- Formation and reactions of S-nitroso proteins
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Nitrosation of Bovine Serum Albumin (BSA) by nitrous acid occurs in two stages: a rapid step, which is consistent with an S-nitrosation reaction of a free cysteine unit, followed by a slower reaction which is consistent with an N-nitrosation reaction of a tryptophan residue. The fast reaction is catalysed by chloride and bromide ions (as is the reaction of free cysteine), whereas the slower reaction is not halide ion catalysed (like the reaction of tryptophan). Kinetic results were obtained for both reactions. The derived rate constants for the first stage for the reaction of ClNO and BrNO are reasonably close to the reported values for the reactions of cysteine. The second stage is a reversible process and we can estimate from measured infinity values and also from the variation in the measured rate constant for reactions at different [HNO2], values for the equilibrium constant of 3500 +/- 200 and 2600 +/- 200 dm3 mol-1 which compare reasonably with the reported value for the reaction of tryptophan of 850 dm3 mol-1. The pKa values of the cysteine residue in both BSA and Human Serum Albumin (HSA) were determined from rate measurements of the reactions with dipyridin-4-yl disulfide (4-aldrithiol), and yielded values of 8.32 and 8.18 respectively, which are close to the accepted value of 8.4 for cysteine itself, and which are substantially higher than the much quoted literature values. The S-nitroso derivatives of both BSA and HSA generated in solution (at ca. 1 x 10-4 mol dm-3) showed very little sign of decomposition at pH 7.4 when measured spectrophotometrically, even in the presence of added Cu2+. There was, however, clear evidence of rapid decomposition at much lower reactant concentration (ca. 1 x 10-6 mol dm-3) yielding nitric oxide in increasing amounts and rates, as Cu2+ is added. These results are discussed in terms of the complexation of the Cu2+ catalyst at different albumin derivative concentrations. Transnitrosation between the S-nitroso derivatives of both BSA and HSA and excess cysteine occurred very readily. These experiments were carried out in the presence of added Cu2+, and the decomposition of the resulting S-nitrosocysteine (S-NOCys) was monitored. The results support the suggestion that S-nitroso proteins can, in theory, act as a reservoir for NO which can readily be made available, either by the Cu2+-catalysed reaction, or more readily by a direct NO+ transfer to a low molecular weight thiol, such as cysteine, which is much more prone to yield NO rapidly and quantitatively by the Cu2+-catalysed pathway. The S-nitroso derivative of BSA also underwent a relatively slow decomposition reaction initiated by cysteine, even in the presenc...
- Noble, Darren R.,Williams, D. Lyn H.
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- Controlled Intercalation and Chemical Exfoliation of Layered Metal-Organic Frameworks Using a Chemically Labile Intercalating Agent
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Creating ordered two-dimensional (2D) metal-organic framework (MOF) nanosheets has attracted extensive interest. However, it still remains a great challenge to synthesize ultrathin 2D MOF nanosheets with controlled thickness in high yields. In this work, we demonstrate a novel intercalation and chemical exfoliation approach to obtain MOF nanosheets from intrinsically layered MOF crystals. This approach involves two steps: first, layered porphyrinic MOF crystals are intercalated with 4,4′-dipyridyl disulfide through coordination bonding with the metal nodes; subsequently, selective cleavage of the disulfide bond induces exfoliation of the intercalated MOF crystals, leading to individual freestanding MOF nanosheets. This chemical exfoliation process can proceed efficiently at room temperature to produce ultrathin (～1 nm) 2D MOF nanosheets in ～57% overall yield. The obtained ultrathin nanosheets exhibit efficient and far superior heterogeneous photocatalysis performance compared with the corresponding bulk MOF.
- Ding, Yanjun,Chen, Ying-Pin,Zhang, Xinlei,Chen, Liang,Dong, Zhaohui,Jiang, Hai-Long,Xu, Hangxun,Zhou, Hong-Cai
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supporting information
p. 9136 - 9139
(2017/07/22)
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- Ago-allosteric modulators of human glucagon-like peptide 2 receptor
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Glucagon-like peptide 2 (GLP-2) is an intestinotropic peptide that binds to GLP-2 receptor (GLP-2R), a class-B G protein-coupled receptor (GPCR). Few synthetic agonists have been reported so far for class-B GPCRs. Here, we report the first scaffold compounds of ago-allosteric modulators for human GLP-2R, derived from methyl 2-{[(2Z)-2-(2,5-dichlorothiophen-3-yl)-2-(hydroxyimino) ethyl]sulfanyl}benzoate (compound 1).
- Yamazaki, Kazuto,Terauchi, Hiroki,Iida, Daisuke,Fukumoto, Hironori,Suzuki, Shuichi,Kagaya, Takaki,Aoki, Mika,Koyama, Koichiro,Seiki, Takashi,Takase, Kazuma,Watanabe, Misako,Arai, Tohru,Tsukahara, Kappei,Nagakawa, Junichi
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p. 6126 - 6135
(2012/10/30)
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- N-Acylhydrazones as inhibitors of PDE10A
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Cyclic nucleotide phosphodiesterases (PDEs) are represented by a large superfamily of enzymes. A series of hydrazone-based inhibitors was synthesized and shown to be novel, potent, and selective against PDE10A. Optimized compounds of this class were efficacious in animal models of schizophrenia and may be useful for the treatment of this disease.
- Gage, Jennifer L.,Onrust, Rene,Johnston, Derek,Osnowski, Andrew,MacDonald, Wendy,Mitchell, Lee,ür?gdi, László,Rohde, Alex,Harbol, Kevin,Gragerov, Sasha,Dormán, Gy?rgy,Wheeler, Tom,Florio, Vince,Cutshall, Neil S.
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scheme or table
p. 4155 - 4159
(2011/08/10)
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- NOVEL AROMATIC COMPOUND AND POLYARYLENE COPOLYMER HAVING NITROGEN-CONTAINING HETEROCYCLE INCLUDING SULFONIC ACID GROUP IN SIDE CHAIN
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Provided is a solid polymer electrolyte having increased heat resistance and high proton conductivity and a proton conductive membrane composed of the electrolyte. Also provided is a copolymer having a sulfonic acid group. The copolymer includes a repeating unit represented by Formula (1): (in the formula, Y denotes at least one kind of structure selected from the group consisting of —CO—, —SO2—, —SO—, —CONH—, —COO—, —(CF2)l— (l is an integer of 1 to 10), and —C(CF3)2—; W denotes at least one kind of structure selected from the group consisting of a direct bond, —CO—, —SO2—, —SO—, —CONH—, —COO—, —(CF2)l— (l is an integer of 1 to 10), —C(CF3)2—, —O—, and —S—; Z denotes a direct bond or at least one kind of structure selected from the group consisting of —(CH2)l—(l is an integer of 1 to 10), —C(CH3)2—, —O—, —S—, —CO—, and —SO2—; R30 denotes a nitrogen-containing aromatic ring having a substituent represented by —SO3H, —O(CH2)hSO3H, or —O(CF2)hSO3H (h is an integer of 1 to 12); p is an integer of 0 to 10; q is an integer of 0 to 10; r is an integer of 1 to 5; and k is an integer of 0 to 4).
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- Precious metal composition
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Gold thiolates of formula AuSR'' or a salt thereof, in which R'' is such that HSR'' represents: 4,6-dihydroxy-2-mercaptopyrimidine; N-(2-mercaptoacetyl)glycine; N-(3-mercaptopropionyl)glycine; and N-(2-mercaptopropionyl)glycine. The invention provides also processes for preparing novel gold thiolates.
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- Nucleophilic properties of thiourea towards aromatic halides
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Arylsulfides (and diaryldisulfides obtained spontaneously by oxidation of the arylsulfides during the work-up) and diarylsulfides can be obtained by substituting aryl radicals by the thiourea onion in liquid ammonia under an electrochemical inducement.
- Combellas,Dellerue,Mathey,Thiebault
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p. 539 - 542
(2007/10/03)
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- Synthesis and Kinetic Evaluation of Inhibitors of the Phosphatidylinositol-Specific Phospholipase C from Bacillus cereus
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Substrate analogues of phosphatidylinositol (1) were synthesized and evaluated as potential inhibitors of the bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus cereus.The chiral analogues of the water-soluble phospholipid substrate 5 were designed to probe the effects of varying the inositol C-2 hydroxyl group, which generally believed to serve as the nucleophile in the first step of the hydrolysis of phosphatidylinositols by PI-PLC.In the analogues 6-9, the C-2 hydroxyl group on the inositol ring of the phosphatidylinositol derivatives was rationally altered in several ways.Inversion of the stereochemistry at C-2 of the inositol ring led to the scyllo derivative 6.The inositol C-2 hydroxy group was replaced with inversion by a fluorine to produce the scyllo-fluoro inositol 7 and with a hydrogen atom to furnish the 2-deoxy compound 8.The C-2 hydroxyl group was O-methylated to prepare the methoxy derivative 9.The natural inositol configuration at C-2 was retained in the nonhydrolyzable phosphorodithioate analogue 10.The inhibition of PI-PLC by each of these analogues was then analyzed in a continuous assay using D-myo-inositol 1-(4-nitrophenyl phosphate) (25) as a chromogenic substrate.The kinetic parameters for each of these phosphatidylinositol derivatives were determined, and each was found to be a competitive inhibitor with Ki's as follows: 6, 0.2 mM; 10, 0.6 mM; 8, 2.6 mM; 9, 6.6 mM; and 7, 8.8 mM.This study further establishes that the hydrolysis of phosphatidylinositol analogues by bacterial PI-PLC requires not only the presence of a C-2 hydroxyl group on the inositol ring, but the stereochemistry at this position must also correspond to the natural myo-configuration.For future inhibitor design, it is perhaps noteworthy that the best inhibitors 6 and 10 each possess a hydroxyl group at the 2-position.Several of the inhibitors identified in this study are now being used to obtain crystallographic information for an enzyme-inhibitor complex to gain further insights regarding the mechanism of hydrolysis of phosphatidylinositides by this PI-PLC.
- Matrin, Stephen F.,Wagman, Allan S.
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p. 8016 - 8023
(2007/10/03)
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- SYNTHESIS OF SOME DIPYRIDYL DISULFIDES AND RELATED PYRIDINE-4-SULFONIC ACIDS
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Dipyridyl disulphides and pyridine-4-sulphonic acids were synthesized and their pK constant were measured.
- Boduszek, B.
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p. 787 - 790
(2007/10/02)
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- Cephalosporin compounds and antibacterial agents
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Cephalosporin compounds of the formula (I): STR1 wherein R1 and R2 may be the same or different and are a hydrogen atom or a lower alkyl group of 1-5 carbon atoms and A is a hydrogen atom or a nucleophilic compound residue or pharmacologically acceptable salts thereof have excellent antibacterial activity against Gram positive and Gram negative microorganisms.
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- Cephalosporin derivatives and bactericides containing the same
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Cephalosporin compounds represented by the following formula (I) and pharmaceutically acceptable salts thereof have a broad bactericidal spectrum against various pathogenic bacteria including Psuedomonas aeruginosa and are useful as bactericidal remedies for pathogenic diseases of human and animals: STR1 wherein A represents an unsubstituted or substituted pyridylthio group of a formula (I-1); STR2 or an unsubstituted or substituted pyridiniumthio group of a formula (I-2): STR3 or an unsubstituted or substituted pyridinium group of a formula (I-3); STR4 or a 5- or 6-membered heterocyclicthio or bicycloheterocyclicthio group of a formula (I-4):
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- Syntheses of Mercaptobenzoic Acids and Mercaptopyridines Using Elemental Sulfur in the Presence of NaOH-KOH
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Mercaptobenzoic acids and mercaptopyridines were synthesized by using mercaptylation of halogeno compounds with elemental sulfur in the presence of molten salts (NaOH-KOH).This procedure was also applied to the preparation of selenoaryl compounds by using elemental selenium.Based on the behavior of the molten salts and sulfur, Na2S and K2S were considered to be the active species for the mercaptylation.KEYWORDS-mercaptylation; molten salt; o-mercaptobenzoic acid; o-selenobenzoic acid; 2-mercaptopyridine
- Kamiyama, Tsutomu,Enomoto, Saburo,Inoue, Masami
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p. 5184 - 5189
(2007/10/02)
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- Quantitative Model of Solvent Effects on Hydroxypyridine-Pyridone and Mercaptopyridine-Thiopyridone Equilibria: Correlation with Reaction-Field and Hydrogen-Bonding Effects
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A model for the effect of reaction field and hydrogen bonding on the relative energies of protomers is applied to the equilibria between 6-chloro-2-hydroxypyridine and 6-chloro-2-pyridone, 2-mercaptopyridine and 2-thiopyridone, 6-chloro-2-mercaptopyridine and 6-chloro-2-thiopyridone, and 4-mercaptopyridine and 4-thiopyridone in a wide range of solvents.Quantitative correlation is obtained by a multivariable analysis.In addition to satisfactory statistical tests of the correlations, estimates of the differences in free energies between the isomers in the vapor phase and of the dipole moment component of the reaction-field term are obtained which compare well with the available independent values.These criteria are shown to signal an unacceptable correlation for the case of 2-chloro-4-hydroxypyridine and 2-chloro-4-pyridone.The advantage of this model, which provides an understanding of the effect of molecular environment on protomeric equilibria in terms of reasonable physical interactions, over empirical approaches is noted.
- Beak, Peter,Covington, Johnny B.,White, J. Matthew
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p. 1347 - 1353
(2007/10/02)
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- 7-(3-Substituted ureido) cephalosporins
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Cephalosporin compounds with 3-substituted ureido or -thioureido group at position 7 and hydrogen or heterocyclicthiomethyl groups at position 3 are prepared. These compounds are antibacterial agents.
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