cm3. The mineral is optically biaxial (-), α = 1.561(2), β = 1.615(3), γ = 1.620(2), 2 V meas = 25(10)°, 2 V calc = 33°. Pleochroism is strong, Z ≈ Y (deep blue) ≫ X (pale blue with gray tint). IR spectrum is given. The chemical composition (electron microprobe data for Cu, Fe and Cl; gas chromatography data for H, N, C and O) is as follows (wt %): 32.23 Cu, 1.14 Fe, 16.13 Cl, 3.1 H, 29.9 N, 12.2 C, 3.4 O, total is 98.1. The empirical formula is ( Z = 4): Cu1.92Fe0.08Cl1.72N8.09C3.85H11.66O0.81. The structural model was based on the single-crystal X-ray diffraction data ( R = 0.1627). Chanabayaite is orthorhombic, space group Imma, a = 19.484(3), b = 7.2136(10), c = 11.999(4) Å, V = 1686.5(7) Å3, Z = 2. In chanabayaite, chains of the corner-sharing Cu(l)-centered octahedra and single Cu(2)-centered octahedra are linked via 1,2,4-triazolate anions C2N3H2 -. NH3 and Cl- are additional ligands coordinating Cu2+. Chanabayaite is a transformational mineral species formed by leaching of Na and one third of Cl and partial dehydration of the protophase Na2Cu2Cl3(N3C2H2)2(NH3)2 • 4H2O. The strongest reflections in the powder X-ray diffraction pattern [ d, Å ( I, %) ( hkl)] are detected: 10.19 (100) (101), 6.189 (40) (011), 5.729 (23) (301), 5.216 (75) (211, 202), 4.964 (20) (400), 2.830 (20) (602, 413, 503), 2.611 (24) (123, 422, 404).

  1. (Phosphinoalkyl)silanes. 4.(1) Hydrozirconation as a Non-Photochemical Route to (Phosphinopropyl)silanes: Facile Assembly of the Bis(3-(diphenylphosphino)propyl)silyl ("biPSi") Ligand Framework. Access to the Related Poly(3-(dimethylsilyl)propyl)phosphines R(n)()P(CH(2)CH(2)CH(2)SiMe(2)H)(3)(-)(n)() (n = 1, R = Ph; n = 0).

    PubMed

    Zhou, Xiaobing; Stobart, Stephen R.; Gossage, Robert A.

    1997-08-13

    Treatment of SiEt(3)(CH=CH(2)) with ZrCp(2)HCl (Schwartz's reagent) followed by reaction with PPh(2)Cl provides a high-yield (75%) route to Ph(2)PCH(2)CH(2)SiEt(3), and accordingly hydrozirconation of CH(2)=CHCH(2)SiHMe(2) affords the intermediate ZrCp(2)(CH(2)CH(2)CH(2)SiHMe(2))Cl (2). The latter, which is very sensitive to hydrolysis and reacts with HCl forming SiHMe(2)Pr(n)() and with NBS or I(2) affording SiHMe(2)CH(2)CH(2)CH(2)X (X = Br (3), I (4)), behaves similarly with PPh(2)Cl, PPhCl(2), or PBr(3) undergoing cleavage to the known Ph(2)PCH(2)CH(2)CH(2)SiMe(2)H (i.e. chelH, A) and the novel bis- and tris(silylpropyl)phosphines PhP(CH(2)CH(2)CH(2)SiMe(2)H)(2) (5) and P(CH(2)CH(2)CH(2)SiMe(2)H)(3) (6), respectively, with concomitant formation of ZrCp(2)Cl(2). Corresponding hydroboration of allylsilanes is facile, but subsequent phosphine halide cleavage yields (phosphinoalkyl)silanes only as constituents of intractable mixtures. Hydrozirconation followed by phosphination with PPh(2)Cl also converts SiHMe(CH(2)CH=CH(2))(2) to SiHMe(CH(2)CH(2)CH(2)PPh(2))(2) (i.e. biPSiH, B) together with a propyl analogue Ph(2)PCH(2)CH(2)CH(2)SiMe(Pr(n)())H (7) of A (ca. 2:1 ratio), as well as SiH(CH(2)CH=CH(2))(3) to a mixture (ca. 5:2:1 ratio) of SiH(CH(2)CH(2)CH(2)PPh(2))(3) (i.e. triPSiH, C), a new analogue SiH(Pr(n)())(CH(2)CH(2)CH(2)PPh(2))(2) (8) of B, and a further analogue Ph(2)PCH(2)CH(2)CH(2)SiHPr(n)()(2) (9) of A. A further analogue SiH(2)(CH(2)CH(2)CH(2)PPh(2))(2) (10) of biPSiH (B) is obtained similarly starting from SiH(2)(CH(2)CH=CH(2))(2). Steric control of silylalkyl cleavage from 2 is indicated by the fact that, like PPh(2)Cl (which forms B), two further biPSiH analogues SiH(Me)[CH(2)CH(2)CH(2)P(n-hex)(2)](2) (11) and SiH(Me)(CH(2)CH(2)CH(2)PPhBz)(2) (12) were obtained using P(n-hex)(2)Cl (i.e. n-hex = CH(3)(CH(2))(4)CH(2)-) or PPhBzCl (i.e. Bz = -CH(2)C(6)H(5)), respectively, whereas neither PPr(i)(2)Cl nor PBu(t)(2)Cl led to (phosphinoalkyl)silane formation

  2. Isolation of (CO)1- and (CO2)1- radical complexes of rare earths via Ln(NR2)3/K reduction and [K2(18-crown-6)2]2+ oligomerization.

    PubMed

    Fang, Ming; Farnaby, Joy H; Ziller, Joseph W; Bates, Jefferson E; Furche, Filipp; Evans, William J

    2012-04-11

    Deep-blue solutions of Y(2+) formed from Y(NR(2))(3) (R = SiMe(3)) and excess potassium in the presence of 18-crown-6 at -45 °C under vacuum in diethyl ether react with CO at -78 °C to form colorless crystals of the (CO)(1-) radical complex, {[(R(2)N)(3)Y(μ-CO)(2)][K(2)(18-crown-6)(2)]}(n), 1. The polymeric structure contains trigonal bipyramidal [(R(2)N)(3)Y(μ-CO)(2)](2-) units with axial (CO)(1-) ligands linked by [K(2)(18-crown-6)(2)](2+) dications. Byproducts such as the ynediolate, [(R(2)N)(3)Y](2)(μ-OC≡CO){[K(18-crown-6)](2)(18-crown-6)}, 2, in which two (CO)(1-) anions are coupled to form (OC≡CO)(2-), and the insertion/rearrangement product, {(R(2)N)(2)Y[OC(═CH(2))Si(Me(2))NSiMe(3)]}[K(18-crown-6)], 3, are common in these reactions that give variable results depending on the specific reaction conditions. The CO reduction in the presence of THF forms a solvated variant of 2, the ynediolate [(R(2)N)(3)Y](2)(μ-OC≡CO)[K(18-crown-6)(THF)(2)](2), 2a. CO(2) reacts analogously with Y(2+) to form the (CO(2))(1-) radical complex, {[(R(2)N)(3)Y(μ-CO(2))(2)][K(2)(18-crown-6)(2)]}(n), 4, that has a structure similar to that of 1. Analogous (CO)(1-) and (OC≡CO)(2-) complexes of lutetium were isolated using Lu(NR(2))(3)/K/18-crown-6: {[(R(2)N)(3)Lu(μ-CO)(2)][K(2)(18-crown-6)(2)]}(n), 5, [(R(2)N)(3)Lu](2)(μ-OC≡CO){[K(18-crown-6)](2)(18-crown-6)}, 6, and [(R(2)N)(3)Lu](2)(μ-OC≡CO)[K(18-crown-6)(Et(2)O)(2)](2), 6a. © 2012 American Chemical Society

  3. On the Large R-charge Expansion in N=2 Superconformal Field Theories

    NASA Astrophysics Data System (ADS)

    Hellerman, Simeon; Maeda, Shunsuke

    2017-12-01

    In this note we study two point functions of Coulomb branch chiral ring elements with large R-charge, in quantum field theories with N=2 superconformal symmetry in four spacetime dimensions. Focusing on the case of one-dimensional Coulomb branch, we use the effective-field-theoretic methods of [1], to estimate the two-point correlation function Y_n≡ {|x-y|}^{2n{Δ}_O}< {(O(x))}^n{(\\overlineO(y))}^n> in the limit where the operator insertion O^n has large total R-charge J=n{Δ}_O . We show that Y_n has a nontrivial but universal asymptotic expansion at large J , of the form Y_n from "Euclid Math One" (0x3D)J!{(|{N}_O|/2π)}^{2J}J^{α }{\\tildeY}_n, where {\\tildeY}_n approaches a constant as n → ∞, and {N}_O is an n-independent constant describing on the normalization of the operator relative to the effective Abelian gauge coupling. The exponent α is a positive number proportional to the difference between the a-anomaly coefficient of the underlying CFT and that of the effective theory of the Coulomb branch. For Lagrangian SCFT, we check our predictions for the logarithm B_n= log (Y_n) , up to and including order log J against exact results from supersymmetric localization [2-5]. In the case of N=4 we find precise agreement and in the case N=2 we find reasonably good numerical agreement at J˜eq 60 using the no-instanton approximation to the S 4 partition function. We also give predictions for the growth of two-point functions in all rank-one SCFT in the classification of [6-9]. In this way, we show the large- R-charge expansion serves as a bridge from the world of unbroken superconformal symmetry, OPE data, and bootstraps, to the world of the low-energy dynamics of the moduli space of vacua.

  4. Synthesis and reactivity of bis(tetramethylcyclopentadienyl) yttrium metallocenes including the reduction of Me(3)SiN(3) to [(Me(3)Si)(2)N](-) with [(C(5)Me(4)H)(2)Y(THF)](2)(mu-eta(2):eta(2)-N(2)).

    PubMed

    Lorenz, Sara E; Schmiege, Benjamin M; Lee, David S; Ziller, Joseph W; Evans, William J

    2010-07-19

    The metallocene precursors needed to provide the tetramethylcyclopentadienyl yttrium complexes (C(5)Me(4)H)(3)Y, [(C(5)Me(4)H)(2)Y(THF)](2)(mu-eta(2):eta(2)-N(2)), and [(C(5)Me(4)H)(2)Y(mu-H)](2) for reactivity studies have been synthesized and fully characterized, and their reaction chemistry has led to an unexpected conversion of an azide to an amide. (C(5)Me(4)H)(2)Y(mu-Cl)(2)K(THF)(x), 1, synthesized from YCl(3) and KC(5)Me(4)H reacts with allylmagnesium chloride to make (C(5)Me(4)H)(2)Y(eta(3)-C(3)H(5)), 2, which is converted to [(C(5)Me(4)H)(2)Y][(mu-Ph)(2)BPh(2)], 3, with [Et(3)NH][BPh(4)]. Complex 3 reacts with KC(5)Me(4)H to form (C(5)Me(4)H)(3)Y, 4. The reduced dinitrogen complex, [(C(5)Me(4)H)(2)Y(THF)](2)(mu-eta(2):eta(2)-N(2)), 5, can be synthesized from either [(C(5)Me(4)H)(2)Y](2)[(mu-Ph)(2)BPh(2)], 3, or (C(5)Me(4)H)(3)Y, 4, with potassium graphite under a dinitrogen atmosphere. The (15)N labeled analogue, [(C(5)Me(4)H)(2)Y(THF)](2)(mu-eta(2):eta(2)-(15)N(2)), 5-(15)N, has also been prepared, and the (15)N NMR data have been compared to previously characterized reduced dinitrogen complexes. Complex 2 reacts with H(2) to form the corresponding hydride, [(C(5)Me(4)H)(2)Y(mu-H)](2), 6. Complex 5 displays similar reactivity to that of the analogous [(C(5)Me(4)H)(2)Ln(THF)](2)(mu-eta(2):eta(2)-N(2)) complexes (Ln = La, Lu), with substrates such as phenazine, anthracene, and CO(2). In addition, 5 reduces Me(3)SiN(3) to form (C(5)Me(4)H)(2)Y[N(SiMe(3))(2)], 7.

  5. Antiausterity activity of arctigenin enantiomers: importance of (2R,3R)-absolute configuration.

    PubMed

    Awale, Suresh; Kato, Mamoru; Dibwe, Dya Fita; Li, Feng; Miyoshi, Chika; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro

    2014-01-01

    From a MeOH extract of powdered roots of Wikstroemia indica, six dibenzyl-gamma-butyrolactone-type lignans with (2S,3S)-absolute configuration [(+)-arctigenin (1), (+)-matairesinol (2), (+)-trachelogenin (3), (+)-nortrachelogenin (4), (+)-hinokinin (5), and (+)-kusunokinin (6)] were isolated, whereas three dibenzyl-gamma-butyrolactone-type lignans with (2R,3R)-absolute configuration [(-)-arctigenin (1*), (-)-matairesinol (2*), (-)-trachelogenin (3*)] were isolated from Trachelospermum asiaticum. The in vitro preferential cytotoxic activity of the nine compounds was evaluated against human pancreatic PANC-1 cancer cells in nutrient-deprived medium (NDM), but none of the six lignans (1-6) with (2S,3S)-absolute configuration showed preferential cytotoxicity. On the other hand, three lignans (1*-3*) with (2R,3R)-absolute configuration exhibited preferential cytotoxicity in a concentration-dependent manner with PC50 values of 0.54, 6.82, and 5.85 microM, respectively. Furthermore, the effect of (-)- and (+)-arctigenin was evaluated against the activation of Akt, which is a key process in the tolerance to nutrition starvation. Interestingly, only (-)-arctigenin (1*) strongly suppressed the activation of Akt. These results indicate that the (2R,3R)-absolute configuration of (-)-enantiomers should be required for the preferential cytotoxicity through the inhibition of Akt activation.

  6. 2-Methyltetrahydro-3-benzazepin-1-ols - The missing link in SAR of GluN2B selective NMDA receptor antagonists.

    PubMed

    Dey, Sougata; Schepmann, Dirk; Wünsch, Bernhard

    2018-01-15

    The NMDA receptor containing GluN2B subunits represents a promising target for the development of drugs for the treatment of various neurological disorders including neurodegenerative diseases. In order to study the role of CH 3 and OH moieties trisubstituted tetrahydro-3-benzazepines 4 were designed as missing link between tetra- and disubstituted 3-benzazepines 2 and 5. The synthesis of 4 comprises eight reaction steps starting from alanine. The intramolecular Friedel-Crafts acylation to obtain the ketone 12 and the base-catalyzed elimination of trifluoromethanesulfinate (CF 3 SO 2 - ) followed by NaBH 4 reduction represent the key steps. The GluN2B affinity of the cis-configured 3-benzazepin-1-ol cis-4a with a 4-phenylbutyl side chain (K i  = 252 nM) is considerably lower than the GluN2B affinity of (R,R)-2 (K i  = 17 nM) indicating the importance of the phenolic OH moiety for the interaction with the receptor protein. Introduction of an additional CH 3 moiety in 2-position led to a slight decrease of GluN2B affinity as can be seen by comparing the affinity data of cis-4a and 5. The homologous phenylpentyl derivative cis-4b shows the highest GluN2B affinity (K i  = 56 nM) of this series of compounds. According to docking studies cis-4a adopts the same binding mode as the cocrystallized ligand ifenprodil-keto 1A and 5 at the interface of the GluN2B and GluN1a subunits. The same crucial H-bonds are formed between the C(O)NH 2 moiety of Gln110 within the GluN2B subunit and the protonated amino moiety and the OH moiety of (R,R)-cis-4a. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. SSR126768A (4-chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)-benzamide, hydrochloride): a new selective and orally active oxytocin receptor antagonist for the prevention of preterm labor.

    PubMed

    Serradeil-Le Gal, Claudine; Valette, Gérard; Foulon, Loïc; Germain, Guy; Advenier, Charles; Naline, Emmanuel; Bardou, Marc; Martinolle, Jean-Pierre; Pouzet, Brigitte; Raufaste, Danielle; Garcia, Corinne; Double-Cazanave, Eléonore; Pauly, Maxime; Pascal, Marc; Barbier, Alain; Scatton, Bernard; Maffrand, Jean-Pierre; Le Fur, Gérard

    2004-04-01

    4-chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)benzamide, hydrochloride (SSR126768A), a new potent and selective, orally active oxytocin (OT) receptor antagonist was characterized in several biochemical and pharmacological models. In binding studies, SSR126768A showed nanomolar affinity for rat and human recombinant and native OT receptors (K(i) = 0.44 nM) and exhibited much lower affinity for V(1a), V(1b), and V(2) receptors. In addition, it did not interact with a large number of other receptors, enzymes, and ion channels (1 microM). In autoradiographic experiments performed on at-term human pregnant uterus sections, SSR126768A dose dependently displaced [I(125)]d(CH(2))(5)[Tyr(Me)(2), Thr(4), Orn(8) (125)I-Tyr-NH(2)(9)]VT in situ labeling to OT receptors highly expressed in these tissues. In functional studies, SSR126768A behaved as a full antagonist and potently antagonized OT-induced intracellular Ca(2+) increase (K(i) = 0.50 nM) and prostaglandin release (K(i) = 0.45 nM) in human uterine smooth muscle cells. In rat isolated myometrium, OT-induced uterine contractions were competitively antagonized by SSR126768A (pA(2) = 8.47). Similarly, in human pregnant myometrial strips, SSR126768A inhibited the contractile uterine response to OT. In conscious telemetrated rats, oral administration of SSR126768A (1-10 mg/kg) produced a competitive inhibition of the dose response to OT on uterine contractions up to 24 h at 3 mg/kg p.o.; no tachyphylaxis was observed after 4-day repeated treatment. Finally, SSR126768A (30 mg/kg p.o.) significantly delayed parturition in pregnant rats in labor similar to ritodrine (10 mg/kg p.o.). Thus, SSR126768A is a potent, highly selective, orally active OT receptor antagonist with a long duration of action. This molecule could find therapeutic application as a tocolytic agent for acute and chronic oral management of preterm labor.

  8. Aqua­(dicyanamido-κN 1)(nitrato-κ2 O,O′)(2,3,5,6-tetra-2-pyridylpyrazine-κ3 N 2,N 1,N 6)manganese(II)

    PubMed Central

    Callejo, Lorena; De la Pinta, Noelia; Vitoria, Pablo; Cortés, Roberto

    2009-01-01

    In the title compound, [Mn(C2N3)(NO3)(C24H16N6)(H2O)], the central manganese(II) ion is hepta­coordinated to a tridentate 2,3,5,6-tetra-2-pyridylpyrazine ligand (tppz), a bidentate nitrate ligand, a terminal monodentate dicyanamide ligand (dca) and a water mol­ecule. The structure contains isolated neutral complexes, which are linked by O(water)—H⋯N hydrogen bonds generating chains along [010]. PMID:21581535

  9. Reaction of (carbonylimido)sulfur(IV) derivatives with TAS-fluoride, (Me2N)3S+Me3SiF2-.

    PubMed

    Lork, E; Viets, D; Mews, R; Oberhammer, H

    2000-10-16

    In the reaction of TAS-fluoride, (Me2N)3S+Me3SiF2-, with carbonyl sulfur difluoride imides RC(O)NSF2 (R = F, CF3), C-N bond, cleavage is observed, and TAS+RC(O)F2- and NSF are the final products. From TASF and RC(O)NS(CF3)F, the salts TAS+RC(O)NS(CF3)F2- (R = F (14), CF3 (15)), with psi-pentacoordinate sulfur centers in the anions, are formed. An X-ray structure investigation of 14 shows that the fluorine atoms occupy axial positions and CF3, NC(O)F, and the sulfur lone pair occupy equatorial positions of the trigonal bipyramid. The -C(O)F group lies in the equatorial plane with the CO bond synperiplanar to the SN bond. According to B3LYP calculations, this structure corresponds to a global minimum and the expected axial orientation of the -C(O)F group represents a transition state. Calculations for the unstable FC(O)NSF3- anion show a different geometry. The -C(O)F group deviates 40 degrees from axial orientation, and the equatorially bonded fluorine is, in contrast to the -CF3 group in 14, syn positioned.

  10. Evaluation of protective efficacy of three novel H3N2 canine influenza vaccines.

    PubMed

    Tu, Liqing; Zhou, Pei; Li, Lutao; Li, Xiuzhen; Hu, Renjun; Jia, Kun; Sun, Lingshuang; Yuan, Ziguo; Li, Shoujun

    2017-11-17

    Canine influenza virus (CIV) has the potential risk to spread in different areas and dog types. Thus, there is a growing need to develop an effective vaccine to control CIV disease. Here, we developed three vaccine candidates: 1) a recombinant pVAX1 vector expressing H3N2 CIV hemagglutinin (pVAX1-HA); 2) a live attenuated canine adenovirus type 2 expressing H3N2 CIV hemagglutinin (rCAV2-HA); and 3) an inactivated H3N2 CIV (A/canine/Guangdong/01/2006 (H3N2)). Mice received an initial intramuscular immunization that followed two booster injections at 2 and 4 weeks post-vaccination (wpv). The splenic lymphocytes were collected to assess the immune responses at 6 wpv. The protective efficacy was evaluated by challenging H3N2 CIV after vaccination (at 6 wpv). Our results demonstrated that all three vaccine candidates elicited cytokine and antibody responses in mice. The rCAV2-HA vaccine and the inactivated vaccine generated efficient protective efficacy in mice, whereas limited protection was provided by the pVAX1-HA DNA vaccine. Therefore, both the rCAV2-HA live recombinant virus and the inactivated CIV could be used as potential novel vaccines against H3N2CIV. This study provides guidance for choosing the most appropriate vaccine for the prevention and control of CIV disease.

  11. Polydopamine-Coated TiO2 Nanotubes for Selective Photocatalytic Oxidation of Benzyl Alcohol to Benzaldehyde Under Visible Light.

    PubMed

    Tripathy, Jyotsna; Loget, Gabriel; Altomare, Marco; Schmuki, Patrik

    2016-05-01

    TiO2 nanotube arrays grown by anodization were coated with thin layers of polydopamine as visible light sensitizer. The PDA-coated TiO2 scaffolds were used as photocatalyst for selective oxidation of benzyl alcohol under monochromatic irradiation at 473 nm. Benzaldehyde was selectively formed and no by-products could be detected. A maximized reaction yield was obtained in O2-saturated acetonitrile. A mechanism is proposed that implies firstly the charge carrier generation in polydopamine as a consequence of visible light absorption. Secondly, photo-promoted electrons are injected in TiO2 conduction band, and subsequently transferred to dissolved O2 to form O*2- radicals. These radicals react with benzyl alcohol and lead to its selective dehydrogenation oxidation towards benzaldehyde.

  12. Laser-diode-excited blue upconversion in Tm3+/Yb3+ -codoped TeO2-Ga2O3-R2O (R=Li, Na, K) glasses.

    PubMed

    Zhao, Chun; Zhang, Qinyuan; Yang, Gangfeng; Jiang, Zhonghong

    2008-01-01

    This paper reports on intense blue upconversion in Tm(3+)/Yb(3+) codoped TeO(2)-Ga(2)O(3)-R(2)O(R=Li, Na, K) glasses upon excitation with commercial available laser diode (LD). Effects of alkali ions on the Raman spectra, thermal stability and spectroscopic properties of the tellurite-gallium glasses have also been investigated. Energy transfer and the involved upconversion mechanisms have been discussed. Intense blue upconversion emission centered at 476 nm along with a weak red emission at 650 nm has been observed upon excitation of 977 nm LD, assigned to the transitions of 1G4-->3H6, and 1G4-->3H4 and/or 3F(2,3)-->3H6 of Tm(3+), respectively. The blue upconversion intensity has a cubelike dependence on incident pump laser power, indicating a three-photon process. However, a quadratic dependence of the 476 nm upconversion intensity on the incident pump laser power has been observed when samples under excitation of 808 nm LD due to a two-photon absorption process. Enhanced upconversion luminescence have been observed with replacing K(+) for Na(+) and Li(+).

  13. 2C-R4WM Spectroscopy of Jet Cooled NO_3

    NASA Astrophysics Data System (ADS)

    Fukushima, Masaru; Ishiwata, Takashi; Hirota, Eizi

    2016-06-01

    We have generated NO_3 from pyrolysis of N_2O_5 following supersonic free jet expansion, and carried out two color resonant four wave mixing ( 2C-R4WM ) spectroscopy of the tilde{B} ^2E' - tilde{X} ^2A_2' electronic transition. One laser was fixed to pump NO_3 to a ro-vibronic level of the tilde{B} state, and the other laser ( probe ) was scanned across two levels of the tilde{X} ^2A_2' state lying at 1051 and 1492 cm-1, the ν_1 (a_1') and ν_3 (e') fundamentals, respectively. The 2C-R4WM spectra have unexpected back-ground signal of NO_3 ( stray signal due to experimental set-up is also detected ) similar to laser induced fluorescence ( LIF ) excitation spectrum of the 0-0 band, although the back-ground signal was not expected in considering the 2C-R4WM scheme. Despite the back-ground interference, we have observed two peaks at 1051.61 and 1055.29 cm-1 in the ν_1 region of the spectrum, and the frequencies agree with the two bands, 1051.2 and 1055.3 cm-1, of our relatively higher resolution dispersed fluorescence spectrum, the former of which has been assigned to the ν_1 fundamental. Band width of both peaks, ˜ 0.2 cm-1, is broader than twice the experimental spectral-resolution, 0.04 cm-1 ( because this experiment is double resonance spectroscopy ), and the 1051.61 cm-1 peak is attributed to a Q branch band head ( a line-like Q branch ) of the ν_1 fundamental. The other branches are suspected to be hidden in noise of the back-ground signal. The 1055.29 cm-1 peak is also attributed to a Q band head. The tilde{B} ^2E'1/2 ( J' = 3/2, K' = 1 ) - tilde{X} ^2A_2' ( N'' = 1, K'' = 0 ) ro-vibronic transition was used as the pump transition. The dump ( probe ) transition to both a_1' and e' vibronic levels are then allowed as perpendicular transition. Accordingly, it cannot be determined from present results whether the 1055.29 cm-1 band is attributed to a_1' or e' (ν_3), unfortunately. The 2C-R4WM spectrum of the 1492 cm-1 band region shows one Q head at 1499.79 cm

  14. Additive In Vitro Antiplasmodial Effect of N-Alkyl and N-Benzyl-1,10-Phenanthroline Derivatives and Cysteine Protease Inhibitor E64

    PubMed Central

    Wijayanti, Mahardika Agus; Sholikhah, Eti Nurwening; Hadanu, Ruslin; Jumina, Jumina; Supargiyono, Supargiyono; Mustofa, Mustofa

    2010-01-01

    Potential new targets for antimalarial chemotherapy include parasite proteases, which are required for several cellular functions during the Plasmodium falciparum life cycle. Four new derivatives of N-alkyl and N-benzyl-1,10-phenanthroline have been synthesized. Those are (1)-N-methyl-1,10-phenanthrolinium sulfate, (1)-N-ethyl-1,10-phenanthrolinium sulfate, (1)-N-benzyl-1,10-phenanthrolinium chloride, and (1)-N-benzyl-1,10-phenanthrolinium iodide. Those compounds had potential antiplasmodial activity with IC50 values from 260.42 to 465.38 nM. Cysteine proteinase inhibitor E64 was used to investigate the mechanism of action of N-alkyl and N-benzyl-1,10-phenanthroline derivatives. A modified fixed-ratio isobologram method was used to study the in vitro interactions between the new compounds with either E64 or chloroquine. The interaction between N-alkyl and N-benzyl-1,10-phenanthroline derivatives and E64 was additive as well as their interactions with chloroquine were also additive. Antimalarial mechanism of chloroquine is mainly on the inhibition of hemozoin formation. As the interaction of chloroquine and E64 was additive, the results indicated that these new compounds had a mechanism of action by inhibiting Plasmodium proteases. PMID:22332022

  15. Ethyl 2-{4-[(1,5-dibenzyl-2,4-dioxo-2,3,4,5-tetra-hydro-1H-1,5-benzo-diazepin-3-yl)meth-yl]-1H-1,2,3-triazol-1-yl}acetate.

    PubMed

    Jabli, Hind; Kandri Rodi, Y; Ladeira, Sonia; Essassi, El Mokhtar; Ng, Seik Weng

    2009-12-12

    The reaction of 1,5-dibenzyl-3-propargyl-1,5-benzodiazepine-2,4-dione with ethyl azido-acetate in the presence of copper sulfate pentahydrate and sodium ascorbate leads to the formation of the title regioisomer, C(30)H(29)N(5)O(4), which features a phenyl-ene ring fused with a seven-membered diazepinyl ring. The latter ring adopts a boat conformation (with the methyl-triazolylacetate-bearing C atom as the prow and the fused-ring C atoms as the stern). The benzyl groups connected to the diazepinyl ring jprotrude from the sides; the methyl-triazolylacetate substituent occupies an axial position.

  16. Evaluation of protective efficacy of three novel H3N2 canine influenza vaccines

    PubMed Central

    Li, Lutao; Li, Xiuzhen; Hu, Renjun; Jia, Kun; Sun, Lingshuang; Yuan, Ziguo; Li, Shoujun

    2017-01-01

    Canine influenza virus (CIV) has the potential risk to spread in different areas and dog types. Thus, there is a growing need to develop an effective vaccine to control CIV disease. Here, we developed three vaccine candidates: 1) a recombinant pVAX1 vector expressing H3N2 CIV hemagglutinin (pVAX1-HA); 2) a live attenuated canine adenovirus type 2 expressing H3N2 CIV hemagglutinin (rCAV2-HA); and 3) an inactivated H3N2 CIV (A/canine/Guangdong/01/2006 (H3N2)). Mice received an initial intramuscular immunization that followed two booster injections at 2 and 4 weeks post-vaccination (wpv). The splenic lymphocytes were collected to assess the immune responses at 6 wpv. The protective efficacy was evaluated by challenging H3N2 CIV after vaccination (at 6 wpv). Our results demonstrated that all three vaccine candidates elicited cytokine and antibody responses in mice. The rCAV2-HA vaccine and the inactivated vaccine generated efficient protective efficacy in mice, whereas limited protection was provided by the pVAX1-HA DNA vaccine. Therefore, both the rCAV2-HA live recombinant virus and the inactivated CIV could be used as potential novel vaccines against H3N2CIV. This study provides guidance for choosing the most appropriate vaccine for the prevention and control of CIV disease. PMID:29228675

  17. Density functional theory study of 3R- and 2H-CuAlO2 under pressure

    NASA Astrophysics Data System (ADS)

    Liu, Qi-Jun; Liu, Zheng-Tang; Feng, Li-Ping; Tian, Hao; Liu, Wen-Ting; Yan, Feng

    2010-10-01

    We present a first-principles density-functional theory based study of the impact of pressure on the structural and elastic properties of bulk 3R- and 2H-CuAlO2. The ground state properties of 3R- and 2H-CuAlO2 are obtained, which are in good agreement with previous experimental and theoretical data. The analysis of enthalpy variation with pressure indicates the phase transition pressure between 3R and 2H is 15.4 GPa. The independent elastic constants of 3R- and 2H-CuAlO2 are calculated. As the applied pressure increases, the calculations show the presences of mechanical instability at 26.2 and 27.8 GPa for 3R- and 2H-CuAlO2, which are possibly related with the phase transitions.

  18. Structure of substituted 2-(phenoxy)benzimidazoles

    NASA Astrophysics Data System (ADS)

    Pavlova, I. S.; Pervova, I. G.; Lipunova, G. N.; Novikova, R. K.; Slepukhin, P. A.; Lipunov, I. N.

    2013-03-01

    The synthesis and X-ray diffraction study of 1-benzyl-2-[2-(5-ethyltetrazole-2-yl)-phenoxy]-1H-benzimidazole and 1-benzyl-2-[2-(5-ethyltetrazole-2-yl)-4-nitrophenoxy]-1H-benzimidazole single crystals have been performed. The oxidative splitting of an azo-hydrazone group of 1-(2-hydroxy-(5-nitro)phenyl)-3-ethyl-5-(benzylbenzimidazolyl)formazans, a break in the C2-N1 bond, the interaction of o-hydroxyl group of aryl fragment with oxygen, and the formation of new 2-(phenoxy)benzimidazoles are found to occur in the presence of perchlorate iron(III).

  19. Roles for N-terminal Extracellular Domains of Nicotinic Acetylcholine Receptor (nAChR) β3 Subunits in Enhanced Functional Expression of Mouse α6β2β3- and α6β4β3-nAChRs*

    PubMed Central

    Dash, Bhagirathi; Li, Ming D.; Lukas, Ronald J.

    2014-01-01

    Functional heterologous expression of naturally expressed mouse α6*-nicotinic acetylcholine receptors (mα6*-nAChRs; where “*” indicates the presence of additional subunits) has been difficult. Here we expressed and characterized wild-type (WT), gain-of-function, chimeric, or gain-of-function chimeric nAChR subunits, sometimes as hybrid nAChRs containing both human (h) and mouse (m) subunits, in Xenopus oocytes. Hybrid mα6mβ4hβ3- (∼5–8-fold) or WT mα6mβ4mβ3-nAChRs (∼2-fold) yielded higher function than mα6mβ4-nAChRs. Function was not detected when mα6 and mβ2 subunits were expressed together or in the additional presence of hβ3 or mβ3 subunits. However, function emerged upon expression of mα6mβ23V9′S-nAChRs containing β3 subunits having gain-of-function V9′S (valine to serine at the 9′-position) mutations in transmembrane domain II and was further elevated 9-fold when hβ3V9′S subunits were substituted for mβ3V9′S subunits. Studies involving WT or gain-of-function chimeric mouse/human β3 subunits narrowed the search for domains that influence functional expression of mα6*-nAChRs. Using hβ3 subunits as templates for site-directed mutagenesis studies, substitution with mβ3 subunit residues in extracellular N-terminal domain loops “C” (Glu221 and Phe223), “E” (Ser144 and Ser148), and “β23” (Gln94 and Glu101) increased function of mα6mβ2*- (∼23-fold) or mα6mβ4* (∼2–4-fold)-nAChRs. EC50 values for nicotine acting at mα6mβ4*-nAChR were unaffected by β3 subunit residue substitutions in loop C or E. Thus, amino acid residues located in primary (loop C) or complementary (loops β23 and E) interfaces of β3 subunits are some of the molecular impediments for functional expression of mα6mβ2β3- or mα6mβ4β3-nAChRs. PMID:25028511

  20. Impact of CO2-solvent separators on the degradation of benzyl-2,3-dihydroxypiperidine-1-carboxylate during preparative supercritical fluid chromatographic (SFC) purification.

    PubMed

    Asokan, Kathiravan; Naidu, Harshavardhan; Madam, Ratalababu; Shaikh, Khaja Mohiuddin; Reddy, Manjunath; Kumar, Hemantha; Shirude, Pravin S; Rajendran, Muruganantham; Sarabu, Ramakanth; Wu, Dauh-Rurng; Bajpai, Lakshmikant; Zhang, Yingru

    2017-12-29

    During a preparative separation of the cis enantiomeric pair of benzyl-2,3-dihydroxypiperidine-1-carboxylate using supercritical-fluid chromatography (SFC) with methanol modifier, significant degradation of the products in the collected fractions was observed when a Waters SFC-350 ® (Milford, MA, USA) was used, but same was not observed when a Waters SFC-80q ® (Milford, MA, USA) was used. Through a systematic investigation, we discovered that the compound degraded over time under an acidic condition created by the formation of methyl carbonic acid from methanol and CO 2. The extent of the product degradation was dependent on the time and the concentration of CO 2 remained in the product fraction, which was governed by the efficiency of CO 2 -methanol separation during the fraction collection. Hence, we demonstrated that the different designs of CO 2 -solvent separator (high pressurized cyclone in Waters SFC-350 ® and low-pressurized vortexing separator in Waters SFC-80q ®® ) had a significant impact on the degradation of an acid-sensitive compound. The acidity caused by CO 2 in methanol was supported by diminished degradation after a nitrogen purging or after neutralizing the collected fractions with a base. Three different solutions to overcome the degradation problem of the acid sensitive compounds using SFC-350 ® with the high pressurized separator were investigated and demonstrated. The degraded products were isolated as four enantiomers and their relative stereochemistry were established based on 2D NMR data along with the plausible mechanism of degradation. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Crystal structure of 3-[(4-benzyl-piperazin-1-yl)meth-yl]-5-(thio-phen-2-yl)-2,3-di-hydro-1,3,4-oxa-diazole-2-thione.

    PubMed

    Al-Omary, Fatmah A M; El-Emam, Ali A; Ghabbour, Hazem A; Chidan Kumar, C S; Quah, Ching Kheng; Fun, Hoong-Kun

    2015-03-01

    The title 1,3,4-oxa-diazole-2-thione derivative, C18H20N4OS2, crystallized with two independent mol-ecules (A and B) in the asymmetric unit. The 2-thienyl rings in both mol-ecules are rotationally disordered over two orientations by approximately 180° about the single C-C bond that connects it to the oxa-diazole thione ring; the ratios of site occupancies for the major and minor components were fixed in the structure refinement at 0.8:0.2 and 0.9:0.1 in mol-ecules A and B, respectively. The 1,3,4-oxa-diazole-2-thione ring forms dihedral angles of 7.71 (16), 10.0 (11) and 77.50 (12)° (mol-ecule A), and 6.5 (3), 6.0 (9) and 55.30 (12)° (mol-ecule B) with the major and minor parts of the disordered thio-phene ring and the mean plane of the adjacent piperazine ring, respectively, resulting in approximately V-shaped conformations for the mol-ecules. The piperazine ring in both mol-ecules adopts a chair conformation. The terminal benzene ring is inclined towards the mean plane of the piperazine ring with N-C-C-C torsion angles of -58.2 (3) and -66.2 (3)° in mol-ecules A and B, respectively. In the crystal, no inter-molecular hydrogen bonds are observed. The crystal packing features short S⋯S contacts [3.4792 (9) Å] and π-π inter-actions [3.661 (3), 3.664 (11) and 3.5727 (10) Å], producing a three-dimensional network.

  2. Genotype patterns of contemporary reassorted H3N2 virus in U.S. swine

    USDA-ARS?s Scientific Manuscript database

    To understand the evolution of H3N2v influenza viruses that have infected 288 humans since July 2011, we performed the largest phylogenetic analysis at a whole genome scale of influenza viruses from North American swine to date (n = 200). At least ten distinct reassorted H3N2/pandemic H1N1 (rH3N2p)...

  3. A limit for large R-charge correlators in N = 2 theories

    NASA Astrophysics Data System (ADS)

    Bourget, Antoine; Rodriguez-Gomez, Diego; Russo, Jorge G.

    2018-05-01

    Using supersymmetric localization, we study the sector of chiral primary operators (Tr ϕ 2) n with large R-charge 4 n in N = 2 four-dimensional superconformal theories in the weak coupling regime g → 0, where λ ≡ g 2 n is kept fixed as n → ∞, g representing the gauge theory coupling(s). In this limit, correlation functions G 2 n of these operators behave in a simple way, with an asymptotic behavior of the form {G}_{2n}≈ {F}_{∞}(λ){(λ/2π e)}^{2n} n α , modulo O(1 /n) corrections, with α =1/2 \\dim (g) for a gauge algebra g and a universal function F ∞(λ). As a by-product we find several new formulas both for the partition function as well as for perturbative correlators in N=2 su(N) gauge theory with 2 N fundamental hypermultiplets.

  4. Varying the Lewis base coordination of the Y2N2 core in the reduced dinitrogen complexes {[(Me3Si)2N]2(L)Y}2(μ-η22-N2) (L = benzonitrile, pyridines, triphenylphosphine oxide, and trimethylamine N-oxide).

    PubMed

    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.

  5. 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).

    PubMed

    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

  6. Vector correlation between the alignment of reactant N{sub 2} (A {sup 3}Σ{sub u}{sup +}) and the alignment of product NO (A {sup 2}Σ{sup +}) rotation in the energy transfer reaction of aligned N{sub 2} (A {sup 3}Σ{sub u}{sup +}) + NO (X {sup 2}Π) → NO (A {sup 2}Σ{sup +}) + N{sub 2} (X {sup 1}Σ{sub g}{sup +})

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ohoyama, H., E-mail: ohyama@chem.sci.osaka-u.ac.jp

    2013-12-21

    The vector correlation between the alignment of reactant N{sub 2} (A {sup 3}Σ{sub u}{sup +}) and the alignment of product NO (A {sup 2}Σ{sup +}) rotation has been studied in the energy transfer reaction of aligned N{sub 2} (A {sup 3}Σ{sub u}{sup +}) + NO (X {sup 2}Π) → NO (A {sup 2}Σ{sup +}) + N{sub 2} (X {sup 1}Σ{sub g}{sup +}) under the crossed beam condition at a collision energy of ∼0.07 eV. NO (A {sup 2}Σ{sup +}) emission in the two linear polarization directions (i.e., parallel and perpendicular with respect to the relative velocity vector v{sub R}) hasmore » been measured as a function of the alignment of N{sub 2} (A {sup 3}Σ{sub u}{sup +}) along its molecular axis in the collision frame. The degree of polarization of NO (A {sup 2}Σ{sup +}) emission is found to depend on the alignment angle (θ{sub v{sub R}}) of N{sub 2} (A {sup 3}Σ{sub u}{sup +}) in the collision frame. The shape of the steric opacity function at the two polarization conditions turns out to be extremely different from each other: The steric opacity function at the parallel polarization condition is more favorable for the oblique configuration of N{sub 2} (A {sup 3}Σ{sub u}{sup +}) at an alignment angle of θ{sub v{sub R}} ∼ 45° as compared with that at the perpendicular polarization condition. The alignment of N{sub 2} (A {sup 3}Σ{sub u}{sup +}) is found to give a significant effect on the alignment of NO (A {sup 2}Σ{sup +}) rotation in the collision frame: The N{sub 2} (A {sup 3}Σ{sub u}{sup +}) configuration at an oblique alignment angle θ{sub v{sub R}} ∼ 45° leads to a parallel alignment of NO (A {sup 2}Σ{sup +}) rotation (J-vector) with respect to v{sub R}, while the axial and sideways configurations of N{sub 2} (A {sup 3}Σ{sub u}{sup +}) lead to a perpendicular alignment of NO (A {sup 2}Σ{sup +}) rotation with respect to v{sub R}. These stereocorrelated alignments of the product rotation have a good correlation with the stereocorrelated reactivity observed

  7. Growing up Radical: Investigation of Benzyl-Like Radicals with Increasing Chain Lengths

    NASA Astrophysics Data System (ADS)

    Korn, Joseph A.; Jawad, Khadija M.; Hewett, Daniel M.; Zwier, Timothy S.

    2015-06-01

    Combustion processes involve complex chemistry including pathways leading to polyaromatic hydrocarbons (PAHs) from small molecule precursors. Resonance stabilized radicals (RSRs) likely play an important role in the pathways to PAHs due to their unusual stability. Benzyl radical is a prototypical RSR that is stabilized by conjugation with the phenyl ring. Earlier work on α-methyl benzyl radical showed perturbations to the spectroscopy due to a hindered methyl rotor. If the alkyl chain is lengthened then multiple conformations become possible. This talk will discuss the jet-cooled spectroscopy of α-ethyl benzyl radical and α-propyl benzyl radical produced from the discharge of 1-phenyl propanol and 1-phenyl butanol respectively. Electronic spectra were obtained via resonant two-photon ionization, and IR spectra were obtained by resonant ion-dip infrared spectroscopy. Kidwell, N. M.; Reilly, N. J.; Nebgen, B.; Mehta-Hurt, D. N.; Hoehn, R. D.; Kokkin, D. L.; McCarthy, M. C.; Slipchenko, L. V.; Zwier, T. S. The Journal of Physical Chemistry A 2013, 117, 13465.

  8. Synthesis and NMR analysis of model compounds related to fucosylated chondroitin sulfates: GalNAc and Fuc(1 → 6)GalNAc derivatives.

    PubMed

    Vinnitskiy, Dmitry Z; Ustyuzhanina, Nadezhda E; Dmitrenok, Andrey S; Shashkov, Alexander S; Nifantiev, Nikolay E

    2017-01-13

    Unsubstituted and 6-O-α-L-fucosylated propyl 2-acetamido-2-deoxy-β-D-galactopyranosides and their selectively O-sulfated (both in GalNAc and Fuc units) derivatives were synthesized as model compounds representing the fragments of fucosylated chondroitin sulfates (FCS) from sea cucumbers. Per-O-acetylated 2-deoxy-2-N-phthalimido-D-glucopyranose was used as a key precursor for the preparation of all 2-acetamido-2-deoxy-D-galactopyranoside containing products. Attempts at 6-O-glycosylation of propyl 3-O-benzoyl-2-deoxy-2-N-phthalimido-D-galactoside by 2-O-benzyl-3,4-di-O-chloracetyl-L-fucosyl trichloracetimidate in the presence of TMSOTf gave a 1:1 mixture of the corresponding α- and β-isomeric disaccharides, while the use of structurally related fucosyl bromide donor with promotion by Bu 4 NBr led to the formation of desired α-isomeric disaccharide exclusively. Selective removal of orthogonal O-protections permitted subsequent O-sulfation both at the GalNAc and Fuc units. Further removal of blocking groups yielded the target products which were systematically studied by 1 H and 13 C NMR spectroscopy in order to determine the spectral effects of O-sulfation and α-L-fucosylation needed for the development of computer assisted structural analysis of natural FCS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Crystal structures of isomeric 3,5-di-chloro-N-(2,3-di-methyl-phen-yl)benzene-sulfonamide, 3,5-di-chloro-N-(2,6-di-methyl-phen-yl)benzene-sulfonamide and 3,5-di-chloro-N-(3,5-di-methyl-phen-yl)benzene-sulfonamide.

    PubMed

    Shakuntala, K; Naveen, S; Lokanath, N K; Suchetan, P A

    2017-05-01

    The crystal structures of three isomeric compounds of formula C 14 H 13 Cl 2 NO 2 S, namely 3,5-di-chloro- N -(2,3-di-methyl-phen-yl)-benzene-sulfonamide (I), 3,5-di-chloro- N -(2,6-di-methyl-phen-yl)benzene-sulfonamide (II) and 3,5-di-chloro- N -(3,5-di-methyl-phen-yl)benzene-sulfonamide (III) are described. The mol-ecules of all the three compounds are U-shaped with the two aromatic rings inclined at 41.3 (6)° in (I), 42.1 (2)° in (II) and 54.4 (3)° in (III). The mol-ecular conformation of (II) is stabilized by intra-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions. The crystal structure of (I) features N-H⋯O hydrogen-bonded R 2 2 (8) loops inter-connected via C (7) chains of C-H⋯O inter-actions, forming a three-dimensional architecture. The structure also features π-π inter-actions [ Cg ⋯ Cg = 3.6970 (14) Å]. In (II), N-H⋯O hydrogen-bonded R 2 2 (8) loops are inter-connected via π-π inter-actions [inter-centroid distance = 3.606 (3) Å] to form a one-dimensional architecture running parallel to the a axis. In (III), adjacent C (4) chains of N-H⋯O hydrogen-bonded mol-ecules running parallel to [010] are connected via C-H⋯π inter-actions, forming sheets parallel to the ab plane. Neighbouring sheets are linked via offset π-π inter-actions [inter-centroid distance = 3.8303 (16) Å] to form a three-dimensional architecture.

  10. {μ-2-[(3-Amino-2,2-dimethyl-prop-yl)imino-meth-yl]-6-meth-oxy-phenolato-1:2κ(5)O(1),O(6):N,N',O(1)}{2-[(3-amino-2,2-dimethyl-prop-yl)imino-meth-yl]-6-meth-oxy-phenolato-1κ(3)N,N',O(1)}-μ-azido-1:2κ(2)N:N-azido-2κN-methanol-2κO-dinickel(II).

    PubMed

    Ghaemi, Akbar; Rayati, Saeed; Fayyazi, Kazem; Ng, Seik Weng; Tiekink, Edward R T

    2012-08-01

    Two distinct coordination geometries are found in the binuclear title complex, [Ni(2)(C(13)H(19)N(2)O(2))(2)(N(3))(2)(CH(3)OH)], as one Schiff base ligand is penta-dentate, coordinating via the anti-cipated oxide O, imine N and amine N atoms (as for the second, tridentate, ligand) but the oxide O is bridging and coordination also occurs through the meth-oxy O atom. The Ni(II) atoms are linked by a μ(2)-oxide atom and one end of a μ(2)-azide ligand, forming an Ni(2)ON core. The coordination geometry for the Ni(II) atom coordinated by the tridentate ligand is completed by the meth-oxy O atom derived from the penta-dentate ligand, with the resulting N(3)O(3) donor set defining a fac octa-hedron. The second Ni(II) atom has its cis-octa-hedral N(4)O(2) coordination geometry completed by the imine N and amine N atoms of the penta-dentate Schiff base ligand, a terminally coordinated azide N and a methanol O atom. The arrangement is stabilized by an intra-molecular hydrogen bond between the methanol H and the oxide O atom. Linear supra-molecular chains along the a axis are formed in the crystal packing whereby two amine H atoms from different amine atoms hydrogen bond to the terminal N atom of the monodentate azide ligand.

  11. Reactions of CH3SH and CH3SSCH3 with gas-phase hydrated radical anions (H2O)n(•-), CO2(•-)(H2O)n, and O2(•-)(H2O)n.

    PubMed

    Höckendorf, Robert F; Hao, Qiang; Sun, Zheng; Fox-Beyer, Brigitte S; Cao, Yali; Balaj, O Petru; Bondybey, Vladimir E; Siu, Chi-Kit; Beyer, Martin K

    2012-04-19

    The chemistry of (H(2)O)(n)(•-), CO(2)(•-)(H(2)O)(n), and O(2)(•-)(H(2)O)(n) with small sulfur-containing molecules was studied in the gas phase by Fourier transform ion cyclotron resonance mass spectrometry. With hydrated electrons and hydrated carbon dioxide radical anions, two reactions with relevance for biological radiation damage were observed, cleavage of the disulfide bond of CH(3)SSCH(3) and activation of the thiol group of CH(3)SH. No reactions were observed with CH(3)SCH(3). The hydrated superoxide radical anion, usually viewed as major source of oxidative stress, did not react with any of the compounds. Nanocalorimetry and quantum chemical calculations give a consistent picture of the reaction mechanism. The results indicate that the conversion of e(-) and CO(2)(•-) to O(2)(•-) deactivates highly reactive species and may actually reduce oxidative stress. For reactions of (H(2)O)(n)(•-) with CH(3)SH as well as CO(2)(•-)(H(2)O)(n) with CH(3)SSCH(3), the reaction products in the gas phase are different from those reported in the literature from pulse radiolysis studies. This observation is rationalized with the reduced cage effect in reactions of gas-phase clusters. © 2012 American Chemical Society

  12. R-matrix calculations for electron-impact excitation of C(+), N(2+), and O(3+) including fine structure

    NASA Technical Reports Server (NTRS)

    Luo, D.; Pradhan, A. K.

    1990-01-01

    The new R-matrix package for comprehensive close-coupling calculations for electron scattering with the first three ions in the boron isoelectronic sequence, the astrophysically significant C(+), N(2+), and O(3+), is presented. The collision strengths are calculated in the LS coupling approximation, as well as in pair-coupling scheme, for the transitions among the fine-structure sublevels. Calculations are carried out at a large number of energies in order to study the detailed effects of autoionizing resonances.

  13. Novel Analogues of (R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist Selectivity

    PubMed Central

    2016-01-01

    Novel 1-, 5-, and 8-substituted analogues of sumanirole (1), a dopamine D2/D3 receptor (D2R/D3R) agonist, were synthesized. Binding affinities at both D2R and D3R were higher when determined in competition with the agonist radioligand [3H]7-hydroxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT) than with the antagonist radioligand [3H]N-methylspiperone. Although 1 was confirmed as a D2R-preferential agonist, its selectivity in binding and functional studies was lower than previously reported. All analogues were determined to be D2R/D3R agonists in both GoBRET and mitogenesis functional assays. Loss of efficacy was detected for the N-1-substituted analogues at D3R. In contrast, the N-5-alkyl-substituted analogues, and notably the n-butyl-arylamides (22b and 22c), all showed improved affinity at D2R over 1 with neither a loss of efficacy nor an increase in selectivity. Computational modeling provided a structural basis for the D2R selectivity of 1, illustrating how subtle differences in the highly homologous orthosteric binding site (OBS) differentially affect D2R/D3R affinity and functional efficacy. PMID:27035329

  14. Optically active antifungal azoles. XII. Synthesis and antifungal activity of the water-soluble prodrugs of 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone.

    PubMed

    Ichikawa, T; Kitazaki, T; Matsushita, Y; Yamada, M; Hayashi, R; Yamaguchi, M; Kiyota, Y; Okonogi, K; Itoh, K

    2001-09-01

    1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1: TAK-456) was selected as a candidate for clinical trials, but since its water-solubility was insufficient for an injectable formulation, the quaternary triazolium salts 2 were designed as water-soluble prodrugs. Among the prodrugs prepared, 4-acetoxymethyl-1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1-terazolyl)phenyl]-1-imidazolidinyl]butyl]-1H-1,2,4-triazolium chloride (2a: TAK-457) was selected as an injectable candidate for clinical trials based on the results of evaluations on solubility, stability, hemolytic effect and in vivo antifungal activities.

  15. Endocytosis and recycling of AMPA receptors lacking GluR2/3.

    PubMed

    Biou, Virginie; Bhattacharyya, Samarjit; Malenka, Robert C

    2008-01-22

    Excitatory synapses in the mammalian brain contain two types of ligand-gated ion channels: AMPA receptors (AMPARs) and NMDA receptors (NMDARs). AMPARs are responsible for generating excitatory synaptic responses, whereas NMDAR activation triggers long-lasting changes in these responses by modulating the trafficking of AMPARs toward and away from synapses. AMPARs are tetramers composed of four subunits (GluR1-GluR4), which current models suggest govern distinct AMPAR trafficking behavior during synaptic plasticity. Here, we address the roles of GluR2 and GluR3 in controlling the recycling- and activity-dependent endocytosis of AMPARs by using cultured hippocampal neurons prepared from knockout (KO) mice lacking these subunits. We find that synapses and dendritic spines form normally in cells lacking GluR2/3 and that upon NMDAR activation, GluR2/3-lacking AMPARs are endocytosed in a manner indistinguishable from GluR2-containing AMPARs in wild-type (WT) neurons. AMPARs lacking GluR2/3 also recycle to the plasma membrane identically to WT AMPARs. However, because of their permeability to calcium, GluR2-lacking but not WT AMPARs exhibited robust internalization throughout the dendritic tree in response to AMPA application. Dendritic endocytosis of AMPARs also was observed in GABAergic neurons, which express a high proportion of GluR2-lacking AMPARs. These results demonstrate that GluR2 and GluR3 are not required for activity-dependent endocytosis of AMPARs and suggest that the most important property of GluR2 in the context of AMPAR trafficking may be its influence on calcium permeability.

  16. Atropisomeric property of 1-(2,6-difluorobenzyl)-3-[(2R)-amino-2-phenethyl]-5-(2-fluoro-3-methoxyphenyl)-6-methyluracil.

    PubMed

    Tucci, Fabio C; Hu, Tao; Mesleh, Michael F; Bokser, Allan; Allsopp, Eric; Gross, Timothy D; Guo, Zhiqiang; Zhu, Yun-Fei; Struthers, R Scott; Ling, Nicholas; Chen, Chen

    2005-11-01

    1-(2,6-Difluorobenzyl)-3-[(2R)-amino-2-phenethyl]-5-(2-fluoro-3-methoxyphenyl)-6-methyluracil (6), a potent and orally active antagonist of the human gonadotropin-releasing hormone receptor, exists as a pair of atropisomers in solution, which was detected by NMR spectroscopy, and separable by HPLC. In addition to a (R)-configured benzylamine, there is a second stereogenic element due to the presence of a chiral axis between the substituted 5-phenyl group and the uracil core. The rate constant of the interconversion (k = 5.07 x 10(-5) s(-1)) of these two atropisomers was determined by proton NMR analysis of a diastereoisomer-enriched sample in aqueous solution at 25 degrees C, and the corresponding Gibbs free energy DeltaG(#) of rotation barrier (97.4 kJ mol(-1)) was calculated using the Eyring equation. The diastereoisomer half-life at physiological temperature (37 degrees C) in aqueous media was estimated to be about 46 min. Copyright 2005 Wiley-Liss, Inc.

  17. Reduced graphene oxide wrapped Cu2O supported on C3N4: An efficient visible light responsive semiconductor photocatalyst

    NASA Astrophysics Data System (ADS)

    Ganesh Babu, S.; Vinoth, R.; Surya Narayana, P.; Bahnemann, Detlef; Neppolian, B.

    2015-10-01

    Herein, Cu2O spheres were prepared and encapsulated with reduced graphene oxide (rGO). The Cu2O-rGO-C3N4 composite covered the whole solar spectrum with significant absorption intensity. rGO wrapped Cu2O loading caused a red shift in the absorption with respect to considering the absorption of bare C3N4. The photoluminescence study confirms that rGO exploited as an electron transport layer at the interface of Cu2O and C3N4 heterojunction. Utmost, ˜2 fold synergistic effect was achieved with Cu2O-rGO-C3N4 for the photocatalytic reduction of 4-nitrophenol to 4-aminophenol in comparison with Cu2O-rGO and C3N4. The Cu2O-rGO-C3N4 photocatalyst was reused for four times without loss in its activity.

  18. Mutation tryptophan to leucine at position 222 of haemagglutinin could facilitate H3N2 influenza A virus infection in dogs

    PubMed Central

    Yang, Guohua; Li, Shoujun; Blackmon, Sherry; Ye, Jianqiang; Bradley, Konrad C.; Cooley, Jim; Smith, Dave; Hanson, Larry; Cardona, Carol; Steinhauer, David A.; Webby, Richard; Liao, Ming

    2013-01-01

    An avian-like H3N2 influenza A virus (IAV) has recently caused sporadic canine influenza outbreaks in China and Korea, but the molecular mechanisms involved in the interspecies transmission of H3N2 IAV from avian to canine species are not well understood. Sequence analysis showed that residue 222 in haemagglutinin (HA) is predominantly tryptophan (W) in the closely related avian H3N2 IAV, but was leucine (L) in canine H3N2 IAV. In this study, reassortant viruses rH3N2-222L (canine-like) and rH3N2-222W (avian-like) with HA mutation L222W were generated using reverse genetics to evaluate the significance of the L222W mutation on receptor binding and host tropism of H3N2 IAV. Compared with rH3N2-222W, rH3N2-222L grew more rapidly in MDCK cells and had significantly higher infectivity in primary canine tracheal epithelial cells. Tissue-binding assays demonstrated that rH3N2-222L had a preference for canine tracheal tissues rather avian tracheal tissues, whereas rH3N2-222W favoured slightly avian rather canine tracheal tissues. Glycan microarray analysis suggested both rH3N2-222L and rH3N2-222W bound preferentially to α2,3-linked sialic acids. However, the rH3N2-222W had more than twofold less binding affinity than rH3N2-222L to a set of glycans with Neu5Aca23Galb1–4(Fuca-)-like or Neu5Aca23Galb1–3(Fuca-)-like structures. These data suggest the W to L mutation at position 222 of the HA could facilitate infection of H3N2 IAV in dogs, possibly by increasing the binding affinities of the HA to specific receptors with Neu5Aca23Galb1–4(Fuca-) or Neu5Aca23Galb1–3(Fuca-)-like structures that are present in dogs. PMID:23994833

  19. 1,2-Dibenzyl and -Diaryltetradimethylamido-dimolybdenum and -Ditungsten Compounds: M2R2(NMe2)4 (M=M). Structural Effects of Me2N-to-M Alpha-Bonding.

    DTIC Science & Technology

    1982-07-07

    CHETCUTI, M H CHISHOLM. K FOLTING N00OON 79-C 00144 UNCL’ASS IF IED INDU/DC/TR-82/2-MC NL mh~hEhEEo. OFFICE OF NAVAL RESEARCH Contract No. N00014-79...ldo i, n,.aowy a"d Identf ’ mko.) ’ / a, From the reactions between RMgCI (R = CH C H and CH-p-tolyl) or LiR.(R C6H, ~~,-- ;n 6o5 C"-tolyl) (2euv . 6...ligands u-donate to metal atomic Availability Codes V Avail and/or D special 4 orbitals which would otherwise be available for mischevious M--- H -C

  20. Stereochemical and electronic control of M-SO/sub 2/ bonding geometry in d/sup 6/ molybdenum and tungsten SO/sub 2/ complexes: novel n/sup 1/reverse arrown/sup 2/ SO/sub 2/ linkage isomerization in Mo(CO)/sub 2/(PPh/sub 3/)/sub 2/(CNR)(SO/sub 2/) and structures of Mo(CO)/sub 3/(P-i-Pr/sub 3/)/sub 2/(SO/sub 2/) and (Mo(CO)/sub 2/(py)(PPh/sub 3/)(. mu. -SO/sub 2/))/sub 2/

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kubas, G.J.; Jarvinen, G.D.; Ryan, R.R.

    1983-04-06

    New complexes, mer,trans,M(CO)/sub 3/(PR/sub 3/)/sub 2/(SO/sub 2/) (M = Mo,W; R = Ph,Cy,i-Pr) (I), cis,trans-Mo(CO)/sub 2/-(PPh/sub 3/)/sub 2/(SO/sub 2/)(L) (L = NCMe,py,CNCy,CN-t-Bu and CN(p-tolyl))(II), and (Mo(CO)/sub 2/(py)(PPh/sub 3/)(..mu..-SO/sub 2/))/sub 2/, have been prepared and characterized by infrared spectroscopy, /sup 17/O and /sup 31/P NMR spectroscopy, and X-ray crystallography. Syntheses for fac-Mo(CO)/sub 3/(n/sup 2/-SO/sub 2/)(LL) (LL = dppe,bpy,phen,2 py) have also been developed. Depending upon L, II has been found to coordinate SO/sub 2/ either in the S-bonded (n/sup 1/ planar) or O,S-bonded (n/sup 2/) geometries. Remarkably, for L = CNCy or CN-t-Bu, II has been found to contain, in themore » solid state, an apparent equimixture of both coordination types. Isomerization of fac-M(CO)/sub 3/(dppe)(n/sup 2/-SO/sub 2/) (M=Mo,w; dppe = 1,2-bis(diphenylphosphino)ethane) to an n/sup 1/-planar SO/sub 2/ form, mer-M(CO)/sub 3/(dppe)(SO/sub 2/), has also been found to occur. Thus, control of the SO/sub 2/ coordination geometry has been achieved by varying either the electronic properties of the ancillary ligands or their disposition with respect to the SO/sub 2/. The X-ray crystal structure of mer,trans-Mo(CO)/sub 3/(P-i-Pr/sub 3/)/sub 2/(SO/sub 2/) revealed n/sup 1/-planar SO/sub 2/ binding, the first example of this geometry for group 6 metals. The M-S distance, 2.239 (3) angstrom, is the longest such distance for this geometry recorded to date. Crystal data: Pbca, Z=8, a=24.712(8) angstrom, b=16.033(6) angstrom, c=14.058(5) angstrom, R=0.079 for 2934 reflections with Igreater than or equal to2sigma(I). The structure of (Mo(CO)/sub 2/(py)(PPh/sub 3/)(..mu..-SO/sub 2/))/sub 2/ showed a novel SO/sub 2/ bridging geometry in which all three atoms of SO/sub 2/ are metal coordinated. Crystal data: P1, Z=1, a=14.883(4) angstrom, b=9.264(2) angstrom, c=10.808(2) angstrom, R=0.039 for 3282 reflections with Igreater than or equal to2sigma(I).« less

  1. Multicomponent Synthesis of a N-Protected Alpha-Amino Ester: Ethyl 2-((4-Methoxyphenyl)Amino)-3-Phenylpropanoate

    ERIC Educational Resources Information Center

    Le Gall, Erwan; Pignon, Antoine

    2012-01-01

    This laboratory experiment describes the preparation of a N-protected phenylalanine ethyl ester by a zinc-mediated Mannich-like multicomponent reaction between benzyl bromide, "p"-anisidine, and ethyl glyoxylate. The one-step reaction involves the in situ metallation of benzyl bromide into a benzylzinc reagent and its addition onto imine (Barbier…

  2. A Simple and Mild Synthesis of 1H-Isochromenes and (Z)-1-Alkylidene-1,3-dihydroisobenzofurans by the Iodocyclization of 2-(1-Alkynyl)benzylic Alcohols

    PubMed Central

    Mancuso, Raffaella; Mehta, Saurabh; Gabriele, Bartolo; Salerno, Giuseppe; Jenks, William S.; Larock, Richard C.

    2010-01-01

    A variety of iodo-substituted isochromenes, dihydroisobenzofurans, and pyranopyridines are readily prepared in good to excellent yields under mild conditions by the iodocyclization of readily available 2-(1-alkynyl)benzylic alcohols or 2-(1-alkynyl)-3-(hydroxymethyl)pyridines. Reactions are carried out in MeCN at 15 °C using 3 equiv of I2 as the iodine source and NaHCO3 (3 equiv) as the base. The regiochemical outcome of the reaction strongly depends on the substitution pattern of the starting material. In particular, the 5-exo-dig cyclization mode, leading to dihydroisobenzofurans, is observed in the case of substrates bearing a tertiary alcoholic group, owing to the gem-dialkyl effect, while the 6-endo-dig cyclization mode, leading to isochromene or pyranopyridines, is the usually preferred pathway in the case of substrates bearing a primary or secondary alcoholic group PMID:20043652

  3. R{sup 2}log R quantum corrections and the inflationary observables

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ben-Dayan, Ido; Westphal, Alexander; Jing, Shenglin

    2014-09-01

    We study a model of inflation with terms quadratic and logarithmic in the Ricci scalar, where the gravitational action is f(R)=R+α R{sup 2}+β R{sup 2} ln R. These terms are expected to arise from one loop corrections involving matter fields in curved space-time. The spectral index n{sub s} and the tensor to scalar ratio yield 4 × 10{sup -4}∼< r∼<0.03 and 0.94∼< n{sub s} ∼< 0.99. i.e. r is an order of magnitude bigger or smaller than the original Starobinsky model which predicted r∼ 10{sup -3}. Further enhancement of r gives a scale invariant n{sub s}∼ 1 or higher. Other inflationary observables are d n{sub s}/dln k ∼> -5.2 × 10{sup -4}, μ ∼< 2.1 × 10{sup -8} , y ∼< 2.6 × 10{sup -9}. Despite the enhancement inmore » r, if the recent BICEP2 measurement stands, this model is disfavoured.« less

  4. α-Al2O3/Ga2O3 superlattices coherently grown on r-plane sapphire

    NASA Astrophysics Data System (ADS)

    Oshima, Takayoshi; Kato, Yuji; Imura, Masataka; Nakayama, Yoshiko; Takeguchi, Masaki

    2018-06-01

    Ten-period binary α-Al2O3/Ga2O3 superlattices were fabricated on r-plane sapphire substrates by molecular beam epitaxy. By systematic variation of α-Ga2O3 thickness and evaluation through X-ray reflectivity and diffraction measurements and scanning transmission electron microscopy, we verified that the superlattice with α-Ga2O3 thickness up to ∼1 nm had coherent interfaces without misfit dislocation in spite of the large lattice mismatches. This successful fabrication of coherent α-Al2O3/Ga2O3 superlattices will encourage further development of α-(Al x Ga1‑ x )2O3-based heterostructures including superlattices.

  5. N,N′-Bis(3,5-dichloro­benzyl­idene)­ethane-1,2-diamine

    PubMed Central

    Fun, Hoong-Kun; Kia, Reza

    2008-01-01

    The mol­ecule of the title Schiff base compound, C16H12Cl4N2, lies across an inversion centre and adopts an E configuration with respect to the azomethine C=N bond. The imine groups are coplanar with the aromatic rings. Within the mol­ecule, the planar units are parallel but extend in opposite directions from the dimethyl­ene bridge. In the crystal structure, mol­ecules are linked together by inter­molecular C—H⋯Cl hydrogen bonds along the a axis. PMID:21580993

  6. Cyclic guanidines: synthesis and antiplatelet activity of 4,6,7,8-tetrahydro-1H-imidazo[1,2-a]pyrazolo[3,4-d]pyrimidin-7-ones and 1,4,6,7,8,9-hexahydropyrazolo [3',4':4,5]pyrimido[2,1-c] [1,2,4]triazin-7-ones.

    PubMed

    Ferroni, R; Simoni, D; Orlandini, P; Bardi, A; Franze, G P; Guarneri, M

    1990-12-01

    A series of 4,6,7,8-tetrahydro-1H-imidazo[1,2-a]pyrazolo [3,4-d]pyrimidin-7-ones (1b-n) and 1,4,6,7,8,9-hexahydropyrazolo [3',4':4,5]pyrimido [2,1-c][1,2,4]triazin-7-ones (2a-d) has been synthesized. In view of their potential anti-aggregating activity the compounds were tested in vitro for inhibitory activity towards ADP- and collagen-induced aggregation of human platelets. Among the compounds studied, 8-benzyl-1-(2,5-dichlorophenyl)-4,6,7,8-tetrahydro-1H-imidazo [1,2-a]pyrazolo[3,4-d]pyrimidin-7-one (1n) exhibited the most favorable activity. The 2,5-dichlorophenyl side chain is an important lipophilic and/or steric pharmacophore.

  7. (S)-N-{1-[5-(4-Chloro-benzyl-sulfanyl)-1,3,4-oxadiazol-2-yl]eth-yl}-4-methyl-benzene-sulfonamide.

    PubMed

    Syed, Tayyaba; Hameed, Shahid; Jones, Peter G

    2011-10-01

    The title compound, C(18)H(18)ClN(3)O(3)S(2), adopts by folding the form of a distorted disc. Inter-planar angles are 29.51 (7) and 63.43 (7)° from the five-membered ring to the aromatic systems and 34.80 (6)° between these two latter rings. The absolute configuration was confirmed by determination of the Flack parameter. In the crystal, the mol-ecules are linked by four hydrogen bonds, one classical (N-H⋯N) and three 'weak' (C-H⋯O), forming layers parallel to the ac plane; these are in turn linked in the third dimension by Cl⋯N [3.1689 (16) Å] and Cl⋯O [3.3148 (13) Å] contacts to the heterocyclic ring.

  8. Architecture of the hydrophobic and hydrophilic layers as found from crystal structure analysis of N-benzyl-N,N-dimethylalkylammonium bromides.

    PubMed

    Hodorowicz, Maciej; Stadnicka, Katarzyna; Czapkiewicz, Jan

    2005-10-01

    The molecular and crystal structures of N-benzyl-N,N-dimethylalkylammonium bromides monohydrates with chain length n=8-10 have been determined. The crystals are isostructural with the N-benzyl-N,N-dimethyldodecylammonium bromide monohydrate. The structures consist of alternated hydrophobic and hydrophilic layers perpendicular to [001]. The attraction between N+ of the cation head-groups and Br- anions is achieved through weak C_H...Br interactions. The water molecules incorporated into ionic layers are donors for two O_H...Br hydrogen bonds and serve as the acceptors in two weak interactions of C_H...O type. The methylene chains, with the slightly curved general shape, have the extended all-trans conformation. The mutual packing of the chains in the hydrophobic layers is governed by weak C_H...pi interactions.

  9. Expansion of antimonato polyoxovanadates with transition metal complexes: (Co(N3C5H15)2)2[{Co(N3C5H15)2}V15Sb6O42(H2O)]·5H2O and (Ni(N3C5H15)2)2[{Ni(N3C5H15)2}V15Sb6O42(H2O)]·8H2O.

    PubMed

    Antonova, Elena; Näther, Christian; Kögerler, Paul; Bensch, Wolfgang

    2012-02-20

    Two new polyoxovanadates (Co(N(3)C(5)H(15))(2))(2)[{Co(N(3)C(5)H(15))(2)}V(15)Sb(6)O(42)(H(2)O)]·5H(2)O (1) and (Ni(N(3)C(5)H(15))(2))(2)[{Ni(N(3)C(5)H(15))(2)}V(15)Sb(6)O(42)(H(2)O)]·8H(2)O (2) (N(3)C(5)H(15) = N-(2-aminoethyl)-1,3-propanediamine) were synthesized under solvothermal conditions and structurally characterized. In both structures the [V(15)Sb(6)O(42)(H(2)O)](6-) shell displays the main structural motif, which is strongly related to the {V(18)O(42)} archetype cluster. Both compounds crystallize in the triclinic space group P1 with a = 14.3438(4), b = 16.6471(6), c = 18.9186(6) Å, α = 87.291(3)°, β = 83.340(3)°, γ = 78.890(3)°, and V = 4401.4(2) Å(3) (1) and a = 14.5697(13), b = 15.8523(16), c = 20.2411(18) Å, α = 86.702(11)°, β = 84.957(11)°, γ = 76.941(11)°, and V = 4533.0(7) Å(3) (2). In the structure of 1 the [V(15)Sb(6)O(42)(H(2)O)](6-) cluster anion is bound to a [Co(N(3)C(5)H(15))(2)](2+) complex via a terminal oxygen atom. In the Co(2+)-centered complex, one of the amine ligands coordinates in tridentate mode and the second one in bidentate mode to form a strongly distorted CoN(5)O octahedron. Similarly, in compound 2 an analogous NiN(5)O complex is joined to the [V(15)Sb(6)O(42)(H(2)O)](6-) anion via the same attachment mode. A remarkable difference between the two compounds is the orientation of the noncoordinated propylamine group leading to intermolecular Sb···O contacts in 1 and to Sb···N interactions in 2. In the solid-state lattices of 1 and 2, two additional [M(N(3)C(5)H(15))(2)](2+) complexes act as countercations and are located between the [{M(N(3)C(5)H(15))(2)}V(15)Sb(6)O(42)(H(2)O)](4-) anions. Between the anions and cations strong N-H···O hydrogen bonds are observed. In both compounds the clusters are stacked along the b axis in an ABAB fashion with cations and water molecules occupying the space between the clusters. Magnetic characterization demonstrates that the Ni(2+) and Co(2+) cations do not

  10. 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.

    PubMed

    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.

  11. A new and efficient synthetic method for 15N3-labeled cytosine nucleosides: Dimroth rearrangement of cytidine N3-oxides.

    PubMed

    Sako, Magoichi; Kawada, Hiroyoshi

    2004-11-12

    The treatment of (15)N(4)-labeled cytidine N(3)-oxide and (15)N(4)-labeled 2'-deoxycytidine N(3)-oxide, prepared from the appropriate unprotected uridines in three reaction steps, with benzyl bromide in the presence of excess lithium methoxide allowed the smooth occurrence of their Dimroth rearrangement even under mild conditions leading to the corresponding (15)N(3)-labeled uridine 4-O-benzyloximes which can easily undergo the reductive N-O bond cleavage to give the desirable (15)N(3)-labeled cytosine nucleosides in high total yields.

  12. Co-Dopant Influence on the Persistent Luminescence of BaAl2O4:Eu2+,R3+

    NASA Astrophysics Data System (ADS)

    Rodrigues, Lucas C. V.; Hölsä, Jorma; Carvalho, José M.; Pedroso, Cássio C. S.; Lastusaari, Mika; Felinto, Maria C. F. C.; Watanabe, Shigeo; Brito, Hermi F.

    2014-04-01

    The R3+ (rare earth) co-dopants may have a surprisingly important role in persistent luminescence - enhancement of up to 1-3 orders of magnitude may be obtained in the performance of these phosphor materials - depending strongly on the R3+ ion, of course. In this work, the effects of the R3+ co-dopants in the BaAl2O4:Eu2+,R3+ materials were studied using mainly thermoluminescence (TL) and synchrotron radiation XANES methods. In BaAl2O4, the conventional and persistent luminescence both arise from the 4f7→4f65d1 transition of Eu2+, yielding blue-green emission color. The former, in the presence of humidity, turns to more bluish because of creation of an additional Eu2+ luminescence centre which is not, however, visible in persistent luminescence. The trap structure in the non-co-doped BaAl2O4:Eu2+ is rather complex with 4-5 TL bands above room temperature. With R3+ co-doping, this basic structure is modified though no drastic change can be observed. This underlines the fact that even very small changes in the trap depths can produce significant modifications in the persistent luminescence efficiency. It should be remembered that basically the persistent luminescence performance is controlled by the Boltzmann population law depending exponentially on both the temperature and trap depth. Some mechanisms for persistent luminescence have suggested the presence of either divalent R2+ or tetravalent RIV during the charging of the Eu2+ doped materials. The present XANES measurements on BaAl2O4:Eu2+,R3+ confirmed the presence of only the trivalent form of the R3+ co-dopants excluding both of these pathways. It must thus be concluded, that the energy is stored in intrinsic and extrinsic defects created by the synthesis conditions and charge compensation due to R3+ co-doping. Even though the effect of the R3+ co-dopants was carefully exploited and characterized, the differences in the effect of different R3+ ions with very similar chemical and spectroscopic properties could

  13. HIV lipodystrophy in participants randomised to lopinavir/ritonavir (LPV/r) +2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTI) or LPV/r + raltegravir as second-line antiretroviral therapy.

    PubMed

    Martin, Allison; Moore, Cecilia L; Mallon, Patrick W G; Hoy, Jennifer F; Emery, Sean; Belloso, Waldo H; Phanuphak, Praphan; Ferret, Samuel; Cooper, David A; Boyd, Mark A

    2013-01-01

    To compare changes over 48 weeks in body fat, lipids, Metabolic Syndrome and cardiovascular disease risk between patients randomised 1:1 to lopinavir/ritonavir (r/LPV) plus raltegravir (RAL) compared to r/LPV plus 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second-line therapy. Participants were HIV-1 positive (>16 years) failing first-line treatment (2 consecutive HIV RNA >500 copies/mL) of NNRTI +2N(t)RTI. Whole body dual energy x-ray absorptiometry was performed at baseline and week 48. Data were obtained to calculate the Metabolic Syndrome and Framingham cardiovascular disease (CVD) risk score. Linear regression was used to compare mean differences between arms. Logistic regression compared incidence of metabolic syndrome. Associations between percent limb fat changes at 48 weeks with baseline variables were assessed by backward stepwise multivariate linear regression. Analyses were adjusted for gender, body mass index and smoking status. 210 participants were randomised. The mean (95% CI) increase in limb fat over 48 weeks was 15.7% (5.3, 25.9) or 0.9 kg (0.2, 1.5) in the r/LPV+N(t)RTI arm and 21.1% (11.1, 31,1) or 1.3 kg (0.7, 1.9) in the r/LPV+RAL arm, with no significant difference between treatment arms (-5.4% [-0.4 kg], p>0.1). Increases in total body fat mass (kg) and trunk fat mass (kg) were also similar between groups. Total:HDL cholesterol ratio was significantly higher in the RAL arm (mean difference -0.4 (1.4); p = 0.03), there were no other differences in lipid parameters between treatment arms. There were no statistically significant differences in CVD risk or incidence of Metabolic Syndrome between the two treatment arms. The baseline predictors of increased limb fat were high viral load, high insulin and participant's not taking lipid lowering treatment. In patients switching to second line therapy, r/LPV combined with RAL demonstrated similar improvements in limb fat as an N(t)RTI + r/LPV regimen, but a worse total

  14. Bis(2,3,5,6-tetra-2-pyridyl­pyrazine-κ3 N 2,N 1,N 6)nickel(II) dithio­cyanate dihydrate

    PubMed Central

    De la Pinta, Noelia; Fidalgo, M. Luz; Ezpeleta, José M.; Cortés, Roberto; Madariaga, Gotzon

    2011-01-01

    In the title compound, [Ni(C24H16N6)2](NCS)2·2H2O, the central NiII ion is octahedrally coordinated by six N atoms of two tridentate 2,3,5,6-tetra-2-pyridyl­pyrazine ligands (tppz). Two thio­cyanate anions act as counter-ions and two water mol­ecules act as solvation agents. O—H⋯N hydrogen bonds are observed in the crystral structure. PMID:21522540

  15. μ(3)-Carbonato-κO:O':O''-tris-{(η-ben-zene)[(R)-1-(1-amino-ethyl)naphthyl-κC,N]ruthenium(II)} hexa-fluorido-phosphate dichloro-methane solvate.

    PubMed

    Sortais, Jean-Baptiste; Brelot, Lydia; Pfeffer, Michel; Barloy, Laurent

    2008-02-15

    The title compound, [Ru(3)(C(12)H(12)N)(3)(CO(3))(C(6)H(6))(3)]PF(6)·CH(2)Cl(2), was obtained unintentionally as the product of an attempted deprotonation of the monomeric parent ruthenium complex [Ru(C(12)H(12)N)(C(6)H(6))(C(2)H(3)N)]PF(6). The carbonate ligand bridges three half-sandwich cyclo-ruthenated fragments, each of them exhibiting a pseudo-tetra-hedral geometry. The configuration of the Ru atoms is S. The naphthyl groups of the enanti-opure cyclo-ruthenated benzylic amine ligands point in the same direction, adopting a propeller shape.

  16. 4-{2-[2-(4-Chloro­benzyl­idene)hydrazinyl­idene]-3,6-dihydro-2H-1,3,4-thia­diazin-5-yl}-3-phenyl­sydnone

    PubMed Central

    Fun, Hoong-Kun; Loh, Wan-Sin; Nithinchandra; Kalluraya, Balakrishna

    2011-01-01

    The title compound, C18H13ClN6O2S, exists in trans and cis configurations with respect to the acyclic C=N bonds [C=N = 1.2837 (15) and 1.3000 (14) Å, respectively]. The 3,6-dihydro-2H-1,3,4-thia­diazine ring adopts a half-boat conformation. The sydnone ring is approximately planar [maximum deviation = 0.002 (1) Å] and forms dihedral angles of 50.45 (7) and 61.21 (6)° with the aromatic rings. In the crystal, inter­molecular N—H⋯N, C—H⋯Cl and C—H⋯S hydrogen bonds link the mol­ecules into layers parallel to ab plane. The crystal packing is stabilized by C—H⋯π inter­actions and further consolidated by π–π inter­actions involving the phenyl rings [centroid–centroid distance = 3.6306 (7) Å]. PMID:21754481

  17. Chemical looping of metal nitride catalysts: low-pressure ammonia synthesis for energy storage† †Electronic supplementary information (ESI) available: Experimental and computational details, free energy plots for the NH3 evolution and N2 reduction with Co3N/Co, Fe4N/Fe, Mn5N2/Mn4N, Mo2N/Mo, CrN/Cr2N, TaN/Ta2N, NbN/Nb2N, Li3N/LiH, Ba3N2/BaH2, Sr3N2/SrH2, and Ca3N2/CaH2, surface oxidation energetics, ΔGvac[NH*x, yH*] based on gas phase H2 as hydrogen source, NH3 evolution with Fe-doped Mn4N, NH3 evolution with Mn6N2.58, Ca3N2 and Sr2N after correcting for partial nitride hydrolysis, NH3 yield from Ca3N2vs. time and H2 gas flow rate. See DOI: 10.1039/c5sc00789e

    PubMed Central

    Avram, A. M.; Peterson, B. A.; Pfromm, P. H.; Peterson, A. A.

    2015-01-01

    The activity of many heterogeneous catalysts is limited by strong correlations between activation energies and adsorption energies of reaction intermediates. Although the reaction is thermodynamically favourable at ambient temperature and pressure, the catalytic synthesis of ammonia (NH3), a fertilizer and chemical fuel, from N2 and H2 requires some of the most extreme conditions of the chemical industry. We demonstrate how ammonia can be produced at ambient pressure from air, water, and concentrated sunlight as renewable source of process heat via nitrogen reduction with a looped metal nitride, followed by separate hydrogenation of the lattice nitrogen into ammonia. Separating ammonia synthesis into two reaction steps introduces an additional degree of freedom when designing catalysts with desirable activation and adsorption energies. We discuss the hydrogenation of alkali and alkaline earth metal nitrides and the reduction of transition metal nitrides to outline a promoting role of lattice hydrogen in ammonia evolution. This is rationalized via electronic structure calculations with the activity of nitrogen vacancies controlling the redox-intercalation of hydrogen and the formation and hydrogenation of adsorbed nitrogen species. The predicted trends are confirmed experimentally with evolution of 56.3, 80.7, and 128 μmol NH3 per mol metal per min at 1 bar and above 550 °C via reduction of Mn6N2.58 to Mn4N and hydrogenation of Ca3N2 and Sr2N to Ca2NH and SrH2, respectively. PMID:29218166

  18. miR-146a facilitates osteoarthritis by regulating cartilage homeostasis via targeting Camk2d and Ppp3r2.

    PubMed

    Zhang, Xudong; Wang, Chuandong; Zhao, Jingyu; Xu, Jiajia; Geng, Yiyun; Dai, Liming; Huang, Yan; Fu, Sai-Chuen; Dai, Kerong; Zhang, Xiaoling

    2017-04-06

    Osteoarthritis (OA), characterized by insufficient extracellular matrix synthesis and cartilage degeneration, is known as an incurable disease because its pathogenesis is poorly elucidated. Thus far, limited information is available regarding the pathophysiological role of microRNAs (miRNAs) in OA. In this study, we investigated the specific function of miR-146a in OA pathophysiology using mouse OA models. We found that the articular cartilage degeneration of miR-146a knockout (KO) mice was alleviated compared with that of the wild-type (WT) mice in spontaneous and instability-induced OA models. We demonstrate that miR-146a aggravated pro-inflammatory cytokines induced suppressing the expression of cartilage matrix-associated genes. We further identified calcium/calmodulin-dependent protein kinase II delta (Camk2d) and protein phosphatase 3, regulatory subunit B, beta isoform (Ppp3r2, also known as calcineurin B, type II) were essential targets of miR-146a in regulating cartilage homeostasis. Moreover, we found that surgical-induced OA mice treated with a miR-146a inhibitor significantly alleviated the destruction of articular cartilage via targeting Camk2d and Ppp3r2. These results suggested that miR-146a has a crucial role in maintaining cartilage homeostasis. MiR-146a inhibition in chondrocytes can be a potential therapeutic strategy to ameliorate OA.

  19. 4-Nitro­benzyl 2-bromo­acetate

    PubMed Central

    Zhu, Kai; Liu, Hui; Wang, Yan-Hua; Han, Ping-Fang; Wei, Ping

    2009-01-01

    In the mol­ecule of the title compound, C9H8BrNO4, the acetate group is close to planar [maximum deviation = 0.042 (3) Å] and is oriented at a dihedral angle of 73.24 (3)° with respect to the aromatic ring. In the crystal structure, inter­molecular C—H⋯O inter­actions link the mol­ecules into a three-dimensional network, forming R 2 2(10) ring motifs. PMID:21582813

  20. Synthesis, characterization and crystal structure of (2RS,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid

    NASA Astrophysics Data System (ADS)

    Muche, Simon; Müller, Matthias; Hołyńska, Małgorzata

    2018-03-01

    The condensation reaction of ortho-vanillin and L-cysteine leads to formation of a racemic mixture of (2RS,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid and not, as reported in the available literature, to a Schiff base. The racemic mixture was fully characterized by 1D and 2D NMR techniques, ESI-MS and X-ray diffraction. Addition of ZnCl2 led to formation of crystals in form of colorless needles, suitable for X-ray diffraction studies. The measured crystals were identified as the diastereomer (2R,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid 1. The bulk material is racemic. Thiazolidine exists as zwitterion in solid state, as indicated by the crystal structure.

  1. Tuning of magnetic frustration in S = 1 / 2 Kagomé lattices {[Cu3(CO3)2(bpe)3](CLO4)2}n and {[Cu3(CO3)2(bpy)3](CLO4)2}n through rigid and flexible ligands

    NASA Astrophysics Data System (ADS)

    Ajeesh, M. O.; Yogi, A.; Padmanabhan, M.; Nath, R.

    2015-04-01

    Single crystalline and polycrystalline samples of S = 1 / 2 Kagomé lattices { [Cu3(CO3)2(bpe)3 ](CLO4)2 } n and { [Cu3(CO3)2(bpy)3 ](CLO4)2 } n, respectively were synthesized. Their structural and magnetic properties were characterized by means of x-ray diffraction and magnetization measurements. Both compounds crystalize in a hexagonal structure (space group P-6) consisting of CuO4 Kagomé layers in the ab-plane but linked along c direction through either rigid bpy or flexible bpe ligands to form 3D frame works. Magnetic measurements reveal that both the compounds undergo ferromagnetic ordering (TC) at low temperatures and the TC and the extent of frustration could be tuned by changing the nature of the pillar ligands. {[Cu3(CO3)2(bpe)3](CLO4)2}n which is made up of flexible bpe ligands has a TC of 5.7 K and a Curie-Weiss temperature (θCW) of -39.7 K giving rise to a frustration parameter of |θCW | /TC ≃ 6.96. But the replacement of bpe by a more rigid and electronically delocalized bpy ligand leads to an enhanced TC ≃ 9.3 K and a reduced frustration parameter of |θCW | /TC ≃ 3.54.

  2. Crystal structure of 2-((1E)-{2-[bis-(2-methyl-benzyl-sulfan-yl)methyl-idene]hydrazin-1-yl-idene}meth-yl)-6-meth-oxy-phenol.

    PubMed

    Yusof, Enis Nadia Md; Ravoof, Thahira Begum S A; Tahir, Mohamed Ibrahim Mohamed; Tiekink, Edward R T

    2015-04-01

    In the title compound, C25H26N2O2S2, the central CN2S2 atoms are almost coplanar (r.m.s. deviation = 0.0058 Å). One phenyl ring clearly lies to one side of the central plane, while the other is oriented in the plane but splayed. Despite the different relative orientations, the phenyl rings form similar dihedral angles of 64.90 (3) and 70.06 (3)° with the central plane, and 63.28 (4)° with each other. The benzene ring is twisted with respect to the central plane, forming a dihedral angle of 13.17 (7)°. The S2C=N, N-N and N-N=C bond lengths of 1.2919 (19), 1.4037 (17) and 1.2892 (19) Å, respectively, suggest limited conjugation over these atoms; the configuration about the N-N=C bond is E. An intra-molecular O-H⋯N hydrogen bond is noted. In the crystal, phen-yl-meth-oxy C-H⋯O and phen-yl-phenyl C-H⋯π inter-actions lead to supra-molecular double chains parallel to the b axis. These are connected into a layer via meth-yl-phenyl C-H⋯π inter-actions, and layers stack along the a axis, being connected by weak π-π inter-actions between phenyl rings [inter-centroid distance = 3.9915 (9) Å] so that a three-dimensional architecture ensues.

  3. (1H-pyrazole-κN2)(2,2':6',2''-terpyridine-κ3N,N',N'')platinum(II) bis(perchlorate) nitromethane monosolvate.

    PubMed

    Akerman, Matthew; Akerman, Kate; Jaganyi, Deogratius; Reddy, Desigan

    2011-09-01

    The reaction between [PtCl(terpy)]·2H(2)O (terpy is 2,2':6',2''-terpyridine) and pyrazole in the presence of two equivalents of AgClO(4) in nitromethane yields the title compound, [Pt(C(3)H(4)N(2))(C(15)H(11)N(3))](ClO(4))(2)·CH(3)NO(2), as a yellow crystalline solid. Single-crystal X-ray diffraction shows that the dicationic platinum(II) chelate is square planar with the terpyridine ligand occupying three sites and the pyrazole ligand occupying the fourth. The torsion angle subtended by the pyrazole ring relative to the terpyridine chelate is 62.4 (6)°. Density functional theory calculations at the LANL2DZ/PBE1PBE level of theory show that in vacuo the lowest-energy conformation has the pyrazole ligand in an orientation perpendicular to the terpyridine ligand (i.e. 90°). Seemingly, the stability gained by the formation of hydrogen bonds between the pyrazole NH group and the perchlorate anion in the solid-state structure is sufficient for the chelate to adopt a higher-energy conformation.

  4. Structure-Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist (2S,3R)-3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid.

    PubMed

    Krogsgaard-Larsen, Niels; Storgaard, Morten; Møller, Charlotte; Demmer, Charles S; Hansen, Jeanette; Han, Liwei; Monrad, Rune N; Nielsen, Birgitte; Tapken, Daniel; Pickering, Darryl S; Kastrup, Jette S; Frydenvang, Karla; Bunch, Lennart

    2015-08-13

    Herein we describe the first structure-activity relationship study of the broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring the pharmacological effect of substituents in the 4, 4', or 5' positions and the bioisosteric substitution of the distal carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4' position 2a which induced a preference in binding affinity for homomeric GluK3 over GluK1 (Ki = 0.87 and 4.8 μM, respectively). Two X-ray structures of ligand binding domains were obtained: 2e in GluA2-LBD and 2f in GluK1-LBD, both at 1.9 Å resolution. Compound 2e induces a D1-D2 domain opening in GluA2-LBD of 17.3-18.8° and 2f a domain opening in GluK1-LBD of 17.0-17.5° relative to the structures with glutamate. The pyrrolidine-2-carboxylate moiety of 2e and 2f shows a similar binding mode as kainate. The 3-carboxyphenyl ring of 2e and 2f forms contacts comparable to those of the distal carboxylate in kainate.

  5. Synthesis of methyl 3-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside and methyl 3-O-alpha-D-talopyranosyl-alpha-D-talopyranoside.

    PubMed

    Dubey, R; Jain, R K; Abbas, S A; Matta, K L

    1987-08-01

    Methyl 2-O-benzyl-3-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-alpha- D-mannopyranoside (4) and methyl 2-O-benzyl-3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (6) were prepared from a common intermediate, namely, methyl 2-O-benzyl-4,6-O-benzylidene-3-O-(2,3,4,6-tetra-O-acetyl-alpha-D- mannopyranosyl)-alpha-D-mannopyranoside. On treatment with tert-butylchlorodiphenylsilane, in N,N-dimethylformamide in the presence of imidazole, 4 and 6 afforded methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-mannopyranoside (7), and methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(6-O-tert- butyldiphenylsilyl-alpha-D-mannopyranosyl)-alpha-D-mannopyranoside (8), respectively. Compound 8 was converted into its 2,3-O-isopropylidene derivative (9), and oxidation of 7 and 9 with pyridinium chlorochromate, and reduction of the resulting carbonyl intermediates gave methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-talopyranoside and methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(6-O-tert-butyldiphe nylsilyl- 2,3-O-isopropylidene-alpha-D-talopyranosyl)-alpha-D-talopyranoside , respectively. Removal of the protecting groups furnished the title disaccharides.

  6. Investigation of luminescence and laser transition of Dy3+ ion in P2O5sbnd PbOsbnd Bi2O3sbnd R2O3 (R = Al, Ga, In) glasses

    NASA Astrophysics Data System (ADS)

    Ram, G. Chinna; Narendrudu, T.; Suresh, S.; Kumar, A. Suneel; Rao, M. V. Sambasiva; Kumar, V. Ravi; Rao, D. Krishna

    2017-04-01

    P2O5sbnd PbOsbnd Bi2O3sbnd R2O3 (R = Al, Ga, In) glasses doped with Dy2O3 were prepared by melt quenching technique. The prepared glasses were characterized by XRD, optical absorption, FTIR, luminescence studies. Judd-Ofelt parameters have been evaluated for three glass systems from optical absorption spectra and in turn radiative parameters for excited luminescent levels of Dy3+ ion are also calculated. Emission cross section and branching ratio values are observed to high for 6H13/2 level for Dy3+ ion. The yellow to blue intensity ratios and CIE chromaticity coordinates were calculated. Decay curves exhibit non exponential behavior. Quantum efficiency of prepared glasses was measured by using radiative and calculated life times. IR studies, J-O parameters and Y/B ratio values indicate that more asymmetry around Dy3+ ions in Ga2O3 mixed glass was observed. Chromaticity coordinates lie near ideal white light region. These coordinates and CCT values have revealed that all the prepared glasses emit quality white light especially the glasses mixed with Ga2O3 are suitable for development of white LEDs.

  7. An A{sub r} threesome: Matrix models, 2d conformal field theories, and 4dN=2 gauge theories

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schiappa, Ricardo; Wyllard, Niclas

    We explore the connections between three classes of theories: A{sub r} quiver matrix models, d=2 conformal A{sub r} Toda field theories, and d=4N=2 supersymmetric conformal A{sub r} quiver gauge theories. In particular, we analyze the quiver matrix models recently introduced by Dijkgraaf and Vafa (unpublished) and make detailed comparisons with the corresponding quantities in the Toda field theories and the N=2 quiver gauge theories. We also make a speculative proposal for how the matrix models should be modified in order for them to reproduce the instanton partition functions in quiver gauge theories in five dimensions.

  8. The N-CoR complex enables chromatin remodeler SNF2H to enhance repression by thyroid hormone receptor

    PubMed Central

    Alenghat, Theresa; Yu, Jiujiu; Lazar, Mitchell A

    2006-01-01

    Unliganded thyroid hormone receptor (TR) actively represses transcription via the nuclear receptor corepressor (N-CoR)/histone deacetylase 3 (HDAC3) complex. Although transcriptional activation by liganded receptors involves chromatin remodeling, the role of ATP-dependent remodeling in receptor-mediated repression is unknown. Here we report that SNF2H, the mammalian ISWI chromatin remodeling ATPase, is critical for repression of a genomically integrated, TR-regulated reporter gene. N-CoR and HDAC3 are both required for recruitment of SNF2H to the repressed gene. SNF2H does not interact directly with the N-CoR/HDAC3 complex, but binds to unacetylated histone H4 tails, suggesting that deacetylase activity of the corepressor complex is critical to SNF2H function. Indeed, HDAC3 as well as SNF2H are required for nucleosomal organization on the TR target gene. Consistent with these findings, reduction of SNF2H induces expression of an endogenous TR-regulated gene, dio1, in liver cells. Thus, although not apparent from studies of transiently transfected reporter genes, gene repression by TR involves the targeting of chromatin remodeling factors to repressed genes by the HDAC activity of nuclear receptor corepressors. PMID:16917504

  9. Resolution and some properties of enzymes involved in enantioselective transformation of 1,3-dichloro-2-propanol to (R)-3-chloro-1,2-propanediol by Corynebacterium sp. strain N-1074.

    PubMed Central

    Nakamura, T; Nagasawa, T; Yu, F; Watanabe, I; Yamada, H

    1992-01-01

    During the course of the transformation of 1,3-dichloro-2-propanol (DCP) into (R)-3-chloro-1,2-propanediol [(R)-MCP] with the cell extract of Corynebacterium sp. strain N-1074, epichlorohydrin (ECH) was transiently formed. The cell extract was fractionated into two DCP-dechlorinating activities (fractions Ia and Ib) and two ECH-hydrolyzing activities (fractions IIa and IIb) by TSKgel DEAE-5PW column chromatography. Fractions Ia and Ib catalyzed the interconversion of DCP to ECH, and fractions IIa and IIb catalyzed the transformation of ECH into MCP. Fractions Ia and IIa showed only low enantioselectivity for each reaction, whereas fractions Ib and IIb exhibited considerable enantioselectivity, yielding R-rich ECH and MCP, respectively. Enzymes Ia and Ib were isolated from fractions Ia and Ib, respectively. Enzyme Ia had a molecular mass of about 108 kDa and consisted of four subunits identical in molecular mass (about 28 kDa). Enzyme Ib was a protein of 115 kDa, composed of two different polypeptides (about 35 and 32 kDa). The specific activity of enzyme Ib for DCP was about 30-fold higher than that of enzyme Ia. Both enzymes catalyzed the transformation of several halohydrins into the corresponding epoxides with liberation of halides and its reverse reaction. Their substrate specificities and immunological properties differed from each other. Enzyme Ia seemed to be halohydrin hydrogen-halide-lyase which was already purified from Escherichia coli carrying a gene from Corynebacterium sp. strain N-1074. Images PMID:1447132

  10. 2-Amino-2,3-dimethyl­butanamide

    PubMed Central

    Yin, Yongbiao

    2010-01-01

    The title compound, C6H14N2O, was synthesized by the reaction between 2-amino-2,3-dimethyl­butanonitrile and oil of vitriol (sulfuric acid). A racemic mixture of L- and R-2-amino-2,3-di­methyl­butanamide was characterized crystallographically. In the crystal structure, inter­molecular N—H⋯O hydrogen bonds link the two enanti­omers into a three-dimensional network. PMID:21579361

  11. The Molybdenum(V) and Tungsten(VI) Oxoazides [MoO(N3 )3 ], [MoO(N3 )32 CH3 CN], [(bipy)MoO(N3 )3 ], [MoO(N3 )5 ](2-) , [WO(N3 )4 ], and [WO(N3 )4 ⋅CH3 CN].

    PubMed

    Haiges, Ralf; Skotnitzki, Juri; Fang, Zongtang; Dixon, David A; Christe, Karl O

    2015-12-14

    A series of novel molybdenum(V) and tungsten(VI) oxoazides was prepared starting from [MOF4 ] (M=Mo, W) and Me3 SiN3 . While [WO(N3 )4 ] was formed through fluoride-azide exchange in the reaction of Me3 SiN3 with WOF4 in SO2 solution, the reaction with MoOF4 resulted in a reduction of Mo(VI) to Mo(V) and formation of [MoO(N3 )3 ]. Carried out in acetonitrile solution, these reactions resulted in the isolation of the corresponding adducts [MoO(N3 )32 CH3 CN] and [WO(N3 )4 ⋅CH3 CN]. Subsequent reactions of [MoO(N3 )3 ] with 2,2'-bipyridine and [PPh4 ][N3 ] resulted in the formation and isolation of [(bipy)MoO(N3 )3 ] and [PPh4 ]2 [MoO(N3 )5 ], respectively. Most molybdenum(V) and tungsten(VI) oxoazides were fully characterized by their vibrational spectra, impact, friction and thermal sensitivity data and, in the case of [WO(N3 )4 ⋅CH3 CN], [(bipy)MoO(N3 )3 ], and [PPh4 ]2 [MoO(N3 )5 ], by their X-ray crystal structures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Use of vibrational spectroscopy to study 4-benzyl-3-(thiophen-2-yl)-4,5-dihydro-1H-1,2,4-triazole-5-thione: A combined theoretical and experimental approach

    NASA Astrophysics Data System (ADS)

    Sert, Yusuf; El-Emam, Ali A.; Al-Abdullah, Ebtehal S.; Al-Tamimi, Abdul-Malek S.; Çırak, Çağrı; Ucun, Fatih

    In this study, the experimental and theoretical vibrational frequencies of a newly synthesized potential anti-inflammatory agent namely, 4-benzyl-3-(thiophen-2-yl)-4,5-dihydro-1H-1,2,4-triazole-5-thione have been investigated. The experimental FT-IR (4000-400 cm-1) and Laser-Raman spectra (4000-100 cm-1) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and the optimized geometric parameters (bond lengths, bond angles and dihedral angles) have been calculated using density functional theory methods (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr and DFT/M06-2X: the highly parameterized, empirical exchange correlation function) with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis using VEDA 4 software program. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data and results in the literature. In addition, the highest occupied molecular orbital (HOMO) energy, the lowest unoccupied molecular orbital (LUMO) energy and the other related molecular energy values of the compound have been investigated using the same theoretical calculations.

  13. High efficient photocatalytic selective oxidation of benzyl alcohol to benzaldehyde by solvothermal-synthesized ZnIn{sub 2}S{sub 4} microspheres under visible light irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Zhixin, E-mail: czx@fzu.edu.cn; Instrumental Measurement and Analysis Center, Fuzhou University, Fuzhou 350002; Xu, Jingjing

    Hexagonal ZnIn{sub 2}S{sub 4} samples have been synthesized by a solvothermal method. Their properties have been determined by X-ray diffraction, ultraviolet–visible-light diffuse reflectance spectra, field emission scanning electron microscopy, nitrogen adsorption–desorption and X-ray photoelectron spectra. These results demonstrate that ethanol solvent has significant influence on the morphology, optical and electronic nature for such marigold-like ZnIn{sub 2}S{sub 4} microspheres. The visible light photocatalytic activities of the ZnIn{sub 2}S{sub 4} have been evaluated by selective oxidation of benzyl alcohol to benzaldehyde using molecular oxygen as oxidant. The results show that 100% conversion along with >99% selectivity are reached over ZnIn{sub 2}S{sub 4}more » prepared in ethanol solvent under visible light irradiation (λ>420 nm) of 2 h, but only 58% conversion and 57% yield are reached over ZnIn{sub 2}S{sub 4} prepared in aqueous solvent. A possible mechanism of the high photocatalytic activity for selective oxidation of benzyl alcohol over ZnIn{sub 2}S{sub 4} is proposed and discussed. - Graphical abstract: Marigold-like ZnIn{sub 2}S{sub 4} microspheres were synthesized by a solvothermal method. The high visible photocatalytic activities of ZnIn{sub 2}S{sub 4} were evaluated by selective oxidation of benzyl alcohol to benzaldehyde under mild conditions. Display Omitted - Highlights: • Marigold-like ZnIn{sub 2}S{sub 4} microspheres were synthesized by a solvothermal method. • The solvents have a remarkably influence on the morphology and properties of samples. • It is the first time to apply ZnIn{sub 2}S{sub 4} for selective oxidation of benzyl alcohol. • ZnIn{sub 2}S{sub 4} shows high photocatalytic activity for selective oxidation of benzyl alcohol.« less

  14. Syntheses of the enantiomers of 1-deoxynojirimycin and 1-deoxyaltronojirimycin via chemo- and diastereoselective olefinic oxidation of unsaturated amines.

    PubMed

    Bagal, Sharan K; Davies, Stephen G; Lee, James A; Roberts, Paul M; Scott, Philip M; Thomson, James E

    2010-12-03

    Oxidation of enantiomerically pure (R)-N(1)-1'-(1''-naphthyl)ethyl-2,7-dihydro-1H-azepine with m-CPBA in the presence of HBF(4) and BnOH gave (3S,4R,5S,6S,1'R)-N(1)-1'-(1''-naphthyl)ethyl-3-hydroxy-4-benzyloxy-5,6-epoxyazepane as the major product and as a single diastereoisomer after chromatography. Elaboration of this highly functionalized intermediate via ring contraction to (2S,3R,4S,5S,1'R)-N(1)-benzyl-2-chloromethyl-3-benzyloxy-4,5-epoxypiperidine followed by regioselective epoxide ring opening, functional group manipulation, and deprotection gave (+)-1-deoxyaltronojirimycin. Alternatively, resolution of (RS,RS)-N(1)-benzyl-3-hydroxy-4-benzyloxy-2,3,4,7-tetrahydro-1H-azepine or (3RS,4SR,5RS,6RS)-N(1)-benzyl-3-hydroxy-4-benzyloxy-5,6-epoxyazepane by preparative chiral HPLC and subsequent elaboration allows access to the enantiomers of 1-deoxynojirimycin and 1-deoxyaltronojirimycin, respectively.

  15. Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives.

    PubMed

    Shakhatreh, Muhamad Ali K; Al-Smadi, Mousa L; Khabour, Omar F; Shuaibu, Fatima A; Hussein, Emad I; Alzoubi, Karem H

    2016-01-01

    Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-( N , N -dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a-b) as well as chalcone derivatives (3a-c) showed no activity against all the tested strains except for ketone (2c), which showed moderate activity against Candida albicans .

  16. Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives

    PubMed Central

    Shakhatreh, Muhamad Ali K; Al-Smadi, Mousa L; Khabour, Omar F; Shuaibu, Fatima A; Hussein, Emad I; Alzoubi, Karem H

    2016-01-01

    Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-(N,N-dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a–b) as well as chalcone derivatives (3a–c) showed no activity against all the tested strains except for ketone (2c), which showed moderate activity against Candida albicans. PMID:27877017

  17. Gabapentin-base synthesis and theoretical studies of biologically active compounds: N-cyclohexyl-3-oxo-2-(3-oxo-2-azaspiro[4.5] decan-2-yl)-3-arylpropanamides and N-(tert-butyl)-2-(3-oxo-2-azaspiro[4.5]decan-2-yl)-2-arylacetamide derivatives

    NASA Astrophysics Data System (ADS)

    Amirani Poor, Mahboobe; Darehkordi, Ali; Anary-Abbasinejad, Mohammad; Mohammadi, Marziyeh

    2018-01-01

    An intermolecular Ugi reaction of 2-(1-(aminomethyl)cyclohexyl)acetic acid (gabapentin) with glyoxal and cyclohexyl isocyanide or aromatic aldehyde and tertbutyl isocyanide under mild conditions in ethanol have been developed to produce two novel class of N-cyclohexyl-3-(aryl)-3-oxo-2-(3-oxo-2-azaspiro[4.5]decan-2-yl)propanamideins and N-(tert-butyl)-2-(3-oxo-2-azaspiro[4.5]decan-2-yl)-2-arylacetamide derivatives in good to excellent yields. This presents the first report for the intermolecular Ugi three component reaction of gabapentin, glyoxal, and an isocyanide. Also according to the theoretical studies the electron-donating groups increase the strength of intramolecular hydrogen bond and electron-withdrawing groups decrease the strength of intramolecular hydrogen bond.

  18. Direct arylation/alkylation/magnesiation of benzyl alcohols in the presence of Grignard reagents via Ni-, Fe-, or Co-catalyzed sp3 C-O bond activation.

    PubMed

    Yu, Da-Gang; Wang, Xin; Zhu, Ru-Yi; Luo, Shuang; Zhang, Xiao-Bo; Wang, Bi-Qin; Wang, Lei; Shi, Zhang-Jie

    2012-09-12

    Direct application of benzyl alcohols (or their magnesium salts) as electrophiles in various reactions with Grignard reagents has been developed via transition metal-catalyzed sp(3) C-O bond activation. Ni complex was found to be an efficient catalyst for the first direct cross coupling of benzyl alcohols with aryl/alkyl Grignard reagents, while Fe, Co, or Ni catalysts could promote the unprecedented conversion of benzyl alcohols to benzyl Grignard reagents in the presence of (n)hexylMgCl. These methods offer straightforward pathways to transform benzyl alcohols into a variety of functionalities.

  19. Computation provides chemical insight into the diverse hydride NMR chemical shifts of [Ru(NHC)4(L)H]0/+ species (NHC = N-heterocyclic carbene; L = vacant, H2, N2, CO, MeCN, O2, P4, SO2, H-, F- and Cl-) and their [Ru(R2PCH2CH2PR2)2(L)H]+ congeners.

    PubMed

    Häller, L Jonas L; Mas-Marzá, Elena; Cybulski, Mateusz K; Sanguramath, Rajashekharayya A; Macgregor, Stuart A; Mahon, Mary F; Raynaud, Christophe; Russell, Christopher A; Whittlesey, Michael K

    2017-02-28

    Relativistic density functional theory calculations, both with and without the effects of spin-orbit coupling, have been employed to model hydride NMR chemical shifts for a series of [Ru(NHC) 4 (L)H] 0/+ species (NHC = N-heterocyclic carbene; L = vacant, H 2 , N 2 , CO, MeCN, O 2 , P 4 , SO 2 , H - , F - and Cl - ), as well as selected phosphine analogues [Ru(R 2 PCH 2 CH 2 PR 2 ) 2 (L)H] + (R = i Pr, Cy; L = vacant, O 2 ). Inclusion of spin-orbit coupling provides good agreement with the experimental data. For the NHC systems large variations in hydride chemical shift are shown to arise from the paramagnetic term, with high net shielding (L = vacant, Cl - , F - ) being reinforced by the contribution from spin-orbit coupling. Natural chemical shift analysis highlights the major orbital contributions to the paramagnetic term and rationalizes trends via changes in the energies of the occupied Ru d π orbitals and the unoccupied σ* Ru-H orbital. In [Ru(NHC) 4 (η 2 -O 2 )H] + a δ-interaction with the O 2 ligand results in a low-lying LUMO of d π character. As a result this orbital can no longer contribute to the paramagnetic shielding, but instead provides additional deshielding via overlap with the remaining (occupied) d π orbital under the L z angular momentum operator. These two effects account for the unusual hydride chemical shift of +4.8 ppm observed experimentally for this species. Calculations reproduce hydride chemical shift data observed for [Ru( i Pr 2 PCH 2 CH 2 P i Pr 2 ) 22 -O 2 )H] + (δ = -6.2 ppm) and [Ru(R 2 PCH 2 CH 2 PR 2 ) 2 H] + (ca. -32 ppm, R = i Pr, Cy). For the latter, the presence of a weak agostic interaction trans to the hydride ligand is significant, as in its absence (R = Me) calculations predict a chemical shift of -41 ppm, similar to the [Ru(NHC) 4 H] + analogues. Depending on the strength of the agostic interaction a variation of up to 18 ppm in hydride chemical shift is possible and this factor (that is not necessarily

  20. Negative ion photoelectron spectroscopy of P 2N 3 –: Electron affinity and electronic structures of P 2N 3 ˙

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hou, Gao -Lei; Chen, Bo; Transue, Wesley J.

    2016-04-19

    The recent successful synthesis of P 2N 3 –, a planar all-inorganic aromatic molecule, represents a breakthrough in inorganic chemistry, because, like its isolobal counterparts C 5H 5– and cyclo-P 5 –, P 2N 3 – has potential to serve as a new ligand for transition metals and a building block in solid-state molecular architectures. In light of its importance, we report here a negative ion photoelectron spectroscopy (NIPES) and ab initio study of P 2N 3 –, to investigate the electronic structures of P 2N 3 – and its neutral P 2N 3• radical. The adiabatic detachment energy ofmore » P 2N 3 – (electron affinity of P 2N 3•) was determined to be 3.765 ± 0.010 eV, indicating high stability for the P 2N 3 – anion. Ab initio electronic structure calculations reveal five low-lying electronic states in the neutral P 2N 3• radical. Calculation of the Franck-Condon factors (FCFs) for each anion-to-neutral electronic transition and comparison of the resulting simulated NIPE spectrum with the vibrational structure in the observed spectrum allows the first four excited states of P 2N 3• to be determined to lie 6.2, 6.7, 11.5, and 22.8 kcal/mol -1 above the ground state of the radical, which is found to be a 6π-electron, 2A 1, σ state.« less

  1. Comparisons of switching characteristics between Ti/Al2O3/Pt and TiN/Al2O3/Pt RRAM devices with various compliance currents

    NASA Astrophysics Data System (ADS)

    Qi, Yanfei; Zhao, Ce Zhou; Liu, Chenguang; Fang, Yuxiao; He, Jiahuan; Luo, Tian; Yang, Li; Zhao, Chun

    2018-04-01

    In this study, the influence of the Ti and TiN top electrodes on the switching behaviors of the Al2O3/Pt resistive random access memory devices with various compliance currents (CCs, 1-15 mA) has been compared. Based on the similar statistical results of the resistive switching (RS) parameters such as V set/V reset, R HRS/R LRS (measured at 0.10 V) and resistance ratio with various CCs for both devices, the Ti/Al2O3/Pt device differs from the TiN/Al2O3/Pt device mainly in the forming process rather than in the following switching cycles. Apart from the initial isolated state, the Ti/Al2O3/Pt device has the initial intermediate state as well. In addition, its forming voltage is relatively lower. The conduction mechanisms of the ON and OFF state for both devices are demonstrated as ohmic conduction and Frenkel-Poole emission, respectively. Therefore, with the combined modulations of the CCs and the stop voltages, the TiN/Al2O3/Pt device is more stable for nonvolatile memory applications to further improve the RS performance.

  2. Arabidopsis TRANSPARENT TESTA GLABRA2 is directly regulated by R2R3 MYB transcription factors and is involved in regulation of GLABRA2 transcription in epidermal differentiation.

    PubMed

    Ishida, Tetsuya; Hattori, Sayoko; Sano, Ryosuke; Inoue, Kayoko; Shirano, Yumiko; Hayashi, Hiroaki; Shibata, Daisuke; Sato, Shusei; Kato, Tomohiko; Tabata, Satoshi; Okada, Kiyotaka; Wada, Takuji

    2007-08-01

    Arabidopsis thaliana TRANSPARENT TESTA GLABRA2 (TTG2) encodes a WRKY transcription factor and is expressed in young leaves, trichomes, seed coats, and root hairless cells. An examination of several trichome and root hair mutants indicates that MYB and bHLH genes regulate TTG2 expression. Two MYB binding sites in the TTG2 5' regulatory region act as cis regulatory elements and as direct targets of R2R3 MYB transcription factors such as WEREWOLF, GLABRA1, and TRANSPARENT TESTA2. Mutations in TTG2 cause phenotypic defects in trichome development and seed color pigmentation. Transgenic plants expressing a chimeric repressor version of the TTG2 protein (TTG2:SRDX) showed defects in trichome formation, anthocyanin accumulation, seed color pigmentation, and differentiation of root hairless cells. GLABRA2 (GL2) expression was markedly reduced in roots of ProTTG2:TTG2:SRDX transgenic plants, suggesting that TTG2 is involved in the regulation of GL2 expression, although GL2 expression in the ttg2 mutant was similar to that in the wild type. Our analysis suggests a new step in a regulatory cascade of epidermal differentiation, in which complexes containing R2R3 MYB and bHLH transcription factors regulate the expression of TTG2, which then regulates GL2 expression with complexes containing R2R3 MYB and bHLH in the differentiation of trichomes and root hairless cells.

  3. 2'-Deoxy-3,7-dideazaguanosine and related compounds. Synthesis of 6-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl) and 1-beta-D-arabinofuranosyl-1H-pyrrolo[3,2-c]pyridin-4(5H)-one via direct glycosylation of a pyrrole precursor.

    PubMed Central

    Girgis, N S; Cottam, H B; Larson, S B; Robins, R K

    1987-01-01

    The synthesis of two new analogs of 2'-deoxyguanosine, 6-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1H-pyrrolo[3,2-c] pyridin-4(5H)-one (8) and 6-amino-1-beta-D-arabinofuranosyl-1H-pyrrolo[3,2-c]-pyridin-4(5H)-one (13) has been accomplished by glycosylation of the sodium salt of ethyl 2-cyanomethyl-1H-pyrrole-3-carboxylate (4c) using 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranose( 5) and 1-chloro-2,3,5-tri-O-benzyl-alpha-D-arabinofuranose (9), respectively. The resulting blocked nucleosides, ethyl 2-cyanomethyl-1-(2-deoxy-3,5-di-O-p-toluoyl-beta-D-erythro- pentofuranosyl)-1H-pyrrole-3-carboxylate (6) and ethyl 2-cyanomethyl-1-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)- 1H-pyrrole-3-carboxylate, were ring closed with hydrazine to form 5-amino-6-hydrazino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1H- pyrrolo[3,2-c]-pyridin-4(5H)-one (7) and 5,6-diamino-1-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)-1H- pyrrolo[3,2-c]pyridin-4(5H)-one (11), respectively. Treatment of 7 with Raney nickel provided the 2'-deoxyguanosine analog 8 while reaction of 11 with Raney nickel followed by palladium hydroxide/cyclohexene treatment gave the 2'-deoxyguanosine analog 13. The anomeric configuration of 8 was assigned as beta by proton NMR, while that of 13 was confirmed as beta by single-crystal X-ray analysis of the deblocked precursor ethyl 2-cyanomethyl-1-beta-D-arabinofuranosyl-1H-pyrrole-3-carboxylate (10a). PMID:3593477

  4. Major Groove Orientation of the (2S)-N6-(2-Hydroxy-3-buten-1-yl)-2′-deoxyadenosine DNA Adduct Induced by 1,2-Epoxy-3-butene

    PubMed Central

    2015-01-01

    1,3-Butadiene (BD) is an environmental and occupational toxicant classified as a human carcinogen. It is oxidized by cytochrome P450 monooxygenases to 1,2-epoxy-3-butene (EB), which alkylates DNA. BD exposures lead to large numbers of mutations at A:T base pairs even though alkylation of guanines is more prevalent, suggesting that one or more adenine adducts of BD play a role in BD-mediated genotoxicity. However, the etiology of BD-mediated genotoxicity at adenine remains poorly understood. EB alkylates the N6 exocyclic nitrogen of adenine to form N6-(hydroxy-3-buten-1-yl)-2′-dA ((2S)-N6-HB-dA) adducts (TretyakovaN., LinY., SangaiahR., UptonP. B., and SwenbergJ. A. (1997) Carcinogenesis18, 137−1479054600). The structure of the (2S)-N6-HB-dA adduct has been determined in the 5′-d(C1G2G3A4C5Y6A7G8A9A10G11)-3′:5′-d(C12T13T14C15T16T17G18T19 C20C21G22)-3′ duplex [Y = (2S)-N6-HB-dA] containing codon 61 (underlined) of the human N-ras protooncogene, from NMR spectroscopy. The (2S)-N6-HB-dA adduct was positioned in the major groove, such that the butadiene moiety was oriented in the 3′ direction. At the Cα carbon, the methylene protons of the modified nucleobase Y6 faced the 5′ direction, which placed the Cβ carbon in the 3′ direction. The Cβ hydroxyl group faced toward the solvent, as did carbons Cγ and Cδ. The Cβ hydroxyl group did not form hydrogen bonds with either T16O4 or T17O4. The (2S)-N6-HB-dA nucleoside maintained the anti conformation about the glycosyl bond, and the modified base retained Watson–Crick base pairing with the complementary base (T17). The adduct perturbed stacking interactions at base pairs C5:G18, Y6:T17, and A7:T16 such that the Y6 base did not stack with its 5′ neighbor C5, but it did with its 3′ neighbor A7. The complementary thymine T17 stacked well with both 5′ and 3′ neighbors T16 and G18. The presence of the (2S)-N6-HB-dA resulted in a 5 °C reduction in the Tm of the duplex, which is attributed to less

  5. Bis(2,3,5,6-tetra-2-pyridylpyrazine-κ3 N 2,N 1,N 6)iron(II) bis­(dicyanamidate) 4.5-hydrate

    PubMed Central

    Callejo, L.; De la Pinta, N.; Madariaga, G.; Fidalgo, M.L.; Cortés, R.

    2010-01-01

    In the title compound, [Fe(C24H16N6)2][N(CN)2]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(CN)2 −] 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. PMID:21580205

  6. Zinc affects miR-548n, SMAD4, SMAD5 expression in HepG2 hepatocyte and HEp-2 lung cell lines.

    PubMed

    Grider, Arthur; Lewis, Richard D; Laing, Emma M; Bakre, Abhijeet A; Tripp, Ralph A

    2015-12-01

    MicroRNAs affect disease progression and nutrient status. miR-548n increased 57 % in Zn supplemented plasma from adolescent females (ages 9 to 13 years). The purpose of this study was to determine the effects of Zn concentration in cell culture on the expression of miR-548n, SMAD4 and SMAD5 in hepatocyte (HepG2) and lung epithelium (HEp-2) cell lines. Cells were incubated for 48 h in media containing 10 % Chelex 100-treated FBS (0 μM Zn), or with 15 or 50 μM Zn, before isolation of total RNA and cDNA. Expression of miR-548n, SMAD4 and SMAD5 was measured by qPCR. The ΔΔCT method was used to calculate the fold-change, and 15 µM expression levels were used as reference values. HepG2 miR-548n expression decreased 5-fold, and SMAD4 expression increased 4-fold in the absence of Zn, while HEp-2 miR-548n expression increased 10.5-fold, and SMAD5 expression increased 20-fold in the absence of Zn. HEp-2 miR-548n expression increased 23-fold, while SMAD4 expression decreased twofold, in 50 μM Zn-treated cells. However, SMAD4 and SMAD5 expression was not correlated. These data indicate that miR-548n expression is in part regulated by Zn in a cell-specific manner. SMAD4 and SMAD5 are genes in the TGF-β/BMP signaling pathway, and SMAD5 is a putative target for miR-548n; Zn participates in regulating this pathway through controlling SMAD4 and SMAD5 expression. However, SMAD5 expression may be more sensitive to Zn than to miR-548n since SMAD5 expression was not inversely correlated with miR-548n expression.

  7. Formation mechanisms of Si3N4 and Si2N2O in silicon powder nitridation

    NASA Astrophysics Data System (ADS)

    Yao, Guisheng; Li, Yong; Jiang, Peng; Jin, Xiuming; Long, Menglong; Qin, Haixia; Kumar, R. Vasant

    2017-04-01

    Commercial silicon powders are nitrided at constant temperatures (1453 K; 1513 K; 1633 K; 1693 K). The X-ray diffraction results show that small amounts of Si3N4 and Si2N2O are formed as the nitridation products in the samples. Fibroid and short columnar Si3N4 are detected in the samples. The formation mechanisms of Si3N4 and Si2N2O are analyzed. During the initial stage of silicon powder nitridation, Si on the outside of sample captures slight amount of O2 in N2 atmosphere, forming a thin film of SiO2 on the surface which seals the residual silicon inside. And the oxygen partial pressure between the SiO2 film and free silicon is decreasing gradually, so passive oxidation transforms to active oxidation and metastable SiO(g) is produced. When the SiO(g) partial pressure is high enough, the SiO2 film will crack, and N2 is infiltrated into the central section of the sample through cracks, generating Si2N2O and short columnar Si3N4 in situ. At the same time, metastable SiO(g) reacts with N2 and form fibroid Si3N4. In the regions where the oxygen partial pressure is high, Si3N4 is oxidized into Si2N2O.

  8. The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones.

    PubMed

    Maurizy, Chloé; Quinternet, Marc; Abel, Yoann; Verheggen, Céline; Santo, Paulo E; Bourguet, Maxime; C F Paiva, Ana; Bragantini, Benoît; Chagot, Marie-Eve; Robert, Marie-Cécile; Abeza, Claire; Fabre, Philippe; Fort, Philippe; Vandermoere, Franck; M F Sousa, Pedro; Rain, Jean-Christophe; Charpentier, Bruno; Cianférani, Sarah; Bandeiras, Tiago M; Pradet-Balade, Bérengère; Manival, Xavier; Bertrand, Edouard

    2018-05-29

    R2TP is an HSP90 co-chaperone that assembles important macro-molecular machineries. It is composed of an RPAP3-PIH1D1 heterodimer, which binds the two essential AAA+ATPases RUVBL1/RUVBL2. Here, we resolve the structure of the conserved C-terminal domain of RPAP3, and we show that it directly binds RUVBL1/RUVBL2 hexamers. The human genome encodes two other proteins bearing RPAP3-C-terminal-like domains and three containing PIH-like domains. Systematic interaction analyses show that one RPAP3-like protein, SPAG1, binds PIH1D2 and RUVBL1/2 to form an R2TP-like complex termed R2SP. This co-chaperone is enriched in testis and among 68 of the potential clients identified, some are expressed in testis and others are ubiquitous. One substrate is liprin-α2, which organizes large signaling complexes. Remarkably, R2SP is required for liprin-α2 expression and for the assembly of liprin-α2 complexes, indicating that R2SP functions in quaternary protein folding. Effects are stronger at 32 °C, suggesting that R2SP could help compensating the lower temperate of testis.

  9. A series of coordination polymers constructed from R-isophthalic acid (R=-SO3H, -NO2, and -OH) and N-donor ligands: Syntheses, structures and fluorescence properties

    NASA Astrophysics Data System (ADS)

    Zhou, Yong-Hong; Zhou, Xu-Wan; Zhou, Su-Rong; Tian, Yu-Peng; Wu, Jie-Ying

    2017-01-01

    Six novel Zn(II), Cd(II), and Cu(II) mixed-ligand coordination complexes, namely, [Zn2Na(sip)2(bpp)3(Hbpp)(H2O)2]·8H2O (1), [Cd3(sip)2(nbi)6(H2O)2]·7H2O (2), [Zn(sip)(nbi)2(H2O)]·Hnbi·3H2O (3), [Cd(hip)(nbi)2(H2O)]·nbi·5H2O (4), [Cd2(nip)2(nbi)2(H2O)2]·DMF (5), and [Cu(nip)(nbi)(H2O)2]·H2O (6) (H3sip=5-sulfoisophthalic acid, H2hip=5-hydroxylisophthalic acid, H2nip=5-nitroisophthalic acid, bpp=1,3-bis(4-pyridyl)propane, and nbi=6-nitrobenzimidazole) have been synthesized hydrothermally by the self-assembly of R-isophthalic acid (R=-SO3H, -NO2, and -OH) and N-donor ligands. Single crystal X-ray analyses reveal that two Zn(II) ions and one Na(I) ion of complex 1 are linked through O atoms to generate a 1D linear chain. Then the 2D supramolecular architectures are constructed via intermolecular interactions. In complex 2, the Cd1 ions are connected by bridging carboxyl groups from sip3- anions to form 1D double chain, which are further connected by Cd2 ions to afford 2D layer structure. The adjacent 2D layers are further linked via hydrogen-bonding interactions to give 3D supramolecular network. Compounds 3-5 show 1D chain structures, which are assembled into 2D or 3D supramolecular frameworks via weak interactions. In compound 6, the Cu(II) ions are bridged by the nip2- ligands to form 48-membered ring, which is assembled into 1Dchain via the π-π stacking interaction. In addition, the thermal stabilities and fluorescence properties of these compounds have also been studied.

  10. Local Order-Disorder Transition Driving by Structural Heterogeneity in a Benzyl Functionalized Ionic Liquid.

    PubMed

    Faria, Luiz F O; Paschoal, Vitor H; Lima, Thamires A; Ferreira, Fabio F; Freitas, Rafael S; Ribeiro, Mauro C C

    2017-10-26

    A local order-disorder transition has been disclosed in the thermophysical behavior of the ionic liquid 1-benzyl-3-methylimidazolium dicyanamide, [Bzmim][N(CN) 2 ], and its microscopic nature revealed by spectroscopic techniques. Differential scanning calorimetry and specific heat measurements show a thermal event of small enthalpy variation taking place in the range 250-260 K, which is not due to crystallization or melting. Molecular dynamic simulations and X-ray diffraction measurements have been used to discuss the segregation of domains in the liquid structure of [Bzmim][N(CN) 2 ]. Raman and NMR spectroscopy measurements as a function of temperature indicate that the microscopic origin of the event observed in the calorimetric measurements comes from structural rearrangement involving the benzyl group. The results indicate that the characteristic structural heterogeneity allow for rearrangements within local domains implying the good glass-forming ability for the low viscosity ionic liquid [Bzmim][N(CN) 2 ]. This work sheds light on our understanding of the microscopic origin behind complex thermal behavior of ionic liquids.

  11. tert-Butyl N-hydr­oxy-N-[(1S*,2R*)-2-(1-naphth­yl)cyclo­pent-3-en-1-yl]carbamate

    PubMed Central

    Lough, Alan J.; Machin, Ben P.; Tam, William

    2009-01-01

    The relative stereochemistry of the title compound, C20H23NO3, was established by X-ray analysis. The asymmetric unit contains two independent mol­ecules. In the crystal structure, each type of mol­ecule forms a centrosymmetric dimer via pairs of inter­molecular O—H⋯O hydrogen bonds, resulting in an R 2 2(10) loop in each case. PMID:21582783

  12. Biosynthesis of (R)-phenyl-1,2-ethanediol from racemic styrene oxide by using bacterial and marine fish epoxide hydrolases.

    PubMed

    Kim, Hee Sook; Lee, Ok Kyung; Hwang, Seungha; Kim, Beum Jun; Lee, Eun Yeol

    2008-01-01

    Enantio-convergent hydrolysis of racemic styrene oxides was achieved to prepare enantiopure (R)-phenyl-1,2-ethanediol by using two recombinant epoxide hydrolases (EHs) of a bacterium, Caulobacter crescentus, and a marine fish, Mugil cephalus. The recombinant C. crescentus EH primarily attacked the benzylic carbon of (S)-styrene oxide, while the M. cephalus EH preferentially attacked the terminal carbon of (R)-styrene oxide, thus leading to the formation of (R)-phenyl-1,2-ethanediol as the main product. (R)-Phenyl-1,2-ethanediol was obtained with 90% enantiomeric excess and yield as high as 94% from 50 mM racemic styrene oxides in a one-pot process.

  13. 2D polymeric cadmium(II) complexes containing 1,3-imidazolidine-2-thione (Imt) ligand, [Cd(Imt)(H2O)2(SO4)]n and [Cd(Imt)2(N3)2]n

    NASA Astrophysics Data System (ADS)

    Mahmood, Rashid; Ahmad, Saeed; Fettouhi, Mohammed; Roisnel, Thierry; Gilani, Mazhar Amjad; Mehmood, Kashif; Murtaza, Ghulam; Isab, Anvarhusein A.

    2018-03-01

    The present study aims at preparing and carrying out the structural investigation of two polymeric cadmium(II) complexes of imidazolidine-2-thione (Imt) based on sulfate or azide ions, [Cd(Imt)(H2O)2(SO4)]n (1) and [Cd(Imt)2(N3)2]n (2). The structures of the complexes were determined by single crystal X-ray analysis. Both compounds, 1 and 2 crystallize in the form of 2D coordination polymers and the cadmium(II) ion is six-coordinate having a distorted octahedral geometry in each compound. In 1, the metal ion is bonded to one sulfur atom of Imt and five oxygen atoms with two from water and three of bridging sulfate ions. In 2, the cadmium coordination sphere is completed by two Imt molecules binding through the sulfur atoms and four nitrogen atoms of bridging azide ions. The crystal structures are stabilized by intra and intermolecular hydrogen bonding interactions. The complexes were also characterized by IR and NMR spectroscopy and the spectroscopic data is consistent with the binding of the ligands.

  14. Structural insights into the human RyR2 N-terminal region involved in cardiac arrhythmias

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Borko, Ľubomír; Bauerová-Hlinková, Vladena, E-mail: vladena.bauerova@savba.sk; Hostinová, Eva

    2014-11-01

    X-ray and solution structures of the human RyR2 N-terminal region were obtained under near-physiological conditions. The structure exhibits a unique network of interactions between its three domains, revealing an important stabilizing role of the central helix. Human ryanodine receptor 2 (hRyR2) mediates calcium release from the sarcoplasmic reticulum, enabling cardiomyocyte contraction. The N-terminal region of hRyR2 (amino acids 1–606) is the target of >30 arrhythmogenic mutations and contains a binding site for phosphoprotein phosphatase 1. Here, the solution and crystal structures determined under near-physiological conditions, as well as a homology model of the hRyR2 N-terminal region, are presented. The N-terminusmore » is held together by a unique network of interactions among its three domains, A, B and C, in which the central helix (amino acids 410–437) plays a prominent stabilizing role. Importantly, the anion-binding site reported for the mouse RyR2 N-terminal region is notably absent from the human RyR2. The structure concurs with the differential stability of arrhythmogenic mutations in the central helix (R420W, I419F and I419F/R420W) which are owing to disparities in the propensity of mutated residues to form energetically favourable or unfavourable contacts. In solution, the N-terminus adopts a globular shape with a prominent tail that is likely to involve residues 545–606, which are unresolved in the crystal structure. Docking the N-terminal domains into cryo-electron microscopy maps of the closed and open RyR1 conformations reveals C{sup α} atom movements of up to 8 Å upon channel gating, and predicts the location of the leucine–isoleucine zipper segment and the interaction site for spinophilin and phosphoprotein phosphatase 1 on the RyR surface.« less

  15. (E)-4-Meth-oxy-N'-(2,4,5-tri-meth-oxy-benzyl-idene)benzohydrazide hemihydrate.

    PubMed

    Chantrapromma, Suchada; Boonnak, Nawong; Horkaew, Jirapa; Quah, Ching Kheng; Fun, Hoong-Kun

    2014-02-01

    The title compound crystallizes as a hemihydrate, C18H20N2O5·0.5H2O. The mol-ecule exists in an E conformation with respect to the C=N imine bond. The 4-meth-oxy-phenyl unit is disordered over two sets of sites with a refined occupancy ratio of 0.54 (2):0.46 (2). The dihedral angles between the benzene rings are 29.20 (9) and 26.59 (9)°, respectively, for the major and minor components of the 4-meth-oxy-substituted ring. All meth-oxy substituents lie close to the plane of the attached benzene rings [the Cmeth-yl-O-C-C torsion angles range from -4.0 (12) to 3.9 (2)°]. In the crystal, the components are linked into chains propagating along [001] via N-H⋯O and O-H⋯O hydrogen bonds and weak C-H⋯O inter-actions.

  16. (R,S)-3-Carb-oxy-2-(isoquinolinium-2-yl)propanoate monohydrate.

    PubMed

    Stilinović, Vladimir; Frkanec, Leo; Kaitner, Branko

    2010-05-22

    The title compound, C(13)H(11)NO(4)·H(2)O, is a monohydrate of a betaine exhibiting a positively charged N-substituted isoquino-line group and a deprotonated carboxyl group. In the crystal, mol-ecules are connected via short O-H⋯O hydrogen bonds between protonated and deprotonated carboxyl groups into chains of either R or S enanti-omers along [001]. These chains are additionally connected by hydrogen bonding between water mol-ecules and the deprotonated carb-oxy groups of neighbouring mol-ecules.

  17. Collision energy dependent cross section and rotational alignment of NO (A 2Σ+) in the energy-transfer reaction of N2 (A 3Σu+) + NO (X 2Π) → N2 (X 1Σg+) + NO (A 2Σ+).

    PubMed

    Ohoyama, H

    2014-10-16

    We have studied the collision energy dependent cross section and alignment of NO (A (2)Σ(+)) rotation in the energy-transfer reaction of N2 (A (3)Σ(u)(+)) + NO (X (2)Π) → N2 (X (1)Σ(g)(+)) + NO (A (2)Σ(+)) at the collision energy (E) region of 0.03-0.2 eV. NO (A (2)Σ(+)) emission in two linear polarization directions in the collision frame (parallel (∥) and perpendicular (⊥) with respect to the relative velocity vector (vR)) has been measured as a function of collision energy. NO (A (2)Σ(+)) rotation (J-vector) turns out to be aligned perpendicular to vR. In addition, collision energy is found to enhance the degree of alignment of NO (A (2)Σ(+)) rotation. The collision energy dependent cross sections σ(∥,(⊥))(E) (excitation functions) show a rapid fall-off following an initial rise with a threshold less than 0.02 eV. The excitation function at the parallel alignment of NO (A (2)Σ(+)) rotation, σ(J∥v(R), (E), is slightly shifted to the low collision energy region as compared with σ(J ⊥ vR, E). We propose that the rapid fall-off feature in the excitation function is attributed to the multidimensional nonadiabatic transitions.

  18. Rigid Dipeptide Mimics: Synthesis of Enantiopure 5- and 7-Benzyl and 5,7-Dibenzyl Indolizidinone Amino Acids via Enolization and Alkylation of delta-Oxo alpha,omega-Di-[N-(9-(9-phenylfluorenyl))amino]azelate Esters.

    PubMed

    Polyak, Felix; Lubell, William D.

    1998-08-21

    Azabicyclo[X.Y.0]alkane amino acids are tools for constructing mimics of peptide structure and templates for generating combinatorial libraries for drug discovery. Our methodology for synthesizing these conformationally rigid dipeptides has been elaborated such that alkyl groups can be appended onto the heterocycle to generate mimics of peptide backbone and side-chain structure. Inexpensive glutamic acid was employed as chiral educt in a Claisen condensation/ketone alkylation/reductive amination/lactam cyclization sequence that furnished alkyl-branched azabicyclo[4.3.0]alkane amino acid. Enantiopure 5-benzyl-, 7-benzyl-, and 5,7-dibenzylindolizidinone amino acids 2-4 were stereoselectively synthesized via efficient reaction sequences featuring the alkylation of di-tert-butyl alpha,omega-di-[N-(PhF)amino]azelate delta-ketone 5. A variety of alkyl halides were readily added to the enolate of ketone 5 to provide mono- and dialkylated ketones 6 and 7. Hydride additions to 6 and 7, methanesulfonations, and intramolecular S(N)2 displacements by the PhF amine gave 5-alkylprolines that were converted by lactam cyclizations into 7- and 5-benzyl-, as well as 5,7-dibenzyl-2-oxo-3-N-(BOC)amino-1-azabicyclo[4.3.0]nonane-9-carboxylate methyl esters 10, 11, and 14. Epimerization of the alkyl-branched stereocenter via an iminium-enaminium equilibrium proved effective for controlling diastereoselectivity in reductive aminations with 6 and 7 in order to furnish 5-alkylprolines that were similarly converted to 7- benzyl- and 5,7-dibenzylindolizidinone N-(BOC)amino esters 10 and 14. Ester hydrolysis with hydroxide ion and potassium trimethylsilanolate then gave enantiopure indolizidinone amino acids 2-4. Epimerization at C-9 of benzylindolizidinone amino esters was also used to provide alternative diastereomers of 10, 11, and 14. This practical methodology for introducing side-chain groups onto the heterocycle with regioselective and diastereoselective control is designed to enhance

  19. Masking of Lewis acidity trends in the solid-state structures of trichlorido- and tribromido(2,2':6',2''-terpyridine-κ(3)N,N',N'')gallium(III).

    PubMed

    Kazakov, Igor V; Bodensteiner, Michael; Timoshkin, Alexey Y

    2014-03-01

    The molecular structures of trichlorido(2,2':6',2''-terpyridine-κ(3)N,N',N'')gallium(III), [GaCl3(C15H11N3)], and tribromido(2,2':6',2''-terpyridine-κ(3)N,N',N'')gallium(III), [GaBr3(C15H11N3)], are isostructural, with the Ga(III) atom displaying an octahedral geometry. It is shown that the Ga-N distances in the two complexes are the same within experimental error, in contrast to expected bond lengthening in the bromide complex due to the lower Lewis acidity of GaBr3. Thus, masking of the Lewis acidity trends in the solid state is observed not only for complexes of group 13 metal halides with monodentate ligands but for complexes with the polydentate 2,2':6',2''-terpyridine donor as well.

  20. Quantifying N2O reduction to N2 based on N2O isotopocules - validation with independent methods (helium incubation and 15N gas flux method)

    NASA Astrophysics Data System (ADS)

    Lewicka-Szczebak, Dominika; Augustin, Jürgen; Giesemann, Anette; Well, Reinhard

    2017-02-01

    Stable isotopic analyses of soil-emitted N2O (δ15Nbulk, δ18O and δ15Nsp = 15N site preference within the linear N2O molecule) may help to quantify N2O reduction to N2, an important but rarely quantified process in the soil nitrogen cycle. The N2O residual fraction (remaining unreduced N2O, rN2O) can be theoretically calculated from the measured isotopic enrichment of the residual N2O. However, various N2O-producing pathways may also influence the N2O isotopic signatures, and hence complicate the application of this isotopic fractionation approach. Here this approach was tested based on laboratory soil incubations with two different soil types, applying two reference methods for quantification of rN2O: helium incubation with direct measurement of N2 flux and the 15N gas flux method. This allowed a comparison of the measured rN2O values with the ones calculated based on isotopic enrichment of residual N2O. The results indicate that the performance of the N2O isotopic fractionation approach is related to the accompanying N2O and N2 source processes and the most critical is the determination of the initial isotopic signature of N2O before reduction (δ0). We show that δ0 can be well determined experimentally if stable in time and then successfully applied for determination of rN2O based on δ15Nsp values. Much more problematic to deal with are temporal changes of δ0 values leading to failure of the approach based on δ15Nsp values only. For this case, we propose here a dual N2O isotopocule mapping approach, where calculations are based on the relation between δ18O and δ15Nsp values. This allows for the simultaneous estimation of the N2O-producing pathways' contribution and the rN2O value.

  1. One-pot synthesis of β-acetamido ketones using boric acid at room temperature.

    PubMed

    Karimi-Jaberi, Zahed; Mohammadi, Korosh

    2012-01-01

    β-acetamido ketones were synthesized in excellent yields through one-pot condensation reaction of aldehydes, acetophenones, acetyl chloride, and acetonitrile in the presence of boric acid as a solid heterogeneous catalyst at room temperature. It is the first successful report of boric acid that has been used as solid acid catalyst for the preparation of β-acetamido ketones. The remarkable advantages offered by this method are green catalyst, mild reaction conditions, simple procedure, short reaction times, and good-to-excellent yields of products.

  2. Photocatalytic decomposition of N2O over TiO2/g-C3N4 photocatalysts heterojunction

    NASA Astrophysics Data System (ADS)

    Kočí, K.; Reli, M.; Troppová, I.; Šihor, M.; Kupková, J.; Kustrowski, P.; Praus, P.

    2017-02-01

    TiO2/g-C3N4 photocatalysts with the various TiO2/g-C3N4 weight ratios from 1:2 to 1:6 were fabricated by mechanical mixing in water suspension followed by calcination. Pure TiO2 was prepared by thermal hydrolysis and pure g-C3N4 was prepared from commercial melamine by thermal annealing at 620 °C. All the nanocomposites were characterized by X-ray powder diffraction, UV-vis diffuse reflectance spectroscopy, Raman spectroscopy, infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, photoelectrochemical measurements and nitrogen physisorption. The prepared mixtures along with pure TiO2 and g-C3N4 were tested for the photocatalytic decomposition of nitrous oxide under UVC (λ = 254 nm), UVA (λ = 365 nm) and Vis (λ > 400 nm) irradiation. The TiO2/g-C3N4 nanocomposites showed moderate improvement compared to pure g-C3N4 but pure TiO2 proved to be a better photocatalyst under UVC irradiation. However, under UVA irradiation conditions, the photocatalytic activity of TiO2/g-C3N4 (1:2) nanocomposite exhibited an increase compared to pure TiO2. Nevertheless, further increase of g-C3N4 amount leads/led to a decrease in reactivity. These results are suggesting the nanocomposite with the optimal weight ratio of TiO2 and g-C3N4 have shifted absorption edge energy towards longer wavelengths and decreased the recombination rate of charge carriers compared to pure g-C3N4. This is probably due to the generation of heterojunction on the TiO2/g-C3N4 interface.

  3. Kinetics of the benzyl + O(3P) reaction: a quantum chemical/statistical reaction rate theory study.

    PubMed

    da Silva, Gabriel; Bozzelli, Joseph W

    2012-12-14

    The resonance stabilized benzyl radical is an important intermediate in the combustion of aromatic hydrocarbons and in polycyclic aromatic hydrocarbon (PAH) formation in flames. Despite being a free radical, benzyl is relatively stable in thermal, oxidizing environments, and is predominantly removed through bimolecular reactions with open-shell species other than O(2). In this study the reaction of benzyl with ground-state atomic oxygen, O((3)P), is examined using quantum chemistry and statistical reaction rate theory. C(7)H(7)O energy surfaces are generated at the G3SX level, and include several novel pathways. Transition state theory is used to describe elementary reaction kinetics, with canonical variational transition state theory applied for barrierless O atom association with benzyl. Apparent rate constants and branching ratios to different product sets are obtained as a function of temperature and pressure from solving the time-dependent master equation, with RRKM theory for microcanonical k(E). These simulations indicate that the benzyl + O reaction predominantly forms the phenyl radical (C(6)H(5)) plus formaldehyde (HCHO), with lesser quantities of the C(7)H(6)O products benzaldehyde, ortho-quinone methide, and para-quinone methide (+H), along with minor amounts of the formyl radical (HCO) + benzene. Addition of O((3)P) to the methylene site in benzyl produces a highly vibrationally excited C(7)H(7)O* adduct, the benzoxyl radical, which can β-scission to benzaldehyde + H and phenyl + HCHO. In order to account for the experimental observation of benzene as the major reaction product, a roaming radical mechanism is proposed that converts the nascent products phenyl and HCHO to benzene + HCO. Oxygen atom addition at the ortho and para ring sites in benzyl, which has not been previously considered, is shown to lead to the quinone methides + H; these species are less-stable isomers of benzaldehyde that are proposed as important combustion intermediates, but

  4. Infrared spectra and anharmonic coupling of proton-bound nitrogen dimers N2-H+-N2, N2-D+-N2, and 15N2-H+-15N2 in solid para-hydrogen.

    PubMed

    Liao, Hsin-Yi; Tsuge, Masashi; Tan, Jake A; Kuo, Jer-Lai; Lee, Yuan-Pern

    2017-08-09

    The proton-bound nitrogen dimer, N 2 -H + -N 2 , and its isotopologues were investigated by means of vibrational spectroscopy. These species were produced upon electron bombardment of mixtures of N 2 (or 15 N 2 ) and para-hydrogen (p-H 2 ) or normal-D 2 (n-D 2 ) during deposition at 3.2 K. Reduced-dimension anharmonic vibrational Schrödinger equations were constructed to account for the strong anharmonic effects in these protonated species. The fundamental lines of proton motions in N 2 -H + -N 2 were observed at 715.0 (NH + N antisymmetric stretch, ν 4 ), 1129.6 (NH + N bend, ν 6 ), and 2352.7 (antisymmetric NN/NN stretch, ν 3 ) cm -1 , in agreement with values of 763, 1144, and 2423 cm -1 predicted with anharmonic calculations using the discrete-variable representation (DVR) method at the CCSD/aug-cc-pVDZ level. The lines at 1030.2 and 1395.5 cm -1 were assigned to combination bands involving nν 2 + ν 4 (n = 1 and 2) according to theoretical calculations; ν 2 is the N 2 N 2 stretching mode. For 15 N 2 -H + - 15 N 2 in solid p-H 2 , the corresponding major lines were observed at 710.0 (ν 4 ), 1016.7 (ν 2 + ν 4 ), 1124.3 (ν 6 ), 1384.8 (2ν 2 + ν 4 ), and 2274.9 (ν 3 ) cm -1 . For N 2 -D + -N 2 in solid n-D 2 , the corresponding major lines were observed at 494.0 (ν 4 ), 840.7 (ν 2 + ν 4 ), 825.5 (ν 6 ), and 2356.23 ) cm -1 . In addition, two lines at 762.0 (weak) and 808.3 cm -1 were tentatively assigned to be some modes of N 2 -H + -N 2 perturbed or activated by a third N 2 near the proton.

  5. Comparative analysis of MicroRNA expression in dog lungs infected with the H3N2 and H5N1 canine influenza viruses.

    PubMed

    Zheng, Yun; Fu, Xinliang; Wang, Lifang; Zhang, Wenyan; Zhou, Pei; Zhang, Xin; Zeng, Weijie; Chen, Jidang; Cao, Zongxi; Jia, Kun; Li, Shoujun

    2018-05-14

    MicroRNAs, a class of noncoding RNAs 18 to 23 nucleotides (nt) in length, play critical roles in a wide variety of biological processes. The objective of this study was to examine differences in microRNA expression profiles derived from the lungs of beagle dogs infected with the avian-origin H3N2 canine influenza virus (CIV) or the highly pathogenic avian influenza (HPAI) H5N1 virus (canine-origin isolation strain). After dogs were infected with H3N2 or H5N1, microRNA expression in the lungs was assessed using a deep-sequencing approach. To identify the roles of microRNAs in viral pathogenicity and the host immune response, microRNA target genes were predicted, and their functions were analyzed using bioinformatics software. A total of 229 microRNAs were upregulated in the H5N1 infection group compared with those in the H3N2 infection group, and 166 microRNAs were downregulated. MicroRNA target genes in the H5N1 group were more significantly involved in metabolic pathways, such as glycerolipid metabolism and glycerophospholipid metabolism, than those in the H3N2 group. The inhibition of metabolic pathways may lead to appetite loss, weight loss and weakened immunity. Moreover, miR-485, miR-144, miR-133b, miR-4859-5p, miR-6902-3p, miR-7638, miR-1307-3p and miR-1346 were significantly altered microRNAs that potentially led to the inhibition of innate immune pathways and the heightened pathogenicity of H5N1 compared with that of H3N2 in dogs. This study deepens our understanding of the complex relationships among microRNAs, the influenza virus-mediated immune response and immune injury in dogs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Arabidopsis TRANSPARENT TESTA GLABRA2 Is Directly Regulated by R2R3 MYB Transcription Factors and Is Involved in Regulation of GLABRA2 Transcription in Epidermal Differentiation[W

    PubMed Central

    Ishida, Tetsuya; Hattori, Sayoko; Sano, Ryosuke; Inoue, Kayoko; Shirano, Yumiko; Hayashi, Hiroaki; Shibata, Daisuke; Sato, Shusei; Kato, Tomohiko; Tabata, Satoshi; Okada, Kiyotaka; Wada, Takuji

    2007-01-01

    Arabidopsis thaliana TRANSPARENT TESTA GLABRA2 (TTG2) encodes a WRKY transcription factor and is expressed in young leaves, trichomes, seed coats, and root hairless cells. An examination of several trichome and root hair mutants indicates that MYB and bHLH genes regulate TTG2 expression. Two MYB binding sites in the TTG2 5′ regulatory region act as cis regulatory elements and as direct targets of R2R3 MYB transcription factors such as WEREWOLF, GLABRA1, and TRANSPARENT TESTA2. Mutations in TTG2 cause phenotypic defects in trichome development and seed color pigmentation. Transgenic plants expressing a chimeric repressor version of the TTG2 protein (TTG2:SRDX) showed defects in trichome formation, anthocyanin accumulation, seed color pigmentation, and differentiation of root hairless cells. GLABRA2 (GL2) expression was markedly reduced in roots of ProTTG2:TTG2:SRDX transgenic plants, suggesting that TTG2 is involved in the regulation of GL2 expression, although GL2 expression in the ttg2 mutant was similar to that in the wild type. Our analysis suggests a new step in a regulatory cascade of epidermal differentiation, in which complexes containing R2R3 MYB and bHLH transcription factors regulate the expression of TTG2, which then regulates GL2 expression with complexes containing R2R3 MYB and bHLH in the differentiation of trichomes and root hairless cells. PMID:17766401

  7. Synthesis, spectral and antifungal analysis of diaryldithiophosphates of mono- and dibutyltin(IV): x-ray structure of [{(3,5-CH3)2C6H3O)2PS2}2Sn(nBu)2].

    PubMed

    Syed, Atiya; Khajuria, Ruchi; Kumar, Sandeep; Jassal, Amanpreet Kaur; Hundal, Maninder S; Pandey, Sushil K

    2014-01-01

    Diaryldithiophosphate complexes of mono- and dibutyltin(IV) corresponding to [(ArO)(2)PS(2)(n)Sn(nBu)xCl(4-x-n)] (Ar = o-CH(3)C(6)H(4), m-CH(3)C(6)H(4), p-CH(3)C(6)H(4), 4-Cl-3-CH(3)C(6)H(3), (3,5-CH(3))(2)C(6)H(3); n = 1, 2 for x = 1 and n = 2 for x = 2) were successfully isolated and characterized by elemental analyses, IR, multinuclear NMR ((1)H, (13)C, (31)P and (119)Sn) spectroscopy and X-ray analysis. The thermal properties of the complex [(3,5-CH(3))(2)C(6)H(3)O(2)PS(2)](2)Sn(nBu)(2) (12) have been examined by combined DTA/ DTG thermal analyses. Single crystal X-ray analysis of [(3,5-CH(3))(2)C(6)H(3)O(2)PS(2)](2)S(n)(nBu)(2) (12) revealed that two diaryldithiophosphate ions are coordinated to tin atom in an anisobidentate fashion through the sulfur atoms of each dithiophosphate moiety leading to distorted skew-trapezoidal bipyramidal geometry. The antifungal activity depicts that these complexes are active against fungus Penicillium chrysogenium.

  8. Structural determination of a 5-acetamido-3,5,7, 9-tetradeoxy-7-(3-hydroxybutyramido)-L-glycero-L-manno-nonulos onic acid-containing homopolysaccharide isolated from Sinorhizobium fredii HH103.

    PubMed Central

    Gil-Serrano, A M; Rodríguez-Carvajal, M A; Tejero-Mateo, P; Espartero, J L; Menendez, M; Corzo, J; Ruiz-Sainz, J E; BuendíA-Clavería, A M

    1999-01-01

    The structure of a polysaccharide from Sinorhizobium fredii HH103 has been determined. This polysaccharide was isolated by following the protocol for lipopolysaccharide extraction. On the basis of monosaccharide analysis, methylation analysis, fast atom bombardment MS, matrix-assisted laser desorption ionization MS, electron-impact high-resolution MS, one-dimensional (1)H-NMR and (13)C-NMR and two-dimensional NMR experiments, the structure was shown to consist of a homopolymer of a 3:1 mixture of 5-acetamido-3,5,7, 9-tetradeoxy-7-[(R)- and (S)-3-hydroxybutyramido]-l-glycero-l-manno-nonulosonic acid. The sugar residues are attached via a glycosidic linkage to the OH group of the 3-hydroxybutyramido substituent and thus the monomers are linked via both glycosidic and amidic linkages. In contrast with the Sinorhizobium K-antigens previously reported, which are composed of a disaccharide repeating unit, the K-antigen polysacharide of S. fredii HH103 is a homopolysaccharide. PMID:10477263

  9. Di-μ-cyanido-1:2κC:N,2:3κN:C-hexa-cyanido-1κC,3κC-tetra-kis(1,10-phenanthroline)-1κN,N';2κN,N';3κN,N'-1,3-dicobalt(III)-2-iron(II) tetra-hydrate.

    PubMed

    Zhang, Ying; Yuan, Ai-Hua; Zhou, Hu; Guo, Ji-Xi; Liu, Lang

    2009-08-08

    The hydro-thermal reaction of CoCl(2)·6H(2)O, 1,10-phenanthroline (phen) and K(3)[Fe(CN)(6)] in deionized water yielded the title cyanide-bridged trinuclear cluster, [Co(2)Fe(CN)(8)(C(12)H(8)N(2))(4)]·4H(2)O or [{Co(III)(phen)(CN)(4)}(2){Fe(II)(phen)(2)}]·4H(2)O, which contains two Co(III) centers and one Fe(II) center linked by cyanide bridges. The combination of coordinative bonds, O-H⋯N and O-H⋯O hydrogen bonds and π-π stacking inter-actions [centroid-centroid distance = 3.630 (2) Å] results in the stabilization of a supra-molecular structure. All uncoordinated water molecules are disordered. Thermogravimetric analysis reveals that the title complex loses the four crystal water mol-ecules at about 333 K, then the anhydrous phase loses no further mass up to about 573 K, above which decomposition occurs.

  10. Diels-Alder Synthesis of endo-cis-N-phenylbicyclo[2.2.2]oct-5-en-2,3-dicarboximide

    ERIC Educational Resources Information Center

    Baar, Marsha R.; Wustholz, Kristin

    2005-01-01

    A study investigated the Diels-Alder synthesis of endo-cis-N-phenylbicyclo [2.2.2]oct-5-en-2,3-dicarboximide. The amount of time taken by a reaction between the 1,3-cyclohexadiene and N-phenylmaleimide at room temperature and also whether the desired cycloadduct would precipitate directly from the reaction mixture was examined.

  11. Experimental binding energies for the metal complexes [Mg(CH3OH)n](2+), [Ca(CH3OH)n](2+), and [Sr(CH3OH)n](2+) for n in the range 4-20.

    PubMed

    Bruzzi, E; Stace, A J

    2014-10-09

    A supersonic source of clusters has been used to prepare neutral complexes of methanol in association with an alkaline earth metal atom. From these complexes the following metal-containing dications have been generated through electron ionization: [Mg(CH3OH)n](2+), [Ca(CH3OH)n](2+), and [Sr(CH3OH)n](2+), and for n in the range 4-20, kinetic energy release measurements following the evaporation of a single molecule have been undertaken using a high resolution mass spectrometer. Using finite heat bath theory, these data have been transformed into binding energies for individual methanol molecules attached to each of the three cluster systems. In the larger complexes (n > 6) the results exhibit a consistent trend, whereby the experimental binding energy data for all three metal ions are similar, suggesting that the magnitude of the charge rather than charge density influences the strength of the interaction. From a comparison with data recorded previously for (CH3OH)nH(+) it is found that the 2+ charge on a metal ion has an effect on the binding energy of molecules in complexes containing up to 20 solvent molecules. The results recorded for [Ca(CH3OH)n](2+) show evidence of a very marked transition between n = 6 and 7, which is thought to coincide with the completion of a primary solvation shell and the onset of molecules starting to occupy a second and most probably a third shell.

  12. The CaV2.3 R-Type Voltage-Gated Ca2+ Channel in Mouse Sleep Architecture

    PubMed Central

    Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

    2014-01-01

    Study Objectives: Voltage-gated Ca2+ channels (VGCCs) are key elements in mediating thalamocortical rhythmicity. Low-voltage activated (LVA) CaV 3 T-type Ca2+ channels have been related to thalamic rebound burst firing and to generation of non-rapid eye movement (NREM) sleep. High-voltage activated (HVA) CaV 1 L-type Ca2+ channels, on the opposite, favor the tonic mode of action associated with higher levels of vigilance. However, the role of the HVA Non-L-type CaV2.3 Ca2+ channels, which are predominantly expressed in the reticular thalamic nucleus (RTN), still remains unclear. Recently, CaV2.3−/− mice were reported to exhibit altered spike-wave discharge (SWD)/absence seizure susceptibility supported by the observation that CaV2.3 mediated Ca2+ influx into RTN neurons can trigger small-conductance Ca2+-activated K+-channel type 2 (SK2) currents capable of maintaining thalamic burst activity. Based on these studies we investigated the role of CaV2.3 R-type Ca2+ channels in rodent sleep. Methods: The role of CaV2.3 Ca2+ channels was analyzed in CaV2.3−/− mice and controls in both spontaneous and artificial urethane-induced sleep, using implantable video-EEG radiotelemetry. Data were analyzed for alterations in sleep architecture using sleep staging software and time-frequency analysis. Results: CaV2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS). Whereas mean sleep stage durations remained unchanged, the total number of SWS epochs was increased in CaV2.3−/− mice. Additional changes were observed for sleep stage transitions and EEG amplitudes. Furthermore, urethane-induced SWS mimicked spontaneous sleep results obtained from CaV2.3 deficient mice. Quantitative Real-time PCR did not reveal changes in thalamic CaV3 T-type Ca2+ channel expression. The detailed mechanisms of SWS increase in CaV2.3−/− mice remain to be determined. Conclusions: Low-voltage activated CaV2.3 R-type Ca2+ channels in the thalamocortical

  13. Design, synthesis, characterisation, conformation and biological investigation of N-acyl r-2,c-6-bis (4-methoxyphenyl)-c-3,t-3-dimethylpiperidin-4-ones

    NASA Astrophysics Data System (ADS)

    Mohanraj, V.; Ponnuswamy, S.

    2017-09-01

    In a wide research programme towards the study of piperidin-4-ones with efficient pharmacological effect, a new series of N-acyl r-2,c-6-bis(4-methoxyphenyl)-c-3,t-3-dimethylpiperidin-4-ones 2-5 are synthesized and characterized by IR spectra, 1H, 13C, DEPT - 135 and 2D (COSY and HSQC) NMR and mass spectra. The parent compound 1 prefers to exist in a chair conformation whereas the extracted coupling constant, chemical shifts and estimated dihedral angles show that the N-acyl piperdine-4-ones 2-5 prefer to exist in a distorted boat conformation B1 (with C2 and C5 in prow and stern positions) with coplanar orientation of Nsbnd Cdbnd O moiety. The existence of a fast Nsbnd CO rotational equilibrium between the boat conformations B (I) and B (II) has also been observed. Anti bacterial activity of the above test compounds 1-5 is determined against pseudomonas sp. and salmonella sp. The antioxidant activities are determined by the ABTS, DPPH and superoxide assays. Furthermore, molecular docking studies have been carried out for the compounds 1-5 with target protein CHK1.

  14. Substitution Effects and Linear Free Energy Relationships During Reduction of 4- Benzoyl-n-(4-substituted Benzyl)pyridinium Cations

    NASA Technical Reports Server (NTRS)

    Leventis, Nicholas; Zhang, Guo-Hui; Rawashdeh, Abdel-Monem M.; Sotiriou-Leventis, Chariklia; Gray, Hugh R. (Technical Monitor)

    2003-01-01

    In analogy to 4-(para-substituted benzoyl)-N-methylpyridinium cations (1-X's), the title species (2-X's, -X = -OCH3, -CH3, -H, -Br, -COCH3, -NO2) undergo two reversible, well-separated (E(sub 1/2) greater than or equal to 650 mV) one-electron reductions. The effect of substitution on the reduction potentials of 2-X's is much weaker than the effect of the same substituents on 1-X's: the Hammett rho-values are 0.80 and 0.93 for the 1st- and 2nd-e reduction of 2-X's vs. 2.3 and 3.3 for the same reductions of 1-X's, respectively. Importantly, the nitro group of 2-NO2 undergoes reduction before the 2nd-e reduction of the 4-benzoylpyridinium system. These results suggest that the redox potentials of the 4-benzoylpyridinium system can be course-tuned via p-benzoyl substitution and fine-tuned via para-benzyl substitution. Introducing the recently derived substituent constant of the -NO2(sup)- group (sigma para-NO2(sup)- = -0.97) yields an excellent correlation for the 3rd-e reduction of 2- NO2 (corresponding to the reduction of the carbonyl group) with the 2nd-e reduction of the other 2-X's, and confirms the electron donating properties of -NO2(sup)-.

  15. One-Pot Synthesis of β-Acetamido Ketones Using Boric Acid at Room Temperature

    PubMed Central

    Karimi-Jaberi, Zahed; Mohammadi, Korosh

    2012-01-01

    β-acetamido ketones were synthesized in excellent yields through one-pot condensation reaction of aldehydes, acetophenones, acetyl chloride, and acetonitrile in the presence of boric acid as a solid heterogeneous catalyst at room temperature. It is the first successful report of boric acid that has been used as solid acid catalyst for the preparation of β-acetamido ketones. The remarkable advantages offered by this method are green catalyst, mild reaction conditions, simple procedure, short reaction times, and good-to-excellent yields of products. PMID:22666168

  16. MiR-344b-1-3p targets TLR2 and negatively regulates TLR2 signaling pathway

    PubMed Central

    Xu, Hong; Wu, Yuting; Li, Li; Yuan, Weifeng; Zhang, Deming; Yan, Qitao; Guo, Zhenhui; Huang, Wenjie

    2017-01-01

    Objectives COPD is an abnormal inflammatory response characterized by decreased expression of TLR2 in patients, which is suggested to induce invasive pulmonary aspergillosis (IPA). MicroRNAs (miRNAs) have been shown to play important roles in the pathogenesis of human respiratory system disorders. Therefore, the aim of this study was to identify the miRNAs involved in the regulation of TLR2 signaling in COPD. Materials and methods miRNA microarray analysis was performed to screen for the dysregulated miRNAs in alveolar macrophages (AMs) isolated from COPD rats. The interaction between these miRNAs and TLR2 gene was predicted using miRBase and validated using dual luciferase assay. Based on the analysis, a novel miR-344b-1-3p was identified as a novel modulator of TLR2 gene. Then, the mechanism through which miR-344b-1-3p regulated TLR2 expression was explored using cigarette smoke extract (CSE)-pretreated NR8383 cells. Moreover, by subjecting CSE-pretreated NR8383 cells to Pam3CSK4, the effect of miR-344b-1-3p on NF-κB activity and other important mediators of COPD, including IRAK-1, ERK, TNF-α, IL-1β, and MIP-2, was also assessed. Results COPD rat model was successfully induced by smoke inhalation. Among the 11 upregulated miRNAs in AMs from COPD rats, miR-344b-1-3p was predicted to be a novel miRNA targeting TLR2 gene. In the CSE pretreated NR8383 cells exposed to Pam3CSK4, miR-344b-1-3p inhibition increased the expression levels of TLR2, TNF-α, and IL-1β and decreased the expression levels of MIP-2. In addition, the phosphorylation of IRAK-1, IκBα, and IRK was augmented by miR-344b-1-3p inhibition. Conclusion Findings outlined in this study suggest that miR-344b-1-3p was an effective modulator of TLR2 gene, which can be employed as a promising therapeutic and preventive target of IPA in COPD patients. PMID:28243080

  17. Use of vibrational spectroscopy to study 4-benzyl-3-(thiophen-2-yl)-4,5-dihydro-1H-1,2,4-triazole-5-thione: A combined theoretical and experimental approach.

    PubMed

    Sert, Yusuf; El-Emam, Ali A; Al-Abdullah, Ebtehal S; Al-Tamimi, Abdul-Malek S; Cırak, Cağrı; Ucun, Fatih

    2014-05-21

    In this study, the experimental and theoretical vibrational frequencies of a newly synthesized potential anti-inflammatory agent namely, 4-benzyl-3-(thiophen-2-yl)-4,5-dihydro-1H-1,2,4-triazole-5-thione have been investigated. The experimental FT-IR (4000-400cm(-1)) and Laser-Raman spectra (4000-100cm(-1)) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and the optimized geometric parameters (bond lengths, bond angles and dihedral angles) have been calculated using density functional theory methods (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr and DFT/M06-2X: the highly parameterized, empirical exchange correlation function) with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis using VEDA 4 software program. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data and results in the literature. In addition, the highest occupied molecular orbital (HOMO) energy, the lowest unoccupied molecular orbital (LUMO) energy and the other related molecular energy values of the compound have been investigated using the same theoretical calculations. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Metal-free g-C{sub 3}N{sub 4} photocatalyst by sulfuric acid activation for selective aerobic oxidation of benzyl alcohol under visible light

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Ligang; University of Chinese Academy of Sciences, Beijing 100049; Liu, Di

    2014-11-15

    Highlights: • A novel visible-light-driven acid-modified g-C{sub 3}N{sub 4} was prepared. • The texture, electronic and surface property were tuned by acid modification. • Acid-modified g-C{sub 3}N{sub 4} shows much higher activity for photocatalytic activity. • Acid sites on the surface of g-C{sub 3}N{sub 4} favor efficient charge separation. - Abstract: In this work, modification of graphitic carbon nitride photocatalyst with acid was accomplished with a facile method through reflux in different acidic substances. The g-C{sub 3}N{sub 4}-based material was found to be a metal-free photocatalyst useful for the selective oxidation of benzyl alcohol with dioxygen as the oxidant undermore » visible light irradiation. Acid modification had a significant influence on the photocatalytic performance of g-C{sub 3}N{sub 4}. Among all acid tested, sulfuric acid-modified g-C{sub 3}N{sub 4} showed the highest catalytic activity and gave benzaldehyde in 23% yield for 4 h under visible light irradiation, which was about 2.5 times higher than that of g-C{sub 3}N{sub 4}. The acid modification effectively improved surface area, reduced structural size, enlarged band gap, enhanced surface chemical state, and facilitated photoinduced charge separation, contributing to the enhanced photocatalytic activity. It is hoped that our work can open promising prospects for the utilization of metal free g-C{sub 3}N{sub 4}-based semiconductor as visible-light photocatalyst for selective organic transformation.« less

  19. 57Fe Mössbauer study of unusual magnetic structure of multiferroic 3R-AgFeO2

    NASA Astrophysics Data System (ADS)

    Sobolev, A.; Rusakov, V.; Moskvin, A.; Gapochka, A.; Belik, A.; Glazkova, I.; Akulenko, A.; Demazeau, G.; Presniakov, I.

    2017-07-01

    We report new results of a 57Fe Mössbauer study of hyperfine magnetic interactions in the layered multiferroic 3R-AgFeO2 demonstrating two magnetic phase transitions at T N1 and T N2. The asymptotic value β *  ≈  0.34 for the critical exponent obtained from the temperature dependence of the hyperfine field H hf(T) at 57Fe the nuclei below T N1  ≈  14 K indicates that 3R-AgFeO2 shows quasi-3D critical behavior. The spectra just above T N1 (T N1  <  T  <  T  *  ≈  41 K) demonstrate a relaxation behavior due to critical spin fluctuations which indicates the occurrence of short-range correlations. At the intermediate temperature range, T N2  <  T  <  T N1, the 57Fe Mössbauer spectra are described in terms of collinear spin-density-waves (SDW) with the inclusion of many high-order harmonics, indicating that the real magnetic structure of the ferrite appears to be more complicated than a pure sinusoidally modulated SDW. Below T  <  T N2  ≈  9 K, the hyperfine field H hf reveals a large spatial anisotropy (ΔH anis  ≈  30 kOe) which is related with a local intra-cluster (FeO6) spin-dipole term that implies a conventional contribution of the polarized oxygen ions. We proposed a simple two-parametric formula to describe the dependence of H anis on the distortions of the (FeO6) clusters. Analysis of different mechanisms of spin and hyperfine interactions in 3R-AgFeO2 and its structural analogue CuFeO2 points to a specific role played by the topology of the exchange coupling and the oxygen polarization in the delafossite-like structures.

  20. Perovskite-type La0.8Sr0.2Co0.8Fe0.2O3 with uniform dispersion on N-doped reduced graphene oxide as an efficient bi-functional Li-O2 battery cathode.

    PubMed

    Cheng, Junfang; Jiang, Yuexing; Zhang, Ming; Zou, Lu; Huang, Yizhen; Wang, Ziling; Chi, Bo; Pu, Jian; Li, Jian

    2017-04-19

    A composite cathode including N-rGO with homogeneously dispersed perovskite La 0.8 Sr 0.2 Co 0.8 Fe 0.2 O 3 on the surface is studied. Li-O 2 batteries with LSCF@N-rGO cathode show better performance than those with LSCF-SP or N-rGO cathode. EIS and morphology analysis indicate that LSCF is beneficial to remold the shape of Li 2 O 2 and catalyze the decomposition of Li 2 O 2 .

  1. Design and in vitro activities of N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, novel small molecule Hypoxia Inducible Factor-1 (HIF-1) pathway inhibitors and anti-cancer agents

    PubMed Central

    Mun, Jiyoung; Jabbar, Adnan Abdul; Devi, Narra Sarojini; Yin, Shaoman; Wang, Yingzhe; Tan, Chalet; Culver, Deborah; Snyder, James P.; Van Meir, Erwin G.; Goodman, Mark M.

    2013-01-01

    The Hypoxia Inducible Factor (HIF) pathway is an attractive target for cancer as it controls tumor adaptation to growth under hypoxia and mediates chemo- and radiation resistance. We previously discovered 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, as a novel small molecule HIF-1 pathway inhibitor in a high-throughput cell-based assay, but its in vivo delivery is hampered by poor aqueous solubility (0.009 μM in water; logP7.4: 3.7). Here we describe the synthesis of twelve N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, which were designed to possess optimal lipophilicities and aqueous solubilities by in silico calculations. Experimental logP7.4 values of 8 of the 12 new analogs ranged from 1.23.1. Aqueous solubilities of 3 analogs were measured, among which the most soluble N-[(8-methoxy-2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)pyridine-2-sulfonamide had an aqueous solubility of 80 μM, e.g. a solubility improvement of ∼9,000-fold. The pharmacological optimization had minimal impact on drug efficacy as the compounds retained IC50 values at or below 5 μM in our HIF-dependent reporter assay. PMID:22746274

  2. Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells.

    PubMed

    Zhou, Yuanfei; Ren, Jiao; Song, Tongxing; Peng, Jian; Wei, Hongkui

    2016-10-11

    The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca 2+ stimulation and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca 2+ -ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

  3. Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3.

    PubMed

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system.

  4. 3 d printing of 2 d N=(0,2) gauge theories

    NASA Astrophysics Data System (ADS)

    Franco, Sebastián; Hasan, Azeem

    2018-05-01

    We introduce 3 d printing, a new algorithm for generating 2 d N=(0,2) gauge theories on D1-branes probing singular toric Calabi-Yau 4-folds using 4 d N=1 gauge theories on D3-branes probing toric Calabi-Yau 3-folds as starting points. Equivalently, this method produces brane brick models starting from brane tilings. 3 d printing represents a significant improvement with respect to previously available tools, allowing a straightforward determination of gauge theories for geometries that until now could only be tackled using partial resolution. We investigate the interplay between triality, an IR equivalence between different 2 d N=(0,2) gauge theories, and the freedom in 3 d printing given an underlying Calabi-Yau 4-fold. Finally, we present the first discussion of the consistency and reduction of brane brick models.

  5. Characterization of Water Coordination to Ferrous Nitrosyl Complexes with fac-N2O, cis-N2O2, and N2O3 Donor Ligands.

    PubMed

    McCracken, John; Cappillino, Patrick J; McNally, Joshua S; Krzyaniak, Matthew D; Howart, Michael; Tarves, Paul C; Caradonna, John P

    2015-07-06

    Electron paramagnetic resonance (EPR) experiments were done on a series of S = (3)/2 ferrous nitrosyl model complexes prepared with chelating ligands that mimic the 2-His-1-carboxylate facial triad iron binding motif of the mononuclear nonheme iron oxidases. These complexes formed a comparative family, {FeNO}(7)(N2Ox)(H2O)3-x with x = 1-3, where the labile coordination sites for the binding of NO and solvent water were fac for x = 1 and cis for x = 2. The continuous-wave EPR spectra of these three complexes were typical of high-spin S = (3)/2 transition-metal ions with resonances near g = 4 and 2. Orientation-selective hyperfine sublevel correlation (HYSCORE) spectra revealed cross peaks arising from the protons of coordinated water in a clean spectral window from g = 3.0 to 2.3. These cross peaks were absent for the {FeNO}(7)(N2O3) complex. HYSCORE spectra were analyzed using a straightforward model for defining the spin Hamiltonian parameters of bound water and showed that, for the {FeNO}(7)(N2O2)(H2O) complex, a single water conformer with an isotropic hyperfine coupling, Aiso = 0.0 ± 0.3 MHz, and a dipolar coupling of T = 4.8 ± 0.2 MHz could account for the data. For the {FeNO}(7)(N2O)(H2O)2 complex, the HYSCORE cross peaks assigned to coordinated water showed more frequency dispersion and were analyzed with discrete orientations and hyperfine couplings for the two water molecules that accounted for the observed orientation-selective contour shapes. The use of three-pulse electron spin echo envelope modulation (ESEEM) data to quantify the number of water ligands coordinated to the {FeNO}(7) centers was explored. For this aspect of the study, HYSCORE spectra were important for defining a spectral window where empirical integration of ESEEM spectra would be the most accurate.

  6. Swine influenza virus vaccine serologic cross-reactivity to contemporary US swine H3N2 and efficacy in pigs infected with an H3N2 similar to 2011-2012 H3N2v.

    PubMed

    Kitikoon, Pravina; Gauger, Phillip C; Anderson, Tavis K; Culhane, Marie R; Swenson, Sabrina; Loving, Crystal L; Perez, Daniel R; Vincent, Amy L

    2013-12-01

    Swine influenza A virus (IAV) reassortment with 2009 H1N1 pandemic (H1N1pdm09) virus has been documented, and new genotypes and subclusters of H3N2 have since expanded in the US swine population. An H3N2 variant (H3N2v) virus with the H1N1pdm09 matrix gene and the remaining genes of swine triple reassortant H3N2 caused outbreaks at agricultural fairs in 2011-2012. To assess commercial swine IAV vaccines' efficacy against H3N2 viruses, including those similar to H3N2v, antisera to three vaccines were tested by hemagglutinin inhibition (HI) assay against contemporary H3N2. Vaccine 1, with high HI cross-reactivity, was further investigated for efficacy against H3N2 virus infection in pigs with or without maternally derived antibodies (MDA). In addition, efficacy of a vaccine derived from whole inactivated virus (WIV) was compared with live attenuated influenza virus (LAIV) against H3N2. Hemagglutinin inhibition cross-reactivity demonstrated that contemporary swine H3N2 viruses have drifted from viruses in current swine IAV vaccines. The vaccine with the highest level of HI cross-reactivity significantly protected pigs without MDA. However, the presence of MDA at vaccination blocked vaccine efficacy. The performance of WIV and LAIV was comparable in the absence of MDA. Swine IAV in the United States is complex and dynamic. Vaccination to minimize virus shedding can help limit transmission of virus among pigs and people. However, vaccines must be updated. A critical review of the use of WIV in sows is required in the context of the current IAV ecology and vaccine application in pigs with MDA. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  7. Effect of Si3N4 powder reactivity on the preparation of the Si2N2O-Al2O3 silicon aluminum oxynitride solid solution

    NASA Technical Reports Server (NTRS)

    Sekercioglu, I.; Wills, R. R.

    1979-01-01

    Dense high-purity silicon aluminum oxynitride was prepared by reactive hot-pressing of an Si3N4-Al2O3-SiO2 mixture. The formation of a single-phase material was found to be critically dependent on the Si3N4 powder in the starting mixture. It is suggested that evolution of a chlorine- and nitrogen-containing species may enhance the reactivity of Si3N4 in this reaction. Densities of O prime sialons are very similar to that of Si2N2O, the widely quoted value in the ceramics literature of 3.1 g/cu cm for the density of Si2N2O being incorrect.

  8. C-C bond formation and related reactions at the CNC backbone in (smif)FeX (smif = 1,3-di-(2-pyridyl)-2-azaallyl): dimerizations, 3 + 2 cyclization, and nucleophilic attack; transfer hydrogenations and alkyne trimerization (X = N(TMS)2, dpma = (di-(2-pyridyl-methyl)-amide)).

    PubMed

    Frazier, Brenda A; Williams, Valerie A; Wolczanski, Peter T; Bart, Suzanne C; Meyer, Karsten; Cundari, Thomas R; Lobkovsky, Emil B

    2013-03-18

    Molecular orbital analysis depicts the CNC(nb) backbone of the smif (1,3-di-(2-pyridyl)-2-azaallyl) ligand as having singlet diradical and/or ionic character where electrophilic or nucleophilic attack is plausible. Reversible dimerization of (smif)Fe{N(SiMe3)2} (1) to [{(Me3Si)2N}Fe]2(μ-κ(3),κ(3)-N,py2-smif,smif) (2) may be construed as diradical coupling. A proton transfer within the backbone-methylated, and o-pyridine-methylated smif of putative ((b)Me2(o)Me2smif)FeN(SiMe3)2 (8) provides a route to [{(Me3Si)2N}Fe]2(μ-κ(4),κ(4)-N,py2,C-((b)Me,(b)CH2,(o)Me2(smif)H))2 (9). A 3 + 2 cyclization of ditolyl-acetylene occurs with 1, leading to the dimer [{2,5-di(pyridin-2-yl)-3,4-di-(p-tolyl-2,5-dihydropyrrol-1-ide)}FeN(SiMe3)2]2 (11), and the collateral discovery of alkyne cyclotrimerization led to a brief study that identified Fe(N(SiMe3)2(THF) as an effective catalyst. Nucleophilic attack by (smif)2Fe (13) on (t)BuNCO and (2,6-(i)Pr2C6H3)NCO afforded (RNHCO-smif)2Fe (14a, R = (t)Bu; 14b, 2,6-(i)PrC6H3). Calculations suggested that (dpma)2Fe (15) would favorably lose dihydrogen to afford (smif)2Fe (13). H2-transfer to alkynes, olefins, imines, PhN═NPh, and ketones was explored, but only stoichiometric reactions were affected. Some physical properties of the compounds were examined, and X-ray structural studies on several dinuclear species were conducted.

  9. Synthesis, spectroscopic characterization, X-ray structure and DFT studies on 2,6-bis(1-benzyl-1H-benzo[d]imidazol-2-yl)pyridine.

    PubMed

    İnkaya, Ersin; Günnaz, Salih; Özdemir, Namık; Dayan, Osman; Dinçer, Muharrem; Çetinkaya, Bekir

    2013-02-15

    The title molecule, 2,6-bis(1-benzyl-1H-benzo[d]imidazol-2-yl)pyridine (C(33)H(25)N(5)), was synthesized and characterized by elemental analysis, FT-IR spectroscopy, one- and two-dimensional NMR spectroscopies, and single-crystal X-ray diffraction. In addition, the molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) (1)H and (13)C NMR chemical shift values of the title compound in the ground state have been calculated using the density functional theory at the B3LYP/6-311G(d,p) level, and compared with the experimental data. The complete assignments of all vibrational modes were performed by potential energy distributions using VEDA 4 program. The geometrical parameters of the optimized structure are in good agreement with the X-ray crystallographic data, and the theoretical vibrational frequencies and GIAO (1)H and (13)C NMR chemical shifts show good agreement with experimental values. Besides, molecular electrostatic potential (MEP) distribution, frontier molecular orbitals (FMO) and non-linear optical properties of the title compound were investigated by theoretical calculations at the B3LYP/6-311G(d,p) level. The linear polarizabilities and first hyper polarizabilities of the molecule indicate that the compound is a good candidate of nonlinear optical materials. The thermodynamic properties of the compound at different temperatures were calculated, revealing the correlations between standard heat capacity, standard entropy, standard enthalpy changes and temperatures. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Synthesis, spectroscopic characterization, X-ray structure and DFT studies on 2,6-bis(1-benzyl-1H-benzo[d]imidazol-2-yl)pyridine

    NASA Astrophysics Data System (ADS)

    İnkaya, Ersin; Günnaz, Salih; Özdemir, Namık; Dayan, Osman; Dinçer, Muharrem; Çetinkaya, Bekir

    2013-02-01

    The title molecule, 2,6-bis(1-benzyl-1H-benzo[d]imidazol-2-yl)pyridine (C33H25N5), was synthesized and characterized by elemental analysis, FT-IR spectroscopy, one- and two-dimensional NMR spectroscopies, and single-crystal X-ray diffraction. In addition, the molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) 1H and 13C NMR chemical shift values of the title compound in the ground state have been calculated using the density functional theory at the B3LYP/6-311G(d,p) level, and compared with the experimental data. The complete assignments of all vibrational modes were performed by potential energy distributions using VEDA 4 program. The geometrical parameters of the optimized structure are in good agreement with the X-ray crystallographic data, and the theoretical vibrational frequencies and GIAO 1H and 13C NMR chemical shifts show good agreement with experimental values. Besides, molecular electrostatic potential (MEP) distribution, frontier molecular orbitals (FMO) and non-linear optical properties of the title compound were investigated by theoretical calculations at the B3LYP/6-311G(d,p) level. The linear polarizabilities and first hyper polarizabilities of the molecule indicate that the compound is a good candidate of nonlinear optical materials. The thermodynamic properties of the compound at different temperatures were calculated, revealing the correlations between standard heat capacity, standard entropy, standard enthalpy changes and temperatures.

  11. 3D-QSAR studies on 1,2,4-triazolyl 5-azaspiro [2.4]-heptanes as D3R antagonists

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Zhang, Hui

    2018-07-01

    Dopamine D3 receptor has become an attractive target in the treatment of abused drugs. 3D-QSAR studies were performed on a novel series of D3 receptor antagonists, 1,2,4-triazolyl 5-azaspiro [2.4]-heptanes, using CoMFA and CoMSIA methods. Two predictive 3D-QSAR models have been generated for the modified design of D3R antagonists. Based on the steric, electrostatic, hydrophobic and hydrogen-bond acceptor information of contour maps, key structural factors affecting the bioactivity were explored. This work gives helpful suggestions on the design of novel D3R antagonists with increased activities.

  12. Solid state coordination chemistry: structural consequences of variations in tether length in the oxovanadium-copper-bisterpy-[O3P(CH2)nPO3]4- system, n= 1-6 (bisterpy = 2,2':4',4'':2'',2'''-quarterpyridyl-6',6''-di-2-pyridine).

    PubMed

    Ouellette, Wayne; Koo, Bon-Kweon; Burkholder, Eric; Golub, Vladimir; O'Connor, C J; Zubieta, Jon

    2004-05-21

    Hydrothermal reactions of Na3VO4, an appropriate Cu(II) source, bisterpy and an organodiphosphonate, H2O3P(CH2)nPO3H2 (n = 1-6) yielded a family of materials of the type [Cu2(bisterpy)]4+/VxOy(n-)/[O3P(CH2)nPO3]4-. This family of bimetallic oxides is characterized by an unusual structural diversity. The oxides [[Cu2(bisterpy)]V2O4[O3PCH2PO3H]2] (1), [[Cu2(bisterpy)(H2O)]VO2[O3P(CH2)3PO3][HO3P(CH2)3PO3H2

  13. The selective 5-hydroxytryptamine 1A antagonist, AZD7371 [3(R)-(N,N-dicyclobutylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide (R,R)-tartrate monohydrate] (robalzotan tartrate monohydrate), inhibits visceral pain-related visceromotor, but not autonomic cardiovascular, responses to colorectal distension in rats.

    PubMed

    Lindström, E; Ravnefjord, A; Brusberg, M; Hjorth, S; Larsson, H; Martinez, V

    2009-06-01

    5-Hydroxytryptamine 1A (5-HT(1A)) receptors have been suggested as a target for the treatment of irritable bowel syndrome (IBS). A recent clinical trial investigating the efficacy of the selective 5-HT(1A) antagonist AZD7371 [3(R)-(N,N-dicyclobutylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide (R,R)-tartrate monohydrate] showed no symptomatic improvement in IBS patients. We characterized the mechanisms mediating potential analgesic effects of AZD7371 in a model of colorectal distension (CRD)-induced visceral pain in rats to understand its mechanism of action and the lack of clinical efficacy. Visceromotor and cardiovascular responses (telemetry) were assessed in conscious rats during noxious CRD (80 mm Hg). Effects of AZD7371 (3-300 nmol/kg i.v.; 1-30 micromol/kg p.o.) and a reference 5-HT(1A) antagonist, WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide maleate salt; 3-300 nmol/kg i.v.), were assessed. Effects of intracerebroventricular AZD7371 were also evaluated. Intravenous AZD7371 or WAY-100635 and oral AZD7371 dose-dependently inhibited visceromotor responses to CRD (ED(50), 203, 231, and 14 micromol/kg, respectively). In telemetrized rats, oral AZD7371 inhibited visceromotor responses to CRD without affecting the concomitant hypertensive and tachycardic responses. Intracerebroventricular AZD7371 did not affect visceromotor responses, whereas it inhibited micturition. None of the doses tested induced visible gross side effects. AZD7371, likely acting at a spinal site, inhibited the visceromotor but not the cardiovascular responses to visceral pain in the CRD model in rats. Although agents effective on multiple pain-related readouts in the CRD model (e.g., pregabalin or clonidine) alleviate IBS symptoms, AZD7371, which is effective on only one pain-related pseudoaffective readout, does not. Data from preclinical CRD models of visceral pain need to be interpreted cautiously as it relates to their clinical

  14. Investigation the influences of B2O3 and R2O on the structure and crystallization behaviors of CaO-Al2O3 based F-free mold flux

    NASA Astrophysics Data System (ADS)

    Li, Jiangling; Kong, Bowen; Gao, Xiangyu; Liu, Qingcai; Shu, Qifeng; Chou, Kuochih

    2018-04-01

    The influences of B2O3 and R2O on the structure and crystallization of CaO-Al2O3 based F-free mold flux were investigated by Raman Spectroscopy and Differential Scanning Calorimetry Technique, respectively, for developing a new type of F-free mold flux. The results of structural investigations showed that B3+ is mainly in the form of [BO3]. And [BO3] appears to form BIII-O-Al linkage which will produce a positive effect on forming [AlO4] network. The number of bridging oxygen and the degree of polymerization of [AlO4] network structure for CaO-Al2O3 system were also increased with the increasing of B2O3. On the contrary, with the addition of R2O into CaO-Al2O3-B2O3 system, the number of bridging oxygen and the degree of polymerization of [AlO4] network were decreased. DSC results showed that the crystallization process became more sluggish with the increase of B2O3, which indicated that the crystallization ability was weakened. While the quenched mold fluxes crystallized more rapidly when introducing R2O. In other word, the crystallization rates of CaO-Al2O3 based slags were accelerated by the introduction of R2O. The liquidus temperature and crystallization temperature were decreased with the increasing amount of B2O3 or by addition of R2O into CaO-Al2O3 system. Only one kind of crystal was precipitated in 8% B2O3 and %R2O-containing samples, which was CaAl2O4 identified by SEM-EDS. When the content of B2O3 increased from 8% to 16%, Ca3B2O6 is clearly observed, demonstrating that the crystallization ability of Ca3B2O6 is enhanced by the increasing concentration of B2O3 in mold flux. The Ca/Al ratio of the generated calcium aluminate has been altered from 1:2 to 1:4 with the increasing of B2O3. The size of CaAl2O4 crystal is gradually increased with the addition of R2O. The crystallization ability of CaAl2O4 is promoted by R2O.

  15. C{sub 1}-C{sub 15} alkyl nitrates, benzyl nitrate, and bifunctional nitrates: Measurements in California and South Atlantic air and global comparison using C{sub 2}Cl{sub 4} and CHBr{sub 3} as marker molecules

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schneider, M.; Luxenhofer, O.; Deissler, A.

    1998-10-15

    Measurements of C{sub 1}--C{sub 15} alkyl nitrates, perchloroethylene, and bromoform at two different sampling sites near Santa Cruz, CA, were conducted in 1995. The halocarbons were used as marker molecules to differentiate the air parcels collected into marine and continental groups. The average concentration of {Sigma}n/i-C{sub 3}--C{sub 12} alkyl nitrates at the California Coast was lower than the levels obtained in the coastal mountains. This difference was shown to be most significant for the long chain n/i-C{sub 6}--C{sub 12} alkyl nitrates. It is concluded that the {ge}C{sub 6} alkyl nitrates in continental air can contribute 1--2% to the total NO{submore » y}. The results are summarized together with earlier data sets to give a picture of contemporary levels and of the global occurrence of C{sub 3}--C{sub 12} alkyl nitrates. In comparison with South Atlantic air, pattern analysis of n-alkyl nitrates suggests a marine source of primary n-alkyl nitrates. It is also shown that liquid chromatographic preseparation of the air sample extracts leads to a fraction that contains more polar organic nitrates. Several alkyl dinitrates and benzyl nitrate are detected in air samples from California, the South Atlantic region, and Europe. The vicinal alkyl dinitrates show increased abundance in a nighttime sample. The relative abundance of benzyl nitrate compared to alkyl (mono) nitrates is used as a tool for global air mass characterization.« less

  16. A pure inorganic 1D chain based on {Mo8O28} clusters and Mn(II) ions: [Mn(H2O)2Mo8O28 ] n 6 n -

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaofen; Yan, Yonghong; Wu, Lizhou; Yu, Chengxin; Dong, Xinbo; Hu, Huaiming; Xue, Ganglin

    2016-01-01

    A new pure inorganic polymer, (NH4)6n[Mn(H2O)2Mo8O28)]n(H2O)2n(1), has been synthesized and characterized by elemental analyses, IR spectrum, UV-vis absorption spectra, TG-DSC and electrochemical studies. In 1, [Mo8O28]8- anions act as tetradentate ligands and are alternately linked by Mn(H2O)2 2 + ions into a one-dimensional chain structure. It is interesting that 1 represents the first example of pure inorganic-inorganic hybrid based on octamolybdate and transition metal ions. Moreover, it was indicated that 1 had definite catalytic activities on the probe reaction of benzyl alcohol oxidation to benzaldehyde with H2O2.

  17. Compositional Analysis of Asymmetric and Symmetric Dimethylated H3R2 Using Liquid Chromatography-Tandem Mass Spectrometry-Based Targeted Proteomics.

    PubMed

    Xu, Qingqing; Xu, Feifei; Liu, Liang; Chen, Yun

    2016-09-06

    Protein arginine methylation is one of the common post-translational modifications in cellular processes. To date, two isomeric forms of dimethylated arginine have been identified: asymmetric N(G),N(G)-dimethylarginine (aDMA), and symmetric N(G),N'(G)-dimethylarginine (sDMA). Evidence indicated that these isomers can coexist and have different or even opposite functions, with aDMA and sDMA forms of arginine 2 on histone H3 (i.e., H3R2me2a and H3R2me2s) being an example. Thus, specific detection and quantification of each isomeric form is important. Current methods are capable of predicting and detecting thousands of methylarginine sites in proteins, whereas differentiation and stoichiometric measurement of dimethylated protein isomers are still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted proteomics has emerged as a promising technique for site-specific quantification of protein methylation using enzymatic peptides as surrogates of target proteins. However, it should be pointed out that a routine targeted proteomics strategy cannot easily distinguish sDMA- and aDMA-containing surrogate peptides due to their common nature. The estimated amount should be considered as the sum of both arginine dimethylated isomers. In this study, compositional analysis based on a linear algebra algorithm as an add-on to targeted proteomics was employed to quantify H3R2me2a and H3R2me2s (i.e., surrogate peptides of AR(me2a)TK(me1/2)QT and AR(me2s)TK(me1/2)QT). To achieve this simultaneous quantification, a targeted proteomics assay was developed and validated for each isomer first. With the slope and intercept of their calibration curves for each multiple reaction monitoring (MRM) transition, linear algebraic equations were derived. Using a series of mock mixtures consisting of isomers in varying concentrations, the reliability of the method was confirmed. Finally, the H3R2 dimethylation status was analyzed in normal MCF-10A cells

  18. Limited brain distribution of [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (Oat3/Slc22a8) and multidrug resistance-associated protein 4 (Mrp4/Abcc4).

    PubMed

    Ose, Atsushi; Ito, Mototsugu; Kusuhara, Hiroyuki; Yamatsugu, Kenzo; Kanai, Motomu; Shibasaki, Masakatsu; Hosokawa, Masakiyo; Schuetz, John D; Sugiyama, Yuichi

    2009-02-01

    [3R,4R,5S]-4-Acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802) is a pharmacologically active form of the anti-influenza virus drug oseltamivir. Abnormal behavior is a suspected adverse effect of oseltamivir on the central nervous system. This study focused on the transport mechanisms of Ro 64-0802 across the blood-brain barrier (BBB). Ro 64-0802 was found to be a substrate of organic anion transporter 3 (OAT3/SLC22A8) and multidrug resistance-associated protein 4 (MRP4/ABCC4). Human embryonic kidney 293 cells expressing OAT3 exhibited a greater intracellular accumulation of Ro 64-0802 than mock-transfected cells (15 versus 1.2 microl/mg protein/10 min, respectively). The efflux of Ro 64-0802 was 3-fold greater when MRP4 was expressed in MDCKII cells and was significantly inhibited by indomethacin. After its microinjection into the cerebrum, the amount of Ro 64-0802 in brain was significantly greater in both Oat3(-/-) mice and Mrp4(-/-) mice compared with the corresponding wild-type mice (0.36 versus 0.080 and 0.32 versus 0.060 nmol at 120 min after injection, respectively). The brain/plasma concentration ratio (K(p,) (brain)) of Ro 64-0802, determined in wild-type mice after subcutaneous continuous infusion for 24 h, was close to the capillary volume (approximately 10 microl/g brain). Although the K(p,) (brain) of Ro 64-0802 was unchanged in Oat3(-/-) mice, it was significantly greater in Mrp4(-/-) mice (41 microl/g of brain). These results suggest that Ro 64-0802 can cross the BBB from the blood, but its brain distribution is limited by its active efflux by Mrp4 and Oat3 across the BBB. The transporter responsible for the brain uptake of Ro 64-0802 remains unknown, but Oat3 is a candidate transporter.

  19. Investigation of long-term retention of unchanged (-)-N-{2-[(R)-3-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)piperidino]ethyl}-4-fluorobenzamide, a novel "funny" If current channel inhibitor, and its metabolites in the eyeball and thoracic aorta of rats.

    PubMed

    Umehara, Ken-ichi; Nakada, Naoyuki; Noguchi, Kiyoshi; Iwatsubo, Takafumi; Usui, Takashi; Kamimura, Hidetaka

    2009-11-01

    (-)-N-{2-[(R)-3-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)piperidino]ethyl}-4-fluorobenzamide (YM758), a novel "funny" If current channel inhibitor, was being developed as a treatment for stable angina and atrial fibrillation. After a single oral administration of (14)C-YM758, extensive accumulation and long-term retention of radioactivity were observed in the eyeballs of nonalbino rats and in the thoracic aorta of albino/nonalbino rats. Radioluminograms of the eyeballs of nonalbino rats indicated that the radioactivity was localized to the uveal tract, which suggests that the radioactivity may be positively charged and bound mainly to the melanins. Treatment with a mixture of 2 mol/l hydrochloric acid and methanol (5:95, v/v) allowed for the recovery of the major portion of radioactivity from the eyeball, which suggests reversible binding. The radioactive constituents in eyeballs consisted of the unchanged drug (YM758) and three metabolites [mainly 6,7-dimethoxy-2-[(3R)-piperidin-3-ylcarbonyl]-1,2,3,4-tetrahydroisoquinoline (YM-252124)]. Using the organic solvent mixture described above, almost all of the radioactivity was not collected from the thoracic aorta, and approximately 90% was recovered by treatment with elastase, which suggests that some metabolites covalently bind to the elastin fiber localized in the tunica media.

  20. Simple Quaternary Ammonium Ions R4N + ( R= nPr, nBu, nPen) as Versatile Structure Directors for the Synthesis of Zeolite-Like, Heterobimetallic Cyanide Frameworks

    NASA Astrophysics Data System (ADS)

    Poll, Eyck-Michael; Samba, Sabine; Dieter Fischer, R.; Olbrich, Falk; Davies, Nicola A.; Avalle, Paolo; Apperley, David C.; Harris, Robin K.

    2000-06-01

    The preparation of three new examples of water insoluble host/guest assemblies of the general composition: [(R4N)(Me3Sn)2M(CN)6·zH2O] (R=n-propyl or n-pentyl, M=Fe or Co, 0≤z≤2) from likewise polymeric super-Prussian-blue derivatives [(Me3Sn)3M(CN)6] and aqueous (R4N)X solutions are reported. According to combined single-crystal X-ray (3a and 3a*: R=nPr, M=Co, z=2; 5b: R=nPen, M=Fe, z=0.5), powder X-ray diffraction (XRD), and multinuclear (13C, 15N, 59Co, 119Sn) CPMAS solid-state magnetic resonance studies, 3a and 3a* contain cis- and trans-isomeric [Co(CN)4(CNSnMe3OH2)2]- building blocks, respectively, which are held together exclusively by Sn←OH2···NC-Co hydrogen bonds. In striking contrast, the building blocks of 5b and 5a are infinite [M-CN-Sn-NC] chains. In all these assemblies, also significant C-H···NC hydrogen bonds between the encapsulated R4N+ guest ion and exclusively terminal cyanide ligands of the host seem to play a notable auxiliary role.

  1. The role of MiR-324-3p in polycystic ovary syndrome (PCOS) via targeting WNT2B.

    PubMed

    Jiang, Y-C; Ma, J-X

    2018-06-01

    To investigate the expression of microRNA-324-3p (miR-324-3p) in polycystic ovary syndrome (PCOS) and its effects on the proliferation and apoptosis of ovarian granulosa cells. A total of 60 Sprague-Dawley (SD) rats were randomly divided into normal group (n=30) and experimental group (n=30). Rats in the experimental group were intramuscularly injected with dehydroepiandrosterone (DHEA) (6 mg/100 g of body weight) and 0.2 mL oil for injection, while those in normal group were intramuscularly injected with 0.2 mL oil for injection. The ovarian tissues of PCOS model rats were removed to extract the total ribose nucleic acid (RNA). The expression of miR-324-3p was detected via reverse transcription-polymerase chain reaction (RT-PCR). Primary ovarian granulosa cells were isolated and cultured, and NC-miRNA and miR-324-3p mimic were transfected into cells. After 48 h, cell proliferation and apoptosis were detected via cell counting kit 8 (CCK-8) and flow cytometry assay, respectively. The targeted molecule of miR-324-3p was explored using bioinformatics, and dual-luciferase assay was performed to verify the effect of miR-324-3p on WNT2B expression. Granulosa cells were co-transfected with WNT2B-small-interfering RNA (siRNA) and miR-324-3p mimic, and then cell proliferation and apoptosis were detected via CCK-8 and flow cytometry assay, respectively. The expression of miR-324-3p in ovarian tissues of PCOS group was significantly lower than that of normal group (p < 0.01). After transfection with miR-324-3p mimic into granulosa cells, cell proliferation was significantly inhibited and cell apoptosis was promoted (p < 0.01). MiR-324-3p exerted its effect on granulosa cells by directly targeting WNT2B. Silencing WNT2B expression could reverse the effects of miR-324-3p on proliferation and apoptosis of granulosa cells (p < 0.05). The expression of miR-324-3p in the ovary of PCOS rats is decreased significantly. Overexpression of miR-324-3p can reduce the proliferation and

  2. Kinetic study of benzyl [1-14C]acetate as a potential probe for astrocytic energy metabolism in the rat brain: Comparison with benzyl [2-14C]acetate.

    PubMed

    Okada, Maki; Yanamoto, Kazuhiko; Kagawa, Tomohiko; Yoshino, Keiko; Hosoi, Rie; Abe, Kohji; Zhang, Ming-Rong; Inoue, Osamu

    2016-02-01

    Brain uptake of [(14)C]acetate has been reported to be a useful marker of astrocytic energy metabolism. In addition to uptake values, the rate of radiolabeled acetate washout from the brain appears to reflect CO2 exhaustion and oxygen consumption in astrocytes. We measured the time-radioactivity curves of benzyl [1-(14)C]acetate ([1-(14)C]BA), a lipophilic probe of [1-(14)C]acetate, and compared it with that of benzyl [2-(14)C]acetate ([2-(14)C]BA) in rat brains. The highest brain uptake was observed immediately after injecting either [1-(14)C]BA or [2-(14)C]BA, and both subsequently disappeared from the brain in a single-exponential manner. Estimated [1-(14)C]BA washout rates in the cerebral cortex and cerebellum were higher than those of [2-(14)C]BA. These results suggested that [1-(14)C]BA could be a useful probe for estimating the astrocytic oxidative metabolism. The [1-(14)C]BA washout rate in the cerebral cortex of immature rats was lower than that of mature rats. An autoradiographic study showed that the washout rates of [1-(14)C]BA from the rat brains of a lithium-pilocarpine-induced status epilepticus model were not significantly different from the values in control rat brains except for the medial septal nucleus. These results implied that the enhancement of amino acid turnover rate rather than astrocytic oxidative metabolism was increased in status epilepticus. © The Author(s) 2015.

  3. Catena-poly[[bis(1H-benzotriazole-kappaN3)cobalt(II)]-di-mu-tricyanomethanido-kappa2N:N'] and catena-poly[[bis(3,5-dimethyl-1H-pyrazole-kappaN2)manganese(II)]-di-mu-tricyanomethanido-kappa2N:N'].

    PubMed

    Shao, Ze-Huai; Luo, Jun; Cai, Rui-Fang; Zhou, Xi-Geng; Weng, Lin-Hong; Chen, Zhen-Xia

    2004-06-01

    Two new one-dimensional coordination polymers, viz. the title compounds, [Co[C(CN)(3)](2)(C(6)H(5)N(3))(2)](n), (I), and [Mn[C(CN)(3)](2)(C(5)H(8)N(2))(2)](n), (II), have been synthesized and characterized by X-ray diffraction. Both complexes consist of linear chains with double 1,5-tricyanomethanide bridges between neighbouring divalent metal ions. The Co and Mn atoms are located on centres of inversion. In (I), the coordination environment of the Co(II) atom is that of an elongated octahedron. The Co(II) atom is coordinated in the equatorial plane by four nitrile N atoms of four bridging tricyanomethanide ions, with Co-N distances of 2.106 (2) and 2.110 (2) A, and in the apical positions by two N atoms from the benzotriazole ligands, with a Co-N distance of 2.149 (2) A. The [Co[C(CN)(3)](2)(C(6)H(5)N(3))(2)] units form infinite chains extending along the a axis. These chains are crosslinked via a hydrogen bond between the uncoordinated nitrile N atom of a tricyanomethanide anion and the H atom on the uncoordinated N atom of a benzotriazole ligand from an adjacent chain, thus forming a three-dimensional network structure. In (II), the Mn(II) atom also adopts a slightly distorted octahedral geometry, with four nitrile N atoms of tricyanomethanide ligands [Mn-N = 2.226 (2) and 2.227 (2) A] in equatorial positions and two N atoms of the monodentate 3,5-dimethylpyrazole ligands [Mn-N = 2.231 (2) A] in the axial sites. In (II), one-dimensional polymeric chains extending along the b axis are formed, with tricyanomethanide anions acting as bidentate bridging ligands. A hydrogen bond between the uncoordinated nitrile N atom of the tricyanomethanide ligand and the H atom on the uncoordinated N atom of a 3,5-dimethylpyrazole group from a neighbouring chain links the molecule into a two-dimensional layered structure.

  4. Observation of CH A 2X 2Πr and 2Σ--->X 2Πr emissions in gas-phase collisions of fast O(3P) atoms with acetylene

    NASA Astrophysics Data System (ADS)

    Orient, O. J.; Chutjian, A.; Murad, E.

    1995-03-01

    Optical emissions in single-collision, beam-beam reactions of fast (3-22-eV translational energy) O(3P) atoms with C2H2 have been measured in the wavelength range 300-850 nm. Two features were observed, one with a peak wavelength at 431 nm, corresponding to the CH A 2X 2Πr transition, and a second weaker emission in the range 380-400 nm corresponding to the B 2Σ--->X 2Πr transition. Both the A-->X and B-->X emissions were fit to a synthetic spectrum of CH(A) at a vibrational temperature Tv of 10 000 K (0.86 eV) and a rotational temperature Tr of approximately 5000 K (0.43 eV); and CH(B) to Tv=2500 K (0.22 eV) and Tr=1000 K (0.09 eV). The energy threshold for the A-->X emission was measured to be 7.3+/-0.4 eV (lab) or 4.5+/-0.2 eV (c.m.). This agrees with the energy threshold of 7.36 eV (lab) for the reaction O(3P)+C2H2-->CH(A)+HCO.

  5. Hydroxyalkylation with cyclic sulfates: synthesis of carbazole derived CB(2) ligands with increased polarity.

    PubMed

    Lueg, Corinna; Galla, Fabian; Frehland, Bastian; Schepmann, Dirk; Daniliuc, Constantin G; Deuther-Conrad, Winnie; Brust, Peter; Wünsch, Bernhard

    2014-01-01

    In order to increase the polarity of the potent CB2 ligand 1a, the homologous hydroxyalkyl carbazoles 2a-c were prepared and pharmacologically evaluated. An important step in the synthesis is the hydroxyalkylation of carbazole with cyclic sulfates providing the 2-hydroxyethyl and 3-hydroxypropyl derivatives 5a and 5b in a one-step reaction. The final propionamides 2a-c were prepared using the recently reported coupling reagent COMU®. The X-ray crystal structure of 2c displays an almost coplanar arrangement of the 3-phenyl-1,2,4-oxadiazole biaryl system. The increased polarity of 2a is associated with an almost 100-fold reduced CB2 affinity. The 3-hydroxypropyl derivative 2b represents the best compromise between lipophilicity and CB2 affinity (Ki  = 33 nM). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function.

    PubMed

    Takasu, Toshiyuki; Ukai, Masashi; Sato, Shuichi; Matsui, Tetsuo; Nagase, Itsuro; Maruyama, Tatsuya; Sasamata, Masao; Miyata, Keiji; Uchida, Hisashi; Yamaguchi, Osamu

    2007-05-01

    We evaluated the pharmacological characteristics of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]-ethyl} acetanilide (YM178). YM178 increased cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing human beta3-adrenoceptor (AR). The half-maximal effective concentration (EC50) value was 22.4 nM. EC50 values of YM178 for human beta1- and beta2-ARs were 10,000 nM or more, respectively. The ratio of intrinsic activities of YM178 versus maximal response induced by isoproterenol (nonselective beta-AR agonist) was 0.8 for human beta3-ARs, 0.1 for human beta1-ARs, and 0.1 for human beta2-ARs. The relaxant effects of YM178 were evaluated in rats and humans bladder strips precontracted with carbachol (CCh) and compared with those of isoproterenol and 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP-12177A) (beta3-AR agonist). EC50 values of YM178 and isoproterenol in rat bladder strips precontracted with 10(-6) M CCh were 5.1 and 1.4 microM, respectively, whereas those in human bladder strips precontracted with 10(-7) M CCh were 0.78 and 0.28 microM, respectively. In in vivo study, YM178 at a dose of 3 mg/kg i.v. decreased the frequency of rhythmic bladder contraction induced by intravesical filling with saline without suppressing its amplitude in anesthetized rats. These findings suggest the suitability of YM178 as a therapeutic drug for the treatment of symptoms of overactive bladder such as urinary frequency, urgency, and urge incontinence.

  7. A series of coordination polymers constructed from R-isophthalic acid (R=–SO{sub 3}H, –NO{sub 2}, and –OH) and N-donor ligands: Syntheses, structures and fluorescence properties

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhou, Yong-Hong, E-mail: zhou21921@sina.com; Zhou, Xu-Wan; Zhou, Su-Rong

    Six novel Zn(II), Cd(II), and Cu(II) mixed-ligand coordination complexes, namely, [Zn{sub 2}Na(sip){sub 2}(bpp){sub 3}(Hbpp)(H{sub 2}O){sub 2}]·8H{sub 2}O (1), [Cd{sub 3}(sip){sub 2}(nbi){sub 6}(H{sub 2}O){sub 2}]·7H{sub 2}O (2), [Zn(sip)(nbi){sub 2}(H{sub 2}O)]·Hnbi·3H{sub 2}O (3), [Cd(hip)(nbi){sub 2}(H{sub 2}O)]·nbi·5H{sub 2}O (4), [Cd{sub 2}(nip){sub 2}(nbi){sub 2}(H{sub 2}O){sub 2}]·DMF (5), and [Cu(nip)(nbi)(H{sub 2}O){sub 2}]·H{sub 2}O (6) (H{sub 3}sip=5-sulfoisophthalic acid, H{sub 2}hip=5-hydroxylisophthalic acid, H{sub 2}nip=5-nitroisophthalic acid, bpp=1,3-bis(4-pyridyl)propane, and nbi=6-nitrobenzimidazole) have been synthesized hydrothermally by the self-assembly of R-isophthalic acid (R=–SO{sub 3}H, –NO{sub 2}, and –OH) and N-donor ligands. Single crystal X-ray analyses reveal that two Zn(II) ions and one Na(I) ion of complex 1 are linked through Omore » atoms to generate a 1D linear chain. Then the 2D supramolecular architectures are constructed via intermolecular interactions. In complex 2, the Cd1 ions are connected by bridging carboxyl groups from sip{sup 3−} anions to form 1D double chain, which are further connected by Cd2 ions to afford 2D layer structure. The adjacent 2D layers are further linked via hydrogen-bonding interactions to give 3D supramolecular network. Compounds 3–5 show 1D chain structures, which are assembled into 2D or 3D supramolecular frameworks via weak interactions. In compound 6, the Cu(II) ions are bridged by the nip{sup 2−} ligands to form 48-membered ring, which is assembled into 1Dchain via the π-π stacking interaction. In addition, the thermal stabilities and fluorescence properties of these compounds have also been studied. - Graphical abstract: A series of Cd(II)/Zn(II)/ Cu(II) coordination polymers based on R-isophthalic acid (R=–SO{sub 3}H, –NO{sub 2}, and –OH) and N-donor ligands have been synthesized under hydrothermal conditions and structurally characterized. Photoluminescent

  8. [Influences of R2O-Al2O3-B2O3-SiO2 system glass and superfine alpha-Al2O3 on the sintering and phase transition of hydroxyapatite ceramics].

    PubMed

    Wang, Zhiqiang; Chen, Xiaoxu; Cai, Yingji; Lü, Bingling

    2003-06-01

    The effects of R2O-Al2O3-B2O3-SiO2 system glass and superfine alpha-Al2O3 on the sintering and phase transition of hydroxyapatite (HAP) ceramics were assessed. The results showed that alpha-Al2O3 impeded the sintering of HAP and raised the sintering temperature. When glass and alpha-Al2O3 were used together to reinforce HAP ceramics, better results could be obtained; the bending strength of multiphase HAP ceramics approached 106 MPa when 10% (wt) alpha-Al2O3 and 20%(wt) glass were used and sintered at 1200 for 1 h.

  9. Investigation of N2O Production from 266 and 532 nm Laser Flash Photolysis of O3/N2/O2 Mixtures

    NASA Technical Reports Server (NTRS)

    Estupinan, E. G.; Nicovich, J. M.; Li, J.; Cunnold, D. M.; Wine, P. H.

    2002-01-01

    Tunable diode laser absorption spectroscopy has been employed to measure the amount of N2O produced from laser flash photolysis of O3/N2/O2 mixtures at 266 and 532 nm. In the 532 nm photolysis experiments very little N2O is observed, thus allowing an upper limit yield of 7 x 10(exp -8) to be established for the process O3 + N2 yield N2O + O2, where O3 is nascent O3 that is newly formed via O(3P(sub J)) + O2 recombination (with vibrational excitation near the dissociation energy of O3). The measured upper limit yield is a factor of approx. 600 smaller than a previous literature value and is approximately a factor of 10 below the threshold for atmospheric importance. In the 266 nm photolysis experiments, significant N2O production is observed and the N2O quantum yield is found to increase linearly with pressure over the range 100 - 900 Torr in air bath gas. The source of N2O in the 266 nm photolysis experiments is believed to be the addition reaction O(1D(sub 2)) + N2 + M yields (k(sub sigma)) N2O + M, although reaction of (very short-lived) electronically excited O3 with N2 cannot be ruled out by the available data. Assuming that all observed N2O comes from the O(1D(sub 2)) + N2 + M reaction, the following expression describes the temperature dependence of k(sub sigma) (in its third-order low-pressure limit) that is consistent with the N2O yield data: k(sub sigma) = (2.8 +/- 0.1) x 10(exp -36)(T/300)(sup -(0-88+0.36)) cm(sup 6) molecule(sup -2)/s, where the uncertainties are 2(sigma) and represent precision only. The accuracy of the reported rate coefficients at the 95% confidence level is estimated to be 30 - 40% depending on the temperature. Model calculations suggest that gas phase processes initiated by ozone absorption of a UV photon represent about 1.4% of the currently estimated global source strength of atmospheric N2O. However, these processes could account for a significant fraction of the oxygen mass-independent enrichment observed in atmospheric N2O, and

  10. TAS2R bitter taste receptors regulate thyroid function

    PubMed Central

    Clark, Adam A.; Dotson, Cedrick D.; Elson, Amanda E. T.; Voigt, Anja; Boehm, Ulrich; Meyerhof, Wolfgang; Steinle, Nanette I.; Munger, Steven D.

    2015-01-01

    Dysregulation of thyroid hormones triiodothyronine and thyroxine (T3/T4) can impact metabolism, body composition, and development. Thus, it is critical to identify novel mechanisms that impact T3/T4 production. We found that type 2 taste receptors (TAS2Rs), which are activated by bitter-tasting compounds such as those found in many foods and pharmaceuticals, negatively regulate thyroid-stimulating hormone (TSH)-dependent Ca2+ increases and TSH-dependent iodide efflux in thyrocytes. Immunohistochemical Tas2r-dependent reporter expression and real-time PCR analyses reveal that human and mouse thyrocytes and the Nthy-Ori 3-1 human thyrocyte line express several TAS2Rs. Five different agonists for thyrocyte-expressed TAS2Rs reduced TSH-dependent Ca2+ release in Nthy-Ori 3-1 cells, but not basal Ca2+ levels, in a dose-dependent manner. Ca2+ responses were unaffected by 6-n-propylthiouracil, consistent with the expression of an unresponsive variant of its cognate receptor, TAS2R38, in these cells. TAS2R agonists also inhibited basal and TSH-dependent iodide efflux. Furthermore, a common TAS2R42 polymorphism is associated with increased serum T4 levels in a human cohort. Our findings indicate that TAS2Rs couple the detection of bitter-tasting compounds to changes in thyrocyte function and T3/T4 production. Thus, TAS2Rs may mediate a protective response to overingestion of toxic materials and could serve as new druggable targets for therapeutic treatment of hypo- or hyperthyroidism.—Clark, A. A., Dotson, C. D., Elson, A. E. T., Voigt, A., Boehm, U., Meyerhof, W., Steinle, N. I., Munger, S. D. TAS2R bitter taste receptors regulate thyroid function. PMID:25342133

  11. Synthesis ofN-(2-chloro-5-methylthiophenyl)-N'-(3-methyl-thiophenyl)-N'-[3H3]methylguanidine, l brace [3H3]CNS-5161 r brace

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gibbs, Andrew R.; Morimoto, Hiromi; VanBrocklin, Henry F.

    2001-09-28

    The preparation of the title compound, [{sup 3}H{sub 3}]CNS-5161, was accomplished in three steps starting with the production of [{sup 3}H{sub 3}]iodomethane (CT{sub 3}I). The intermediate N-[{sup 3}H{sub 3}]methyl-3-(thiomethylphenyl)cyanamide was prepared in 77% yield by the addition of CT{sub 3}I to 3-(thiomethylphenyl)cyanamide, previously treated with sodium hydride. Reaction of this tritiated intermediate with 2-chloro-5-thiomethylaniline hydrochloride formed the guanidine compound [{sup 3}H{sub 3}]CNS-5161. Purification by HPLC gave the desired labeled product in an overall yield of 9% with greater than 96% radiochemical purity and a final specific activity of 66 Ci mmol{sup -1}.

  12. New cobalt(II) and nickel(II) complexes of benzyl carbazate Schiff bases: Syntheses, crystal structures, in vitro DNA and HSA binding studies.

    PubMed

    Nithya, Palanivelu; Helena, Sannasi; Simpson, Jim; Ilanchelian, Malaichamy; Muthusankar, Aathi; Govindarajan, Subbiah

    2016-12-01

    In the present study, new Schiff base complexes with the composition [M(NCS) 2 (L1) 2nH 2 O, where M=Co (n=0) (1) and Ni (n=2) (2); [M(NCS) 2 (L2) 2 ], M=Co (3) and Ni (4) as well as [M(NCS) 2 (L3) 2 ], M=Co (5) and Ni (6); (L1=benzyl 2-(propan-2-ylidene)hydrazinecarboxylate, L2=benzyl 2-(butan-2-ylidene)hydrazinecarboxylate and L3=benzyl 2-(pentan-3-ylidene)hydrazinecarboxylate) have been synthesized by a template method. The complexes were characterised by analytical methods, spectroscopic studies, thermal and X-ray diffraction techniques. The structures of all the complexes explore that the metal(II) cation has a trans-planar coordination environment, the monomeric units containing a six-coordinated metal center in octahedral geometry with N-bound isothiocyanate anions coordinated as terminal ligands. Furthermore, the binding of the two Schiff base ligands to the metal centers involves the azomethine nitrogen and the carbonyl oxygen in mutually trans configuration. The binding interactions of all the complexes with Calf thymus-deoxyribonucleic acid (CT-DNA) and human serum albumin (HSA) have been investigated using absorption and emission spectral techniques. The CT-DNA binding properties of these complexes reveal that they bind to CT-DNA through a partial intercalation mode and the binding constant values were calculated using the absorption and emission spectral data. The binding constant values (~10×10 6 moldm -3 ) indicate strong binding of metal complexes with CT-DNA. HSA binding interaction studies showed that the cobalt and nickel complexes can quench the intrinsic fluorescence of HSA through static quenching process. Also, molecular docking studies were supported out to apprehend the binding interactions of these complexes with DNA and HSA which offer new understandings into the experimental model observations. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Synthesis and biological screening of 2'-aryl/benzyl-2-aryl-4-methyl-4',5-bithiazolyls as possible anti-tubercular and antimicrobial agents.

    PubMed

    Abhale, Yogita K; Sasane, Amit V; Chavan, Abhijit P; Deshmukh, Keshav K; Kotapalli, Sudha Sravanti; Ummanni, Ramesh; Sayyad, Sadikali F; Mhaske, Pravin C

    2015-04-13

    A series of 2'-aryl/benzyl-2-aryl-4-methyl-4',5-bithiazolyl derivatives, 25-64 were synthesized and evaluated for inhibitory activity against Mycobacterium smegmatis MC(2) 155 strain and antimicrobial activities against four pathogenic bacteria Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Proteus vulgaris. Among them, compounds 40, 49, 50, and 54 exhibited moderate to good inhibition on the growth of the bacteria Mycobacterium smegmatis at the concentration of 30 μM. Compounds 26, 40, 44, 54 and 56 exhibited moderate to good antibacterial activity. Compound 5-(2'-(4-fluorobenzyl)thiazol-4'-yl)-2-(4-fluorophenyl)-4-methyl-thiazole (54) exhibited both antitubercular as well as antimicrobial activity against all tested strains. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Facile radiosynthesis of fluorine-18 labeled beta-blockers. Synthesis, radiolabeling, and ex vivo biodistribution of [18F]-(2S and 2R)-1-(1-fluoropropan-2-ylamino)-3-(m-tolyloxy)propan-2-ol.

    PubMed

    Stephenson, Karin A; Wilson, Alan A; Meyer, Jeffrey H; Houle, Sylvain; Vasdev, Neil

    2008-08-28

    An efficient and general method has been developed for fluorine-18 labeling of beta-blockers that possess the propanolamine moiety. A new synthetically versatile intermediate, 3-(1-(benzyloxy)propan-2-yl)-2-oxooxazolidin-5-yl)methyl 4-methylbenzenesulfonate (13), was prepared and can be conjugated to any phenoxy core. To demonstrate the synthetic methodology, fluorinated derivatives of toliprolol were prepared, namely, [(18)F]-(2S and 2R)-1-(1-fluoropropan-2-ylamino)-3-(m-tolyloxy)propan-2-ol ((2S and 2R)-[(18)F]1). The radiosyntheses were accomplished in <1 h, with 20-24% (uncorrected for decay, n = 7) radiochemical yields, >96% radiochemical and >99% enantiomeric purities, with specific activities of 0.9-1.1 Ci/micromol (EOS). Ex vivo biodistribution studies with the radiotracers demonstrated excessively rapid washout that may limit their use for cerebral PET imaging.

  15. Theoretical microwave spectral constants for C2N, C2N/+/, and C3H

    NASA Technical Reports Server (NTRS)

    Green, S.

    1980-01-01

    Theoretical microwave spectral constants have been computed for C2N, C3H, and C2N(+). For C2N these are compared with values obtained from optical data. Calculated hyperfine constants are also presented for HNC, DNC, and HCNH(+). The possibility of observing these species in dense interstellar clouds is discussed.

  16. Synthesis of 7-azabicyclo[2.2.1]heptane and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives by base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides.

    PubMed

    Gómez-Sanchez, Elena; Soriano, Elena; Marco-Contelles, José

    2007-11-09

    We have studied the base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides, investigating the effect of the nitrogen protecting group and the relative configuration of the leaving group at C3 and C4 on the outcome of this reaction. We have observed that the sodium hydride-promoted heterocyclization of alkyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamates (10, 12, 14, 16, 18) is a convenient method for the synthesis of 7-azabicyclo[2.2.1]heptane derivatives. For instance, the reaction of tert-butyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamate (10) with sodium hydride in DMF at room temperature provides 2-bromo-7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]heptane (2) (52% yield), whose t-BuOK-promoted hydrogen bromide elimination affords 7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]hept-2-ene (31) in 78% yield, an intermediate in the total synthesis of epibatidine (1). However, the NaH/DMF-mediated heterocyclization of alkyl N-(trans-3,cis-4-dibromocyclohex-1-yl)carbamates (11, 13) is a more structure dependent reaction, where the nucleophilic attack of the oxygen atom of the protecting group controls the outcome of the reaction, giving rise to benzooxazolone and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, from low to moderate yields, in complex reaction mixtures. Conversely, the NaH/DMF heterocyclizations of N-(cis-3,trans-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (40) or N-(trans-3,cis-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (42) are very clean reactions giving 7-azabicyclo[2.2.1]heptane or 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, in good yields. Finally, a mechanistic investigation, based on DFT calculations, has been carried out to rationalize the formation of the different adducts.

  17. Nqrs Data for C3H2Cl10N2PSb[C3HCl4N2P·Cl6HSb](Subst. No. 0601)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C3H2Cl10N2PSb [C3HCl4N2P·Cl6HSb] (Subst. No. 0601)

  18. Syntheses and multi-NMR study of fac- and mer-OsO(3)F(2)(NCCH(3)) and the X-ray crystal structure (n = 2) and Raman spectrum (n = 0) of fac-OsO(3)F(2)(NCCH(3)).nCH(3)CN.

    PubMed

    Hughes, Michael J; Gerken, Michael; Mercier, Hélène P A; Schrobilgen, Gary J

    2010-06-07

    Dissolution of the infinite chain polymer, (OsO(3)F(2))(infinity), in CH(3)CN solvent at -40 degrees C followed by solvent removal under vacuum at -40 degrees C yielded fac-OsO(3)F(2)(NCCH(3)).nCH(3)CN (n >/= 2). Continued pumping at -40 degrees C with removal of uncoordinated CH(3)CN yielded fac-OsO(3)F(2)(NCCH(3)). Both fac-OsO(3)F(2)(NCCH(3)).nCH(3)CN and fac-OsO(3)F(2)(NCCH(3)) are yellow-brown solids and were characterized by low-temperature (-150 degrees C) Raman spectroscopy. The crystal structure (-173 degrees C) of fac-OsO(3)F(2)(NCCH(3)).2CH(3)CN consists of two co-crystallized CH(3)CN molecules and a pseudo-octahedral OsO(3)F(2).NCCH(3) molecule in which three oxygen atoms are in a facial arrangement and CH(3)CN is coordinated trans to an oxygen atom in an end-on fashion. The Os---N bond length (2.205(3) A) is among the shortest M---N adduct bonds observed for a d(0) transition metal oxide fluoride. The (19)F NMR spectrum of (OsO(3)F(2))(infinity) in CH(3)CN solvent (-40 degrees C) is a singlet (-99.6 ppm) corresponding to fac-OsO(3)F(2)(NCCH(3)). The (1)H, (15)N, (13)C, and (19)F NMR spectra of (15)N-enriched OsO(3)F(2)(NCCH(3)) were recorded in SO(2)ClF solvent (-84 degrees C). Nitrogen-15 enrichment resulted in splitting of the (19)F resonance of fac-OsO(3)F(2)((15)NCCH(3)) into a doublet ((2)J((15)N-(19)F), 21 Hz). In addition, a doublet of doublets ((2)J((19)F(ax)-(19)F(eq)), 134 Hz; (2)J((15)N-(19)F(eq)), 18 Hz) and a doublet ((2)J((19)F(ax)-(19)F(eq)), 134 Hz) were observed in the (19)F NMR spectrum that have been assigned to mer-OsO(3)F(2)((15)NCCH(3)); however, coupling of (15)N to the axial fluorine-on-osmium environment could not be resolved. The nitrogen atom of CH(3)CN is coordinated trans to a fluorine ligand in the mer-isomer. Quantum-chemical calculations at the SVWN and B3LYP levels of theory were used to calculate the energy-minimized gas-phase geometries, vibrational frequencies of fac- and mer-OsO(3)F(2)(NCCH(3)) and of CH(3)CN. The

  19. Replacing Ag(TS)SCH(2)-R with Ag(TS)O(2)C-R in EGaIn-based tunneling junctions does not significantly change rates of charge transport.

    PubMed

    Liao, Kung-Ching; Yoon, Hyo Jae; Bowers, Carleen M; Simeone, Felice C; Whitesides, George M

    2014-04-07

    This paper compares rates of charge transport by tunneling across junctions with the structures Ag(TS) X(CH2 )2n CH3  //Ga2 O3  /EGaIn (n=1-8 and X= SCH2  and O2 C); here Ag(TS) is template-stripped silver, and EGaIn is the eutectic alloy of gallium and indium. Its objective was to compare the tunneling decay coefficient (β, Å(-1) ) and the injection current (J0 , A cm(-2) ) of the junctions comprising SAMs of n-alkanethiolates and n-alkanoates. Replacing Ag(TS) SCH2 -R with Ag(TS) O2 C-R (R=alkyl chains) had no significant influence on J0 (ca. 3×10(3)  A cm(-2) ) or β (0.75-0.79 Å(-1) )-an indication that such changes (both structural and electronic) in the Ag(TS) XR interface do not influence the rate of charge transport. A comparison of junctions comprising oligo(phenylene)carboxylates and n-alkanoates showed, as expected, that β for aliphatic (0.79 Å(-1) ) and aromatic (0.60 Å(-1) ) SAMs differed significantly. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators.

    PubMed

    Han, Changho; Chatterjee, Arindam; Noetzel, Meredith J; Panarese, Joseph D; Smith, Emery; Chase, Peter; Hodder, Peter; Niswender, Colleen; Conn, P Jeffrey; Lindsley, Craig W; Stauffer, Shaun R

    2015-01-15

    Results from a 2012 high-throughput screen of the NIH Molecular Libraries Small Molecule Repository (MLSMR) against the human muscarinic receptor subtype 1 (M1) for positive allosteric modulators is reported. A content-rich screen utilizing an intracellular calcium mobilization triple-addition protocol allowed for assessment of all three modes of pharmacology at M1, including agonist, positive allosteric modulator, and antagonist activities in a single screening platform. We disclose a dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-one hit (DBPQ, CID 915409) and examine N-benzyl pharmacophore/SAR relationships versus previously reported quinolin-3(5H)-ones and isatins, including ML137. SAR and consideration of recently reported crystal structures, homology modeling, and structure-function relationships using point mutations suggests a shared binding mode orientation at the putative common allosteric binding site directed by the pendant N-benzyl substructure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Vibrational spectroscopy of NO + (H2O)n: Evidence for the intracluster reaction NO + (H2O)n --> H3O + (H2O)n - 2 (HONO) at n => 4

    NASA Astrophysics Data System (ADS)

    Choi, Jong-Ho; Kuwata, Keith T.; Haas, Bernd-Michael; Cao, Yibin; Johnson, Matthew S.; Okumura, Mitchio

    1994-05-01

    Infrared spectra of mass-selected clusters NO+(H2O)n for n=1 to 5 were recorded from 2700 to 3800 cm-1 by vibrational predissociation spectroscopy. Vibrational frequencies and intensities were also calculated for n=1 and 2 at the second-order Møller-Plesset (MP2) level, to aid in the interpretation of the spectra, and at the singles and doubles coupled cluster (CCSD) level energies of n=1 isomers were computed at the MP2 geometries. The smaller clusters (n=1 to 3) were complexes of H2O ligands bound to a nitrosonium ion NO+ core. They possessed perturbed H2O stretch bands and dissociated by loss of H2O. The H2O antisymmetric stretch was absent in n=1 and gradually increased in intensity with n. In the n=4 clusters, we found evidence for the beginning of a second solvation shell as well as the onset of an intracluster reaction that formed HONO. These clusters exhibited additional weak, broad bands between 3200 and 3400 cm-1 and two new minor photodissociation channels, loss of HONO and loss of two H2O molecules. The reaction appeared to go to completion within the n=5 clusters. The primary dissociation channel was loss of HONO, and seven vibrational bands were observed. From an analysis of the spectrum, we concluded that the n=5 cluster rearranged to form H3O+(H2O)3(HONO), i.e., an adduct of the reaction products.

  2. Spectrophotometric determination of cobalt in horse urine using 2-(5-bromo-2-pyridylazo)-5-[N-n-propyl-N-(3-sulfopropyl)amino]aniline as chromogenic reagent

    NASA Astrophysics Data System (ADS)

    Septia Rinda, Arfidyaninggar; Uraisin, Kanchana; Sabarudin, Akhmad; Nacapricha, Duangjai; Wilairat, Prapin

    2018-01-01

    Cobalt has been reported for being abused as an illegal doping agent due to its ability as an erythropoiesis-stimulating agent for enhancing performance in racehorses. Since 2015, cobalt is listed as a prohibited substance by the International Federation of Horseracing Authorities (IFHA) with a urinary threshold of 0.1 μg cobalt per mL urine. To prevent the misuse of cobalt in racehorse, a simple method for detection of cobalt is desirable. In this work, the detection of cobalt is based on the spectrometric detection of the complex formation between cobalt(II) and 2-(5-bromo-2-pyridylazo)-5-[N-n-propyl-N-(3-sulfopropyl)amino]aniline at pH 4. The absorbance of the complex is monitored at 602 nm. The metal:ligand ratio of the complex is 1:2. The calibration graph was linear in the range of 0 - 2.5 μM {Absorbance = (0.0825 ± 0.0013)[Co2+] + (0.0406 ± 0.0003), r2 = 0.999} and the detection limit (3 SD of intercept)/slope) was 0.044 μM. The proposed method has been successfully applied to horse urine samples with the recoveries in the range 91 - 98%.

  3. Two polymorphs of 2,5-dichloro-3,6-bis(dibenzylamino)-p-hydroquinone with flexible dibenzylamino groups.

    PubMed

    Shin, In Sub; Shimada, Yuta; Horiguchi-Babamoto, Emi; Matsumoto, Shinya

    2018-04-01

    We obtained two conformational polymorphs of 2,5-dichloro-3,6-bis(dibenzylamino)-p-hydroquinone, C 34 H 30 Cl 2 N 2 O 2 . Both polymorphs have an inversion centre at the centre of the hydroquinone ring (Z' = 1/2), and there are no significant differences between their bond lengths and angles. The most significant structural difference in the molecular conformations was found in the rotation of the phenyl rings of the two crystallographically independent benzyl groups. The crystal structures of the polymorphs were distinguishable with respect to the arrangement of the hydroquinone rings and the packing motif of the phenyl rings that form part of the benzyl groups. The phenyl groups of one polymorph are arranged in a face-to-edge motif between adjacent molecules, with intermolecular C-H...π interactions, whereas the phenyl rings in the other polymorph form a lamellar stacking pattern with no significant intermolecular interactions. We suggest that this partial conformational difference in the molecular structures leads to the significant structural differences observed in their molecular arrangements.

  4. The D 2 k R 4 invariants of mathcal{N} = 8 supergravity

    NASA Astrophysics Data System (ADS)

    Freedman, Daniel Z.; Tonni, Erik

    2011-04-01

    The existence of a linearized SUSY invariant for mathcal{N} = 8 supergravity whose gravitational components are usually called R 4 was established long ago by on-shell super-space arguments. Superspace and string theory methods have also established analogous higher dimensional D 2 k R 4 invariants. However, very little is known about the SUSY completions of these operators which involve other fields of the theory. In this paper we find the detailed component expansion of the linearized R 4 invariant starting from the corresponding superamplitude which generates all component matrix elements of the operator. It is then quite straightforward to extend results to the entire set of D 2 k R 4 operators.

  5. The influence of NH3 on NO2 conversion in a dc corona discharge in N2:O2:CO2:NO2:NH3 mixture

    NASA Astrophysics Data System (ADS)

    Dors, Mirosław; Mizeraczyk, Jerzy; Czech, Tadeusz; Konieczka, Jerzy

    1996-10-01

    The aim of this paper is to investigate the influence of NH3 additive (540-1470 ppm) on the conversion of NO2 and the creation of NO and N2O in a mixture of N2:O2:CO2: NO2:NH3 subjected to the so-called direct current (dc) corona discharge. The dc corona discharge was generated in a needle-to-plate reactor. Seven positively polarized needles were used as one electrode and a stainless steel plate as the other. The time-averaged discharge current was varied from 0 to 7 mA. It was found that the dc corona discharge decomposed NO2 and produced NO and N2O. The reduction of NO2 was higher without NH3 additive if the residence time of the operating gas was relatively short. However, in a longer corona discharge processing the NH3 additive may be useful for reduction of NO2.

  6. 40 CFR 721.10078 - Butanamide, 2-[(2-methoxy-4-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9,12,15-pentaazaheptadec-1-yl)substituted...-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9,12,15-pentaazaheptadec-1-yl)substituted...]-N-(2-methoxyphenyl)-3-oxo-, 4-[(17-substituted-3,6,9,12,15-pentaazaheptadec-1-yl)substituted]phenyl...

  7. The identification and analytical characterization of 2,2'-difluorofentanyl.

    PubMed

    Liu, Cuimei; Li, Tao; Han, Yu; Hua, Zhendong; Jia, Wei; Qian, Zhenhua

    2018-04-01

    New psychoactive substances (NPS) have expanded their distribution and become widely available in the global market in recent years. The illicit use of fentanyl and its analogs has become an important worldwide concern linked to their high potency and risk of fatal overdose. This study describes the analytical characterization of a new fentanyl derivative N-(1-(2-fluorophenethyl)-4-piperidinyl)-N-(2-fluorophenyl)propionamide (2,2'-difluorofentanyl). Identification was based on ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UHPLC-QTOF-MS), gas chromatography-mass spectrometry (GC-MS), Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. To our knowledge, this study is the first to report on analytical data for this compound. The most abundant fragment ion in the electrospray ionization (ESI) mass spectrum under collision-induced dissociation (CID) mode was formed by the cleavage between the piperidine ring and the N-phenyl-amide moiety of the protonated molecule. Two diagnostic ions in the electron ionization (EI) mass spectrum were formed by the loss of a tropylium ion (M-91), and by the degradation of the piperidine ring and dissociate of the COC 2 H 5 moiety altogether, respectively. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Synthesis and serotonergic activity of substituted 2, N-benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N, N-dimethyltryptamine derivatives: novel antagonists for the vascular 5-HT(1B)-like receptor.

    PubMed

    Moloney, G P; Martin, G R; Mathews, N; Milne, A; Hobbs, H; Dodsworth, S; Sang, P Y; Knight, C; Williams, M; Maxwell, M; Glen, R C

    1999-07-15

    The synthesis and vascular 5-HT(1B)-like receptor activity of a novel series of substituted 2, N-benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N, N-dimethyltryptamine derivatives are described. Modifications to the 5-ethylene-linked heterocycle and to substituents on the 2-benzylamide side chain have been explored. Several compounds were identified which exhibited affinity at the vascular 5-HT(1B)-like receptor of pK(B) > 7.0, up to 100-fold selectivity over alpha(1)-adrenoceptor affinity and 5-HT(2A) receptor affinity, and which exhibited a favorable pharmacokinetic profile. N-Benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(4,4-dimethyl-2, 5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxamide (23) was identified as a highly potent, silent (as judged by the inability of angiotensin II to unmask 5-HT(1B)-like receptor-mediated agonist activity in the rabbit femoral artery), and competitive vascular 5-HT(1B)-like receptor antagonist with a plasma elimination half-life of approximately 4 h in dog plasma and with good oral bioavailability. The selectivity of compounds from this series for the vascular 5-HT(1B)-like receptors over other receptor subtypes is discussed as well as a proposed mode of binding to the receptor pharmacophore. It has been proposed that the aromatic ring of the 2, N-benzylcarboxamide group can occupy an aromatic binding site rather than the indole ring. The resulting conformation allows an amine-binding site to be occupied by the ethylamine nitrogen and a hydrogen-bonding site to be occupied by one of the hydantoin carbonyls. The electronic nature of the 2,N-benzylcarboxamide aromatic group as well as the size of substituents on this aromatic group is crucial for producing potent and selective antagonists. The structural requirement on the 3-ethylamine side chain incorporating the protonatable nitrogen is achieved by the bulky 2, N-benzylcarboxamide group and its close proximity to the 3-side chain.

  9. TCP3 interacts with R2R3-MYB proteins, promotes flavonoid biosynthesis and negatively regulates the auxin response in Arabidopsis thaliana.

    PubMed

    Li, Shutian; Zachgo, Sabine

    2013-12-01

    TCP proteins belong to the plant-specific bHLH transcription factor family, and function as key regulators of diverse developmental processes. Functional redundancy amongst family members and post-transcriptional down-regulation by miRJAW of several TCP genes complicate their functional characterization. Here, we explore the role of TCP3 by analyzing transgenic plants expressing miRJAW-resistant mTCP3 and dominant-negative TCP3SRDX. Seedlings and seeds of mTCP3 plants were found to hyper-accumulate flavonols, anthocyanins and proanthocyanidins, whereas levels of proanthocyanidins were slightly reduced in TCP3SRDX plants. R2R3-MYB proteins control not only early flavonoid biosynthetic steps but also activate late flavonoid biosynthetic genes by forming ternary R2R3-MYB/bHLH/WD40 (MBW) complexes. TCP3 interacted in yeast with R2R3-MYB proteins, which was further confirmed in planta using BiFC experiments. Yeast three-hybrid assays revealed that TCP3 significantly strengthened the transcriptional activation capacity of R2R3-MYBs bound by the bHLH protein TT8. Transcriptome analysis of mTCP3 and TCP3SRDX plants supported a role for TCP3 in enhancing flavonoid biosynthesis. Moreover, several auxin-related developmental abnormalities were observed in mTCP3 plants. Transcriptome data coupled with studies of an auxin response reporter and auxin efflux carriers showed that TCP3 negatively modulates the auxin response, probably by compromising auxin transport capacity. Genetic experiments revealed that the chalcone synthase mutant tt4-11 lacking flavonoid biosynthesis abrogated the auxin-related defects caused by mTCP3. Together, these data suggest that TCP3 interactions with R2R3-MYBs lead to enhanced flavonoid production, which further negatively modulates the auxin response. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  10. N-acetylcysteine Ameliorates Prostatitis via miR-141 Regulating Keap1/Nrf2 Signaling.

    PubMed

    Wang, Liang-Liang; Huang, Yu-Hua; Yan, Chun-Yin; Wei, Xue-Dong; Hou, Jian-Quan; Pu, Jin-Xian; Lv, Jin-Xing

    2016-04-01

    Chronic prostatitis was the most common type of prostatitis and oxidative stress was reported to be highly elevated in prostatitis patients. In this study, we determined the effect of N-acetylcysteine (NAC) on prostatitis and the molecular mechanism involved in it. Male Sprague-Dawley rats were divided into three groups: control group (group A, n = 20), carrageenan-induced chronic nonbacterial prostatitis (CNP) model group (group B, n = 20), and carrageenan-induced CNP model group with NAC injection (group C, n = 20). Eye score, locomotion score, inflammatory cell count, cyclooxygenase 2 (COX2) expression, and Evans blue were compared in these three groups. The expression of miR-141 was determined by quantitative real-time PCR (qRT-PCR). Moreover, protein expressions of Kelch-like ECH-associated protein-1 (Keap1) and nuclear factor erythroid-2 related factor 2 (Nrf2) and its target genes were examined by Western blot. Luciferase reporter assay was performed in RWPE-1 cells transfected miR-141 mimic or inhibitor and the plasmid carrying 3'-UTR of Keap1. The value of eye score, locomotion score, inflammatory cell count, and Evans blue were significantly decreased in group C, as well as the expression of COX2, when comparing to that of group B. These results indicated that NAC relieved the carrageenan-induced CNP. Further, we found that NAC increased the expression of miR-141 and activated the Keap1/Nrf2 signaling. Luciferase reporter assay revealed that miR-141 mimic could suppress the activity of Keap1 and stimulate the downstream target genes of Nrf2. In addition, miR-141 inhibitor could reduce the effect of NAC on prostatitis. NAC ameliorates the carrageenan-induced prostatitis and prostate inflammation pain through miR-141 regulating Keap1/Nrf2 signaling.

  11. Anti-cancer agents based on N-acyl-2, 3-dihydro-1H-pyrrolo[2,3-b] quinoline derivatives and a method of making

    DOEpatents

    Gakh, Andrei; Krasavin, Mikhail; Karapetian, Ruben; Rufanov, Konstantin A; Konstantinov, Igor; Godovykh, Elena; Soldatkina, Olga; Sosnov, Andrey V

    2013-04-16

    The present disclosure relates to novel compounds that can be used as anti-cancer agents in the prostate cancer therapy. In particular, the invention relates to N-acyl derivatives of 2,3-dihydro-1H-pyrrolo[2,3-b]quinolines having the structural Formula (I), ##STR00001## stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof. The meaning of R1 is independently selected from H; C1-C6 Alkyl, cyclo-Alkyl or iso-Alkyl substituents; R2 is selected from C1-C6 Alkyl, cyclo-Alkyl or iso-Alkyl; substituted or non-substituted, fused or non-fused to substituted or non-substituted aromatic ring, aryl or heteroaryl groups. The invention also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

  12. TiO2@Pt@CeO2 nanocomposite as a bifunctional catalyst for enhancing photo-reduction of Cr (VI) and photo-oxidation of benzyl alcohol.

    PubMed

    Li, Shunxing; Cai, Jiabai; Wu, Xueqing; Liu, Biwen; Chen, Qiaoying; Li, Yuehai; Zheng, Fengying

    2018-03-15

    An solar-light-driven and bifunctional photocatalyst was designed for photo-reduction of Cr(VI) and selective photo-oxidation of benzyl alcohol into benzaldehyde in the presence of water under ambient conditions. Double-shelled and sandwiched TiO 2 @Pt@CeO 2 hollow spheres were prepared by using functionalized polystyrene spheres, sol-gel, hydrothermal reaction, and calcination. The Pt nanoparticles (NPs) were controllably loaded between the TiO 2 shell and CeO 2 shell. Under solar-light irradiation, the photo-reduction rate of Cr(VI) (μmol h -1 ) was in the order of TiO 2 @Pt@CeO 2 (1.901) > TiO 2 @CeO 2 (1.424) > TiO 2 (1.040) > CeO 2 (0.992). Among the above-mentioned photocatalysts, the conversion rate of benzyl alcohol for TiO 2 @Pt@CeO 2 was also the best. These results were attributed to the combination of TiO 2 and CeO 2 as photocatalyst and oxygen buffer, the double-shelled and sandwiched nanostructure, and the addition of Pt NPs as cocatalyst and electron trap site, which could store and shuttle photo-generated electrons, reduce the recombination of the electron-hole, and then enhance photo-generation of active radicals. This conclusion was verified by the electron paramagnetic resonance (EPR) spectroscopy. Considering the versatile combination of photocatalyst, oxygen buffer and cocatalyst, this work could provide new insights into the design of high-performance bifunctional photocatalysts for heavy metal removal and selective synthesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. (R,S)-3-Carb­oxy-2-(isoquinolinium-2-yl)propanoate monohydrate

    PubMed Central

    Stilinović, Vladimir; Frkanec, Leo; Kaitner, Branko

    2010-01-01

    The title compound, C13H11NO4·H2O, is a monohydrate of a betaine exhibiting a positively charged N-substituted isoquino­line group and a deprotonated carboxyl group. In the crystal, mol­ecules are connected via short O—H⋯O hydrogen bonds between protonated and deprotonated carboxyl groups into chains of either R or S enanti­omers along [001]. These chains are additionally connected by hydrogen bonding between water mol­ecules and the deprotonated carb­oxy groups of neighbouring mol­ecules. PMID:21579503

  14. 1-Benzyl-2-(1H-indol-3-yl)-5-oxo-pyrrolidine-2-carbonitrile.

    PubMed

    Tamazyan, Rafael; Armen, Ayvazyan; Ashot, Martirosyan; Sahak, Gasparyan; Schinazi, Raymond

    2008-01-04

    In the title compound, C(20)H(17)N(3)O, a potential anti-human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse-transcriptase inhibitor, the pyrrolidine ring has an envelope conformation. In the crystal structure, adjacent mol-ecules are connected into infinite chains via an N-H⋯O hydrogen bond.

  15. A novel S-enantioselective amidase acting on 3,3,3-trifluoro-2-hydroxy-2-methylpropanamide from Arthrobacter sp. S-2.

    PubMed

    Fuhshuku, Ken-ichi; Watanabe, Shunsuke; Nishii, Tetsuro; Ishii, Akihiro; Asano, Yasuhisa

    2015-01-01

    A novel S-enantioselective amidase acting on 3,3,3-trifluoro-2-hydroxy-2-methylpropanamide was purified from Arthrobacter sp. S-2. The enzyme acted S-enantioselectively on 3,3,3-trifluoro-2-hydroxy-2-methylpropanamide to yield (S)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid. Based on the N-terminal amino acid sequence of this amidase, the gene coding S-amidase was cloned from the genomic DNA of Arthrobacter sp. S-2 and expressed in an Escherichia coli host. The recombinant S-amidase was purified and characterized. Furthermore, the purified recombinant S-amidase with the C-His6-tag, which was expressed in E. coli as the C-His6-tag fusion protein, was used in the kinetic resolution of (±)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide to obtain (S)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid and (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide.

  16. The structure, stability, and infrared spectrum of B 2N, B 2N +, B 2N -, BO, B 2O and B 2N 2.

    NASA Astrophysics Data System (ADS)

    Martin, J. M. L.; François, J. P.; Gijbels, R.

    1992-05-01

    The structure, infrared spectrum, and heat of formation of B 2N, B 2N -, BO, and B 2O have been studied ab initio. B 2N is very stable; B 2O even more so. B 2N, B 2N -, B 2O, and probably B 2N + have symmetric linear ground-state structures; for B 2O, an asymmetric linear structure lies about 12 kcal/mol above the ground state. B 2N +, B 2N - and B 2O have intense asymmetric stretching frequencies, predicted near 870, 1590 and 1400 cm -1, respectively. Our predicted harmonic frequencies and isotopic shifts for B 2O confirm the recent experimental identification by Andrews and Burkholder. Absorptions at 1889.5 and 1998.5 cm -1 in noble-gas trapped boron nitride vapor belong the BNB and BNBN ( 3Π), respectively; a tentative assignment of 882.5 cm -1 to BNB + is proposed. Total atomization energies Σ De (Σ D0) are computed (accuracy ±2 kcal/mol) as: BO 193.1 (190.4), B 2O 292.5 (288.7), B 2N 225.0 (250.3) kcal/mol. The ionization potential and electron affinity of B 2N are predicted to be 8.62±0.1 and 3.34±0.1 eV. The MP4-level additivity approximations involved in G1 theory results in errors on the order of 1 kcal/mol in the Σ De values.

  17. A Three-Step Atomic Layer Deposition Process for SiN x Using Si2Cl6, CH3NH2, and N2 Plasma.

    PubMed

    Ovanesyan, Rafaiel A; Hausmann, Dennis M; Agarwal, Sumit

    2018-06-06

    We report a novel three-step SiN x atomic layer deposition (ALD) process using Si 2 Cl 6 , CH 3 NH 2 , and N 2 plasma. In a two-step process, nonhydrogenated chlorosilanes such as Si 2 Cl 6 with N 2 plasmas lead to poor-quality SiN x films that oxidize rapidly. The intermediate CH 3 NH 2 step was therefore introduced in the ALD cycle to replace the NH 3 plasma step with a N 2 plasma, while using Si 2 Cl 6 as the Si precursor. This three-step process lowers the atomic H content and improves the film conformality on high-aspect-ratio nanostructures as Si-N-Si bonds are formed during a thermal CH 3 NH 2 step in addition to the N 2 plasma step. During ALD, the reactive surface sites were monitored using in situ surface infrared spectroscopy. Our infrared spectra show that, on the post-N 2 plasma-treated SiN x surface, Si 2 Cl 6 reacts primarily with the surface -NH 2 species to form surface -SiCl x ( x = 1, 2, or 3) bonds, which are the reactive sites during the CH 3 NH 2 cycle. In the N 2 plasma step, reactive -NH 2 surface species are created because of the surface H available from the -CH 3 groups. At 400 °C, the SiN x films have a growth per cycle of ∼0.9 Å with ∼12 atomic percent H. The films grown on high-aspect-ratio nanostructures have a conformality of ∼90%.

  18. Two mixed-ligand lanthanide–hydrazone complexes: [Pr(NCS)3(pbh)2]·H2O and [Nd(NCS)(NO3)(pbh)2(H2O)]NO3·2.33H2O [pbh is N′-(pyridin-2-ylmethylidene)benzo­hydrazide, C13H11N3O

    PubMed Central

    Paschalidis, Damianos G.; Harrison, William T. A.

    2016-01-01

    The gel-mediated syntheses and crystal structures of [N′-(pyridin-2-ylmethylidene-κN)benzohydrazide-κ2 N′,O]tris(thiocyanato-κN)praseodymium(III) mono­hydrate, [Pr(NCS)3(C13H11N3O)2]·H2O, (I), and aqua(nitrato-κ2 O,O′)[N′-(pyri­din-2-ylmethylidene-κN)benzohydrazide-κ2 N′,O](thiocyanato-κN)neo­dym­ium(III) nitrate 2.33-hydrate, [Nd(NCS)(NO3)(C13H11N3O)2(H2O)]NO3·2.33H2O, (II), are reported. The Pr3+ ion in (I) is coordinated by two N,N,O-tridentate N′-(pyridin-2-ylmethylidene)benzohydrazide (pbh) ligands and three N-bonded thio­cyanate ions to generate an irregular PrN7O2 coordination polyhedron. The Nd3+ ion in (II) is coordinated by two N,N,O-tridentate pbh ligands, an N-bonded thio­cyanate ion, a bidentate nitrate ion and a water mol­ecule to generate a distorted NdN5O5 bicapped square anti­prism. The crystal structures of (I) and (II) feature numerous hydrogen bonds, which lead to the formation of three-dimensional networks in each case. PMID:26958385

  19. TES/Aura L2 Ozone (O3) Nadir V6 (TL2O3N)

    Atmospheric Science Data Center

    2018-01-18

    TES/Aura L2 Ozone (O3) Nadir (TL2O3N) News:  TES News Join ... Project Title:  TES Discipline:  Tropospheric Composition Version:  V6 Level:  L2 Platform:  TES/Aura L2 Ozone Spatial Coverage:  5.3 x 8.5 km nadir ...

  20. Design, synthesis and antimalarial activity of novel bis{N-[(pyrrolo[1,2-a]quinoxalin-4-yl)benzyl]-3-aminopropyl}amine derivatives.

    PubMed

    Guillon, Jean; Cohen, Anita; Gueddouda, Nassima Meriem; Das, Rabindra Nath; Moreau, Stéphane; Ronga, Luisa; Savrimoutou, Solène; Basmaciyan, Louise; Monnier, Alix; Monget, Myriam; Rubio, Sandra; Garnerin, Timothée; Azas, Nadine; Mergny, Jean-Louis; Mullié, Catherine; Sonnet, Pascal

    2017-12-01

    Novel series of bis- and tris-pyrrolo[1,2-a]quinoxaline derivatives 1 were synthesized and tested for in vitro activity upon the intraerythrocytic stage of W2 and 3D7 Plasmodium falciparum strains. Biological results showed good antimalarial activity with IC 50 in the μM range. In attempting to investigate the large broad-spectrum antiprotozoal activities of these new derivatives, their properties toward Leishmania donovani were also investigated and revealed their selective antiplasmodial profile. In parallel, the in vitro cytotoxicity of these molecules was assessed on the human HepG2 cell line. Structure-activity relationships of these new synthetic compounds are discussed here. The bis-pyrrolo[1,2-a]quinoxalines 1n and 1p were identified as the most potent antimalarial candidates with selectivity index (SI) of 40.6 on W2 strain, and 39.25 on 3D7 strain, respectively. As the telomeres of the parasite could constitute an attractive target, we investigated the possibility of targeting Plasmodium telomeres by stabilizing the Plasmodium telomeric G-quadruplexes through a FRET melting assay by our new compounds.

  1. Swine influenza virus vaccine serologic cross-reactivity to contemporary U.S. swine H3N2 and efficacy in pigs infected with an H3N2 similar to 2011-2012 H3N2v

    USDA-ARS?s Scientific Manuscript database

    Background: Swine influenza A virus (IAV) reassortment with 2009 H1N1 pandemic (H1N1pdm09) virus has been documented and new genotypes and sub-clusters of H3N2 have since expanded in the U.S. swine population. An H3N2 variant (H3N2v) virus with the H1N1pdm09 matrix gene and the remaining genes of sw...

  2. Effect of substituent groups (R= sbnd CH3, sbnd Br and sbnd CF3) on the structure, stability and redox property of [Cr(R-pic)2(H2O)2]NO3·H2O complexes

    NASA Astrophysics Data System (ADS)

    Chai, Jie; Liu, Yanfei; Liu, Bin; Yang, Binsheng

    2017-12-01

    Complexes [Cr(3-CH3-pic)2(H2O)2]NO3·H2O (1), [Cr(5-Br-pic)2(H2O)2]NO3·H2O (2) and [Cr(5-CF3-pic)2(H2O)2]NO3·H2O (3) were synthesized (pic = pyridine-2-carboxylic acid) and characterized by X-ray crystal diffraction. Crystal structure indicates that two bidentate ligands occupy equatorial position and two H2O occupy axial positions in trans-configuration. (i) Decomposition of complexes 1, 2 and 3 in different medium (phosphate buffered saline (PBS), apo-ovotransferrin (apootf) and EDTA) indicates that decomposition rate constants of these complexes follow the sequence of 1 < 2 < 3. (ii) The redox potential of Cr(III)/Cr(II) by cyclic voltammetry follows the sequence of 1 (-1.20 V) > 3 (-1.29 V) > 2 (-1.31 V). (iii) In addition, ·OH-generation of the new synthesized complexes was determined by Fenton-like reaction in comparison with Cr(pic)3, and it may be related to the reduction potential of the complexes. (iv) Moreover, Hammett substituent constants σp (inductive) and σm (resonance) (R = 3-CH3, 5-Br, 5-CF3) were introduced to evaluate the impact of substituent groups on the bond length and decomposition kinetics. The substituent group on the ligand has great effect on the properties of the complexes.

  3. TES/Aura L2 Ammonia (NH3) Nadir V6 (TL2NH3N)

    Atmospheric Science Data Center

    2018-01-18

    TES/Aura L2 Ammonia (NH3) Nadir (TL2NH3N) News:  TES News ... Level:  L2 Instrument:  TES/Aura L2 Ammonia Spatial Coverage:  5.3 x 8.5 km nadir ... Contact User Services Parameters:  Ammonia Legacy:  Retired data product , click here for ...

  4. A R2R3-MYB Transcription Factor from Epimedium sagittatum Regulates the Flavonoid Biosynthetic Pathway

    PubMed Central

    Lv, Haiyan; Luo, Ming; Zeng, Shaohua; Pattanaik, Sitakanta; Yuan, Ling; Wang, Ying

    2013-01-01

    Herba epimedii (Epimedium), a traditional Chinese medicine, has been widely used as a kidney tonic and antirheumatic medicine for thousands of years. The bioactive components in herba epimedii are mainly prenylated flavonol glycosides, end-products of the flavonoid pathway. Epimedium species are also used as garden plants due to the colorful flowers and leaves. Many R2R3-MYB transcription factors (TFs) have been identified to regulate the flavonoid and anthocyanin biosynthetic pathways. However, little is known about the R2R3-MYB TFs involved in regulation of the flavonoid pathway in Epimedium. Here, we reported the isolation and functional characterization of the first R2R3-MYB TF (EsMYBA1) from Epimedium sagittatum (Sieb. Et Zucc.) Maxim. Conserved domains and phylogenetic analysis showed that EsMYBA1 belonged to the subgroup 6 clade (anthocyanin-related MYB clade) of R2R3-MYB family, which includes Arabidopsis AtPAP1, apple MdMYB10 and legume MtLAP1. EsMYBA1 was preferentially expressed in leaves, especially in red leaves that contain higher content of anthocyanin. Alternative splicing of EsMYBA1 resulted in three transcripts and two of them encoded a MYB-related protein. Yeast two-hybrid and transient luciferase expression assay showed that EsMYBA1 can interact with several bHLH regulators of the flavonoid pathway and activate the promoters of dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS). In both transgenic tobacco and Arabidopsis, overexpression of EsMYBA1 induced strong anthocyanin accumulation in reproductive and/or vegetative tissues via up-regulation of the main flavonoid-related genes. Furthermore, transient expression of EsMYBA1 in E. sagittatum leaves by Agrobacterium infiltration also induced anthocyanin accumulation in the wounded area. This first functional characterization of R2R3-MYB TFs in Epimedium species will promote further studies of the flavonoid biosynthesis and regulation in medicinal plants. PMID:23936468

  5. Nonstoichiometry in inorganic fluorides: 2. Ionic conductivity of nonstoichiometric M 1 - x R xF2 + x and R 1 - y M yF3 - y crystals ( M = Ca, Sr, Ba; R are rare earth elements)

    NASA Astrophysics Data System (ADS)

    Sobolev, B. P.; Sorokin, N. I.

    2014-11-01

    The peak manifestation of nonstoichiometry in fluoride systems in the number of phases with valuable properties and wide homogeneity ranges is 45 MF2- RF3 systems, where M = Ca, Sr, Ba and R are 15 rare earth elements from La to Lu and Y (with Pm and Sc excluded). A deviation from stoichiometry in crystals of the M 1 - x R xF2 + x (CaF2 fluorite type) and R 1 - y M yF3 - y (LaF3 tysonite type) phases is responsible for the fluorine superionic conductivity σ. The range of variation in σ with changes in the qualitative ( M, R) and quantitative ( x, y) compositions in both structure types is very wide. The σ value changes by a factor of 108 in the M 1 - x R xF2 + x phases (at 500 K) and by a factor of 106 in the R 1 - y M yF3 - y phases (at 293 K). Changing compositions, one can also obtain crystals with σ values large enough for their use as fluorine-conducting solid electrolytes. Phases promising for solid electrolytes were revealed in the MFm- RFn systems ( m < n ≤ 4), which were studied within the program of searching for new multicomponent fluoride materials at the Institute of Crystallography, Russian Academy of Sciences (IC RAS). Superionic conductivity is one of the peak manifestations of the influence of defect structure of nonstoichiometric crystals on their properties. The subject of this review is the results of the studies performed at the IC RAS on the ionic conductivity of single crystals of the M 1 - x R xF2 + x and R 1 - y M yF3 - y nonstoichiometric phases.

  6. Raman study of HgBa 2Ca n-1 Cu nO 2 n+2+ δ ( n=1,2,3,4 and 5) superconductors

    NASA Astrophysics Data System (ADS)

    Zhou, Xingjiang; Cardona, M.; Chu, C. W.; Lin, Q. M.; Loureiro, S. M.; Marezio, M.

    1996-02-01

    Polarized micro-Raman scattering measurements have been performed on the five members of the HgBa 2Ca n-1 Cu nO 2 n+2+ δ ( n=1,2,3,4 and 5) high- Tc superconductor family using different laser frequencies. Local laser annealing measurements were carried out to investigate the variation of the Raman spectra with the excess oxygen content, δ. A systematic evolution of the spectra, which display mainly peaks near 590, 570, 540 and 470 cm -1, with increasing number of CuO 2 layers has been observed; its origin has been shown to lie in the variation of the interstitial oxygen content. In addition to confirming that the 590 cm -1 mode represents vibration of apical oxygens in the absence of neighboring excess oxygen, the 570 cm -1 mode, which may be composed of some finer structures, has been assigned to the vibration of the apical oxygen modified by the presence of the neighboring excess oxygens. The 540 and 470 cm -1 modes may represent the direct vibration of excess oxygens. The implication of possible different distribution sites of excess oxygens is discussed. All other observed lower-frequency modes are also assigned.

  7. Cyclometalated products of [(COE)(2)RhCl](2) and 1,3-(RSCH(2))(2)C(6)H(4) (R = (t)Bu, (i)Pr) Are Dimeric. Synthesis, molecular structures, and solution dynamics of [mu-ClRh(H)(RSCH(2))(2)C(6)H(3)-2,6](2).

    PubMed

    Evans, Daniel R; Huang, Mingsheng; Seganish, W Michael; Chege, Esther W; Lam, Yiu-Fai; Fettinger, James C; Williams, Tracie L

    2002-05-20

    Two tridentate thioether pincer ligands, 1,3-(RSCH(2))(2)C(6)H(4) (R = (t)()Bu, 1a; R = (i)()Pr, 1b) underwent cyclometalation using [(COE)(2)RhCl](2) in air/moisture-free benzene at room temperature. The resultant complexes, [mu-ClRh(H)(RSCH(2))(2)C(6)H(3)-2,6](2) (R = (t)Bu, 2a; R = (i)Pr, 2b) are dimeric both in the solid state and in solution. A battery of variable-temperature one- and two-dimensional (1)H NMR experiments showed conclusively that both complexes undergo dynamic exchange in solution. Exchange between two dimeric diastereomers of 2a in solution occurred via rotation about the Rh-C(ipso) bond. The dynamic exchange of 2b was significantly more complex as an additional exchange mechanism, sulfur inversion, occurred, which resulted in the exchange between several diastereomers in solution.

  8. [Design, synthesis and biological evaluation of novel para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones as human PARP-1 inhibitors].

    PubMed

    Yao, Hai-Ping; Zhu, Zhi-Xiang; Ji, Ming; Chen, Xiao-Guang; Xu, Bai-Ling

    2014-04-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.

  9. (E)-1-(2,4-Di­nitro­phen­yl)-2-(3-eth­oxy-4-hy­droxy­benzyl­idene)hydrazine

    PubMed Central

    Fun, Hoong-Kun; Chantrapromma, Suchada; Ruanwas, Pumsak; Kobkeatthawin, Thawanrat; Chidan Kumar, C. S.

    2014-01-01

    The mol­ecule of the title hydrazine derivative, C15H14N4O6, is essentially planar, the dihedral angle between the substituted benzene rings being 2.25 (9)°. The eth­oxy and hy­droxy groups are almost coplanar with their bound benzene ring [r.m.s. deviation = 0.0153 (2) Å for the ten non-H atoms]. Intra­molecular N—H⋯O and O—H⋯Oeth­oxy hydrogen bonds generate S(6) and S(5) ring motifs, respectively. In the crystal, mol­ecules are linked by O—H⋯Onitro hydrogen bonds into chains propagating in [010]. Weak aromatic π–π inter­actions, with centroid–centroid distances of 3.8192 (19) and 4.0491 (19) Å, are also observed. PMID:24527018

  10. Structure-activity relationship of daptomycin analogues with substitution at (2S, 3R) 3-methyl glutamic acid position.

    PubMed

    Lin, Du'an; Lam, Hiu Yung; Han, Wenbo; Cotroneo, Nicole; Pandya, Bhaumik A; Li, Xuechen

    2017-02-01

    Daptomycin is a highly effective lipopeptide antibiotic against Gram-positive pathogens. The presence of (2S, 3R) 3-methyl glutamic acid (mGlu) in daptomycin has been found to be important to the antibacterial activity. However the role of (2S, 3R) mGlu is yet to be revealed. Herein, we reported the syntheses of three daptomycin analogues with (2S, 3R) mGlu substituted by (2S, 3R) methyl glutamine (mGln), dimethyl glutamic acid and (2S, 3R) ethyl glutamic acid (eGlu), respectively, and their antibacterial activities. The detailed synthesis of dimethyl glutamic acid was also reported. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Catalytic N 2 Reduction to Silylamines and Thermodynamics of N 2 Binding at Square Planar Fe

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Prokopchuk, Demyan E.; Wiedner, Eric S.; Walter, Eric D.

    The geometric constraints imposed by a tetradentate P 4N 2 ligand play an essential role in stabilizing square planar Fe complexes with changes in metal oxidation state. A combination of high-pressure electrochemistry and variable temperature UV-vis spectroscopy were used to obtain these thermodynamic measurements, while X-ray crystallography, 57Fe Mössbauer spectroscopy, and EPR spectroscopy were used to fully characterize these new compounds. Analysis of Fe 0, FeI, and FeII complexes reveals that the free energy of N 2 binding across three oxidation states spans more than 37 kcal mol -1. The square pyramidal Fe0(N 2)(P 4N 2) complex catalyzes the conversionmore » of N 2 to N(SiR 3) 3 (R = Me, Et) at room temperature, representing the highest turnover number (TON) of any Fe-based N 2 silylation catalyst to date (up to 65 equiv N(SiMe 3) 3 per Fe center). Elevated N 2 pressures (> 1 atm) have a dramatic effect on catalysis, increasing N 2 solubility and the thermodynamic N 2 binding affinity at Fe0(N 2)(P 4N 2). Acknowledgment. This research was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences. EPR experiments were performed using EMSL, a national scientific user facility sponsored by the DOE’s Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory (PNNL). PNNL is operated by Battelle for the U.S. DOE. Computational resources were provided by the National Energy Research Scientific Computing Center (NERSC) at Lawrence Berkeley National Laboratory. The authors thank Prof. Yisong Alex Guo at Carnegie Mellon University for recording Mössbauer data for some complexes and Emma Wellington and Kaye Kuphal for their assistance with the collection of Mössbauer data at Colgate University, Dr. Katarzyna Grubel for X-ray assistance, and Dr. Rosalie Chu for mass spectrometry

  12. Benzylic oxidation of gemfibrozil-1-O-beta-glucuronide by P450 2C8 leads to heme alkylation and irreversible inhibition.

    PubMed

    Baer, Brian R; DeLisle, Robert Kirk; Allen, Andrew

    2009-07-01

    Gemfibrozil-1-O-beta-glucuronide (GEM-1-O-gluc), a major metabolite of the antihyperlipidemic drug gemfibrozil, is a mechanism-based inhibitor of P450 2C8 in vitro, and this irreversible inactivation may lead to clinical drug-drug interactions between gemfibrozil and other P450 2C8 substrates. In light of this in vitro finding and the observation that the glucuronide conjugate does not contain any obvious structural alerts, the current study was conducted to determine the potential site of GEM-1-O-gluc bioactivation and the subsequent mechanism of P450 2C8 inhibition (i.e., modification of apoprotein or heme). LC/MS analysis of a reaction mixture containing recombinant P450 2C8 and GEM-1-O-gluc revealed that the substrate was covalently linked to the heme prosthetic heme group during catalysis. A combination of mass spectrometry and deuterium isotope effects revealed that a benzylic carbon on the 2',5'-dimethylphenoxy group of GEM-1-O-gluc was covalently bound to the heme of P450 2C8. The regiospecificity of substrate addition to the heme group was not confirmed experimentally, but computational modeling experiments indicated that the gamma-meso position was the most likely site of modification. The metabolite profile, which consisted of two benzyl alcohol metabolites and a 4'-hydroxy-GEM-1-O-gluc metabolite, indicated that oxidation of GEM-1-O-gluc was limited to the 2',5'-dimethylphenoxy group. These results are consistent with an inactivation mechanism wherein GEM-1-O-gluc is oxidized to a benzyl radical intermediate, which evades oxygen rebound, and adds to the gamma-meso position of heme. Mechanism-based inhibition of P450 2C8 can be rationalized by the formation of the GEM-1-O-gluc-heme adduct and the consequential restriction of additional substrate access to the catalytic iron center.

  13. Juvenile treatment with mGluR2/3 agonist prevents schizophrenia-like phenotypes in adult by acting through GSK3β.

    PubMed

    Xing, Bo; Han, Genie; Wang, Min-Juan; Snyder, Melissa A; Gao, Wen-Jun

    2018-05-14

    Prodromal memory deficits represent an important marker for the development of schizophrenia (SZ), in which glutamatergic hypofunction occurs in the prefrontal cortex (PFC). The mGluR2/3 agonist LY379268 (LY37) attenuates excitatory N-methyl-D-aspartate receptor (NMDAR)-induced neurotoxicity, a central pathological characteristic of glutamatergic hypofunction. We therefore hypothesized that early treatment with LY37 would rescue cognitive deficits and confer benefits for SZ-like behaviors in adults. To test this, we assessed whether early intervention with LY37 would improve learning outcomes in the Morris Water Maze for rats prenatally exposed to methylazoxymethanol acetate (MAM), a neurodevelopmental SZ model. We found that a medium dose of LY37 prevents learning deficits in MAM rats. These effects were mediated through postsynaptic mGluR2/3 via improving GluN2B-NMDAR function by inhibiting glycogen synthase kinase-3β (GSK3β). Furthermore, dendritic spine loss and learning and memory deficits observed in adult MAM rats were restored by juvenile LY37 treatment, which did not change prefrontal neuronal excitability and glutamatergic synaptic transmission in adult normal rats. Our results provide a mechanism for mGluR2/3 agonists against NMDAR hypofunction, which may prove to be beneficial in the prophylactic treatment of SZ. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. General synthesis of 2,1-benzisoxazoles (anthranils) from nitroarenes and benzylic C-H acids in aprotic media promoted by combination of strong bases and silylating agents.

    PubMed

    Wiȩcław, Michał; Bobin, Mariusz; Kwast, Andrzej; Bujok, Robert; Wróbel, Zbigniew; Wojciechowski, Krzysztof

    2015-11-01

    Carbanions of phenylacetonitriles, benzyl sulfones, and dialkyl benzylphosphonates add nitroarenes at the ortho-position to the nitro group to form [Formula: see text]-adducts that, upon treatment with trialkylchlorosilane and additional base (t-BuOK or DBU), transform into 3-aryl-2,1-benzisoxazoles in moderate-to-good yields.

  15. Simple synthesis of graphene nanocomposites MgO-rGO and Fe2O3-rGO for multifunctional applications

    NASA Astrophysics Data System (ADS)

    Abdel-Aal, Seham K.; Ionov, Andrey; Mozhchil, R. N.; Naqvi, Alim H.

    2018-05-01

    Hummer's method was used to prepare graphene oxide (GO) by chemical exfoliation of graphite. Simple precipitation method was used for the preparation of hybrid nanocomposites MgO-rGO and Fe2O3-rGO. A 0.3 Molar of corresponding metal nitrate solution and GO solution are used for the preparation process. XRD, FT-IR, and XPS were used to characterize the prepared nanocomposites. The reduction of GO into reduced rGO in the formed nanocomposites was confirmed. Morphological characterization showed the formation of needle-shaped nanocrystals of MgO successfully grown on graphene nanosheet with average crystallite size 8.4 nm. Hematite nanocomposite Fe2O3-rGO forms rod-shaped crystals with average crystallite size 27.5 nm. The saturation magnetization observed for Fe2O3-rGO is less than reported value for the pure Fe2O3 nanoparticles. Thermal properties of as-prepared hybrid nanocomposites MgO-rGO and Fe2O3-rGO showed thermal stability of the prepared nanocomposite over long range of temperature.

  16. Tomato R2R3-MYB Proteins SlANT1 and SlAN2: Same Protein Activity, Different Roles

    PubMed Central

    Bassolino, Laura; Povero, Giovanni; Spelt, Cornelis; Buti, Sara; Giuliano, Giovanni; Quattrocchio, Francesca; Koes, Ronald; Perata, Pierdomenico; Gonzali, Silvia

    2015-01-01

    Anthocyanins are water-soluble polyphenolic compounds with a high nutraceutical value. Despite the fact that cultivated tomato varieties do not accumulate anthocyanins in the fruit, the biosynthetic pathway can be activated in the vegetative organs by several environmental stimuli. Little is known about the molecular mechanisms regulating anthocyanin synthesis in tomato. Here, we carried out a molecular and functional characterization of two genes, SlAN2 and SlANT1, encoding two R2R3-MYB transcription factors. We show that both can induce ectopic anthocyanin synthesis in transgenic tomato lines, including the fruit. However, only SlAN2 acts as a positive regulator of anthocyanin synthesis in vegetative tissues under high light or low temperature conditions. PMID:26308527

  17. Efficacy of a Recombinant Turkey Herpesvirus H5 Vaccine Against Challenge With H5N1 Clades 1.1.2 and 2.3.2.1 Highly Pathogenic Avian Influenza Viruses in Domestic Ducks (Anas platyrhynchos domesticus).

    PubMed

    Pantin-Jackwood, Mary J; Kapczynski, Darrell R; DeJesus, Eric; Costa-Hurtado, Mar; Dauphin, Gwenaelle; Tripodi, Astrid; Dunn, John R; Swayne, David E

    2016-03-01

    Domestic ducks are the second most abundant poultry species in many Asian countries and have played a critical role in the epizootiology of H5N1 highly pathogenic avian influenza (HPAI).In this study, the protective efficacy of a live recombinant vector vaccine based on a turkey herpesvirus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAI strain (A/Swan/Hungary/4999/ 2006) (rHVT-H5/2.2), given at 3 days of age, was examined in Pekin ducks (Anas platyrhynchos domesticus). The vaccine was given alone or in combination with an inactivated H5N1 clade 2.3.2.1 reverse genetic (rgGD/2.3.2.1) vaccine given at 16 days of age, either as a single vaccination or in a prime-boost regime. At 30 days of age, ducks were challenged with one of two H5N1 HPAI viruses: A/duck/Vietnam/NCVD-2721/2013 (clade 1.1.2) or A/duck/Vietnam/NCVD-1584/2012 (clade 2.3.2.1.C). These viruses produced 100% mortality in less than 5 days in nonvaccinated control ducks. Ducks vaccinated with the rgGD/2.3.2.1 vaccine, with or without the rHVT-H5/2.2 vaccine, were 90%-100% protected against mortality after challenge with either of the two H5N1 HPAI viruses. The rHVT-H5/2.2 vaccine alone, however, conferred only 30% protection against mortality after challenge with either H5N1 HPAI virus; the surviving ducks from these groups shed higher amount of virus and for longer than the single-vaccinated rgGD/2.3.2.1 group. Despite low protection, ducks vaccinated with the rHVT-H5/2.2 vaccine and challenged with the clade 1.1.2 Vietnam virus had a longer mean death time than nonvaccinated controls (P = 0.02). A booster effect was found on reduction of virus shedding when using both vaccines, with lower oropharyngeal viral titers at 4 days after challenge with either HPAI virus (P < 0.05). Neither rHVT-H5/2.2 nor standard HVT vaccine could be detected in samples collected from multiple tissues at different time points, indicting minimal levels of viral replication. In conclusion, although a minor effect on

  18. Prevailing PA Mutation K356R in Avian Influenza H9N2 Virus Increases Mammalian Replication and Pathogenicity.

    PubMed

    Xu, Guanlong; Zhang, Xuxiao; Gao, Weihua; Wang, Chenxi; Wang, Jinliang; Sun, Honglei; Sun, Yipeng; Guo, Lu; Zhang, Rui; Chang, Kin-Chow; Liu, Jinhua; Pu, Juan

    2016-09-15

    Adaptation of the viral polymerase complex comprising PB1, PB2, and PA is necessary for efficient influenza A virus replication in new host species. We found that PA mutation K356R (PA-K356R) has become predominant since 2014 in avian H9N2 viruses in China as with seasonal human H1N1 viruses. The same mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses whose six internal gene segments are derived from the H9N2 virus. We further demonstrated the mammalian adaptive functionality of the PA-K356R mutation. Avian H9N2 virus with the PA-K356R mutation in human A549 cells showed increased nuclear accumulation of PA and increased viral polymerase activity that resulted in elevated levels of viral transcription and virus output. The same mutant virus in mice also enhanced virus replication and caused lethal infection. In addition, combined mutation of PA-K356R and PB2-E627K, a well-known mammalian adaptive marker, in the H9N2 virus showed further cooperative increases in virus production and severity of infection in vitro and in vivo In summary, PA-K356R behaves as a novel mammalian tropism mutation, which, along with other mutations such as PB2-E627K, might render avian H9N2 viruses adapted for human infection. Mutations of the polymerase complex (PB1, PB2, and PA) of influenza A virus are necessary for viral adaptation to new hosts. This study reports a novel and predominant mammalian adaptive mutation, PA-K356R, in avian H9N2 viruses and human isolates of emergent H7N9 and H10N8 viruses. We found that PA-356R in H9N2 viruses causes significant increases in virus replication and severity of infection in human cells and mice and that PA-K356R cooperates with the PB2-E627K mutation, a well-characterized human adaptive marker, to exacerbate mammalian infection in vitro and in vivo Therefore, the PA-K356R mutation is a significant adaptation in H9N2 viruses and related H7N9 and H10N8 reassortants toward human infectivity. Copyright © 2016

  19. Prevailing PA Mutation K356R in Avian Influenza H9N2 Virus Increases Mammalian Replication and Pathogenicity

    PubMed Central

    Xu, Guanlong; Zhang, Xuxiao; Gao, Weihua; Wang, Chenxi; Wang, Jinliang; Sun, Honglei; Sun, Yipeng; Guo, Lu; Zhang, Rui; Chang, Kin-Chow; Liu, Jinhua

    2016-01-01

    ABSTRACT Adaptation of the viral polymerase complex comprising PB1, PB2, and PA is necessary for efficient influenza A virus replication in new host species. We found that PA mutation K356R (PA-K356R) has become predominant since 2014 in avian H9N2 viruses in China as with seasonal human H1N1 viruses. The same mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses whose six internal gene segments are derived from the H9N2 virus. We further demonstrated the mammalian adaptive functionality of the PA-K356R mutation. Avian H9N2 virus with the PA-K356R mutation in human A549 cells showed increased nuclear accumulation of PA and increased viral polymerase activity that resulted in elevated levels of viral transcription and virus output. The same mutant virus in mice also enhanced virus replication and caused lethal infection. In addition, combined mutation of PA-K356R and PB2-E627K, a well-known mammalian adaptive marker, in the H9N2 virus showed further cooperative increases in virus production and severity of infection in vitro and in vivo. In summary, PA-K356R behaves as a novel mammalian tropism mutation, which, along with other mutations such as PB2-E627K, might render avian H9N2 viruses adapted for human infection. IMPORTANCE Mutations of the polymerase complex (PB1, PB2, and PA) of influenza A virus are necessary for viral adaptation to new hosts. This study reports a novel and predominant mammalian adaptive mutation, PA-K356R, in avian H9N2 viruses and human isolates of emergent H7N9 and H10N8 viruses. We found that PA-356R in H9N2 viruses causes significant increases in virus replication and severity of infection in human cells and mice and that PA-K356R cooperates with the PB2-E627K mutation, a well-characterized human adaptive marker, to exacerbate mammalian infection in vitro and in vivo. Therefore, the PA-K356R mutation is a significant adaptation in H9N2 viruses and related H7N9 and H10N8 reassortants toward human

  20. Spectroscopic and theoretical investigation of the electronic states of layered perovskite oxyfluoride S r2Ru O3F2 thin films

    NASA Astrophysics Data System (ADS)

    Chikamatsu, Akira; Kurauchi, Yuji; Kawahara, Keisuke; Onozuka, Tomoya; Minohara, Makoto; Kumigashira, Hiroshi; Ikenaga, Eiji; Hasegawa, Tetsuya

    2018-06-01

    We investigated the electronic structure of a layered perovskite oxyfluoride S r2Ru O3F2 thin film by hard x-ray photoemission spectroscopy (HAXPES) and soft x-ray absorption spectroscopy (XAS) as well as density functional theory (DFT)-based calculations. The core-level HAXPES spectra suggested that S r2Ru O3F2 is a Mott insulator. The DFT calculations described the total and site-projected density of states and the band dispersion for the optimized crystal structure of S r2Ru O3F2 , predicting that R u4 + takes a high-spin configuration of (xy ) ↑(yz ,z x ) ↑↑(3z2-r2 ) ↑ and that S r2Ru O3F2 has an indirect band gap of 0.7 eV with minima at the M ,A and X ,R points. HAXPES spectra near the Fermi level and the angular-dependent O 1 s XAS spectra of the S r2Ru O3F2 thin film, corresponding to the valence band and conduction band density of states, respectively, were drastically different compared to those of the S r2Ru O4 film, suggesting that the changes in the electronic states were mainly driven by the substitution of an oxygen atom coordinated to Ru by fluorine and subsequent modification of the crystal field.

  1. Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

    PubMed

    Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping

    2013-03-01

    Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P < 0.01) than those of the control groups. Complete protection of guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

  2. "Decarbonization" of an imino N-heterocyclic carbene via triple benzyl migration from hafnium

    USDA-ARS?s Scientific Manuscript database

    An imino N-heterocyclic carbene underwent three sequential benzyl migrations upon reaction with tetrabenzylhafnium, resulting in complete removal of the carbene carbon from the ligand. The resulting eneamido-amidinato hafnium complex showed alkene polymerization activity comparable to that of a prec...

  3. Pathogenicity and transmission of the novel A (H3N2v) influenza virus isolated from humans in experimentally inoculated pigs

    USDA-ARS?s Scientific Manuscript database

    Human cases with H3N2 (H3N2v) viruses closely related to swine H3N2 viruses were detected in 2011 and increased to >320 cases by the end of 2012. H3N2-TRIG was the H3N2 genotype endemically circulating in the U.S. swine population prior to the emergence of H1N1pdm09, and rH3N2p are novel H1N1pdm09/H...

  4. 2,3-Dimethyl-6-nitro-2H-indazole

    PubMed Central

    Chen, Yan; Fang, Zheng; Wei, Ping

    2009-01-01

    In the mol­ecule of the title compound, C9H9N3O2, the indazole ring system is almost planar [maximum deviation = 0.019 (3) Å for the C atom bearing the nitro group]. In the crystal structure, inter­molecular C—H⋯O inter­actions link the mol­ecules into centrosymmetric dimers, forming R 2 2(18) ring motifs. Aromatic π–π contacts between indazole rings [centroid–centroid distances = 3.632 (1) and 3.705 (1) Å] may further stabilize the structure. PMID:21583483

  5. Chemistry of the oxophosphinidene ligand. 2. Reactivity of the anionic complexes [MCp{P(O)R*}(CO)(2)](-) (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3)) toward electrophiles based on elements different from carbon.

    PubMed

    Alonso, María; Alvarez, M Angeles; García, M Esther; Ruiz, Miguel A; Hamidov, Hayrullo; Jeffery, John C

    2010-12-20

    The anionic oxophosphinidene complexes (H-DBU)[MCp{P(O)R*}(CO)(2)] (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3); Cp = η(5)-C(5)H(5), DBU = 1,8-diazabicyclo [5.4.0] undec-7-ene) displayed multisite reactivity when faced with different electrophilic reagents. The reactions with the group 14 organochloride compounds ER(4-x)Cl(x) (E = Si, Ge, Sn, Pb) led to either phosphide-like, oxophosphinidene-bridged derivatives [MCp{P(OE')R*}(CO)(2)] (E' = SiMe(3), SiPh(3), GePh(3), GeMe(2)Cl) or to terminal oxophosphinidene complexes [MCp{P(O)R*}(CO)(2)(E')] (E' = SnPh(3), SnPh(2)Cl, PbPh(3); Mo-Pb = 2.8845(4) Å for the MoPb compound). A particular situation was found in the reaction with SnMe(3)Cl, this giving a product existing in both tautomeric forms, with the phosphide-like complex [MCp{P(OSnMe(3))R*}(CO)(2)] prevailing at room temperature and the tautomer [MCp{P(O)R*}(CO)(2)(SnMe(3))] being the unique species present below 203 K in dichloromethane solution. The title anions also showed a multisite behavior when reacting with transition-metal based electrophiles. Thus, the reactions with the complexes [M'Cp(2)Cl(2)] (M' = Ti, Zr) gave phosphide-like derivatives [MCp{P(OM')R*}(CO)(2)] (M = Mo, M' = TiCp(2)Cl, ZrCp(2)Cl; M = W, M' = ZrCp(2)Cl), displaying a bridging κ(1),κ(1)-P,O- oxophosphinidene ligand connecting MCp(CO)(2) and M'Cp(2)Cl metal fragments (W-P = 2.233(1) Å, O-Zr = 2.016(4) Å for the WZr compound]. In contrast, the reactions with the complex [AuCl{P(p-tol)(3)}] gave the metal-metal bonded derivatives trans-[MCp{P(O)R*}(CO)(2){AuP(p-tol)(3)}] (M = Mo, W; Mo-Au = 2.7071(7) Å). From all the above results it was concluded that the terminal oxophosphinidene complexes are preferentially formed under conditions of orbital control, while charge-controlled reactions tend to give derivatives with the electrophilic fragment bound to the oxygen atom of the oxophosphinidene ligand (phosphide-like, oxophosphinidene-bridged derivatives).

  6. 3-(6-Methyl-2-pyrid­yl)-2-phenyl-3,4-dihydro-1,3,2-benzoxaza­phosphinine 2-oxide

    PubMed Central

    Surendra Babu, V. H. H.; Krishnaiah, M.; Anil Kumar, M.; Suresh Reddy, C.; Kant, Rajni

    2009-01-01

    In the title compound, C19H17N2O2P, the six-membered 1,3,2-oxaza­phosphinine ring adopts a boat conformation with the phosphoryl O atom in an equatorial position. The dihedral angle between the 6-methyl-2-pyridyl and phenyl groups is 75.5 (1)°. These substituents are trans to each other, and are oriented at angles of 57.2 (1) and 74.8 (1)°, respectively, to the benzene ring. The crystal structure is stabilized by intra- and inter­molecular hydrogen bonds. The phosphoryl O atom participates in inter­molecular C—H⋯O inter­actions with the neighbouring mol­ecules, forming centrosymmetric R 2 2(14) dimers. PMID:21578300

  7. Mechanistic Study of the Stereoselective Hydroxylation of [2-2 H1 ,3-2 H1 ]Butanes Catalyzed by Cytochrome P450 BM3 Variants.

    PubMed

    Yang, Chung-Ling; Lin, Cheng-Hung; Luo, Wen-I; Lee, Tsu-Lin; Ramu, Ravirala; Ng, Kok Yaoh; Tsai, Yi-Fang; Wei, Guor-Tzo; Yu, Steve S-F

    2017-02-21

    Engineered bacterial cytochrome P450s are noted for their ability in the oxidation of inert small alkanes. Cytochrome P450 BM3 L188P A328F (BM3 PF) and A74E L188P A328F (BM3 EPF) variants are able to efficiently oxidize n-butane to 2-butanol. Esterification of the 2-butanol derived from this reaction mediated by the aforementioned two mutants gives diastereomeric excesses (de) of -56±1 and -52±1 %, respectively, with the preference for the oxidation occurring at the C-H S bond. When tailored (2R,3R)- and (2S,3S)-[2- 2 H 1 ,3- 2 H 1 ]butane probes are employed as substrates for both variants, the obtained de values from (2R,3R)-[2- 2 H 1 ,3- 2 H 1 ]butane are -93 and -92 % for BM3 PF and EPF, respectively; whereas the obtained de values from (2S,3S)-[2- 2 H 1 ,3- 2 H 1 ]butane are 52 and 56 % in the BM3 PF and EPF systems, respectively. The kinetic isotope effects (KIEs) for the oxidation of (2R,3R)-[2- 2 H 1 ,3- 2 H 1 ]butane are 7.3 and 7.8 in BM3 PF and EPF, respectively; whereas KIEs for (2S,3S)-[2- 2 H 1 ,3- 2 H 1 ]butanes are 18 and 25 in BM3 PF and EPF, respectively. The discrepancy in KIEs obtained from the two substrates supports the two-state reactivity (TSR) that is proposed for alkane oxidation in cytochrome P450 systems. Moreover, for the first time, experimental evidence for tunneling in the oxidation mediated by P450 is given through the oxidation of the C-H R bond in (2S,3S)-[2- 2 H 1 ,3- 2 H 1 ]butane. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Development of N(2) Sensor for Determination of PN(2) in Body Tissues.

    DTIC Science & Technology

    1986-08-01

    NK3)4C1 2 ]Cl Acid -140 -340 Acid -120 -280 +500 . + Zn Amalgam +700 +900 2 cis-Ru(N( 3 )4C1 2 C1 Buffer -130 -305 (major) ,450 + Zn Amalgam -210...increase under N 2 -400 mV under N 2 cis- [1u (en) 2C12 )C1 Buffer -125 -350 Buffer + Zn - so -400 .475 Amalgam +780 cis-(Ru(en)2Br 2 ] r Acid -120...375 Acid + Zn - 0 -280 plateau Amalgam 600-8SO cis- ([ (bipyr)C12 1Cl Buffer .455 +320 Buffer + Zn +575 +380 Nme Amalgam 1Acid = 0.1M H2SO42Buffer

  9. New Type of 2D Perovskites with Alternating Cations in the Interlayer Space, (C(NH 2 ) 3 )(CH 3 NH 3 ) n Pb n I 3n+1 : Structure, Properties, and Photovoltaic Performance

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Soe, Chan Myae Myae; Stoumpos, Constantinos C.; Kepenekian, Mikaël

    We present the new homologous series (C(NH2)3)(CH3NH3)nPbnI3n+1 (n = 1, 2, 3) of layered 2D perovskites. Structural characterization by single-crystal X-ray diffraction reveals that these compounds adopt an unprecedented structure type, which is stabilized by the alternating ordering of the guanidinium and methylammonium cations in the interlayer space (ACI). Compared to the more common Ruddlesden–Popper (RP) 2D perovskites, the ACI perovskites have a different stacking motif and adopt a higher crystal symmetry. The higher symmetry of the ACI perovskites is expressed in their physical properties, which show a characteristic decrease of the bandgap with respect to their RP perovskite counterpartsmore » with the same perovskite layer thickness (n). The compounds show a monotonic decrease in the optical gap as n increases: Eg = 2.27 eV for n = 1 to Eg = 1.99 eV for n = 2 and Eg = 1.73 eV for n = 3, which show slightly narrower gaps compared to the corresponding RP perovskites. First-principles theoretical electronic structure calculations confirm the experimental optical gap trends suggesting that the ACI perovskites are direct bandgap semiconductors with wide valence and conduction bandwidths. To assess the potential of the ACI perovskites toward solar cell applications, we studied the (C(NH2)3)(CH3NH3)3Pb3I10 (n = 3) compound. Compact thin films from the (C(NH2)3)(CH3NH3)3Pb3I10 compound with excellent surface coverage can be obtained from the antisolvent dripping method. Planar photovoltaic devices from optimized ACI perovskite films yield a power-conversion-efficiency of 7.26% with a high open-circuit voltage of ~1 V and a striking fill factor of ~80%.« less

  10. Genome-Wide Analysis of Citrus R2R3MYB Genes and Their Spatiotemporal Expression under Stresses and Hormone Treatments

    PubMed Central

    He, Shaolan; Zheng, Yongqiang; Yi, Shilai; Lv, Qiang; Deng, Lie

    2014-01-01

    The R2R3MYB proteins represent one of the largest families of transcription factors, which play important roles in plant growth and development. Although genome-wide analysis of this family has been conducted in many species, little is known about R2R3MYB genes in citrus, In this study, 101 R2R3MYB genes has been identified in the citrus (Citrus sinesis and Citrus clementina) genomes, which are almost equal to the number of rice. Phylogenetic analysis revealed that they could be subdivided into 21 subgroups. The evolutionary relationships and the intro-exon organizations were also analyzed, revealing strong gene conservation but also the expansions of particular functional genes during the plant evolution. Tissue-specific expression profiles showed that 95 citrus R2R3MYB genes were expressed in at least one tissue and the other 6 genes showed very low expression in all tissues tested, suggesting that citrus R2R3MYB genes play important roles in the development of all citrus organs. The transcript abundance level analysis during abiotic conditions (NaCl, abscisic acid, jasmonic acid, drought and low temperature) identified a group of R2R3MYB genes that responded to one or multiple treatments, which showed a promising for improving citrus adaptation to stresses. Our results provided an essential foundation for the future selection of the citrus R2R3MYB genes for cloning and functional dissection with an aim of uncovering their roles in citrus growth and development. PMID:25473954

  11. Synthesis and reactivity of TADDOL-based chiral Fe(II) PNP pincer complexes-solution equilibria between κ(2)P,N- and κ(3)P,N,P-bound PNP pincer ligands.

    PubMed

    Holzhacker, Christian; Stöger, Berthold; Carvalho, Maria Deus; Ferreira, Liliana P; Pittenauer, Ernst; Allmaier, Günter; Veiros, Luis F; Realista, Sara; Gil, Adrià; Calhorda, Maria José; Müller, Danny; Kirchner, Karl

    2015-08-07

    Treatment of anhydrous FeX2 (X = Cl, Br) with 1 equiv. of the asymmetric chiral PNP pincer ligands PNP-R,TAD (R = iPr, tBu) with an R,R-TADDOL (TAD) moiety afforded complexes of the general formula [Fe(PNP)X2]. In the solid state these complexes adopt a tetrahedral geometry with the PNP ligand coordinated in κ(2)P,N-fashion, as shown by X-ray crystallography and Mössbauer spectroscopy. Magnetization studies led to a magnetic moment very close to 4.9μB reflecting the expected four unpaired d-electrons (quintet ground state). In solution there are equilibria between [Fe(κ(3)P,N,P-PNP-R,TAD)X2] and [Fe(κ(2)P,N-PNP-R,TAD)X2] complexes, i.e., the PNP-R,TAD ligand is hemilabile. At -50 °C these equilibria are slow and signals of the non-coordinated P-TAD arm of the κ(2)P,N-PNP-R,TAD ligand can be detected by (31)P{(1)H} NMR spectroscopy. Addition of BH3 to a solution of [Fe(PNP-iPr,TAD)Cl2] leads to selective boronation of the pendant P-TAD arm shifting the equilibrium towards the four-coordinate complex [Fe(κ(2)P,N-PNP-iPr,TAD(BH3))Cl2]. DFT calculations corroborate the existence of equilibria between four- and five-coordinated complexes. Addition of CO to [Fe(PNP-iPr,TAD)X2] in solution yields the diamagnetic octahedral complexes trans-[Fe(κ(3)P,N,P-PNP-iPr,TAD)(CO)X2], which react further with Ag(+) salts in the presence of CO to give the cationic complexes trans-[Fe(κ(3)P,N,P-PNP-iPr,TAD)(CO)2X](+). CO addition most likely takes place at the five coordinate complex [Fe(κ(3)P,N,P-PNP-iPr,TAD)X2]. The mechanism for the CO addition was also investigated by DFT and the most favorable path obtained corresponds to the rearrangement of the pincer ligand first from a κ(2)P,N- to a κ(3)P,N,P-coordination mode followed by CO coordination to [Fe(κ(3)P,N,P-PNP-iPr,TAD)X2]. Complexes bearing tBu substituents do not react with CO. Moreover, in the solid state none of the tetrahedral complexes are able to bind CO.

  12. Inhibition of lipopolysaccharide-induced cyclooxygenase-2 expression and inducible nitric oxide synthase by 4-[(2′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate from Moringa oleifera

    PubMed Central

    Park, Eun-Jung; Cheenpracha, Sarot; Chang, Leng Chee; Kondratyuk, Tamara P.; Pezzuto, John M.

    2011-01-01

    Moringa oleifera Lamarack is commonly consumed for nutritional or medicinal properties. We recently reported the isolation and structure elucidation of novel bioactive phenolic glycosides, including 4-[(2′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate (RBITC), which was found to suppress inducible nitric oxide synthase (iNOS) expression and nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 mouse macrophage cells. Inhibitors of proteins such as cyclooxygenase-2 (COX-2) and iNOS are potential anti-inflammatory and cancer chemopreventive agents. The inhibitory activity of RBITC on NO production (IC50 = 0.96 ± 0.23 µM) was greater than that mediated by other well-known isothiocyanates such as sulforaphane (IC50 = 2.86 ± 0.39 µM) and benzyl isothiocyanate (IC50 = 2.08 ± 0.28 µM). RBITC inhibited expression of COX-2 and iNOS at both the protein and mRNA levels. Major upstream signaling pathways involved mitogen-activated protein kinases and nuclear factor-κB (NF-κB). RBITC inhibited phosphorylation of extracellular signal regulated kinase and stress-activated protein kinase, as well as ubiquitin-dependent degradation of inhibitor κBα (IκBα). In accordance with IκBα degradation, nuclear accumulation of NF-κB, and subsequent binding to NF-κB cis-acting element, was attenuated by treatment with RBITC. These data suggest RBITC should be included in the dietary armamentarium of isothiocyanates potentially capable of mediating anti-inflammatory or cancer chemopreventive activity. PMID:21774591

  13. Electronic spectroscopy and photodissociation dynamics of Co(2+)-methanol clusters: Co2+ (CH3OH)n (n = 4-7).

    PubMed

    Thompson, Christopher J; Faherty, Kieron P; Stringer, Kay L; Metz, Ricardo B

    2005-03-07

    Solvated cluster ions Co2+ (CH3OH)n (n = 4-7) have been produced by electrospray and studied using photofragment spectroscopy. There are notable differences between the photodissociation spectra of these complexes and the analogous water complexes. Co2+ (CH3OH)6 absorbs significantly more strongly than Co2+ (H2O)6. The photodissociation spectra of Co2+ (CH3OH)n (n = 4, 5 and 6) are very similar, which suggests that they share the Co2+ (CH3OH)4 chromophore, with additional solvent molecules in the second shell. In contrast, our earlier studies indicate that Co2+ (H2O)6 is six coordinate, and its spectrum is significantly different from that of Co2+ (H2O)4. The larger clusters Co2+ (CH3OH)n (n = 5-7) dissociate by simple loss of one or more solvent molecules. Larger clusters tend to lose more solvent molecules, especially at higher photon energies. As with the corresponding water cluster, Co2+ (CH3OH)4 photodissociates by proton transfer through a salt-bridge intermediate. This is accompanied by a modest kinetic energy release of 170 kJ mol(-1) and occurs with a lifetime of 145 ns.

  14. Sintering activation energy MoSi2-WSi2-Si3N4 ceramic

    NASA Astrophysics Data System (ADS)

    Titov, D. D.; Lysenkov, A. S.; Kargin, Yu F.; Frolova, M. G.; Gorshkov, V. A.; Perevislov, S. N.

    2018-04-01

    The activation energy of sintering process was calculated based on dilatometric studies of shrinkage processes (Mo,W)Si2 + Si3N4 composite ceramic. (Mo,W)Si2 powders was obtained by solid-phase solutions of 70 wt% MoSi2 and 30 wt% WSi2 by SHS in the ISMAN RAS. The concentration rate Si3N4 was from 1 to 15 wt.%. The sintering was carried out to 1850°C in Ar atmosphere the heating rate of 5, 10, 12 and 15°C/min by the way of dilatometer tests. Based on the differential kinetic analysis method (Friedman’s method), the sintering process activation energy of (Mo,W)Si2 + Si3N4 were calculated. The two-stage sintering process and the dependence of the activation energy on the Si3N4 content was shown. Average value of 370 kJ/mol for Q was obtained.

  15. Discovery, Synthesis, And Structure-Based Optimization of a Series of N-(tert-Butyl)-2-(N-arylamido)-2-(pyridin-3-yl) Acetamides (ML188) as Potent Noncovalent Small Molecule Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) 3CL Protease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jacobs, Jon; Grum-Tokars, Valerie; Zhou, Ya

    A high-throughput screen of the NIH molecular libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (16-(R), (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844). But, unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, 16-(R) is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure–activity relationships within S1', S1, and S2enzyme binding pockets. Moreover, the X-ray structure of SARS-CoV 3CLpromore » bound with 16-(R) was instrumental in guiding subsequent rounds of chemistry optimization. 16-(R) provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.« less

  16. 1-(2,4-Di-nitro-phen-yl)-2-[(E)-(3,4,5-tri-meth-oxy-benzyl-idene)]hydrazine.

    PubMed

    Chantrapromma, Suchada; Ruanwas, Pumsak; Boonnak, Nawong; Chidan Kumar, C S; Fun, Hoong-Kun

    2014-02-01

    Mol-ecules of the title compound, C16H16N4O7, are not planar with a dihedral angle of 5.50 (11)° between the substituted benzene rings. The two meta-meth-oxy groups of the 3,4,5-tri-meth-oxy-benzene moiety lie in the plane of the attached ring [Cmeth-yl-O-C-C torsion angles -0.1 (4)° and -3.7 (3)°] while the para-meth-oxy substituent lies out of the plane [Cmeth-yl-O-C-C, -86.0 (3)°]. An intra-molecular N-H⋯O hydrogen bond involving the 2-nitro substituent generates an S(6) ring motif. In the crystal structure, mol-ecules are linked by weak C-H⋯O inter-actions into screw chains, that are arranged into a sheet parallel to the bc plane. These sheets are connected by π-π stacking inter-actions between the nitro and meth-oxy substituted aromatic rings with a centroid-centroid separation of 3.9420 (13) Å. C-H⋯π contacts further stabilize the two-dimensional network.

  17. Proton-decoupled CPMG: a better experiment for measuring (15)N R2 relaxation in disordered proteins.

    PubMed

    Yuwen, Tairan; Skrynnikov, Nikolai R

    2014-04-01

    (15)N R2 relaxation is one of the most informative experiments for characterization of intrinsically disordered proteins (IDPs). Small changes in nitrogen R2 rates are often used to determine how IDPs respond to various biologically relevant perturbations such as point mutations, posttranslational modifications and weak ligand interactions. However collecting high-quality (15)N relaxation data can be difficult. Of necessity, the samples of IDPs are often prepared with low protein concentration and the measurement time can be limited because of rapid sample degradation. Furthermore, due to hardware limitations standard experiments such as (15)N spin-lock and CPMG can sample the relaxation decay only to ca. 150ms. This is much shorter than (15)N T2 times in disordered proteins at or near physiological temperature. As a result, the sampling of relaxation decay profiles in these experiments is suboptimal, which further lowers the precision of the measurements. Here we report a new implementation of the proton-decoupled (PD) CPMG experiment which allows one to sample (15)N R2 relaxation decay up to ca. 0.5-1s. The new experiment has been validated through comparison with the well-established spin-lock measurement. Using dilute samples of denatured ubiquitin, we have demonstrated that PD-CPMG produces up to 3-fold improvement in the precision of the data. It is expected that for intrinsically disordered proteins the gains may be even more substantial. We have also shown that this sequence has a number of favorable properties: (i) the spectra are recorded with narrow linewidth in nitrogen dimension; (ii) (15)N offset correction is small and easy to calculate; (iii) the experiment is immune to various spurious effects arising from solvent exchange; (iv) the results are stable with respect to pulse miscalibration and rf field inhomogeneity; (v) with minimal change, the pulse sequence can also be used to measure R2 relaxation of (15)N(ε) spins in arginine side chains. We

  18. 2D Frameworks of C2 N and C3 N as New Anode Materials for Lithium-Ion Batteries.

    PubMed

    Xu, Jiantie; Mahmood, Javeed; Dou, Yuhai; Dou, Shixue; Li, Feng; Dai, Liming; Baek, Jong-Beom

    2017-09-01

    Novel layered 2D frameworks (C 3 N and C 2 N-450) with well-defined crystal structures are explored for use as anode materials in lithium-ion batteries (LIBs) for the first time. As anode materials for LIBs, C 3 N and C 2 N-450 exhibit unusual electrochemical characteristics. For example, C 2 N-450 (and C 3 N) display high reversible capacities of 933.2 (383.3) and 40.1 (179.5) mAh g -1 at 0.1 and 10 C, respectively. Furthermore, C 3 N shows a low hypothetical voltage (≈0.15 V), efficient operating voltage window with ≈85% of full discharge capacity secured at >0.45 V, and excellent cycling stability for more than 500 cycles. The excellent electrochemical performance (especially of C 3 N) can be attributed to their inherent 2D polyaniline frameworks, which provide large net positive charge densities, excellent structural stability, and enhanced electronic/ionic conductivity. Stable solid state interface films also form on the surfaces of the 2D materials during the charge/discharge process. These 2D materials with promising electrochemical performance should provide insights to guide the design and development of their analogues for future energy applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture.

    PubMed

    Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

    2014-05-01

    Voltage-gated Ca(2+) channels (VGCCs) are key elements in mediating thalamocortical rhythmicity. Low-voltage activated (LVA) CaV 3 T-type Ca(2+) channels have been related to thalamic rebound burst firing and to generation of non-rapid eye movement (NREM) sleep. High-voltage activated (HVA) CaV 1 L-type Ca(2+) channels, on the opposite, favor the tonic mode of action associated with higher levels of vigilance. However, the role of the HVA Non-L-type CaV2.3 Ca(2+) channels, which are predominantly expressed in the reticular thalamic nucleus (RTN), still remains unclear. Recently, CaV2.3(-/-) mice were reported to exhibit altered spike-wave discharge (SWD)/absence seizure susceptibility supported by the observation that CaV2.3 mediated Ca(2+) influx into RTN neurons can trigger small-conductance Ca(2+)-activated K(+)-channel type 2 (SK2) currents capable of maintaining thalamic burst activity. Based on these studies we investigated the role of CaV2.3 R-type Ca(2+) channels in rodent sleep. The role of CaV2.3 Ca(2+) channels was analyzed in CaV2.3(-/-) mice and controls in both spontaneous and artificial urethane-induced sleep, using implantable video-EEG radiotelemetry. Data were analyzed for alterations in sleep architecture using sleep staging software and time-frequency analysis. CaV2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS). Whereas mean sleep stage durations remained unchanged, the total number of SWS epochs was increased in CaV2.3(-/-) mice. Additional changes were observed for sleep stage transitions and EEG amplitudes. Furthermore, urethane-induced SWS mimicked spontaneous sleep results obtained from CaV2.3 deficient mice. Quantitative Real-time PCR did not reveal changes in thalamic CaV3 T-type Ca(2+) channel expression. The detailed mechanisms of SWS increase in CaV2.3(-/-) mice remain to be determined. Low-voltage activated CaV2.3 R-type Ca(2+) channels in the thalamocortical loop and extra

  20. Lusztig symmetries and Poincare-Birkhoff-Witt basis for wU{sub r,s}{sup d}(osp(1|2n))

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Junli; College of Applied Sciences, Beijing University of Technology, Beijing 100124; Yang, Shilin

    2013-12-15

    We investigate a new kind of two-parameter weak quantized superalgebra wU{sub r,s}{sup d}(osp(1|2n)), which is a weak Hopf superalgebra. It has a homomorphic image which is isomorphic to the usual two-parameter quantum superalgebra U{sub r,s}(osp(1|2n)) of osp(1|2n). We also discuss the basis of wU{sub r,s}{sup d}(osp(1|2n)) by Lusztig's symmetries.

  1. Infrared absorption spectra of N(CxF2x+1)3, x = 2-5 perfluoroamines

    NASA Astrophysics Data System (ADS)

    Bernard, François; Papanastasiou, Dimitrios K.; Papadimitriou, Vassileios C.; Burkholder, James B.

    2018-05-01

    Infrared absorption spectra of the perfluoroamines (N(C2F5)3, N(C3F7)3, N(C4F9)3, and N(C5F11)3) were measured over the 500-4000 cm-1 spectral region at 294 K using Fourier transform infrared (FTIR) spectroscopy at 1 cm-1 resolution. Spectral measurements were performed using static measurements of dilute perfluoroamines mixtures and by infusion of the pure compound into a calibrated gas flow. The perfluoroamines absorb strongly in the "atmospheric window" with integrated band strengths (10-17 cm2 molecule-1 cm-1) between 570 and 1500 cm-1 of 59.9, 74.9, 88.9, and 98.7 for N(C2F5)3, N(C3F7)3, N(C4F9)3, and N(C5F11)3, respectively. Radiative efficiencies (RE) for the perfluoroamines were estimated to be 0.61, 0.75, 0.87, and 0.95 W m-2 ppb-1 for atmospherically well-mixed conditions and including a +10% stratospheric temperature correction for N(C2F5)3, N(C3F7)3, N(C4F9)3, and N(C5F11)3, respectively. Theoretical calculations of the perfluoroamines were performed at the B97-1/6-311++G(2df,2p) level of theory and optimized perfluoroamine geometries, vibrational band positions, and band strengths are reported. The theoretically calculated infrared spectra are in good agreement with the experimental spectra, while comparison of individual bands was not attempted due to the significant overlap of vibrational bands in the experimental spectra.

  2. The crystal structure of the monohydrate R{sub 2}Mo{sub 6}O{sub 21}.H{sub 2}O (R=Pr, Nd, Sm, and Eu): a layer structure containing disordered [Mo{sub 2}O{sub 7}]{sup 2-} groups

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Naruke, Haruo; Yamase, Toshihiro

    2005-03-15

    Although R{sub 2}O{sub 3}:MoO{sub 3}=1:6 (R=rare earth) compounds are known in the R{sub 2}O{sub 3}-MoO{sub 3} phase diagrams since a long time, no structural characterization has been achieved because a conventional solid-state reaction yields powder samples. We obtained single crystals of R{sub 2}Mo{sub 6}O{sub 21}.H{sub 2}O (R=Pr, Nd, Sm, and Eu) by thermal decomposition of [R{sub 2}(H{sub 2}O){sub 12}Mo{sub 8}O{sub 27}].nH{sub 2}O at around 685-715{sup o}C for 2h, and determined their crystal structures. The simulated XRD patterns of R{sub 2}Mo{sub 6}O{sub 21}.H{sub 2}O were consistent with those of previously reported R{sub 2}O{sub 3}:MoO{sub 3}=1:6 compounds. All R{sub 2}Mo{sub 6}O{sub 21}.H{submore » 2}O compounds crystallize isostructurally in tetragonal, P4/ncc (No. 130), a=8.9962(5), 8.9689(6), 8.9207(4), and 8.875(2)A; c=26.521(2), 26.519(2), 26.304(2), and 26.15(1)A; Z=4; R{sub 1}=0.026, 0.024, 0.024, and 0.021, for R=Pr, Nd, Sm, and Eu, respectively. The crystal structure of R{sub 2}Mo{sub 6}O{sub 21}.H{sub 2}O consists of two [Mo{sub 2}O{sub 7}]{sup 2-}-containing layers (A and B layers) and two interstitial R(1){sup 3+} and R(2){sup 3+} cations. Each [Mo{sub 2}O{sub 7}]{sup 2-} group is composed of two corner-sharing [MoO{sub 4}] tetrahedra. The [Mo{sub 2}O{sub 7}]{sup 2-} in the B layer exhibits a disorder to form a pseudo-[Mo{sub 4}O{sub 9}] group, in which four Mo and four O sites are half occupied. R(1){sup 3+} achieves 8-fold coordination by O{sup 2-} to form a [R(1)O{sub 8}] square antiprism, while R(2){sup 3+} achieves 9-fold coordination by O{sup 2-} and H{sub 2}O to form a [R(2)(H{sub 2}O)O{sub 8}] monocapped square antiprism. The disorder of the [Mo{sub 2}O{sub 7}]{sup 2-} group in the B layer induces a large displacement of the O atoms in another [Mo{sub 2}O{sub 7}]{sup 2-} group (in the A layer) and in the [R(1)O{sub 8}] and [R(2)(H{sub 2}O)O{sub 8}] polyhedra. A remarkable broadening of the photoluminescence spectrum of Eu{sub 2}Mo

  3. Mg2+ activates the ryanodine receptor type 2 (RyR2) at intermediate Ca2+ concentrations.

    PubMed

    Chugun, Akihito; Sato, Osamu; Takeshima, Hiroshi; Ogawa, Yasuo

    2007-01-01

    To clarify whether activity of the ryanodine receptor type 2 (RyR2) is reduced in the sarcoplasmic reticulum (SR) of cardiac muscle, as is the case with the ryanodine receptor type 1 (RyR1), Ca(2+)-dependent [(3)H]ryanodine binding, a biochemical measure of Ca(2+)-induced Ca(2+) release (CICR), was determined using SR vesicle fractions isolated from rabbit and rat cardiac muscles. In the absence of an adenine nucleotide or caffeine, the rat SR showed a complicated Ca(2+) dependence, instead of the well-documented biphasic dependence of the rabbit SR. In the rat SR, [(3)H]ryanodine binding initially increased as [Ca(2+)] increased, with a plateau in the range of 10-100 microM Ca(2+), and thereafter further increased to an apparent peak around 1 mM Ca(2+), followed by a decrease. In the presence of these modulators, this complicated dependence prevailed, irrespective of the source. Addition of 0.3-1 mM Mg(2+) unexpectedly increased the binding two- to threefold and enhanced the affinity for [(3)H]ryanodine at 10-100 microM Ca(2+), resulting in the well-known biphasic dependence. In other words, the partial suppression of RyR2 is relieved by Mg(2+). Ca(2+) could be a substitute for Mg(2+). Mg(2+) also amplifies the responses of RyR2 to inhibitory and stimulatory modulators. This stimulating effect of Mg(2+) on RyR2 is entirely new, and is referred to as the third effect, in addition to the well-known dual inhibitory effects. This effect is critical to describe the role of RyR2 in excitation-contraction coupling of cardiac muscle, in view of the intracellular Mg(2+) concentration.

  4. Synthesis and Deprotonation of Aminophosphane Complexes: First K/N(H)R Phosphinidenoid Complexes and Access to a Complex with a P2 N-Ring Ligand.

    PubMed

    Majhi, Paresh Kumar; Kyri, Andreas Wolfgang; Schmer, Alexander; Schnakenburg, Gregor; Streubel, Rainer

    2016-10-17

    Synthesis of 1,1'-bifunctional aminophosphane complexes 3 a-e was achieved by the reaction of Li/Cl phosphinidenoid complex 2 with various primary amines (R=Me, iPr, tBu, Cy, Ph). Deprotonation of complex 3 a (R=Me) with potassium hexamethyldisilazide yielded a mixture of K/NHMe phosphinidenoid complex 4 a and potassium phosphanylamido complex 4 a'. Treatment of complex 3 c (R=tBu) and e (R=Ph) with KHMDS afforded the first examples of K/NHR phosphinidenoid complexes 4 c and e. The reaction of complex 3 c with 2 molar equivalents of KHMDS followed by PhPCl 2 afforded complexes 5 c,c', which possess a P 2 N-ring ligand. All complexes were characterized by NMR, IR, MS, and microanalysis, and additionally, complexes 3 b-e and 5 c' were scrutinized by single-crystal X-ray crystallography. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. A novel amido-pyrophosphate Mn(II) chelate complex with the synthetic ligand O{P(O)[NHC(CH3)3]2}2 (L): [Mn(L)2{OC(H)N(CH3)2}2]Cl2·2H2O.

    PubMed

    Tarahhomi, Atekeh; Pourayoubi, Mehrdad; Fejfarová, Karla; Dušek, Michal

    2013-03-01

    The title complex, trans-bis(dimethylformamide-κO)bis{N,N'-N'',N'''-tetra-tert-butyl[oxybis(phosphonic diamide-κO)]}manganese(II) dichloride dihydrate, [Mn(C16H40N4O3P2)2(C3H7NO)2]Cl2·2H2O, is the first example of a bis-chelate amido-pyrophosphate (pyrophosphoramide) complex containing an O[P(O)(NH)2]2 fragment. Its asymmetric unit contains half of the complex dication, one chloride anion and one water molecule. The Mn(II) atom, located on an inversion centre, is octahedrally coordinated, with a slight elongation towards the monodentate dimethylformamide ligand. Structural features of the title complex, such as the P=O bond lengths and the planarity of the chelate ring, are compared with those of previously reported complexes with six-membered chelates involving the fragments C(O)NHP(O), (X)NP(O) [X = C(O), C(S), S(O)2 and P(O)] and O[P(O)(N)2]2. This analysis shows that the six-membered chelate rings are less puckered in pyrophosphoramide complexes containing a P(O)OP(O) skeleton, such as the title compound. The extended structure of the title complex involves a linear aggregate mediated by N-H...O and N-H...Cl hydrogen bonds, in which the chloride anion is an acceptor in two additional O-H...Cl hydrogen bonds.

  6. Preparation and luminescence properties of Ce3+ and Ce3+/Tb(3+)-activated Y4Si2O7N2 phosphors.

    PubMed

    Xia, Zhiguo; Wu, Weiwei

    2013-09-28

    Ce(3+) and Ce(3+)/Tb(3+)-activated Y4Si2O7N2 phosphors are synthesized by the solid-state method, which can be efficiently excited by near ultraviolet (UV) light emitting diode (LED) chips. The PL spectrum of Y4Si2O7N2:Ce(3+) shows a broad hump between 380 and 650 nm, assigned to the electron transition from the 4f energy level to different 5d sub levels of the Ce(3+) ions at different Y(3+) sites. The color of the Y4Si2O7N2:Ce(3+) phosphor can shift from blue to green by introducing Tb(3+). In addition, the energy transfer process from Ce(3+) to Tb(3+) in the Y4Si2O7N2 host was investigated and discussed in terms of both the luminescence spectra and decay curves. The energy transfer critical distance has been calculated and evaluated by the concentration quenching method. Therefore, the Ce(3+) and Ce(3+)/Tb(3+)-activated Y4Si2O7N2 phosphors can serve as key materials for phosphor-converted white-light UV-LEDs.

  7. Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses.

    PubMed

    Lyoo, Kwang-Soo; Kim, Jeong-Ki; Jung, Kwonil; Kang, Bo-Kyu; Song, Daesub

    2014-09-24

    The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decreased. Both the H1N1 and H1N2 infected pigs lacked gross lesions at PID 2, but they showed moderate to severe pneumonia on PID 4, 7 and 14. The pigs infected with H1N1 had significant scores of gross and histopathological lesions when compared with the other pigs infected with H1N2, H3N2, and mock at PID 14. Mean SIV antigen-positive scores were rarely detected for pigs infected with H1N2 and H3N2 from PID 7, whereas a significantly increased amount of viral antigens were found in the bronchioles and alveolar epithelium of the H1N1infected pigs at PID 14. We demonstrated that Korean SIV subtypes had different pulmonary pathologic patterns. The Korean H3N2 rapidly induced acute lung lesions such as broncho-interstitial pneumonia, while the Korean H1N1 showed longer course of infection as compared to other strains.

  8. Superbasic amidine monodentate ligands in fac-[Re(CO)3(5,5'-Me2bipy)(amidine)]BF4 complexes: dependence of amidine configuration on the remote nitrogen substituents.

    PubMed

    Perera, Theshini; Fronczek, Frank R; Marzilli, Patricia A; Marzilli, Luigi G

    2010-08-02

    Addition of various RNH(2) to fac-[Re(CO)(3)(5,5'-Me(2)bipy)(CH(3)CN)]BF(4) (1) converts the acetonitrile ligand to the amidine ligand (a superbase) in fac-[Re(CO)(3)(5,5'-Me(2)bipy)(HNC(CH(3))NHR)]BF(4) products. Each complex has four conceivable isomers (E, E', Z, and Z') because the amidine CN bonds have double-bond character, and the two remote NHR group substituents are different. The reaction of 1 in acetonitrile is complete in 6 to 96 h (25 degrees C) and forms fac-[Re(CO)(3)(5,5'-Me(2)bipy)(HNC(CH(3))NHR)]BF(4) E' and Z isomers. Only the E' isomer formed crystals (R = methyl, isopropyl, isobutyl, tert-butyl, and benzyl). Upon dissolution of such crystals in acetonitrile-d(3), NMR spectra with highly dominant E' signals gradually changed (approximately 15 min at room temperature) to spectra with signals for an equilibrium mixture of E' and Z isomers. Such slow E'-to-Z isomer interchange is also indicated by 2D ROESY NMR data used primarily to assign solution structure. Equilibrium ratios (E':Z) of approximately 65:35 for R = methyl, isopropyl, and isobutyl and 83:17 for R = tert-butyl demonstrate that increasing the remote NHR group steric bulk above a threshold size favors the E' isomer. Consistent with this trend, fac-[Re(CO)(3)(5,5'-Me(2)bipy)(HNC(CH(3))NH(2))]BF(4), with a remote NH(2) (low bulk) group, favors the Z isomer. In contrast, although the remote NH(benzyl) group in fac-[Re(CO)(3)(5,5'-Me(2)bipy)(HNC(CH(3))NH(CH(2)C(6)H(5))]BF(4) has only moderate bulk, the E' isomer has high abundance as a result of favorable 5,5'-Me(2)bipy/benzyl stacking, evidence for which is present in both solid and solution states. The fac-[Re(CO)(3)(5,5'-Me(2)bipy)(HNC(CH(3))NHR)]BF(4) E isomer can be detected in solvents of low polarity. However, the Z' isomer was not observed, undoubtedly because unfavorable remote-group clashes with the equatorial ligands destabilize this isomer. Challenge studies with a 5-fold excess of 4-dimethylaminopyridine in acetonitrile-d(3

  9. Description and crystal structure of albrechtschraufite, MgCa4F2[UO2(CO3)3]2ṡ17-18H2O

    NASA Astrophysics Data System (ADS)

    Mereiter, Kurt

    2013-04-01

    Albrechtschraufite, MgCa4F2[UO2(CO3)3]2ṡ17-18H2O, triclinic, space group Pī, a = 13.569(2), b = 13.419(2), c = 11.622(2) Å, α = 115.82(1), β = 107.61(1), γ = 92.84(1)° (structural unit cell, not reduced), V = 1774.6(5) Å3, Z = 2, D c = 2.69 g/cm3 (for 17.5 H2O), is a mineral that was found in small amounts with schröckingerite, NaCa3F[UO2(CO3)3](SO4)ṡ10H2O, on a museum specimen of uranium ore from Joachimsthal (Jáchymov), Czech Republic. The mineral forms small grain-like subhedral crystals (≤ 0.2 mm) that resemble in appearance liebigite, Ca2[UO2(CO3)3]ṡ ~ 11H2O. Colour pale yellow-green, luster vitreous, transparent, pale bluish green fluorescence under ultraviolet light. Optical data: Biaxial negative, nX = 1.511(2), nY = 1.550(2), nZ = 1.566(2), 2 V = 65(1)° ( λ = 589 nm), r < v weak. After qualitative tests had shown the presence of Ca, U, Mg, CO2 and H2O, the chemical formula was determined by a crystal structure analysis based on X-ray four-circle diffractometer data. The structure was later on refined with data from a CCD diffractometer to R1 = 0.0206 and wR2 = 0.0429 for 9,236 independent observed reflections. The crystal structure contains two independent [UO2(CO3)3]4- anions of which one is bonded to two Mg and six Ca while the second is bonded to only one Mg and three Ca. Magnesium forms a MgF2(Ocarbonate)3(H2O) octahedron that is linked via the F atoms with three Ca atoms so as to provide each F atom with a flat pyramidal coordination by one Mg and two Ca. Calcium is 7- and 8-coordinate forming CaFO6, CaF2O2(H2O)4, CaFO3(H2O)4 and CaO2(H2O)6 coordination polyhedra. The crystal structure is built up from MgCa3F2[UO2(CO3)3]ṡ8H2O layers parallel to (001) which are linked by Ca[UO2(CO3)3]ṡ5H2O moieties into a framework of the composition MgCa4F2[UO2(CO3)3]ṡ13H2O. Five additional water molecules are located in voids of the framework and show large displacement parameters. One of the water positions is partly vacant, leading to a

  10. Basic surface-active properties in the homologous series of β-alkyl (C12H25/C18H37) polyethyleneoxy (n = 0-20) propionamides

    PubMed Central

    2013-01-01

    Background Heterogeneous β-Alkyl (C12H25/C18H37) polyethyleneoxy (n = 0-20) propionamides [R(EO)nPD] represent new “hybrid” nonionic-ionic colloidal structures in the field of surface-active products (technical products). These “niche” compounds have three structural and compositional characteristics that also define their basic colloidal properties: mixture of R and PEO chain homologues; specific conformations due to the PEO chains; and the presence of side products from the addition of higher alcohols, polyethyleneglycols and traces of water to acrylamide. The proposed major objective of this paper is the basic informative colloidal characterization (functional classification, HLB balance, surface tension, critical micelle concentration) in direct correlation with the structural changes in the homologous series of LM(EO)nPD and CS(EO)nPD. The structures were obtained either indirectly by cyanoethylation followed by partial acid hydrolysis of the corresponding β-propionitriles, or directly by the nucleophilic addition under alkaline catalysis of linear higher alcohols C12H25/C14H29 (7/3) (LM) and C16H33/C18H37 (CS) as such and heterogeneous polyethoxylated (n = 3-20) to acrylamide monomer, through an adapted classic reaction scheme. Results In the series of basic colloidal characteristics investigated the structure-surface activity dependence is confirmed. Their indicative character for R(EO)nPD is based on the assumption that the structures studied are not unitary (heterogeneous) because: a) the hydrophobic chains C12H25/C18H37 have been grouped in two variants, C12H25/C14H29 (LM); C16H33/C18H37 (CS), each with an internal mass ratio of 7/3; b) the hydrophilic polyoxyethylene chains (n = 3-20) have polydisperse character; the meaning and value the oligomerization degree, n, is that of weighted average. In these conditions the surface tension increases proportionally with the oligomerization degree of the polyoxyethylene chain, while the

  11. Synthesis and iron sequestration equilibria of novel exocyclic 3-hydroxy-2-pyridinone donor group siderophore mimics.

    PubMed

    Harrington, James M; Chittamuru, Sumathi; Dhungana, Suraj; Jacobs, Hollie K; Gopalan, Aravamudan S; Crumbliss, Alvin L

    2010-09-20

    The synthesis of a novel class of exocyclic bis- and tris-3,2-hydroxypyridinone (HOPO) chelators built on N(2) and N(3) aza-macrocyclic scaffolds and the thermodynamic solution characterization of their complexes with Fe(III) are described. The chelators for this study were prepared by reaction of either piperazine or N,N',N''-1,4,7-triazacyclononane with a novel electrophilic HOPO iminium salt in good yields. Subsequent removal of the benzyl protecting groups using HBr/acetic acid gave bis-HOPO chelators N(2)(etLH)(2) and N(2)(prLH)(2), and tris-HOPO chelator N(3)(etLH)(3) in excellent yields. Solution thermodynamic characterization of their complexes with Fe(III) was accomplished using spectrophotometric, potentiometric, and electrospray ionization-mass spectrometry (ESI-MS) methods. The pK(a)'s of N(2)(etLH)(2), N(2)(prLH)(2), and N(3)(etLH)(3), were determined spectrophotometrically and potentiometrically. The Fe(III) complex stability constants for the tetradentate N(2)(etLH)(2) and N(2)(prLH)(2), and hexadentate N(3)(etLH)(3), were measured by spectrophotometric and potentiometric titration, and by competition with ethylenediaminetetraacetic acid (EDTA). N(3)(etLH)(3) forms a 1:1 complex with Fe(III) with log β(110) = 27.34 ± 0.04. N(2)(prLH)(2) forms a 3:2 L:Fe complex with Fe(III) where log β(230) = 60.46 ± 0.04 and log β(110) = 20.39 ± 0.02. While N(2)(etLH)(2) also forms a 3:2 L:Fe complex with Fe(III), solubility problems precluded determining log β(230); log β(110) was found to be 20.45 ± 0.04. The pFe values of 26.5 for N(3)(etLH)(3) and 24.78 for N(2)(prLH)(2) are comparable to other siderophore molecules used in the treatment of iron overload, suggesting that these hydroxypyridinone ligands may be useful in the development of new chelation therapy agents.

  12. Correlations for the Viscosity of 2,3,3,3-Tetrafluoroprop-1-ene (R1234yf) and trans-1,3,3,3-Tetrafluoropropene (R1234ze(E))†

    PubMed Central

    Huber, Marcia L.; Assael, Marc J.

    2016-01-01

    Due to concerns about global warming, there is interest in 2,3,3,3-Tetrafluoroprop-1-ene (R1234yf) and trans-1,3,3,3-Tetrafluoropropene (R1234ze(E)) as potential replacements for refrigerants with high global warming potential (GWP). In this manuscript we survey available data and provide viscosity correlations that cover the entire fluid range including vapor, liquid, and supercritical regions. The correlation for R1234yf is valid from the triple point (220 K) to 410 K at pressures up to 30 MPa, and the correlation for R1234ze(E) is valid from the triple point (169 K) to 420 K at pressures up to 100 MPa. The estimated uncertainty for both correlations at a 95 % confidence level is 2 % for the liquid phase over the temperature range 243 K to 363 K at pressures to 30 MPa, and 3 % for the gas phase at atmospheric pressure. PMID:27840461

  13. Genome-Wide Identification of R2R3-MYB Genes and Expression Analyses During Abiotic Stress in Gossypium raimondii

    PubMed Central

    He, Qiuling; Jones, Don C.; Li, Wei; Xie, Fuliang; Ma, Jun; Sun, Runrun; Wang, Qinglian; Zhu, Shuijin; Zhang, Baohong

    2016-01-01

    The R2R3-MYB is one of the largest families of transcription factors, which have been implicated in multiple biological processes. There is great diversity in the number of R2R3-MYB genes in different plants. However, there is no report on genome-wide characterization of this gene family in cotton. In the present study, a total of 205 putative R2R3-MYB genes were identified in cotton D genome (Gossypium raimondii), that are much larger than that found in other cash crops with fully sequenced genomes. These GrMYBs were classified into 13 groups with the R2R3-MYB genes from Arabidopsis and rice. The amino acid motifs and phylogenetic tree were predicted and analyzed. The sequences of GrMYBs were distributed across 13 chromosomes at various densities. The results showed that the expansion of the G. Raimondii R2R3-MYB family was mainly attributable to whole genome duplication and segmental duplication. Moreover, the expression pattern of 52 selected GrMYBs and 46 GaMYBs were tested in roots and leaves under different abiotic stress conditions. The results revealed that the MYB genes in cotton were differentially expressed under salt and drought stress treatment. Our results will be useful for determining the precise role of the MYB genes during stress responses with crop improvement. PMID:27009386

  14. ERP44 inhibits human lung cancer cell migration mainly via IP3R2.

    PubMed

    Huang, Xue; Jin, Meng; Chen, Ying-Xiao; Wang, Jun; Zhai, Kui; Chang, Yan; Yuan, Qi; Yao, Kai-Tai; Ji, Guangju

    2016-06-01

    Cancer cell migration is involved in tumour metastasis. However, the relationship between calcium signalling and cancer migration is not well elucidated. In this study, we used the human lung adenocarcinoma A549 cell line to examine the role of endoplasmic reticulum protein 44 (ERP44), which has been reported to regulate calcium release inside of the endoplasmic reticulum (ER), in cell migration. We found that the inositol 1,4,5-trisphosphate receptors (IP3Rs/ITPRs) inhibitor 2-APB significantly inhibited A549 cell migration by inhibiting cell polarization and pseudopodium protrusion, which suggests that Ca2+ is necessary for A549 cell migration. Similarly, the overexpression of ERP44 reduced intracellular Ca2+ release via IP3Rs, altered cell morphology and significantly inhibited the migration of A549 cells. These phenomena were primarily dependent on IP3R2 because wound healing in A549 cells with IP3R2 rather than IP3R1 or IP3R3 siRNA was markedly inhibited. Moreover, the overexpression of ERP44 did not affect the migration of the human neuroblastoma cell line SH-SY5Y, which mainly expresses IP3R1. Based on the above observations, we conclude that ERP44 regulates A549 cell migration mainly via an IP3R2-dependent pathway.

  15. ERP44 inhibits human lung cancer cell migration mainly via IP3R2

    PubMed Central

    Zhai, Kui; Chang, Yan; Yuan, Qi; Yao, Kai-Tai; Ji, Guangju

    2016-01-01

    Cancer cell migration is involved in tumour metastasis. However, the relationship between calcium signalling and cancer migration is not well elucidated. In this study, we used the human lung adenocarcinoma A549 cell line to examine the role of endoplasmic reticulum protein 44 (ERP44), which has been reported to regulate calcium release inside of the endoplasmic reticulum (ER), in cell migration. We found that the inositol 1,4,5-trisphosphate receptors (IP3Rs/ITPRs) inhibitor 2-APB significantly inhibited A549 cell migration by inhibiting cell polarization and pseudopodium protrusion, which suggests that Ca2+ is necessary for A549 cell migration. Similarly, the overexpression of ERP44 reduced intracellular Ca2+ release via IP3Rs, altered cell morphology and significantly inhibited the migration of A549 cells. These phenomena were primarily dependent on IP3R2 because wound healing in A549 cells with IP3R2 rather than IP3R1 or IP3R3 siRNA was markedly inhibited. Moreover, the overexpression of ERP44 did not affect the migration of the human neuroblastoma cell line SH-SY5Y, which mainly expresses IP3R1. Based on the above observations, we conclude that ERP44 regulates A549 cell migration mainly via an IP3R2-dependent pathway. PMID:27347718

  16. (R)-3-hydroxyhexan-2-one is a major pheromone component of Anelaphus inflaticollis (Coleoptera: Cerambycidae).

    PubMed

    Ray, A M; Swift, I P; Moreira, J A; Millar, J G; Hanks, L M

    2009-10-01

    We report the identification and field bioassays of a major component of the male-produced aggregation pheromone of Anelaphus inflaticollis Chemsak, an uncommon desert cerambycine beetle. Male A. inflaticollis produced a sex-specific blend of components that included (R)-3-hydroxyhexan-2-one, (S)-2-hydroxyhexan-3-one, 2,3-hexanedione, and (2R,3R)- and (2R,3S)-2,3-hexanediols. Field trials with baited bucket traps determined that the reconstructed synthetic pheromone blend and (R)-3-hydroxyhexan-2-one alone attracted adult A. inflaticollis of both sexes, with significantly more beetles being attracted to the blend. We conclude that (R)-3-hydroxyhexan-2-one is a major pheromone component of A. inflaticollis, and our results suggest that one or more of the minor components may further increase attraction of conspecifics. Scanning electron microscopy showed that male A. inflaticollis have pores on the prothorax that are consistent in structure with sex-specific pheromone gland pores in related species. Males also displayed stereotyped calling behavior similar to that observed in other cerambycine species. This study represents the first report of volatile pheromones for a cerambycine species in the tribe Elaphidiini.

  17. Evolution of Novel Reassortant A/H3N2 Influenza Viruses in North American Swine and Humans, 2009–2011

    PubMed Central

    Vincent, Amy L.; Kitikoon, Pravina; Holmes, Edward C.; Gramer, Marie R.

    2012-01-01

    Novel H3N2 influenza viruses (H3N2v) containing seven genome segments from swine lineage triple-reassortant H3N2 viruses and a 2009 pandemic H1N1 (H1N1pdm09) matrix protein segment (pM) were isolated from 12 humans in the United States between August and December 2011. To understand the evolution of these novel H3N2 viruses in swine and humans, we undertook a phylogenetic analysis of 674 M sequences and 388 HA and NA sequences from influenza viruses isolated from North American swine during 2009–2011, as well as HA, NA, and M sequences from eight H3N2v viruses isolated from humans. We identified 34 swine influenza viruses (termed rH3N2p) with the same combination of H3, N2, and pM segments as the H3N2v viruses isolated from humans. Notably, these rH3N2p viruses were generated in swine via reassortment events between H3N2 viruses and the pM segment approximately 4 to 10 times since 2009. The pM segment has also reassorted with multiple distinct lineages of H1 virus, especially H1δ viruses. Importantly, the N2 segment of all H3N2v viruses isolated from humans is derived from a genetically distinct N2 lineage that has circulated in swine since being acquired by reassortment with seasonal human H3N2 viruses in 2001–2002, rather than from the N2 that is associated with the 1998 H3N2 swine lineage. The identification of this N2 variant may have implications for influenza vaccine design and the potential pandemic threat of H3N2v to human age groups with differing levels of prior exposure and immunity. PMID:22696653

  18. Quenching of I(2P1/2) by NO2, N2O4, and N2O.

    PubMed

    Kabir, Md Humayun; Azyazov, Valeriy N; Heaven, Michael C

    2007-10-11

    Quenching of excited iodine atoms (I(5p5, 2P1/2)) by nitrogen oxides are processes of relevance to discharge-driven oxygen iodine lasers. Rate constants at ambient and elevated temperatures (293-380 K) for quenching of I(2P1/2) atoms by NO2, N2O4, and N2O have been measured using time-resolved I(2P1/2) --> I(2P3/2) 1315 nm emission. The excited atoms were generated by pulsed laser photodissociation of CF3I at 248 nm. The rate constants for I(2P1/2) quenching by NO2 and N2O were found to be independent of temperature over the range examined with average values of (2.9 +/- 0.3) x 10(-15) and (1.4 +/- 0.1) x 10(-15) cm3 s(-1), respectively. The rate constant for quenching of I(2P1/2) by N2O4 was found to be (3.5 +/- 0.5) x 10(-13) cm3 s(-1) at ambient temperature.

  19. A new cavity ring-down instrument for airborne monitoring of N2O5, NO3, NO2 and O3 in the upper troposphere lower stratosphere

    NASA Astrophysics Data System (ADS)

    Ruth, Albert A.; Brown, Steven S.; Dinesan, Hemanth; Dubé, William P.; Goulette, Marc; Hübler, Gerhard; Orphal, Johannes; Zahn, Andreas

    2016-04-01

    entirely to provide the sum of NO3 and N2O5, with N2O5 provided by difference to a direct NO3 measurement in a separate, unheated channel. One of the (405)-cavities is flushed continuously with NO in order to measure O3 concentrations via quantitative conversion to NO2. The air sampled underneath the cargo bay of the aircraft is distributed inside the instrument through a dedicated inlet system distributing the flow over all four cavities. Flow control, data collection, analysis, and zeroing procedures are fully automated and controlled by dedicated electronics and software within the device. On the poster the new instrument, its design and application within the CARIBIC program, will be outlined. [1] S.S. Brown, T.B. Ryerson, A.G. Wollny, C.A. Brock, R. Peltier, A.P. Sullivan, R.J. Weber, J.S. Holloway, W.P. Dubé, M. Trainer, J.F. Meagher, F.C. Fehsenfeld, A. R. Ravishankara, Variability in nocturnal nitrogen oxide processing and its role in regional air quality, Science, 311 (2006) 67-70.

  20. Electrochemical Reduction of N2 under Ambient Conditions for Artificial N2 Fixation and Renewable Energy Storage Using N2 /NH3 Cycle.

    PubMed

    Bao, Di; Zhang, Qi; Meng, Fan-Lu; Zhong, Hai-Xia; Shi, Miao-Miao; Zhang, Yu; Yan, Jun-Min; Jiang, Qing; Zhang, Xin-Bo

    2017-01-01

    Using tetrahexahedral gold nanorods as a heterogeneous electrocatalyst, an electrocatalytic N 2 reduction reaction is shown to be possible at room temperature and atmospheric pressure, with a high Faradic efficiency up to 4.02% at -0.2 V vs reversible hydrogen electrode (1.648 µg h -1 cm -2 and 0.102 µg h -1 cm -2 for NH 3 and N 2 H 4 ·H 2 O, respectively). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Crystal structure of 5''-benzyl-idene-1'-methyl-4'-phenyl-tri-spiro-[ace-naphthyl-ene-1,2'-pyrrolidine-3',1''-cyclo-hexane-3'',2'''-[1,3]dioxane]-2,6''-dione.

    PubMed

    Chandralekha, Kuppan; Gavaskar, Deivasigamani; Sureshbabu, Adukamparai Rajukrishnan; Lakshmi, Srinivasakannan

    2016-03-01

    In the title compound, C36H31NO4, two spiro links connect the methyl-substituted pyrrolidine ring to the ace-naphthyl-ene and cyclo-hexa-none rings. The cyclo-hexa-none ring is further connected to the dioxalane ring by a third spiro junction. The five-membered ring of the ace-naphthylen-1-one ring system adopts a flattened envelope conformation with the ketonic C atom as flap, whereas the dioxalane and pyrrolidine rings each have a twist conformation. The cyclo-hexa-none ring assumes a boat conformation. Three intra-molecular C-H⋯O hydrogen bonds involving both ketonic O atoms as acceptors are present. In the crystal, C-H⋯O hydrogen bonds connect centrosymmetrically related mol-ecule into chains parallel to the b axis, forming rings of R 2 (2)(10)and R 2 (2)(8) graph-set motifs.

  2. Dispersion interactions between neighboring Bi atoms in (BiH3 )2 and Te(BiR2 )2.

    PubMed

    Haack, Rebekka; Schulz, Stephan; Jansen, Georg

    2018-03-13

    Triggered by the observation of a short Bi⋯Bi distance and a BiTeBi bond angle of only 86.6° in the crystal structure of bis(diethylbismuthanyl)tellurane quantum chemical computations on interactions between neighboring Bi atoms in Te(BiR 2 ) 2 molecules (R = H, Me, Et) and in (BiH 3 ) 2 were undertaken. Bi⋯Bi distances atoms were found to significantly shorten upon inclusion of the d shells of the heavy metal atoms into the electron correlation treatment, and it was confirmed that interaction energies from spin component-scaled second-order Møller-Plesset theory (SCS-MP2) agree well with coupled-cluster singles and doubles theory including perturbative triples (CCSD(T)). Density functional theory-based symmetry-adapted perturbation theory (DFT-SAPT) was used to study the anisotropy of the interplay of dispersion attraction and steric repulsion between the Bi atoms. Finally, geometries and relative stabilities of syn-syn and syn-anti conformers of Te(BiR 2 ) 2 (R = H, Me, Et) and interconversion barriers between them were computed. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  3. 8-Substituted 1,3-dimethyltetrahydropyrazino[2,1-f]purinediones: Water-soluble adenosine receptor antagonists and monoamine oxidase B inhibitors.

    PubMed

    Brunschweiger, Andreas; Koch, Pierre; Schlenk, Miriam; Rafehi, Muhammad; Radjainia, Hamid; Küppers, Petra; Hinz, Sonja; Pineda, Felipe; Wiese, Michael; Hockemeyer, Jörg; Heer, Jag; Denonne, Frédéric; Müller, Christa E

    2016-11-01

    Multitarget approaches, i.e., addressing two or more targets simultaneously with a therapeutic agent, are hypothesized to offer additive therapeutic benefit for the treatment of neurodegenerative diseases. Validated targets for the treatment of Parkinson's disease are, among others, the A 2A adenosine receptor (AR) and the enzyme monoamine oxidase B (MAO-B). Additional blockade of brain A 1 ARs may also be beneficial. We recently described 8-benzyl-substituted tetrahydropyrazino[2,1-f]purinediones as a new lead structure for the development of such multi-target drugs. We have now designed a new series of tetrahydropyrazino[2,1-f]purinediones to extensively explore their structure-activity-relationships. Several compounds blocked human and rat A 1 and A 2A ARs at similar concentrations representing dual A 1 /A 2A antagonists with high selectivity versus the other AR subtypes. Among the best dual A 1 /A 2A AR antagonists were 8-(3-(4-chlorophenyl)propyl)-1,3-dimethyl-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (41, K i human A 1 : 65.5nM, A 2A : 230nM; K i rat A 1 : 352nM, A 2A : 316nM) and 1,3-dimethyl-8-((2-(thiophen-2-yl)thiazol-4-yl)methyl)-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (57, K i human A 1 : 642nM, A 2A : 203nM; K i rat A 1 : 166nM, A 2A : 121nM). Compound 57 was found to be well water-soluble (0.7mg/mL) at a physiological pH value of 7.4. One of the new compounds showed triple-target inhibition: (R)-1,3-dimethyl-8-(2,1,3,4-tetrahydronaphthalen-1-yl)-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (49) was about equipotent at A 1 and A 2A ARs and at MAO-B (K i human A 1 : 393nM, human A 2A : 595nM, IC 50 human MAO-B: 210nM) thus allowing future in vivo explorations of the intended multi-target approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The Role of 5-HT2A, 5-HT2C and mGlu2 Receptors in the Behavioral Effects of Tryptamine Hallucinogens N,N-Dimethyltryptamine and N,N-Diisopropyltryptamine in Rats and Mice

    PubMed Central

    Carbonaro, Theresa M.; Eshleman, Amy J.; Forster, Michael J.; Cheng, Kejun; Rice, Kenner C.; Gatch, Michael B.

    2014-01-01

    Rationale: Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. Objective: The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Methods: Drug discrimination, head twitch and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084) and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. Results: MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT’s effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low potency full agonist at 5-HT2CR in vitro. Conclusions: The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree. PMID:24985890

  5. The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

    PubMed

    Carbonaro, Theresa M; Eshleman, Amy J; Forster, Michael J; Cheng, Kejun; Rice, Kenner C; Gatch, Michael B

    2015-01-01

    Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro. The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.

  6. The fate of the 23 × 23R(30°) silicene phase on Ag(111)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Zhi-Long; Wang, Mei-Xiao; Liu, Canhua, E-mail: canhualiu@sjtu.edu.cn, E-mail: depadova@ism.cnr.it, E-mail: guy.lelay@univ-amu.fr

    2014-09-01

    Silicon atoms deposited on Ag(111) produce various single layer silicene sheets with different buckling patterns and periodicities. Low temperature scanning tunneling microscopy reveals that one of the silicene sheets, the hypothetical √7 × √7 silicene structure, on 23 × 23 Ag(111), is inherently highly defective and displays no long-range order. Moreover, Auger and photoelectron spectroscopy measurements reveal its sudden death, to end, in a dynamic fating process at ∼300 °C. This result clarifies the real nature of the 23 × 23R(30°) silicene phase and thus helps to understand the diversity of the silicene sheets grown on Ag(111)

  7. 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.

    PubMed

    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.

  8. Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance.

    PubMed

    Migliori, Valentina; Müller, Julius; Phalke, Sameer; Low, Diana; Bezzi, Marco; Mok, Wei Chuen; Sahu, Sanjeeb Kumar; Gunaratne, Jayantha; Capasso, Paola; Bassi, Christian; Cecatiello, Valentina; De Marco, Ario; Blackstock, Walter; Kuznetsov, Vladimir; Amati, Bruno; Mapelli, Marina; Guccione, Ernesto

    2012-01-08

    The asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a) acts as a repressive mark that antagonizes trimethylation of H3 lysine 4. Here we report that H3R2 is also symmetrically dimethylated (H3R2me2s) by PRMT5 and PRMT7 and present in euchromatic regions. Profiling of H3-tail interactors by SILAC MS revealed that H3R2me2s excludes binding of RBBP7, a central component of co-repressor complexes Sin3a, NURD and PRC2. Conversely H3R2me2s enhances binding of WDR5, a common component of the coactivator complexes MLL, SET1A, SET1B, NLS1 and ATAC. The interaction of histone H3 with WDR5 distinguishes H3R2me2s from H3R2me2a, which impedes the recruitment of WDR5 to chromatin. The crystallographic structure of WDR5 and the H3R2me2s peptide elucidates the molecular determinants of this high affinity interaction. Our findings identify H3R2me2s as a previously unknown mark that keeps genes poised in euchromatin for transcriptional activation upon cell-cycle withdrawal and differentiation in human cells.

  9. Tyms double (2R) and triple repeat (3R) confers risk for human oral squamous cell carcinoma.

    PubMed

    Bezerra, Alexandre Medeiros; Sant'Ana, Thalita Araújo; Gomes, Adriana Vieira; de Lacerda Vidal, Aurora Karla; Muniz, Maria Tereza Cartaxo

    2014-12-01

    The oral cancer is responsible for approximately 3 % of cases of cancer in Brazil. Epidemiological studies have associated low folate intake with an increased risk of epithelial cancers, including oral cancer. Folic acid has a key role in DNA synthesis, repair, methylation and this is the basis of explanations for a putative role for folic acid in cancer prevention. The role of folic acid in carcinogenesis may be modulated by polymorphism C677T in MTHFR and tandem repeats 2R/3R in the promoter site of TYMS gene that are related to decreased enzymatic activity and quantity and availability of the enzyme, respectively. These events cause a decrease in the synthesis, repair and DNA methylation, which can lead to a disruption in the expression of tumor suppressor genes as TP53. The objective of this study was investigate the distribution of polymorphisms C677T and tandem repeats 2R/3R associated with the development of oral squamous cell carcinoma (OSCC). 53 paraffin-embedded samples from patients who underwent surgery but are no longer at the institution and 43 samples collected by method of oral exfoliation by cytobrush were selected. 132 healthy subjects were selected by specialists at the dental clinics of the Faculdade de Odontologia de Pernambuco-FOP. The MTHFR genotyping was performed by PCR-RFLP, and the TYMS genotyping was performed by conventional PCR. Fisher's Exact test at significant level of 5 %. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to measure the strength of association between genotype frequency and OSCC development. The results were statistically significant for the tandem repeats of the TYMS gene (p = 0.015). The TYMS 2R3R genotype was significantly associated with the development of OSCC (OR = 3.582; 95 % CI 1.240-10.348; p = 0.0262) and also the genotype 3R3R (OR = 3.553; 95 % CI 1.293-9.760; p = 0.0345). When analyzed together, the TYMS 2R3R + 3R3R genotypes also showed association (OR = 3.518; 95 % CI 11.188-10.348; p

  10. Electrochemical sensing of modified ABO3 perovskite: LaFe0.8 R0.2O3(R= Cr, Co, Al)

    NASA Astrophysics Data System (ADS)

    Vidya Rajan, N.; Alexander, L. K.

    2017-06-01

    Perovskite LaFeO3 with orthorhombic structure has been synthesized by citric acid mediated solution method. The effectiveness of ionic radii and Oxidation state of the doping material on ionic conductivity of the host matrix was evaluated by B-site (Fe) doping on LaFeO3 with Cr, Co and Al, resulting LaFe0.8 R0.2O3 (R = Cr, Co, Al). XRD with Rietveld refinement and Raman spectroscopic analysis demonstrate successful synthesis. The effect of the 20% B site doping on electrochemical activity is reported. The doped materials exhibit a decrease in sensing activity towards the non enzymatic detection of H2O2.

  11. R3D-2-MSA: the RNA 3D structure-to-multiple sequence alignment server

    PubMed Central

    Cannone, Jamie J.; Sweeney, Blake A.; Petrov, Anton I.; Gutell, Robin R.; Zirbel, Craig L.; Leontis, Neocles

    2015-01-01

    The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access. Users can specify up to five ranges of nucleotides and 50 nucleotide positions per range. The R3D-2-MSA server maps these ranges to the appropriate columns of the corresponding MSA and returns the contents of the columns, either for display in a web browser or in JSON format for subsequent programmatic use. The browser output page provides a 3D interactive display of the query, a full list of sequence variants with taxonomic information and a statistical summary of distinct sequence variants found. The output can be filtered and sorted in the browser. Previous user queries can be viewed at any time by resubmitting the output URL, which encodes the search and re-generates the results. The service is freely available with no login requirement at http://rna.bgsu.edu/r3d-2-msa. PMID:26048960

  12. Methanesulfonates of high-valent metals: syntheses and structural features of MoO2(CH3SO3)2, UO2(CH3SO3)2, ReO3(CH3SO3), VO(CH3SO3)2, and V2O3(CH3SO3)4 and their thermal decomposition under N2 and O2 atmosphere.

    PubMed

    Betke, Ulf; Neuschulz, Kai; Wickleder, Mathias S

    2011-11-04

    Oxide methanesulfonates of Mo, U, Re, and V have been prepared by reaction of MoO(3), UO(2)(CH(3)COO)(22H(2)O, Re(2)O(7)(H(2)O)(2), and V(2)O(5) with CH(3)SO(3)H or mixtures thereof with its anhydride. These compounds are the first examples of solvent-free oxide methanesulfonates of these elements. MoO(2)(CH(3)SO(3))(2) (Pbca, a=1487.05(4), b=752.55(2), c=1549.61(5) pm, V=1.73414(9) nm(3), Z=8) contains [MoO(2)] moieties connected by [CH(3)SO(3)] ions to form layers parallel to (100). UO(2)(CH(3)SO(3))(2) (P2(1)/c, a=1320.4(1), b=1014.41(6), c=1533.7(1) pm, β=112.80(1)°, V=1.8937(3) nm(3), Z=8) consists of linear UO(2)(2+) ions coordinated by five [CH(3)SO(3)] ions, forming a layer structure. VO(CH(3)SO(3))(2) (P2(1)/c, a=1136.5(1), b=869.87(7), c=915.5(1) pm, β=113.66(1)°, V=0.8290(2) nm(3), Z=4) contains [VO] units connected by methanesulfonate anions to form corrugated layers parallel to (100). In ReO(3)(CH(3)SO(3)) (P1, a=574.0(1), b=1279.6(3), c=1641.9(3) pm, α=102.08(2), β=96.11(2), γ=99.04(2)°, V=1.1523(4) nm(3), Z=8) a chain structure exhibiting infinite O-[ReO(2)]-O-[ReO(2)]-O chains is formed. Each [ReO(2)]-O-[ReO(2)] unit is coordinated by two bidentate [CH(3)SO(3)] ions. V(2)O(3)(CH(3)SO(3))(4) (I2/a, a=1645.2(3), b=583.1(1), c=1670.2(3) pm, β=102.58(3), V=1.5637(5) pm(3), Z=4) adopts a chain structure, too, but contains discrete [VO]-O-[VO] moieties, each coordinated by two bidentate [CH(3)SO(3)] ligands. Additional methanesulfonate ions connect the [V(2)O(3)] groups along [001]. Thermal decomposition of the compounds was monitored under N(2) and O(2) atmosphere by thermogravimetric/differential thermal analysis and XRD measurements. Under N(2) the decomposition proceeds with reduction of the metal leading to the oxides MoO(2), U(3)O(7), V(4)O(7), and VO(2); for MoO(2)(CH(3)SO(3))(2), a small amount of MoS(2) is formed. If the thermal decomposition is carried out in a atmosphere of O(2) the oxides MoO(3) and V(2)O(5) are formed. Copyright

  13. High efficient photocatalytic selective oxidation of benzyl alcohol to benzaldehyde by solvothermal-synthesized ZnIn2S4 microspheres under visible light irradiation

    NASA Astrophysics Data System (ADS)

    Chen, Zhixin; Xu, Jingjing; Ren, Zhuyun; He, Yunhui; Xiao, Guangcan

    2013-09-01

    Hexagonal ZnIn2S4 samples have been synthesized by a solvothermal method. Their properties have been determined by X-ray diffraction, ultraviolet-visible-light diffuse reflectance spectra, field emission scanning electron microscopy, nitrogen adsorption-desorption and X-ray photoelectron spectra. These results demonstrate that ethanol solvent has significant influence on the morphology, optical and electronic nature for such marigold-like ZnIn2S4 microspheres. The visible light photocatalytic activities of the ZnIn2S4 have been evaluated by selective oxidation of benzyl alcohol to benzaldehyde using molecular oxygen as oxidant. The results show that 100% conversion along with >99% selectivity are reached over ZnIn2S4 prepared in ethanol solvent under visible light irradiation (λ>420 nm) of 2 h, but only 58% conversion and 57% yield are reached over ZnIn2S4 prepared in aqueous solvent. A possible mechanism of the high photocatalytic activity for selective oxidation of benzyl alcohol over ZnIn2S4 is proposed and discussed.

  14. Design, synthesis and anticonvulsant properties of new N-Mannich bases derived from 3-phenylpyrrolidine-2,5-diones.

    PubMed

    Kamiński, Krzysztof; Obniska, Jolanta; Chlebek, Iwona; Wiklik, Beata; Rzepka, Sabina

    2013-11-01

    The synthesis and anticonvulsant properties of new N-Mannich bases of 3-phenyl- (9a-d), 3-(2-chlorophenyl)- (10a-d), 3-(3-chlorophenyl)- (11a-d) and 3-(4-chlorophenyl)-pyrrolidine-2,5-diones (12a-d) were described. The key synthetic strategies involve the formation of 3-substituted pyrrolidine-2,5-diones (5-8), and then aminoalkylation reaction (Mannich-type) with formaldehyde and corresponding secondary amines, which let to obtain the final compounds 9a-d, 10a-d, 11a-d and 12a-d in good yields. Initial anticonvulsant screening was performed in mice (ip) using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizures tests. The most effective compounds in mice were tested after oral administration in rats. The acute neurological toxicity was determined applying the minimal motor impairment rotarod test. The in vivo results revealed that numerous compounds were effective especially in the MES test (model of human tonic-clonic seizures). The most active in the MES seizures in rats was 1-[(4-benzyl-1-piperidyl)methyl]-3-(2-chlorophenyl)pyrrolidine-2,5-dione (10c) which showed ED50 value of 37.64mg/kg. It should be stressed that this molecule along with 9a, 9d and 10d showed protection in the psychomotor seizure test (6-Hz), which is known as an animal model of therapy-resistant epilepsy. Furthermore compounds 9a, 9d and 10d were also tested in the pilocarpine-induced status prevention (PISP) test to assess their potential effectiveness in status epilepticus. For the most promising molecule 9d an influence on human CYP3A4 isoform of P-450 cytochrome was studied in vitro. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Microtropins A-I: 6'-O-(2″S,3R)-2″-ethyl-2″,3″-dihydroxybutyrates of aliphatic alcohol β-D-glucopyranosides from the branches of Microtropis japonica.

    PubMed

    Uemura, Yuka; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki; Takeda, Yoshio; Kawahata, Masatoshi; Yamaguchi, Kentaro

    2013-03-01

    From the branches of Microtropis japonica (Celastraceae), nine aliphatic glucosides, named microtropins A-I, were isolated. The 6-position of glucose was esterified with (2S,3R)-2-ethyl-2,3-dihydroxybutyric acid. Microtropins A-D contained a rare natured product nitrile functional group in their aglycones. The absolute structures of the (2S,3R)-2-ethyl-2,3-dihydroxybutyric acid moiety and aglycone of microtropin A were determined by an X-ray crystallographic method. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Research on the Solid State Fermentation of Jerusalem Artichoke Pomace for Producing R,R-2,3-Butanediol by Paenibacillus polymyxa ZJ-9.

    PubMed

    Cao, Can; Zhang, Li; Gao, Jian; Xu, Hong; Xue, Feng; Huang, Weiwei; Li, Yan

    2017-06-01

    R,R-2,3-butanediol (R,R-2,3-BD) was produced by Paenibacillus polymyxa ZJ-9, which was capable of utilizing inulin without previous hydrolysis. The Jerusalem artichoke pomace (JAP) derived from the conversion of Jerusalem artichoke powder into inulin extract, which was usually used for biorefinery by submerged fermentation (SMF), was utilized in solid state fermentation (SSF) to produce R,R-2,3-BD. In this study, the fermentation parameters of SSF were optimized and determined in flasks. A novel bioreactor was designed and assembled for the laboratory scale-up of SSF, with a maximum yield of R,R-2,3-BD (67.90 g/kg (JAP)). This result is a 36.3% improvement compared with the flasks. Based on the same bath of Jerusalem artichoke powder, the total output of R,R-2,3-BD increased by 38.8% for the SSF of JAP combined with the SMF of inulin extraction. Overall, the utilization of JAP for R,R-2,3-BD production was beneficial to the comprehensive utilization of Jerusalem artichoke tuber.

  17. N′-[(E)-3-Chloro-2-fluoro­benzyl­idene]-6-methyl­nicotinohydrazide monohydrate

    PubMed Central

    Fun, Hoong-Kun; Quah, Ching Kheng; Shyma, P. C.; Kalluraya, Balakrishna; Vidyashree, J. H. S.

    2012-01-01

    The title compound, C14H11ClFN3O·H2O, exists in an E conformation with respect to the N=C bond. The pyridine ring forms a dihedral angle of 5.00 (9)° with the benzene ring. In the crystal, the ketone O atom accepts one O—H⋯O and one C—H⋯O hydrogen bond, the water O atom accepts one N—H⋯O and two C—H⋯O hydrogen bonds and the pyridine N atom accepts one O—H⋯N hydrogen bond, forming layers parallel to the ab plane. PMID:22798798

  18. Evaluation of role 2 (R2) medical resources in the Afghanistan combat theater: Initial review of the joint trauma system R2 registry.

    PubMed

    Mann-Salinas, Elizabeth A; Le, Tuan D; Shackelford, Stacy A; Bailey, Jeffrey A; Stockinger, Zsolt T; Spott, Mary Ann; Wirt, Michael D; Rickard, Rory; Lane, Ian B; Hodgetts, Timothy; Cardin, Sylvain; Remick, Kyle N; Gross, Kirby R

    2016-11-01

    A Role 2 registry (R2R) was developed in 2008 by the US Joint Trauma System (JTS). The purpose of this project was to undertake a preliminary review of the R2R to understand combat trauma epidemiology and related interventions at these facilities to guide training and optimal use of forward surgical capability in the future. A retrospective review of available JTS R2R records; the registry is a convenience sample entered voluntarily by members of the R2 units. Patients were classified according to basic demographics, affiliation, region where treatment was provided, mechanism of injury, type of injury, time and method of transport from point of injury (POI) to R2 facility, interventions at R2, and survival. Analysis included trauma patients aged ≥18 years or older wounded in year 2008 to 2014, and treated in Afghanistan. A total of 15,404 patients wounded and treated in R2 were included in the R2R from February 2008 to September 2014; 12,849 patients met inclusion criteria. The predominant patient affiliations included US Forces, 4,676 (36.4%); Afghan Forces, 4,549 (35.4%); and Afghan civilians, 2,178 (17.0%). Overall, battle injuries predominated (9,792 [76.2%]). Type of injury included penetrating, 7,665 (59.7%); blunt, 4,026 (31.3%); and other, 633 (4.9%). Primary mechanism of injury included explosion, 5,320 (41.4%); gunshot wounds, 3,082 (24.0%); and crash, 1,209 (9.4%). Of 12,849 patients who arrived at R2, 167 (1.3%) were dead; of 12,682 patients who were alive upon arrival, 342 (2.7%) died at R2. This evaluation of the R2R describes the patient profiles of and common injuries treated in a sample of R2 facilities in Afghanistan. Ongoing and detailed analysis of R2R information may provide evidence-based guidance to military planners and medical leaders to best prepare teams and allocate R2 resources in future operations. Given the limitations of the data set, conclusions must be interpreted in context of other available data and analyses, not in isolation

  19. Apoptosis Induction by Targeting Interferon Gamma Receptor 2 (IFNgammaR2) in Prostate Cancer: Ligand (IFNgamma) Independent Novel Function of IFNgammaR2 as a Bax Inhibitor

    DTIC Science & Technology

    2016-10-01

    DATE October 2016 2. REPORT TYPE Final report 3 . DATES COVERED 1 Aug 2012 - 31 Jul 2016 4. TITLE AND SUBTITLE Apoptosis Induction by Targeting...identify the subtype of prostate cancer that can be effectively treated by IFNγR2-targeting technologies (Months 13-36) Task 3 : Determination of the...N-terminal 53 amino acids is known to be auto-inhibitory domain that keeps Bax in the cytosol[ 3 ]. If this domain is cleaved, Bax is known to be

  20. Conversion of (η(5)-C2B9H10R)TaX3 (X = Me, NMe2) to (η(6)-C2B9H10R)TaX' (X' = NMe2, azaallyl) in the absence of a reducing agent: synthesis and structure of tantallacarboranes incorporating an arachno-η(6)-C2B9(4-) ligand.

    PubMed

    Xiang, Li; Xie, Zuowei

    2014-08-04

    Heating a benzene solution of [η(5)-(Me2NCH2CH2)C2B9H10] Ta(NMe2)3 (1) in the presence of pyridine gave an unprecedented complex [η(1):η(6)-(Me2NCH2CH2)C2B9H10]Ta (NMe2)(NC5H5) (2). On the other hand, reaction of (η(5)-C2B9H11)TaMe3 with adamantly isonitrile (AdNC) in dimethoxyethane (DME) at room temperature afforded another unexpected complex (η(6)-C2B9H11)Ta[η(3)-C,C,N-CH2C(CH3)NAd](DME) (4). These results show that pyridine and DME are essential for the formation of 2 and 4, respectively. It is suggested that the nido-η(5)-C2B9H10R(2−) ligand in tantallacarboranes takes up two electrons released by reductive elimination to form an arachno-η(6)-C2B9H10R(4−) fragment via the cage C–C bond cleavage.

  1. Synthesis, characterization, and antifungal evaluation of novel 1,2,3-triazolium-functionalized starch derivative.

    PubMed

    Tan, Wenqiang; Zhang, Jingjing; Luan, Fang; Wei, Lijie; Li, Qing; Dong, Fang; Guo, Zhanyong

    2017-08-01

    1,2,3-Triazolium-functionalized starch derivative was obtained by straightforward quaternization of the synthesized starch derivative bearing 1,2,3-triazole with benzyl bromide by combining the robust attributes of cuprous-catalyzed azide-alkyne cycloaddition. These novel starch derivatives were characterized by FTIR, UV-vis, 1 H NMR, 13 C NMR, and elemental analysis. Their antifungal activities against Colletotrichum lagenarium, Watermelon fusarium, and Phomopsis asparagi were investigated by hypha measurement in vitro. The fungicidal assessment revealed that compared with starch and starch derivative bearing 1,2,3-triazole with inhibitory indices of below 15% at 1.0mg/mL, 1,2,3-triazolium-functionalized starch derivative had superior antifungal activity with inhibitory rates of over 60%. Especially, the best inhibitory index of 1,2,3-triazolium-functionalized starch derivative against Colletotrichum lagenarium attained 90% above at 1.0mg/mL. The results obviously showed that quaternization of 1,2,3-triazole with benzyl bromide could effectively enhance antifungal activity of the synthesized starch derivatives. The synthetic strategy described here could be utilized for the development of starch as novel antifungal biomaterial. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: implications for novel mGluR-based therapeutics.

    PubMed

    Matosin, Natalie; Fernandez-Enright, Francesca; Frank, Elisabeth; Deng, Chao; Wong, Jenny; Huang, Xu-Feng; Newell, Kelly A

    2014-11-01

    Metabotropic glutamate receptors 2/3 (mGluR2/3) and 5 (mGluR5) are novel therapeutic targets for major depression (MD), bipolar disorder (BD) and schizophrenia. We aimed to determine whether mGluR2/3 and mGluR5 binding in the anterior cingulate cortex (ACC), a brain region essential for the regulation of mood, cognition and emotion, were differentially altered in these pathologies. Using postmortem human brains derived from 2 cohorts, [(3)H]LY341495 binding to mGluR2/3 and [(3)H]MPEP binding to mGluR5 were measured by receptor autoradiography in the ACC. The first cohort comprised samples from individuals who had MD with psychosis (MDP), MD without psychosis (MDNP) and matched controls (n = 11-12 per group). The second cohort comprised samples from individuals who had MDNP, BD, schizophrenia and matched controls (n = 15 per group). No differences in mGluR2/3 or mGluR5 binding were observed in the MDP, MDNP, BD or schizophrenia groups compared with the control group (all p > 0.05). Importantly, there were also no differences in binding densities between the psychiatric disorders (p > 0.05). We did, however, observe age-related effects, with consistent negative associations between mGluR2/3 and age in the control group (r < -0.575, p < 0.025) and the psychotic disorder groups (MDP and schizophrenia: r = -0.765 to -0.515, p < 0.05), but not in the mood disorder groups (MDNP, BD). Replication in larger independent cohorts and medication-naive individuals would strengthen these findings. Our findings suggest that mGluRs are unaltered in the ACC; however, the presence of altered receptor function cannot be discounted and requires further investigation. Taken together with previous studies, which report differential changes in mGluR2, 3 and 5 across these disorders, we suggest mGluRs may be affected in a brain region-specific manner.

  3. Spin Polarization of Rb and Cs n p P2 3/2 (n =5 , 6) Atoms by Circularly Polarized Photoexcitation of a Transient Diatomic Molecule

    NASA Astrophysics Data System (ADS)

    Mironov, A. E.; Hewitt, J. D.; Eden, J. G.

    2017-03-01

    We report the selective population of Rb or Cs n p P2 3/2 (n =5 , 6; F =4 , 5) hyperfine states by the photodissociation of a transient, alkali-rare gas diatomic molecule. Circularly polarized (σ-), amplified spontaneous emission (ASE) on the D2 line of Rb or Cs (780.0 and 852.1 nm, respectively) is generated when Rb-Xe or Cs-Xe ground state collision pairs are photoexcited by a σ+-polarized optical field having a wavelength within the D2 blue satellite continuum, associated with the B Σ2 1/2 +←X Σ2 1/2 + (free←free ) transition of the diatomic molecule. The degree of spin polarization of Cs (6 p P3/2 2 ), specifically, is found to be dependent on the interatomic distance (R ) at which the excited complex is born, a result attributed to the structure of the B Σ2 1/2 + state. For Cs-Xe atomic pairs, tuning the wavelength of the optical field from 843 to 848 nm varies the degree of circular polarization of the ASE from 63% to almost unity because of the perturbation, in the 5 ≤R ≤6 Å interval, of the Σ2 1/2 + potential by a d σ molecular orbital associated with a higher Λ 2 electronic state. Monitoring only the Cs 6 p P3/2 2 spin polarization reveals a previously unobserved interaction of CsXe (B Σ2 1/2 + ) with the lowest vibrational levels of a Λ 2 state derived from Cs (5 d )+Xe . By inserting a molecular intermediate into the alkali atom excitation mechanism, these experiments realize electronic spin polarization through populating no more than two n p P2 3/2 hyperfine states, and demonstrate a sensitive spectroscopic

  4. Signatures of spin-orbital states of t2g 2 system in optical conductivity: R VO3 (R =Y and La)

    NASA Astrophysics Data System (ADS)

    Kim, Minjae

    2018-04-01

    We investigate signatures of the spin and orbital states of R VO3 (R =Y and La) in optical conductivity using density functional theory plus dynamical mean-field theory (DFT+DMFT). From the assignment of multiplet state configurations to optical transitions, the DFT+DMFT reproduces experimental temperature-dependent evolutions of optical conductivity for both YVO3 and LaVO3. We also show that the optical conductivity is a useful quantity to probe the evolution of the orbital state even in the absence of spin order. The result provides a reference to investigate the spin and orbital states of t2g 2 vanadate systems, which is an important issue for both fundamental physics on spin and orbital states and applications of vanadates by means of orbital state control.

  5. The Unique α4(+)/(−)α4 Agonist Binding Site in (α4)32)2 Subtype Nicotinic Acetylcholine Receptors Permits Differential Agonist Desensitization Pharmacology versus the (α4)22)3 Subtype

    PubMed Central

    Eaton, J. Brek; Lucero, Linda M.; Stratton, Harrison; Chang, Yongchang; Cooper, John F.; Lindstrom, Jon M.; Lukas, Ronald J.

    2014-01-01

    Selected nicotinic agonists were used to activate and desensitize high-sensitivity (HS) (α4)22)3) or low-sensitivity (LS) (α4)32)2) isoforms of human α4β2-nicotinic acetylcholine receptors (nAChRs). Function was assessed using 86Rb+ efflux in a stably transfected SH-EP1-hα4β2 human epithelial cell line, and two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing concatenated pentameric HS or LS α4β2-nAChR constructs (HSP and LSP). Unlike previously studied agonists, desensitization by the highly selective agonists A-85380 [3-(2(S)-azetidinylmethoxy)pyridine] and sazetidine-A (Saz-A) preferentially reduced α4β2-nAChR HS-phase versus LS-phase responses. The concatenated-nAChR experiments confirmed that approximately 20% of LS-isoform acetylcholine-induced function occurs in an HS-like phase, which is abolished by Saz-A preincubation. Six mutant LSPs were generated, each targeting a conserved agonist binding residue within the LS-isoform-only α4(+)/(−)α4 interface agonist binding site. Every mutation reduced the percentage of LS-phase function, demonstrating that this site underpins LS-phase function. Oocyte-surface expression of the HSP and each of the LSP constructs was statistically indistinguishable, as measured using β2-subunit–specific [125I]mAb295 labeling. However, maximum function is approximately five times greater on a “per-receptor” basis for unmodified LSP versus HSP α4β2-nAChRs. Thus, recruitment of the α4(+)/(−)α4 site at higher agonist concentrations appears to augment otherwise-similar function mediated by the pair of α4(+)/(−)β2 sites shared by both isoforms. These studies elucidate the receptor-level differences underlying the differential pharmacology of the two α4β2-nAChR isoforms, and demonstrate that HS versus LS α4β2-nAChR activity can be selectively manipulated using pharmacological approaches. Since α4β2 nAChRs are the predominant neuronal subtype, these discoveries likely

  6. Why Fix N2 in High N Supply Regions?

    NASA Astrophysics Data System (ADS)

    Landolfi, A.; Koeve, W.; Oschlies, A.

    2016-02-01

    Growing slowly, marine N2 fixers are expected to be competitive where nitrogen (N) supply falls short relative to that of phosphorus (P) with respect to the cellular N:P ratio (R) of non-fixing phytoplankton. Why do N2 fixers persist in the the oligotrophic North Atlantic where the ratio of nutrients supplied to the surface is elevated in N relative to the average R (16:1)? Combining resource competition theory and a global coupled ecosystem-circulation model we find a novel mechanism that can expand the ecological niche of N2 fixers also to regions where the nutrient supply is high in N relative to R, offering a new perspective on the environmental controls of marine N2-fixers.

  7. Substituent effects in a series of 1,7-C[subscript 60](R[subscript F])[subscript 2] compounds (R[subscript F] = CF[subscript 3], C[subscript 2]F[subscript 5], n-C[subscrip 3]F[subscript 7], i-C[subscript 3]F[subscript 7], n-C[subscript 4]F[subscript 9], s-C[subscript 4]F[subscript 9], n-C[subscript 8]F[subscript 17]): electron affinities, reduction potentials and E(LUMO) values are not always correlated

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kuvychko, Igor V.; Whitaker, James B.; Larson, Bryon W.

    2013-04-08

    A series of seven structurally-similar compounds with different pairs of R{sub F} groups were prepared, characterized spectroscopically, and studied by electrochemical methods (cyclic and square-wave voltammetry), low-temperature anion photoelectron spectroscopy, and DFT calculations (five of the compounds are reported here for the first time). This is the first time that a set of seven R{sub F} groups have been compared with respect to their relative effects on E{sub 1/2}(0/-), electron affinity (EA), and the DFT-calculated LUMO energy. The compounds, 1,7-C{sub 60}(R{sub F}){sub 2} (R{sub F} = CF{sub 3}, C{sub 2}F{sub 5}, i-C{sub 3}F{sub 7}, n-C{sub 3}F{sub 7}, s-C{sub 4}F{sub 9},more » n-C{sub 4}F{sub 9} and n-C{sub 8}F{sub 21}), were found to have statistically different electron affinities (EA), at the {+-}10 meV level of uncertainty, but virtually identical first reduction potentials, at the {+-}10 mV level of uncertainty. The lack of a correlation between EA and E{sub 1/2}(0/-), and between E(LUMO) and E{sub 1/2}(0/-), for such similar compounds is unprecedented and suggests that explanations for differences in figures of merit for materials and/or devices that are based on equating easily measurable E{sub 1/2}(0/-) values with EAs or E(LUMO) values should be viewed with caution. The solubilities of the seven compounds in toluene varied by nearly a factor of six, but in an unpredictable way, with the C{sub 2}F{sub 5} and s-C{sub 4}F{sub 9} compounds being the most soluble and the i-C{sub 3}F{sub 7} compound being the least soluble. The effects of the different R{sub F} groups on EAs, E(LUMO) values, and solubilities should help fluorine chemists choose the right R{sub F} group to design new materials with improved morphological, electronic, optical, and/or magnetic properties.« less

  8. Review: Cav2.3 R-type Voltage-Gated Ca2+ Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity

    PubMed Central

    Wormuth, Carola; Lundt, Andreas; Henseler, Christina; Müller, Ralf; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

    2016-01-01

    Background: Researchers have gained substantial insight into mechanisms of synaptic transmission, hyperexcitability, excitotoxicity and neurodegeneration within the last decades. Voltage-gated Ca2+ channels are of central relevance in these processes. In particular, they are key elements in the etiopathogenesis of numerous seizure types and epilepsies. Earlier studies predominantly targeted on Cav2.1 P/Q-type and Cav3.2 T-type Ca2+ channels relevant for absence epileptogenesis. Recent findings bring other channels entities more into focus such as the Cav2.3 R-type Ca2+ channel which exhibits an intriguing role in ictogenesis and seizure propagation. Cav2.3 R-type voltage gated Ca2+ channels (VGCC) emerged to be important factors in the pathogenesis of absence epilepsy, human juvenile myoclonic epilepsy (JME), and cellular epileptiform activity, e.g. in CA1 neurons. They also serve as potential target for various antiepileptic drugs, such as lamotrigine and topiramate. Objective: This review provides a summary of structure, function and pharmacology of VGCCs and their fundamental role in cellular Ca2+ homeostasis. We elaborate the unique modulatory properties of Cav2.3 R-type Ca2+ channels and point to recent findings in the proictogenic and proneuroapoptotic role of Cav2.3 R-type VGCCs in generalized convulsive tonic–clonic and complex-partial hippocampal seizures and its role in non-convulsive absence like seizure activity. Conclusion: Development of novel Cav2.3 specific modulators can be effective in the pharmacological treatment of epilepsies and other neurological disorders. PMID:27843503

  9. Reactive ion etching of GaN using BCl 3, BCl 3/Ar and BCl 3/ N 2 gas plasmas

    NASA Astrophysics Data System (ADS)

    Basak, D.; Nakanishi, T.; Sakai, S.

    2000-04-01

    Reactive ion etching (RIE) of GaN has been performed using BCl 3 and additives, Ar and N 2, to BCl 3 plasma. The etch rate, surface roughness and the etch profile have been investigated. The etch rate of GaN is found to be 104 nm/min at rf power of 200 W, pressure of 2 Pa, with 9.5 sccm flow rate of BCl 3. The addition of 5 sccm of Ar to 9.5 sccm of BCl 3 reduces the etch rate of GaN while the addition of N 2 does not influence the etch rate significantly. The RIE of GaN layer with BCl 3/Ar and BCl 3/N 2 results in a smoother surface compared to surfaces etched with BCl 3 only. The etched side-wall in BCl 3 plasma makes an angle of 60° with the normal surface, and the angle of inclination is more in cases of BCl 3/Ar and BCl 3/N 2 plasmas. The RIE induced damage to the surface is measured qualitatively by PL measurements. It is observed that the damage to the etched surfaces is similar for all the plasmas.

  10. N = (2,0) self-dual non-Abelian tensor multiplet in D = 3 + 3 generates N = (1,1) self-dual systems in D = 2 + 2

    NASA Astrophysics Data System (ADS)

    Nishino, Hitoshi; Rajpoot, Subhash

    2018-03-01

    We formulate an N = (2 , 0) system in D = 3 + 3 dimensions consisting of a Yang-Mills (YM)-multiplet (ˆ μ ˆ IA, λˆI), a self-dual non-Abelian tensor multiplet (ˆ μ ˆ ν ˆ IB, χˆI ,φˆI), and an extra vector multiplet (C ˆ μ ˆ IC, ρˆI). We next perform the dimensional reductions of this system into D = 2 + 2, and obtain N = (1 , 1) systems with a self-dual YM-multiplet (AIμ ,λI), a self-dual tensor multiplet (BIμν , χI , φI), and an extra vector multiplet (CIμ , ρI). In D = 2 + 2, we reach two distinct theories: 'Theory-I' and 'Theory-II'. The former has the self-dual field-strength Hμν(+)I of CIμ already presented in our recent paper, while the latter has anti-self-dual field strength Hμν(-)I. As an application, we show that Theory-II actually generates supersymmetric-KdV equations in D = 1 + 1. Our result leads to a new conclusion that the D = 3 + 3 theory with non-Abelian tensor multiplet can be a 'Grand Master Theory' for self-dual multiplet and self-dual YM-multiplet in D = 2 + 2, that in turn has been conjectured to be the 'Master Theory' for all supersymmetric integrable theories in D ≤ 3.

  11. (2R)-4-Oxo-4[3-(Trifluoromethyl)-5,6-diihydro:1,2,4}triazolo[4,3-a}pyrazin-7(8H)-y1]-1-(2,4,5-trifluorophenyl)butan-2-amine: A Potent, Orally Active Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, D.; Wang, L.; Beconi, M.

    2010-11-10

    A novel series of {beta}-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1) is a potent, orally active DPP-IV inhibitor (IC{sub 50} = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes.

  12. Nature-inspired indolyl-2-azabicyclo[2.2.2]oct-7-ene derivatives as promising agents for the attenuation of withdrawal symptoms: synthesis of 20-desethyl-20-hydroxymethyl-11-demethoxyibogaine.

    PubMed

    Passarella, D; Barilli, A; Efange, S M N; Elisabetsky, E; Leal, M B; Lesma, G; Linck, V M; Mash, D C; Martinelli, M; Peretto, I; Silvani, A; Danieli, B

    2006-07-10

    Microwave assisted Diels-Alder cycloaddition of 5-Br-N-benzylpyridinone (2) with methyl acrylate is described to gain an easy access to 7-bromo-2-benzyl-3-oxo-2-aza-5 or 6-carbomethoxy bicyclo[2.2.2]oct-7-enes (3)-(6). The preparation of the ibogaine analogue 20-desethyl-(20-endo)-hydroxymethyl-11-demethoxyibogaine (17) is described by stereoselective hydrogenation of the C(7)-C(8) double bond. Biological evaluation showed an interesting in vitro binding profile toward dopamine transporter, serotonin transporter and opioid receptor systems accompanied by an antiwithdrawal effect in mice for hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene (14). The simplification of the ibogaine structure appears as a promising approach toward the design of compounds that could reduce the withdrawal symptoms.

  13. BF3·Et2O Catalysed 4-Aryl-3-phenyl-benzopyrones, Pro-SERMs, and Their Characterization

    PubMed Central

    Srivastava, Ambika; Kumar, Rajesh

    2015-01-01

    We have synthesized the novel 4-(4-hydroxy-benzyl)-3-phenyl-chromen-2-one which is a precursor of SERMs with a smaller number of steps and good yield. Two methodologies for the synthesis have been worked out. Anhydrous BF3·Et2O catalyzed reaction was found to be selective for product formation while anhydrous AlCl3, FeCl3, and SnCl4 catalyzed ones were nonselective. PMID:26421007

  14. R3D-2-MSA: the RNA 3D structure-to-multiple sequence alignment server.

    PubMed

    Cannone, Jamie J; Sweeney, Blake A; Petrov, Anton I; Gutell, Robin R; Zirbel, Craig L; Leontis, Neocles

    2015-07-01

    The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access. Users can specify up to five ranges of nucleotides and 50 nucleotide positions per range. The R3D-2-MSA server maps these ranges to the appropriate columns of the corresponding MSA and returns the contents of the columns, either for display in a web browser or in JSON format for subsequent programmatic use. The browser output page provides a 3D interactive display of the query, a full list of sequence variants with taxonomic information and a statistical summary of distinct sequence variants found. The output can be filtered and sorted in the browser. Previous user queries can be viewed at any time by resubmitting the output URL, which encodes the search and re-generates the results. The service is freely available with no login requirement at http://rna.bgsu.edu/r3d-2-msa. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Effect of the cation size on the framework structures of magnesium tungstate, A4Mg(WO4)3 (A = Na, K), R2Mg2(WO4)3 (R = Rb, Cs).

    PubMed

    Han, Shujuan; Wang, Ying; Jing, Qun; Wu, Hongping; Pan, Shilie; Yang, Zhihua

    2015-03-28

    A series of alkali metal magnesium tungstates, A4Mg(WO4)3 (A = Na, K), R2Mg2(WO4)3 (R = Rb, Cs), were synthesized from a high temperature solution, and their structures were determined by single-crystal X-ray diffraction. Interestingly, Na4Mg(WO4)3 crystallizes in the monoclinic space group C2/c, while K4Mg(WO4)3 having an identical stoichiometry with Na4Mg(WO4)3, exhibits a different framework structure belonging to triclinic symmetry with the space group P1[combining macron]. Isostructural Rb2Mg2(WO4)3 and Cs2Mg2(WO4)3 crystallize in the space group P213 of cubic symmetry and reveal a three dimensional framework composed of isolated WO4 tetrahedra, MgO6 octahedra and RO12 (R = Rb, Cs) polyhedra. The effect of the alkali metal cation size on the framework structures of magnesium tungstate has been discussed in detail. In addition, the infrared spectra, as well as the UV-Vis-NIR diffuse reflectance spectroscopy data, are reported. The first-principles theoretical studies are also carried out to aid the understanding of electronic structures and linear optical properties.

  16. Experimental and theoretical investigation of homogeneous gaseous reaction of CO2(g) + nH2O(g) + nNH3(g) → products (n = 1, 2).

    PubMed

    Li, Zhuangjie; Zhang, Baoquan

    2012-09-13

    Decreasing CO2 emissions into the atmosphere is key for reducing global warming. To facilitate the CO2 emission reduction efforts, our laboratory conducted experimental and theoretical investigations of the homogeneous gaseous reaction of CO2(g) + nH2O(g) + nNH3(g) → (NH4)HCO3(s)/(NH4)2CO3(s) (n = 1 and 2) using Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy and ab initio molecular orbital theory. Our FTIR-ATR experimental results indicate that (NH4)2CO3(s) and (NH4)HCO3(s) are formed as aerosol particulate matter when carbon dioxide reacts with ammonia and water in the gaseous phase at room temperature. Ab initio study of this chemical system suggested that the reaction may proceed through formation of NH3·H2O(g), NH3·CO2(g), and CO2·H2O(g) complexes. Subsequent complexes, NH3·H2O·CO2 and (NH3)2·H2O·CO2, can be formed by adding gaseous reactants to the NH3·H2O(g), NH3·CO2(g), and CO2·H2O(g) complexes, respectively. The NH3·H2O·CO2 and (NH3)2·H2O·CO2 complexes can then be rearranged to produce (NH4)HCO3 and (NH4)2CO3 as final products via a transition state, and the NH3 molecule acts as a medium accepting and donating hydrogen atoms in the rearrangement process. Our computational results also reveal that the presence of an additional water molecule can reduce the activation energy of the rearrangement process. The high activation energy predicted in the present work suggests that the reaction is kinetically not favored, and our experimental observation of (NH4)HCO3(s) and (NH4)2CO3(s) may be attributed to the high concentrations of reactants increasing the reaction rate of the title reactions in the reactor.

  17. The mononuclear nickel(II) complex bis(azido-κN)bis[2,5-bis(pyridin-2-yl)-1,3,4-thiadiazole-κ2 N2 ,N3 ]nickel(II) protects tomato from Verticillium dahliae by inhibiting fungal growth and activating plant defences.

    PubMed

    Zine, Hanane; Rifai, Lalla Aicha; Koussa, Tayeb; Bentiss, Fouad; Guesmi, Salaheddine; Laachir, Abdelhakim; Makroum, Kacem; Belfaiza, Malika; Faize, Mohamed

    2017-01-01

    The antifungal properties of the nickel(II) complex bis(azido-κN)bis[2,5-bis(pyridin-2-yl)-1,3,4-thiadiazole-κ 2 N 2 ,N 3 ]nickel(II) [NiL 2 (N 3 ) 2 ] and its parental ligand 2,5-bis(pyridin-2-yl)-1,3,4-thiadiazole were examined to evaluate their ability to protect tomato plants against Verticillium dahliae. Our main objectives were to determine their effects on the in vitro growth of the pathogen, and their aptitude for controlling verticillium wilt and activating plant defence responses in the greenhouse. NiL 2 (N 3 ) 2 exhibited in vitro an elevated inhibition of radial growth of three strains of the pathogen. According to the strain, the EC 50 values ranged from 10 to 29 µg mL -1 for NiL 2 (N 3 ) 2 . In the greenhouse, it induced an elevated protection against V. dahliae when it was applied twice as foliar sprays at 50 µg mL -1 . It reduced the leaf alteration index by 85% and vessel browning by 96%. In addition, its protective ability was associated with the accumulation of H 2 O 2 and the activation of total phenolic content, as well as potentiation of the activity of peroxidase and polyphenol oxidase. These results demonstrated that the coordination of the ligand with Ni associated with the azide as a coligand resulted in an improvement in its biological activity by both inhibiting the growth of V. dahliae and activating plant defence responses. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  18. Crystal structure of bromido-fac-tricarbon-yl[5-(3,4,5-tri-meth-oxy-phen-yl)-3-(pyridin-2-yl)-1H-1,2,4-triazole-κ2N2,N3]rhenium(I) methanol monosolvate.

    PubMed

    Kharlova, Marharyta I; Piletska, Kseniia O; Domasevitch, Kostiantyn V; Shtemenko, Alexander V

    2017-04-01

    In the title compound, [ReBr(C 16 H 16 N 4 O 3 )(CO) 3 ]·CH 3 OH, the Re I atom adopts a distorted octa-hedral coordination sphere with a facial arrangement of the three carbonyl ligands. Two N atoms of the chelating 5-(3,4,5-tri-meth-oxy-phen-yl)-3-(pyridin-2-yl)-1 H -1,2,4-triazole ligand and two carbonyl ligands define the equatorial plane of the complex, with the third carbonyl ligand and the bromide ligand in axial positions. Conventional hydrogen bonds including the methanol solvent mol-ecules assemble the complex mol-ecules through mutual N-H⋯O-H⋯Br links [N⋯O = 2.703 (3) Å and O⋯Br = 3.255 (2) Å] into centrosymmetric dimers, whereas weaker C-H⋯O and C-H⋯Br hydrogen bonds [C⋯O = 3.215 (3)-3.390 (4) Å and C⋯Br = 3.927 (3) Å] connect the dimers into double layers parallel to the (111) plane.

  19. Role of Caspase-3 Cleaved IP3R1 on Ca2+ Homeostasis and Developmental Competence of Mouse Oocytes and Eggs

    PubMed Central

    Zhang, Nan; Fissore, Rafael. A.

    2014-01-01

    Apoptosis in most cell types is accompanied by altered Ca2+ homeostasis. During apoptosis, caspase-3 mediated cleavage of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) generates a 95-kDa C-terminal fragment (C-IP3R1), which represents the channel domain of the receptor. Aged mouse eggs display abnormal Ca2+ homeostasis and express C-IP3R1, although whether or not C-IP3R1 expression contributes to Ca2+ misregulation or a decrease in developmental competency is unknown. We sought to answer these questions by injecting in mouse oocytes and eggs cRNAs encoding CIP3R1. We found that: 1) expression of C-IP3R1 in eggs lowered the Ca2+ content of the endoplasmic reticulum (ER), although, as C-IP3R1 is quickly degraded at this stage, its expression did not impair pre-implantation embryo development; 2) expression of CIP3R1 in eggs enhanced fragmentation associated with aging; 3) endogenous IP3R1 is required for aging associated apoptosis, as its down-regulation prevented fragmentation, and expression of C-IP3R1 in eggs with downregulated IP3R1 partly restored fragmentation; 4) C-IP3R1 expression in GV oocytes resulted in persistent levels of protein, which abolished the increase in the ER releasable Ca2+ pool that occurs during maturation, undermined the Ca2+ oscillatory ability of matured eggs and their activation potential. Collectively, this study supports a role for IP3R1 and C-IP3R1 in regulating Ca2+ homeostasis and the ER Ca2+ content during oocyte maturation. Nevertheless, the role of C-IP3R1 on Ca2+ homeostasis in aged eggs seems minor, as in MII eggs the majority of endogenous IP3R1 remains intact and C-IP3R1 undergoes rapid turnover. PMID:24692207

  20. (Tris{2-[(5-chloro-2-oxido­benzyl­idene-κO)amino-κN]eth­yl}amine-κN)­ytterbium(III): crystal structure and Hirshfeld surface analysis

    PubMed Central

    Lee, See Mun; Lo, Kong Mun; Tan, Sang Loon; Tiekink, Edward R. T.

    2016-01-01

    The YbIII atom in the title complex, [Yb(C27H24Cl3N4O3)] [systematic name: (2,2′,2′′-{(nitrilo)­tris­[ethane-2,1-di­yl(nitrilo)­methylyl­idene]}tris­(4-chloro­phenolato)ytterbium(III)], is coordinated by a trinegative, hepta­dentate ligand and exists within an N4O3 donor set, which defines a capped octa­hedral geometry whereby the amine N atom caps the triangular face defined by the three imine N atoms. The packing features supra­molecular layers that stack along the a axis, sustained by a combination of aryl-C—H⋯O, imine-C—H⋯O, methyl­ene-C—H⋯π(ar­yl) and end-on C—Cl⋯π(ar­yl) inter­actions. A Hirshfeld surface analysis points to the major contributions of C⋯H/ H⋯C and Cl⋯H/H⋯Cl inter­actions (along with H⋯H) to the overall surface but the Cl⋯H contacts are at distances greater than the sum of their van der Waals radii. PMID:27746926

  1. (E)-2′-[(3,5-Di-tert-butyl-2-hy­droxy­benzyl­idene)amino]-1,1′-binaphthalen-2-ol methanol monosolvate

    PubMed Central

    He, Dian; Li, Chong; Wang, Xiaohong

    2011-01-01

    The title compound, C35H35NO2·CH4O, was obtained by the reaction of rac-2-amino-2-hy­droxy-1,1-binaphthyl and 3,5-di-tert-butyl-2-hy­droxy­benzaldehyde in absolute methanol. In the Schiff base mol­ecule, the two naphthyl bicycles are twisted by 71.15 (5)°. One hy­droxy group is involved in intra­molecular O—H⋯N hydrogen bond, while the methanol solvent mol­ecule is linked to another hy­droxy group via an inter­molecular O—H⋯O hydrogen bond. PMID:22219946

  2. High-pressure optical studies on R-line fluorescence lifetime in Al2O3:V2+

    NASA Astrophysics Data System (ADS)

    Jovanić, Branislav R.; Radenković, Božidar; Despotović-Zrakić, Marijana; Bogdanović, Zorica; Barać, Dušan

    2018-04-01

    The effect of high hydrostatic pressure (up to 10.3 GPa) at room temperature on fluorescence lifetime τ for R line (2E→4A2 transition) in ruby Al2O3:V2+ was studied. The performed studies show the linear increase of τ with increasing pressure. At 10.3 GPa, τ is about 1.36 times higher than at ambient pressure. The obtained trend was explained by a model which considered the effect of pressure on τ through an induced change of line position, inter-ionic distance, compressibility, and molecular polarizability. A good agreement between the calculated and experimental values for τ was obtained.

  3. 6-(1-Benzyl-1H-pyrrol-2-yl)-2,4-dioxo-5-hexenoic acids as dual inhibitors of recombinant HIV-1 integrase and ribonuclease H, synthesized by a parallel synthesis approach.

    PubMed

    Costi, Roberta; Métifiot, Mathieu; Esposito, Francesca; Cuzzucoli Crucitti, Giuliana; Pescatori, Luca; Messore, Antonella; Scipione, Luigi; Tortorella, Silvano; Zinzula, Luca; Novellino, Ettore; Pommier, Yves; Tramontano, Enzo; Marchand, Christophe; Di Santo, Roberto

    2013-11-14

    The increasing efficiency of HAART has helped to transform HIV/AIDS into a chronic disease. Still, resistance and drug-drug interactions warrant the development of new anti-HIV agents. We previously discovered hit 6, active against HIV-1 replication and targeting RNase H in vitro. Because of its diketo-acid moiety, we speculated that this chemotype could serve to develop dual inhibitors of both RNase H and integrase. Here, we describe a new series of 1-benzyl-pyrrolyl diketohexenoic derivatives, 7a-y and 8a-y, synthesized following a parallel solution-phase approach. Those 50 analogues have been tested on recombinant enzymes (RNase H and integrase) and in cell-based assays. Approximately half (22) exibited inhibition of HIV replication. Compounds 7b, 7u, and 8g were the most active against the RNase H activity of reverse-transcriptase, with IC50 values of 3, 3, and 2.5 μM, respectively. Compound 8g was also the most potent integrase inhibitor with an IC50 value of 26 nM.

  4. Conformational stability and force field of short-chain linear chlorophosphazenes: MNDO calculations, {sup 31}P NMR, vibrational spectra, and normal coordinate analyses of Cl{sub 3}PN(PCl{sub 2}N){sub n}P(O)Cl{sub 2} and [Cl{sub 3}PN(PCl{sub 2}N){sub n}PCl{sub 3}][PCl{sub 6}] (n = 1,2)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bougeard, D.; Bremard, C.; De Jaeger, R.

    1992-10-29

    The Raman spectra of Cl{sub 3}PN(PCl{sub 2}N){pi}P(O)Cl{sub 2} and [Cl{sub 3}PN(PCl{sub 2}N){pi}PCl{sub 3}]{sup +}PCl{sub 6}{sup {minus}} (n = 1,2) were recorded in the solid and liquid states at different temperatures. The qualitative depolarization ratios were obtained in the liquid phase. A {sup 31}P NMR study for the molecular compounds showed a coalescence phenomenon near 220 K. The potential energy around the PN bonds for the Cl{sub 3}PN(PCl{sub 2}N)P(O)Cl{sub 2} molecule and [Cl{sub 3}PN(PCl{sub 2}N){sub 2}PCl{sub 3}]{sup +} cation are derived from MNDO (modified neglect of diatomic overlap) calculations. The stable conformations are found to be trans-cis for Cl{sub 3}PN(PCl{sub 2}N)P(O)Cl{submore » 2} and [Cl{sub 3}PN(PCl{sub 2}N){sub 2}PCl{sub 3}]{sup +}. The calculated structural parameters agree well with the X-ray experimental data. The frequencies obtained by normal coordinate analysis are in good agreement with the observed ones. The MNDO calculation of the harmonic force field is in reasonable agreement with the experimental values. The force constant values assigned to torsional modes around the PN bonds correspond to low barriers for the internal rotations. The easy internal rotation around the P-N and P{double_bond}N bonds can explain the flexibility of the phosphazene backbone and the elastomeric properties of the phosphazene polymers. 46 refs., 6 figs., 3 tabs.« less

  5. A direct conversion of benzylic and allylic alcohols to phosphonates

    PubMed Central

    Barney, Rocky J.; Richardson, Rebekah M.; Wiemer, David F.

    2011-01-01

    Benzyl phosphonate esters often serve as reagents in Horner-Wadsworth-Emmons reactions. In most cases, they can be prepared from benzylic alcohols via formation of the corresponding halide followed by an Arbuzov reaction. To identify a more direct synthesis of phosphonate esters, we have developed a one-flask procedure for conversion of benzylic and allylic alcohols to the corresponding phosphonates through treatment with triethyl phosphite and ZnI2. PMID:21405073

  6. Transmission electron microscopy study of microstructural properties and dislocation characterization in the GaN film grown on the cone-shaped patterned Al2O3 substrate.

    PubMed

    Park, Jung Sik; Yang, Jun-Mo; Park, Kyung Jin; Park, Yun Chang; Yoo, Jung Ho; Jeong, Chil Seong; Park, Jucheol; He, Yinsheng; Shin, Keesam

    2014-02-01

    Growing a GaN film on a patterned Al2O3 substrate is one of the methods of reducing threading dislocations (TDs), which can significantly deteriorate the performance of GaN-based LEDs. In this study, the microstructural details of the GaN film grown on a cone-shaped patterned Al2O3 substrate were investigated using high-resolution transmission electron microscopy and weak-beam dark-field techniques. Various defects such as misfit dislocations (MDs), recrystallized GaN (R-GaN) islands and nano-voids were observed on the patterned Al2O3 surfaces, i.e. the flat surface (FS), the inclined surface (IS) and the top surface (TS), respectively. Especially, the crystallographic orientation of R-GaN between the GaN film and the inclined Al2O3 substrate was identified as $[\\overline 1 2\\overline 1 0]_{{\\rm GaN}} \\hbox{//}[\\overline 1 101]_{{\\rm R - GaN} \\,{\\rm on}\\,{\\rm IS}} \\hbox{//}[\\overline 1 100]_{ {{\\rm Al}} _{\\rm 2} {\\rm O}_{\\rm 3}} $, $(\\overline 1 012)_{{\\rm GaN}} \\hbox{//}(1\\overline 1 02)_{{\\rm R - Ga}\\,{\\rm Non}\\,{\\rm IS}} \\hbox{//}(\\overline {11} 26)_{ {{\\rm Al}} _{\\rm 2} {\\rm O}_{\\rm 3}} $. In addition, a rotation by 9° between $(10\\overline 1 1)_{{\\rm R - GaN}} $ and $(0002)_{{\\rm GaN}} $ and between $(10\\overline 1 1)_{{\\rm R - GaN}} $ and $(0006)_{ {{\\rm Al}} _{\\rm 2} {\\rm O}_{\\rm 3}} $ was found to reduce the lattice mismatch between the GaN film and the Al2O3 substrate. Many TDs in the GaN film were observed on the FS and TS of Al2O3. However, few TDs were observed on the IS. Most of the TDs generated from the FS of Al2O3 were bent to the inclined facet rather than propagating to the GaN surface, resulting in a reduction in the dislocation density. Most of the TDs generated from the TS of Al2O3 were characterized as edge dislocations.

  7. Uptake properties of Ni2+ by nCaO.Al2O3.2SiO2 (n=1-4) prepared from solid-state reaction of kaolinite and calcite.

    PubMed

    Jha, Vinay Kumar; Kameshima, Yoshikazu; Nakajima, Akira; Okada, Kiyoshi; MacKenzie, Kenneth J D

    2005-08-31

    A series of nCaO.Al2O3.2SiO2 samples (n=1-4) were prepared by solid-state reaction of mechanochemically treated mixtures of kaolinite and calcite fired at 600-1000 degrees C for 24 h. All the samples were X-ray amorphous after firing at 600-800 degrees C but had crystallized by 900 degrees C. The main crystalline phases were anorthite (n=1), gehlenite (n=2 and 3) and larnite (n=4). The uptake of Ni2+ by nCaO.Al2O3.2SiO2 samples fired at 800 and 900 degrees C was investigated at room temperature using solutions with initial Ni2+ concentrations of 0.1-50 mmol/l. Amorphous samples (fired at 800 degrees C) showed a higher Ni2+ uptake capacity than crystalline samples (fired at 900 degrees C). Ni2+ uptake was found to increase with increasing of CaO content. Amorphous 4CaO.Al2O3.2SiO2 showed the highest Ni2+ uptake capacity (about 9 mmol/g). The Ni2+ uptake abilities of the present samples are higher than those of other materials reported in the literature. Since the sorbed Ni2+/released Ca2+ ratios of these samples are close to unity, ion replacement of Ni2+ for Ca2+ is thought to be the principal mechanism of Ni2+ uptake by the present samples.

  8. Synthetic, structural, and computational investigations of N-alkyl benzo-2,1,3-selenadiazolium iodides and their supramolecular aggregates.

    PubMed

    Lee, Lucia M; Corless, Victoria B; Tran, Michael; Jenkins, Hilary; Britten, James F; Vargas-Baca, Ignacio

    2016-02-28

    Despite their versatility, the application of telluradiazoles as supramolecular building blocks is considerably constrained by their sensitivity to moisture. Albeit more robust, their selenium analogues form weaker supramolecular interactions. These, however, are enhanced when one nitrogen atom is bonded to an alkyl group. Here we investigate general methods for the synthesis of such derivatives. Methyl, iso-propyl and tert-butyl benzo-2,1,3-selenadiazolium cations were prepared by direct alkylation or cyclo-condensation of the alkyl-phenylenediamine with selenous acid. While the former reaction only proceeds with the primary and tertiary alkyl iodides, the latter is very efficient. Difficulties reported in earlier literature are attributable to the formation of adducts of benzoselenadiazole with its alkylated cations and side reactions initiated by aerobic oxidation of iodide. However, the cations themselves are resilient to oxidation and stable in acidic to neutral aqueous medium. X-ray crystallography was used in the identification and characterization of the following compounds: [C6H4N2(R)Se](+)X(-), (R = CH(CH3)2, C(CH3)3; X = I(-), I3(-)], [C6H4N2(CH3)Se](+)I(-), and [C6H4N2Se][C6H4N2(CH3)Se]2I2. Formation of SeN secondary bonding interactions (chalcogen bonds) was only observed in the last structure as anion binding to selenium is a strong competitor. The relative strengths of those forces and the structural preferences they enforce were assessed with DFT-D3 calculations supplemented by AIM analysis of the electron density.

  9. Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT2A receptors, in mice

    PubMed Central

    Gray, Bradley W.; Bailey, Jessica M.; Smith, Douglas; Hansen, Martin; Kristensen, Jesper L.

    2014-01-01

    Rationale 2-([2-(4-cyano-2,5-dimethoxyphenyl)ethylamino]methyl)phenol (25CN-NBOH) is structurally similar to N-benzyl substituted phenethylamine hallucinogens currently emerging as drugs of abuse. 25CN-NBOH exhibits dramatic selectivity for 5-HT2A receptors in vitro, but has not been behaviorally characterized. Objective 25CN-NBOH was compared to the traditional phenethylamine hallucinogen R(−)-2,5-dimethoxy-4-iodoamphetamine (DOI) using mouse models of drug-elicited head twitch behavior and drug discrimination. Methods Drug-elicited head twitches were quantified for 10 min following administration of various doses of either DOI or 25CN-NBOH, with and without pretreatments of 0.01 mg/kg 5-HT2A antagonist M100907 or 3.0 mg/kg 5-HT2C antagonist RS102221. The capacity of 25CN-NBOH to attenuate DOI-elicited head twitch was also investigated. Mice were trained to discriminate DOI or M100907 from saline, and 25CN-NBOH was tested for generalization. Results 25CN-NBOH induced a head twitch response in the mouse that was lower in magnitude than that of DOI, blocked by M100907, but not altered by RS102221. DOI-elicited head twitch was dose-dependently attenuated by 25CN-NBOH pretreatment. 25CN-NBOH produced an intermediate degree of generalization (55%) for the DOI training dose, and these interoceptive effects were attenuated by M100907. Finally, 25CN-NBOH did not generalize to M100907 at any dose, but ketanserin fully substituted in these animals. Conclusions 25CN-NBOH was behaviorally active, but less effective than DOI in two mouse models of hallucinogenic effects. The effectiveness with which M100907 antagonized the behavioral actions of 25CN-NBOH strongly suggests that the 5-HT2A receptor is an important site of agonist action for this compound in vivo. PMID:25224567

  10. New family of lanthanide-based inorganic-organic hybrid frameworks: Ln2(OH)4[O3S(CH2)nSO32H2O (Ln = La, Ce, Pr, Nd, Sm; n = 3, 4) and their derivatives.

    PubMed

    Liang, Jianbo; Ma, Renzhi; Ebina, Yasuo; Geng, Fengxia; Sasaki, Takayoshi

    2013-02-18

    We report the synthesis and structure characterization of a new family of lanthanide-based inorganic-organic hybrid frameworks, Ln(2)(OH)(4)[O(3)S(CH(2))(n)SO(3)]·2H(2)O (Ln = La, Ce, Pr, Nd, Sm; n = 3, 4), and their oxide derivatives. Highly crystallized samples were synthesized by homogeneous precipitation of Ln(3+) ions from a solution containing α,ω-organodisulfonate salts promoted by slow hydrolysis of hexamethylenetetramine. The crystal structure solved from powder X-ray diffraction data revealed that this material comprises two-dimensional cationic lanthanide hydroxide {[Ln(OH)(2)(H(2)O)](+)}(∞) layers, which are cross-linked by α,ω-organodisulfonate ligands into a three-dimensional pillared framework. This hybrid framework can be regarded as a derivative of UCl(3)-type Ln(OH)(3) involving penetration of organic chains into two {LnO(9)} polyhedra. Substitutional modification of the lanthanide coordination promotes a 2D arrangement of the {LnO(9)} polyhedra. A new hybrid oxide, Ln(2)O(2)[O(3)S(CH(2))(n)SO(3)], which is supposed to consist of alternating {[Ln(2)O(2)](2+)}(∞) layers and α,ω-organodisulfonate ligands, can be derived from the hydroxide form upon dehydration/dehydroxylation. These hybrid frameworks provide new opportunities to engineer the interlayer chemistry of layered structures and achieve advanced functionalities coupled with the advantages of lanthanide elements.

  11. Crystal structure of bis-[(phenyl-methanamine-κN)(phthalocyaninato-κ(4) N)zinc] phenyl-methan-amine tris-olvate.

    PubMed

    Shamsudin, Norzianah; Tan, Ai Ling; Wimmer, Franz L; Young, David J; Tiekink, Edward R T

    2015-09-01

    The asymmetric unit of the title compound, 2[Zn(C32H16N8)(C7H9N)]·3C7H9N, comprises two independent complex mol-ecules and three benzyl-amine solvent mol-ecules. Each complex mol-ecule features a penta-coordinated Zn(2+) ion within a square-pyramidal geometry, whereby the N5 donor set is defined by four atoms of the phthalocyaninate dianion (PC) and an N-bound benzyl-amine mol-ecule; it is the relative orientations of the latter that differentiate between the independent complex mol-ecules. The uncoordinated benzyl-amine mol-ecules display different conformations in the structure, with syn-Car-Car-Cm-N (ar = aromatic, m = methyl-ene) torsion angles spanning the range -28.7 (10) to 35.1 (14)°. In the crystal, N-H⋯N and N-H⋯π inter-actions lead to supra-molecular layers in the ab plane. The layers have a zigzag topology, have the coordinating and non-coordinating benzyl-amine mol-ecules directed to the inside, and present the essentially flat PC resides to the outside. This arrangement enables adjacent layers to associate via π-π inter-actions [inter-centroid distance between pyrrolyl and fused-benzene rings = 3.593 (2) Å] so that a three-dimensional architecture is formed.

  12. 2-(trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate suppresses osteoclast maturation and bone resorption by targeting macrophage-colony stimulating factor signaling.

    PubMed

    Park, So Jeong; Park, Doo Ri; Bhattarai, Deepak; Lee, Kyeong; Kim, Jaesang; Bae, Yun Soo; Lee, Soo Young

    2014-08-01

    2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.

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

    PubMed

    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.

  14. Synthesis, Characterization and Decomposition Studies of Tris(N,N-dibenzyldithiocarbamato) Indium(III): Chemical Spray Deposition of Polycrystalline CuInS2 on Copper Films

    NASA Technical Reports Server (NTRS)

    Hehemann, David G.; Lau, J. Eva; Harris, Jerry D.; Hoops, Michael D.; Duffy, Norman V.; Fanwick, Philip E.; Khan, Osman; Jin, Michael H.-C.; Hepp, Aloysius F.

    2005-01-01

    Tris(bis(phenylmethyl)carbamodithioato-S,S ), commonly referred to as tris(N,Ndibenzyldithiocarbamato) indium(III), In(S2CNBz2)3, was synthesized and characterized by single crystal X-ray crystallography. The compound crystallizes in the triclinic space group P1 bar with two molecules per unit cell. The material was further characterized using a novel analytical system employing the combined powers of thermogravimetric analysis, gas chromatography/mass spectrometry and Fourier-Transform infrared spectroscopy to investigate its potential use as a precursor for the chemical vapor deposition (CVD) of thin film materials for photovoltaic applications. Upon heating, the material thermally decomposes to release CS2 and benzyl moieties in to the gas phase, resulting in bulk In2S3. Preliminary spray CVD experiments indicate that In(S2CNBz2)3 decomposed on a Cu substrate reacts to produce stoichiometric CuInS2 films.

  15. 2-(1,2,3,4-Tetra-hydro-1-naphth-yl)imidazolium chloride monohydrate.

    PubMed

    Bruni, Bruno; Bartolucci, Gianluca; Ciattini, Samuele; Coran, Silvia

    2010-08-18

    In the title compound, C(13)H(15)N(2) (+)·Cl(-)·H(2)O, the ions and water mol-ecules are -connected by N-H⋯Cl, O-H⋯Cl, NH⋯Cl⋯HO, NH⋯Cl⋯HN and OH⋯Cl⋯HO inter-actions, forming discrete D(2) and D(2) (1)(3) chains, C(2) (1)(6) chains and R(4) (2)(8) rings, leading to a neutral two-dimensional network. The crystal structure is further stabilized by π-π stacking inter-actions [centroid-centroid distance = 3.652 (11) Å].

  16. Single-step synthesis of a new series of meso di-Mannich bases from the cyclic aminal (2S,7R,11S,16R)-1,8,10,17-tetraazapentacyclo[8.8.1.1.8,170.2,7011,16]icosane and p-substituted phenols

    PubMed Central

    2013-01-01

    Background The results presented herein show that the cyclic aminal (2S,7R,11S,16R)-1,8,10,17-tetraazapentacyclo[8.8.1.1.8,170.2,7011,16]icosane (6), derived from cis-(meso)-1,2-diaminocyclohexane and formaldehyde, is a suitable substrate for the preption of a series of cis-meso Mannich bases such as 8a-l by reaction with p-substituted phenols 7a-l in basic media. These compounds are valuable synthetic products and may find application in asymmetric catalysis. Results The products were characterized principally by NMR and IR spectroscopy. Both the benzylic and aminalic protons of the perhydrobenzimidazolidine moiety were diastereotopic due to the presence of stereogenic nitrogen centers. The occurrence of intramolecular hydrogen bonding interactions was confirmed by the broad OH stretching vibration band in the IR spectra. Vibrational spectra were calculated using B3LYP at 6-31G(d,p) level, and the calculated frequencies for the νOH vibrations were compared to those of the experimental spectra. Hydrogen bonding interactions in the solid state were observed through the X-ray crystallography of 8j. Additionally, Mulliken charges and Fukui indices for 6 were calculated as theoretical descriptors of electrophilicity. Conclusion A new series of meso Mannich bases called 4,4′-disubstituted-2,2′-{[(3aR,7aS)-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene)} diphenols (8a-l) which are derived from cis-(meso)-1,2-diaminocyclohexane, were obtained from cyclic aminal 6. These results confirmed the behavior of 6 as an electrophilic preformed reagent in Mannich reactions in basic media. PMID:23758899

  17. Structure of (Ga2O3)2(ZnO)13 and a unified description of the homologous series (Ga2O3)2(ZnO)(2n + 1).

    PubMed

    Michiue, Yuichi; Kimizuka, Noboru; Kanke, Yasushi; Mori, Takao

    2012-06-01

    The structure of (Ga(2)O(3))(2)(ZnO)(13) has been determined by a single-crystal X-ray diffraction technique. In the monoclinic structure of the space group C2/m with cell parameters a = 19.66 (4), b = 3.2487 (5), c = 27.31 (2) Å, and β = 105.9 (1)°, a unit cell is constructed by combining the halves of the unit cell of Ga(2)O(3)(ZnO)(6) and Ga(2)O(3)(ZnO)(7) in the homologous series Ga(2)O(3)(ZnO)(m). The homologous series (Ga(2)O(3))(2)(ZnO)(2n + 1) is derived and a unified description for structures in the series is presented using the (3+1)-dimensional superspace formalism. The phases are treated as compositely modulated structures consisting of two subsystems. One is constructed by metal ions and another is by O ions. In the (3 + 1)-dimensional model, displacive modulations of ions are described by the asymmetric zigzag function with large amplitudes, which was replaced by a combination of the sawtooth function in refinements. Similarities and differences between the two homologous series (Ga(2)O(3))(2)(ZnO)(2n + 1) and Ga(2)O(3)(ZnO)(m) are clarified in (3 + 1)-dimensional superspace. The validity of the (3 + 1)-dimensional model is confirmed by the refinements of (Ga(2)O(3))(2)(ZnO)(13), while a few complex phenomena in the real structure are taken into account by modifying the model.

  18. Molecular evidence for interspecies transmission of H3N2pM/H3N2v influenza A viruses at an Ohio agricultural fair, July 2012

    PubMed Central

    Bowman, Andrew S; Sreevatsan, Srinand; Killian, Mary L; Page, Shannon L; Nelson, Sarah W; Nolting, Jacqueline M; Cardona, Carol; Slemons, Richard D

    2012-01-01

    Evidence accumulating in 2011–2012 indicates that there is significant intra- and inter-species transmission of influenza A viruses at agricultural fairs, which has renewed interest in this unique human/swine interface. Six human cases of influenza A (H3N2) variant (H3N2v) virus infections were epidemiologically linked to swine exposure at fairs in the United States in 2011. In 2012, the number of H3N2v cases in the Midwest had exceeded 300 from early July to September, 2012. Prospective influenza A virus surveillance among pigs at Ohio fairs resulted in the detection of H3N2pM (H3N2 influenza A viruses containing the matrix (M) gene from the influenza A (H1N1) pdm09 virus). These H3N2pM viruses were temporally and spatially linked to several human H3N2v cases. Complete genomic analyses of these H3N2pM isolates demonstrated >99% nucleotide similarity to the H3N2v isolates recovered from human cases. Actions to mitigate the bidirectional interspecies transmission of influenza A virus between people and animals at agricultural fairs may be warranted. PMID:26038404

  19. Synthesis, stereochemical, structural, and biological studies of a series of N‧-(2r,4c-diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)pyrazine-2-carbohydrazides

    NASA Astrophysics Data System (ADS)

    Mangalam, M.; Sebastian Antony Selvan, C.; Sankar, C.

    2017-02-01

    A new series of N‧-(2r,4c-diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)pyrazine-2-carbohydrazides (8-14) were synthesized by the corresponding 2r,4c-diaryl-3-azabicyclo[3.3.1]nonan-9-ones (1-7) reaction with pyrazine-2-carbohydrazide. The stereochemistry of the newly synthesized compounds were unambiguously assigned using FT-IR, 1H, 13C, and 2D (COSY, HSQC, HMBC, ROESY) nuclear magnetic resonance (NMR) spectral data. The chemical shifts suggest that all these compounds adopt twin-chair conformation with equatorial orientation of aryl substitutions in solution. Hydrazones were screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv and antibacterial activity against a set of pathogenic bacteria. Most of the halogenated compounds showed promising antitubercular and antibacterial activities.

  20. 40 CFR 721.10175 - 1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-(C12-18 and C18-unsatd...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1-Propanaminium, N-(3-aminopropyl)-2... 1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-(C12-18 and C18-unsatd. acyl... chemical substance identified as 1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-(C12...