- METAL-CATALYZED OXIDATIVE COUPLING OF THIOLS
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Disclosed are methods for preparing disulfide compounds through oxidative coupling of thiol compounds. Thiols are oxidized to the corresponding disulfide compound in high yield in presence of a base and a metal salt. The method uses low catalyst loadings and provides organic disulfide compounds with little to no byproducts.
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Paragraph 0109; 0110
(2017/02/28)
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- METHODS OF TREAT1NG CANCER AND OTHER DISEASES
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Disclosed are a method of treating cancer in a cell, a method of enhancing the chemotherapeutic treatment of a cancer treatment agent, a method of reducing resistance of a cancer cell to a chemotherapeutic agent, a method of reducing the amount or activity of an ABC-family mRNA and/or protein, a method of reducing the amount or activity of the ABCB1 mRNA and/or protein or the ABCC1 mRNA and/or protein in an animal cell undergoing cancer treatment, a method of reducing the amount or activity of glutathione and/or Bcl2 in the cancer cell, a method of treating other multidrug resistant diseases, and a method of treating a multidrug resistant cell such as a bacterial multidrug resistant Staphylococcus aureus (MRSA), tuberculosis, fungal infection, or MDR malaria, by administering a compound of the Formula (I): a diastereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R1-R4 are as described herein. Also disclosed are pharmaceutical compositions comprising a compound of formula (I), a diastereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier
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Page/Page column 32
(2012/05/19)
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- RETRACTED ARTICLE: Collateral sensitivity of multidrug-resistant cells to the orphan drug tiopronin
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A major challenge in the treatment of cancer is multidrug resistance (MDR) that develops during chemotherapy. Here we demonstrate that tiopronin (1), a thiol-substituted N-propanoylglycine derivative, was selectively toxic to a series of cell lines expressing the drug efflux pump P-glycoprotein (P-gp, ABCB1) and MRP1 (ABCC1). Treatment of MDR cells with 1 led to instability of the ABCB1 mRNA and consequently a reduction in P-gp protein, despite functional assays demonstrating that tiopronin does not interact with P-gp. Long-term exposure of P-gp-expressing cells to 1 sensitized them to doxorubicin and paclitaxel, both P-gp substrates. Treatment of MRP1-overexpressing cells with tiopronin led to a significant reduction in MRP1 protein. Synthesis and screening of analogues of tiopronin demonstrated that the thiol functional group was essential for collateral sensitivity while substitution of the amino acid backbone altered but did not destroy specificity, pointing to future development of targeted analogues. This article not subject to U.S. Copyright. Published 2011 by the American Chemical Society.
- Goldsborough, Andrew S.,Handley, Misty D.,Dulcey, Andrés E.,Pluchino, Kristen M.,Kannan, Pavitra,Brimacombe, Kyle R.,Hall, Matthew D.,Griffiths, Gary,Gottesman, Michael M.
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experimental part
p. 4987 - 4997
(2011/10/01)
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- Rearrangement of oxazolidinethiones to thiazolidinediones or thiazinanediones and their application for the synthesis of chiral allylic ureas and α-methyl-β-amino acids
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A novel rearrangement has been found between oxazolidinethiones and acyl halides under N-acylation reaction conditions to afford N-substituted 2,4-thiazolidinediones and N-substituted 1,3-thiazinane-2,4-diones. These heterocycles were used for the synthesis of chiral allylic ureas and α-methyl-β-amino acids.
- Sabala, Rocio,Hernández, Jacqueline,Carranza, Vladimir,Meza-León, Rosa L.,Bernès, Sylvain,Sansinenea, Estibaliz,Ortiz, Aurelio
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experimental part
p. 111 - 120
(2010/03/01)
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- Oxidation of some thioacids by tetraethylammonium chlorochromate: A kinetic and mechanistic study
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The oxidation of thioglycollic, thiolactic and thiomalic acids by tetraethylammonium chlorochromate (TEACC) is first order both in TEACC and thioacids. The reaction is catalysed by hydrogen ions. The hydrogen ion dependence has taking the form : kobs = a + b [H+]. The oxidation of thiolactic acid has been studied in nineteen different organic solvents. The solvent effect has been analysed by using Kamlet's and Swain's multiparametric equations. A mechanism involving the formation of a thioester and its decomposition in slow step has been proposed.
- Swami, Preeti,Vadera,Prasadrao,Sharma, Pradeep K.
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scheme or table
p. 1320 - 1324
(2010/08/05)
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- Kinetics and mechanism of oxidation of some thioacids by morpholinium chlorochromate
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Oxidation of thioglycollic, thiolactic and thiomalic acids by morpholinium chlorochromate is first order both in MCC and thioacids. The reaction is catalysed by hydrogen ions. The hydrogen ion dependence takes the form k obs=a+b [H+]. Oxidation of the thiolactic acid has been studied in nineteen different organic solvents. The solvent effect has been analysed by using Kamlet's and Swain's multiparametric equations. A mechanism involving the formation of a thioester and its decomposition in slow step is also proposed.
- Malani,Pohani,Baghmar,Sharma, Pradeep K.
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body text
p. 1373 - 1376
(2009/04/13)
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- Kinetics and mechanism of oxidation of some thioacids by benzyltrimethylammonium chlorobromate
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The oxidation of some thioacids, viz., thioplycollic, thiolactic and thiomalic acids by benzyltrimethylammonium chlorobromate (BTMACB) has been studied in acetic acid. The reaction is first order with respect to BTMACB. Michaelis-Menten type of 'kinetics have been observed with respect to the reductants. The reaction has been studied in solvents of different compositions of acetic acid and water. The solvent composition effect has been analysed using Grunwald-Weinstein equation. A mechanism involving the formation of an intermediate complex in the pre-equilibrium and its subsequent decomposition in slow step has been proposed.
- Tiwari, Vandana,Kumbhani,Shastri,Sharma, Vinita
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body text
p. 1520 - 1523
(2009/05/16)
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- Dynamic kinetic resolution of amines involving biocatalysis and in situ free radical mediated racemization
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(Chemical Equation Presented) The association of lipase-catalyzed enzymatic resolution with in situ racemization mediated with the thiyl radical enables the dynamic kinetic resolution of non-benzylic amines. It leads to (R)-amides with high enantioselectivities. It can be applied either to the conversion of racemic mixtures or to the inversion of (S)-enantiomers.
- Gastaldi, Stephane,Escoubet, Stephanie,Vanthuyne, Nicolas,Gil, Gerard,Bertrand, Michele P.
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p. 837 - 839
(2007/10/03)
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- Kinetics and mechanism of the oxidation of some thioacids by tetrabutylammonium tribromide
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The oxidation of some thioacids viz. thioglycollic, thiolactic and thiomalic acids by tetrabutylammonium tribromide (TBATB) has been studied in acetic acid. The reaction is first order with respect to TBATB. Michaelis-Menten type of kinetics were observed with respect to the reductants. The reaction has been studied in solvents of different compositions of acetic acid and water. The solvent composition effect has been analysed using Grunwald-Weinstein equation. A mechanism involving the formation of an intermediate complex in the pre-equilibrium and its subsequent decomposition in slow step has been proposed.
- Chouhan,Sharma, Vinita
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p. 302 - 305
(2007/10/03)
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- Kinetics and mechanism for reduction of the anticancer prodrug trans,trans,trans-[PtCl2(OH)2(c-C6H11NH2)(NH3)] (JM335) by thiols.
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The reduction of the platinum(IV) prodrug trans,trans,trans-[PtCl2(OH)2(c-C6H11NH2)(NH3)] (JM335) by L-cysteine, DL-penicillamine, DL-homocysteine, N-acetyl-L-cysteine, 2-mercaptopropanoic acid, 2-mercaptosuccinic acid, and glutathione has been investigated at 25 degrees C in a 1.0 M aqueous perchlorate medium with 6.8 a reductive elimination process through an attack by sulfur at one of the mutually trans chloride ligands, yielding trans-[Pt(OH)2(c-C6H11NH2)(NH3)] and RSSR as the reaction products, as confirmed by 1H NMR. Second-order rate constants for the reduction of JM335 by the various protolytic species of the thiols span more than 3 orders of magnitude. Reduction with RS- is approximately 30-2000 times faster than with RSH. The linear correlation log(kRS) = (0.52 +/- 0.06)-pKRSH--(2.8 +/- 0.5) is observed, where kRS denotes the second-order rate constant for reduction of JM335 by a particular thiolate RS- and KRSH is the acid dissociation constant for the corresponding thiol RSH. The slope of the linear correlation indicates that the reactivity of the various thiolate species is governed by their proton basicity, and no significant steric effects are observed. The half-life for reduction of JM335 by 6 mM glutathione (40-fold excess) at physiologically relevant conditions of 37 degrees C and pH 7.30 is 23 s. This implies that JM335, in clinical use, is likely to undergo in vivo reduction by intracellular reducing agents such as glutathione prior to binding to DNA. Reduction results in the immediate formation of a highly reactive platinum(II) species, i.e., the bishydroxo complex in rapid protolytic equilibrium with its aqua form.
- Lemma,Shi,Elding
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p. 1728 - 1734
(2008/10/08)
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- Kinetics and mechanism of the oxidation of thiolactic acid by 12-tungstocobaltate(III) ion in acetate buffer
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The reaction between 12-tungstocobaltate(III) and thiolactic acid (TLA) is expressed by the stoichiometric equation, 2[Co(III )W]5- + 2CH3CH(SH)COOH = CH3CH(COO)SS(OOC)HCH3C + 2H+ + 2[Co(II)W]6-, which is consistent with the stoichiometric ratio δ[Co(III)W]5-/Δ[TLA] = 1.00 ± 0.06. The reaction is first-order in [Co(III )W]5-, fractional order in [RSH] and shows a linear correlation between kobs-1 and [H+] with an intercept on the rate ordinate. The formation of a complex between [Co(III)W]5- and CH3CH(SH)COO- is evident both from rapid scanning of the reaction mixture and the kinetics. The formation of the complex from Co(III )W]5- and CH3CH(COOH)S-, suggested in a previous study, is shown to be unlikely. The formation constant (0.025) for the complex is independent of temperature. The activation parameters for the rate limiting step are ΔH? = 15 ± 1 kJ mol-1 and ΔS? = -153 ± 3 J K-1 mol-1. The small ΔH? value is suggestive of a multiple process that included preequilibrium reactions. The rate determining intramolecular electron-transfer from COO- is synchronous with the transfer of H atom, produced by the homolytic S-H fission, to COO resulting in the formation of CH3CH(COOH)S· free radical which dimerises to the oxidation product. Thus the electron-transfer is theoretically inner-sphere. Since the central CoIII is well protected, it is difficult to visualise the manner in which the thiolic proton could form a bridge. It is equally difficult to be specify whether the central CoIII atom is directly reduced to CoII by the inner sphere electron transfer as suggested by the mechanism or it is reduced by the electron first transferred to outer tungstate framework (in outer-sphere pathway) which instantaneously transfers it to the central CoIII atom. In either case the spectrum of the reduced reaction mixture would be identical with that of 12-tungstocobaltate(II). Hence, the theoretical aspect of the electron transfer in such a case might have some bearing on the nature of the reaction.
- Mehrotra, Raj N.,Dholiya, Susheela,Sharma, Kamla,Prakash
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p. 973 - 979
(2007/10/03)
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- Kinetics and mechanism of oxidation of some thioacids by quinolinium fluorochromate
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The oxidation of thioglycollic, thiolactic and thiomalic acids by quinolinium fluorochromate (QFC) is first order in QFC. The reaction exhibits Michaelis-Menten type of kinetics with respect to the thioacid. The reaction is catalyzed by hydrogen ions. The hydrogen ion dependence has the form: kobs= a + b [H+]. The oxidation of thiolactic acid has been studied in 19 oragnic solvents. The solvent effect has been analysed using Kamlet's and Swain's multiparametric equations. A mechanism involving the formation of a thioester and its decomposition in the slow step has been proposed.
- Khurana, Madhu,Sharma, Pradeep K.,Banerji, Kalyan K.
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p. 1011 - 1015
(2007/10/03)
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- Kinetics and mechanism of the oxidation of some thioacids by pyridinium bromochromate
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Oxidation of thioglycollic, thiolactic and thiomalic acids by pyridinium bromochromate (PBC) is first order with respect to PBC. The reaction exhibits Michaelis-Menten type kinetics with respect to the thioacid. Oxidation of thiolactic acid has been studied in 19 organic solvents and the solvent effect has been analysed using Kamlet's and Swain's multiparametric equations. A mechanism involving the formation of a thioester and its decomposition in the slow step has been proposed.
- Kothari, Seema,Banetji, Kalyan K.
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p. 1156 - 1159
(2007/10/03)
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- Kinetics of oxidation of thioacids by tetrabutylammonium-12-tungstocobaltate(III) ion in dimethyl sulphoxide medium
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The oxidation of thioglycolic(TGA), thiomalic(TMA) and thiolactic(TLA) acids in DMSO is first order in tetrabutylammonium-12-tungstocobaltate(III) ion, independent of [H+] and the plots of kobs-1 versus [thioacid]-1 are linear. The reactivity is in the order TLA > TMA > TGA. A comparison with the corresponding oxidation of TLA in aqueous medium has manifested areas of resemblance and strong deviations. The area of agreement includes evidence for the formation of the intermediate complex both from the kinetics and rapid scanning of the reaction mixture. The areas of divergence are (a) no effect of [H+] on kobs (kobs-1 was linearly dependent on [H+] in water), (b) the association constant Kass increases with temperature (independent of temperature in water), (c) value of Kass in DMSO is about 400 times the value in water, and (d) the rate limiting constant in water is about 104 times as high as in DMSO. These differences are explained on the basis of solvation of the ions and the stability and change in reactivity of the solvated ions in protic and aprotic solvents. The solvating nature of the solvent has also explained the differences in the enthalpy and entropy of activation in DMSO and water.
- Dholia, Susheela,Prakash, Aditya,Mehrotra, Raj N.
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p. 959 - 963
(2007/10/03)
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- The mechanism of nitric oxide formation from S-nitrosothiols (thionitrites)
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S-Nitrosothiols (RSNO) are easily made by electrophilic nitrosation of thiols and are a convenient source of nitric oxide. Reaction occurs readily (in many cases) in aqueous buffer at pH 7.4 to give in addition the corresponding disulfide RSSR. If oxygen is not rigorously excluded from the solution, then the nitric oxide is converted quantitatively to nitrite ion, whereas in the absence of oxygen nitric oxide can be detected using a commercial NO-probe. Reaction, however, only occurs (apart from the photochemical pathway) if Cu2+ is present. There is often enough Cu2+ in the distilled water-buffer components to bring about reaction, but decomposition is halted if Cu2+ is complexed with EDTA. Experiments with the specific Cu+ chelator neocuproine however show that the true effective reagent is Cu+, formed by reduction of Cu2+ with thiolate ion. Kinetic experiments show that the most reactive nitrosothiols are those which can coordinate bidentately with Cu+, and there is a wide range of reactivity amongst the structures studied. Reactivity is crucially dependent on the concentrations of Cu2+ and RS-. Reaction also occurs, although somewhat more slowly, if the source of copper is the CuII complex with the tripeptide diglycyl-L-histidine (GGH) or as the CuII complex with human serum albumin (HSA). This allows the possibility that nitrosothiols could in principle generate nitric oxide in vivo using the naturally occurring sources of CuII. Rapid exchange of the NO-group in RSNO with thiols occurs, again in aqueous buffer at pH 7.4. This reaction has been established as a nucleophilic substitution reaction by the thiolate ion at the nitroso nitrogen atom. The implications of these results with regard to possible involvement of nitrosothiols in vivo are discussed.
- Williams, D. Lyn H.
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p. 1085 - 1091
(2007/10/03)
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- Catalysis by Cu2+ of nitric oxide release from S-nitrosothiols (RSNO)
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The decomposition of a range of S-nitrosothiols (thionitrites) RSNO, based on cysteine derivatives, yields in water at pH 7.4 nitrite ion quantitatively.If oxygen is rigorously excluded then no nitrite ion is formed and nitric oxide can be detected using an NO-probe.The reaction is catalysed by trace quantities of Cu2+ (there is often enough present in distilled water samples) and also to a lesser extent by Fe2+, but not by Zn2+, Cu2+, Mg2+, Ni2+, Co2+, Mn2+, Cr3+ or Fe3+.The rate equation (measuring the disappearance of the absorption at ca. 350 nm due to RSNO) was established as v = k*2+> + k' over a range of 2+> typically 5-50 μmol dm-3.The constant term k' represents the component of the rate due to residual Cu2+ in the solvent and buffer components, together with the spontaneous thermal reaction.Decomposition can be virtually halted by the addition of EDTA.Reactions carried out in the presence of N-methylaniline gave a quantitative yield of N-methyl-N-nitrosoaniline, but a negligible yield when oxygen was rigorously excluded.Values of the second-order rate constant k were obtained for a range of S-nitrosothiols.Reactivity is highest for the S-nitrosothiols derived from cysteamine and penicillamine, when Cu2+ can be complexed both with the nitrogen atom of the nitroso group and the nitrogen atom of the amino group, via a six-membered ring intermediate.If there is no amino (or other electron donating group) present, reaction is very slow (as for RSNO derived from a tert-butyl sulfide).N-Acetylation of the amino group reduces the reactivity drastically as does the introduction of another CH2 group in the chain.There is evidence of a significant gem-dimethyl effect.Kinetic results using the S-nitrosothiols derived from mercaptoacetic, thiolactic and thiomalic acids suggests that coordination can also occur via one of the oxygen atoms of the carboxylate group.EPR experiments which examined the Cu2+ signal showed no spectral change during the reaction suggesting that the mechanism does not involve oxidation and reduction with Cu2+ Cu+ interconversion.
- Askew, Stuart C.,Barnett, D. Jonathan,McAninly, John,Williams, D. Lyn H.
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p. 741 - 746
(2007/10/02)
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- Kinetics and Mechanism of the Oxidation of Some Thioacids by 2,2'-Bipyridinium Chlorochromate
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The oxidation of thioglycolic, thiolactic and thiomalic acids by 2,2'-bipyridinium chlorochromate (BPCC) results in the formation of the corresponding disulfide dimer.The reaction is first order with respect to both the thioacid and BPCC.The reaction is catalysed by hydrogen ions.The hydrogen-ion dependence has the form : kobs = a + b+>.The rates of oxidation were determined at different temperatures and the activation parameters were evaluated.The reaction failed to induce polymerization of acrylonitrile.The oxidation of thiolactic acid was studied in nineteen different organic solvent and an analysis of the solvent effect indicated that the cation-solvating power of the solvents plays the major role.Suitable mechanisms have been suggested.
- Rathore, Sangeeta,Sharma, Pradeep K.,Banerji, Kalyan K.
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p. 1636 - 1648
(2007/10/02)
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- OXIDATION OF SOME THIO ACIDS BY 2,6-DICHLOROPHENOL INDOPHENOL IN NEUTRAL AND ALKALINE MEDIUM BY SPECTROPHOTOMETRIC STOPPED FLOW TECHNIQUE
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Using spectrophotometric stopped flow technique, the oxidation of thiolactic acid, thioglycollic acid, 3-mercaptopropionic acid and thiobenzoic acid by the dye, 2,6-dichlorophenol indophenol, has been investigated.The reaction shows first order kinetics with respect to thioacids and 2,6-dichlorophenol indophenol concentrations while zero order kinetics with respect to hydroxide ion concentrations.Neither of the reaction products viz. the disulfide or the leuco-dye, affects the rate.Similarly, the addition of neutral electrolyte also does not influence the rate.The data suggest the formation of an activated complex between thioacids and the oxidant which in turn slowly decomposes into the intermediate product. Key words: Stopped flow technique; thioacids; 2,6-dichlorophenol indophenol; disulphide; leuco-dye.
- Singh, H. S.,Tandon, P. K.,Singh, S. K.,Jaiswal, A. K.
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p. 193 - 204
(2007/10/02)
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- Kinetic Study of the Oxidation of Some Thioacids by Pyridinium Chlorochromate
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Oxidation of thioglycolic, thiolacetic, and thiomalic acids by pyridinium chlorochromate (PCC) leads to the formation of the corresponding disulphides.The reaction is first order with respect to PCC and Michaelis-Menten type kinetics were observed with respect to the thioacid, indicating formation of an intermediate complex in the pre-equilibrium.Equilibrium constants of the complex formation and rates of decomposition of the complexes were determined.The oxidation of thioglycolic acid was studied in 19 different organic solvents.Analysis of the effect of solvents on the reaction indicated that the transition state is more polar than the reactant state.A mechanism involving formation of a sulphenium cation in the rate-determining step has been postulated.
- Agarwal, Sarswati,Chowdhury, Kakuli,Banerji, Kalyan K.
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p. 439 - 451
(2007/10/02)
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- Kinetics of Oxidation of Thiol Acids by 2,6-Dichlorophenolindophenol: Part II Oxidation of 2-Mercaptopropionic Acid in Acetone-Water Medium
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The oxidation kinetics of the title reaction in acetone-water medium (55percent v/v) and in the presence of phosphate buffer are described.The reaction shows first order dependence on the principal reactants.The rate is directly proportional to +>.The external addition of the reaction products, viz., the disulphide and the leuco dye has no effect on the rate.A positive salt effect has been observed.The rate increases on increasing the dielectric constant of the medium.Activation parameters have been determined and a plausible mechanism has been proposed.
- Rastogi, M.,Mishra, K. K.,Sinha, B. P.
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p. 726 - 728
(2007/10/02)
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- STRUCTURAL INFLUENCE ON THE OXIDATION OF THIOL ACIDS BY 2,6-DICHLOROPHENOLINDOPHENOL (A COENZYME Q MODEL)
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The oxidative behaviour of 2,6-dichlorophenolindophenol towards thiol acids has been described with particular reference to steric isomers of mercaptopropionic acid (MPA).The reactions were studied in presence of hydroxyl ion.The rates of oxidation of 2-MPA and 3-MPA have been compared vis-a-vis the influence of ->.The kinetic orders in both cases are two in indophenol and one in thiol acid.Hydroxyl ion retards the rate of oxidation of 2-MPA while accelerating behaviour is shown towards 3-MPA.Mechanisms consistent with the experimental observations have been laid down postulating the formation of an active dimeric intermediate in aqueous medium and adducts of indophenol in non-aqueous medium.
- Mishra, K. K.,Shrivastava, A. K.,Sinha, B. P.
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