Oxyhalogen-sulfur chemistry: Oxidation of N-acetylcysteine by chlorite and acidic bromate

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 3ClO₂^- + 2(CH₃CO)HNCH(CO₂H)CH₂SH → 3Cl^- + 2(CH₃CO)HNCH-(CO₂H)CH₂SO₃H. 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 BrO₃^- + (CH₃CO)HNCH-(CO₂H)CH₂SH → Br^- + (CH₃CO)HNCH(CO₂H)CH₂SO₃H, while in excess bromate it was deduced to be 6BrO₃^- + 5(CH₃CO)HNCH(CO₂H)CH₂SH + 6H⁺ → 3Br₂ + 5(CH₃CO)HNCH(CO₂H)CH₂SO₃H + 3H₂O. This 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.