The kinetics and mechanism of the oxidation of an important organosulfur antioxidant, N-acetylcysteine, by chlorite and acidified bromate have been studied. In both cases, the final product is N-acetylcysteinesulfonic acid without cleavage of the C-S bond to form sulfate. There was also no evidence for the formation of N-chloramine nor N-bromamine as has been observed with other aminothiols such as taurine. N-Acetylcysteine was oxidized via a stepwise S-oxygenation process in which consecutively a sulfenic and a sulfinic acid were formed before formation of the cysteic acid product. The stoichiometry of the chlorite-N-acetylcysteine was experimentally deduced to be 3ClO 2 -+ 2(CH 3 CO)HNCH(CO 2 H)CH 2 SH f 3Cl -+ 2(CH 3 CO)HNCH-(CO 2 H)CH 2 SO 3 H. The reaction is characterized by an immediate and rapid production of chlorine dioxide without a measurable induction period. This is because the oxidation of N-acetylcysteine by chlorine dioxide is slow enough to allow for the chlorine dioxide to instantly accumulate without the induction period that characterizes most chlorite oxidations of organosulfur compounds. The global reaction dynamics for this reaction can be described fully by a truncated mechanism that utilizes only 8 reactions. The stoichiometry of the bromate-N-acetylcysteine reaction at stoichiometric ratios was deduced to be BrO 3 -+ (CH 3 CO)HNCH-(CO 2 H)CH 2 SH f Br -+ (CH 3 CO)HNCH(CO 2 H)CH 2 SO 3 H, while in excess bromate it was deduced to be 6BrOThis reaction proceeded with a prolonged induction period which gave way to a sudden formation of bromine. The rate of reaction between aqueous bromine and N-acetylcysteine is diffusion-limited which indicated that the end of the induction period coincided with a complete oxidation of N-acetylcysteine. The reaction was successfully modeled by the use of a reaction network made up of 12 elementary reactions. Despite their different physiological effects, both cysteine and N-acetylcysteine are oxidized by oxyhalogens via the same S-oxygenation pathway and gave the same oxidation metabolites and final product.

The oxidation reactions of N-acetylthiourea (ACTU) by chlorite and chlorine dioxide were studied in slightly acidic media. The ACTU-ClO(2)(-) reaction has a complex dependence on acid with acid catalysis in pH > 2 followed by acid retardation in higher acid conditions. In excess chlorite conditions the reaction is characterized by a very short induction period followed by a sudden and rapid formation of chlorine dioxide and sulfate. In some ratios of oxidant to reductant mixtures, oligo-oscillatory formation of chlorine dioxide is observed. The stoichiometry of the reaction is 2:1, with a complete desulfurization of the ACTU thiocarbamide to produce the corresponding urea product: 2ClO(2)(-) + CH(3)CONH(NH(2))C=S + H(2)O --> CH(3)CONH(NH(2))C=O + SO(4)(2-) + 2Cl(-) + 2H(+) (A). The reaction of chlorine dioxide and ACTU is extremely rapid and autocatalytic. The stoichiometry of this reaction is 8ClO(2)(aq) + 5CH(3)CONH(NH(2))C=S + 9H(2)O --> 5CH(3)CONH(NH(2))C=O + 5SO(4)(2-) + 8Cl(-) + 18H(+) (B). The ACTU-ClO(2)(-) reaction shows a much stronger HOCl autocatalysis than that which has been observed with other oxychlorine-thiocarbamide reactions. The reaction of chlorine dioxide with ACTU involves the initial formation of an adduct which hydrolyses to eliminate an unstable oxychlorine intermediate HClO(2)(-) which then combines with another ClO(2) molecule to produce and accumulate ClO(2)(-). The oxidation of ACTU involves the successive oxidation of the sulfur center through the sulfenic and sulfinic acids. Oxidation of the sulfinic acid by chlorine dioxide proceeds directly to sulfate bypassing the sulfonic acid. Sulfonic acids are inert to further oxidation and are only oxidized to sulfate via an initial hydrolysis reaction to yield bisulfite, which is then rapidly oxidized. Chlorine dioxide production after the induction period is due to the reaction of the intermediate HOCl species with ClO(2)(-). Oligo-oscillatory behavior arises from the fact that reactions that form ClO(2) are comparable in magnitude to those that consume ClO(2), and hence the assertion of each set of reactions is based on availability of reagents that fuel them. A computer simulation study involving 30 elementary and composite reactions gave a good fit to the induction period observed in the formation of chlorine dioxide and in the autocatalytic consumption of ACTU in its oxidation by ClO(2).

The oxidation of trimethylthiourea (TMTU) by acidic bromate has been studied. The reaction mimics the dynamics observed in the oxidation of unsubstituted thiourea by bromate with an induction period before formation of bromine. The stoichiometry of the reaction was determined to be 4:3, thus 4BrO(3)- + 3R(1)R(2)C=S+ 3H(2)O --> 4Br- + 3R(1)R(2)C=O + 3SO(4)(2-) + 6H+. This substituted thiourea is oxidized at a much faster rate than the unsubstituted thiourea. The oxidation mechanism of TMTU involves initial oxidations through sulfenic and sulfinic acids. At the sulfinic acid stage, the major oxidation pathway is through the cleavage of the C-S bond to form a reducing sulfur leaving group, which is easily oxidized to sulfate. The minor pathway through the sulfonic acid produces a very stable intermediate that is oxidized only very slowly to urea and sulfate. The direct reaction of aqueous bromine with TMTU was faster than reactions that form bromine, with a bimolecular rate constant of (1.50 +/- 0.04) x 10(2) M(-1) s(-1). This rapid reaction ensured that no oligooscillatory bromine formation was observed. The oxidation of TMTU was modeled by a simple reaction scheme containing 20 reactions.

The mechanism of oxidation of the well-known radical scavenger dimethylthiourea, DMTU, by acidic bromate was studied. The stoichiometry of the reaction is 4:3: 4BrO + 3CS(NHMe) + 3HO → 3SO + 3CO(NHMe) + 6H + 4Br. In excess acidic bromate, the reaction stoichiometry is 8:5: 8BrO + 5CS(NHMe) + HO → 5SO + 5CO(NHMe) + 4Br + 2H. In excess bromate, the reaction displays well-defined clock reaction characteristics in which initially there is a quiescent period before formation of bromine. The direct reaction of aqueous bromine with DMTU, with a bimolecular rate constant of k = (1.95 ± 0.15) × 10 M s, is much faster than reactions that form bromine such that formation of bromine indicates complete consumption of DMTU. ESI spectrometry showed evidence for an oxidation pathway that passes through the sulfenic, sulfinic, and sulfonic acids before formation of sulfate. In contrast to the oxidation of tetramethylthiourea, these oxoacid intermediates are not as abundant or as stable. The final product of oxidation was dimethylurea, the desulfurized DMTU. EPR spectroscopy implicates more than one set of radical species. The absence of the dimeric DMTU species, even in excess reductant indicates negligible formation of thiyl radicals. This also precludes substantial formation of the sulfenic acid intermediate which would form the dimer from a condensation-type reaction with unreacted DMTU. A 20-step reaction mechanism network was modeled which gave a reasonable fit with experimental data.

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