- Oxyhalogen-sulfur chemistry: Kinetics and mechanism of oxidation of chemoprotectant, sodium 2-mercaptoethanesulfonate, MESNA, by acidic bromate and aqueous bromine
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The oxidation of a well-known chemoprotectant in anticancer therapies, sodium 2-mercaptoethanesulfonate, MESNA, by acidic bromate and aqueous bromine was studied in acidic medium. Stoichiometry of the reaction is: BrO 3- + HSCH2CH2SO3H - Br- + HO3SCH2CH2SO3H. In excess bromate conditions the stoichiometry was deduced to be: 6BrO 3- + 5HSCH2CH2SO3H + 6H+ - 3Br2 + 5HO3SCH2CH 2SO3H + 3H2O. The direct reaction of bromine and MESNA gave a stoichiometric ratio of 3:1: 3Br2 + HSCH 2CH2SO3H + 3H2O - HO 3SCH2CH2SO3H + 6Br- + 6H+. This direct reaction is very fast; within limits of the mixing time of the stopped-flow spectrophotometer and with a bimolecular rate constant of 1.95 ± 0.05 × 104 M-1 s-1. Despite the strong oxidizing agents utilized, there is no cleavage of the C-S bond and no sulfate production was detected. The ESI-MS data show that the reaction proceeds via a predominantly nonradical pathway of three consecutive 2-electron transfers on the sulfur center to obtain the product 1,2-ethanedisulfonic acid, a well-known medium for the delivery of psychotic drugs. Thiyl radicals were detected but the absence of autocatalytic kinetics indicated that the radical pathway was a minor oxidation route. ESI-MS data showed that the S-oxide, contrary to known behavior of organosulfur compounds, is much more stable than the sulfinic acid. In conditions where the oxidizing equivalents are limited to a 4-electron transfer to only the sulfinic acid, the products obtained are a mixture of the S-oxide and the sulfonic acid with negligible amounts of the sulfinic acid. It appears the S-oxide is the preferred conformation over the sulfenic acid since no sulfenic acids have ever been stabilized without bulky substituent groups. The overall reaction scheme could be described and modeled by a minimal network of 18 reactions in which the major oxidants are HOBr and Br2(aq).
- Adigun, Risikat Ajibola,Mhike, Morgen,Mbiya, Wilbes,Jonnalagadda, Sreekanth B.,Simoyi, Reuben H.
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p. 2196 - 2208
(2014/04/17)
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- Substituted 1-phenyl-3-pyrazolecarboxamides active on neurotensin receptors, their preparation and pharmaceutical compositions containing them
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The invention relates to new substituted 1-phenyl-3-pyrazolecarboxamides having a great affinity for human neurotensin receptors, to a process for preparing them and to pharmaceutical compositions containing them as active principles. More particularly, this invention relates to the discovery that the affinity for neurotensin receptors, especially human neurotensin receptors, is increased by substituting the phenyl group of 1-phenyl-3-pyrazolecarboxamide compounds with particular groups.
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