Mechanism of S-nitrosation of cysteine derivatives in the pH range 6–12 using N-methyl-N-nitrosotoluene-p-sulphonamide

Abstract

N-Methyl-N-nitrosotoluene-p-sulphonamide (MNTS) reacts readily with the thiolate anion of cysteine and some of its derivatives, in aqueous ethanol, to give the corresponding S-nitroso species. The measured second order rate constant k₂ increases with pH, and the experimental points lie close to the S-shaped curve calculated for reaction via the thiolate anion. The pK_a values for SH ionisation were calculated from the experimental results, and gave figures generally in good agreement with the literature. There is no evidence of reaction via the thiol RSH, or of any reaction, under these conditions, with less powerful nucleophiles including amines, alcohols and an enol. There was no evidence of S-nitrosation of cysteine using dimethylnitrosamine, nitrosoproline or nitrososarcosine. The results are consistent with a direct transfer of the nitroso group to the sulphur atom of the thiolate anion. The results are compared with similar reactions of alkyl nitrites.