The role of L-ascorbic acid in S-nitrosothiol decomposition and aspects of the nitrosation of thiones

Abstract

Ascorbic acid has been found to promote nitrosothiol decomposition via two pathways. In the first, ascorbic acid acts as a reducing agent for added or adventitious copper (II), producing copper (I). This reacts with the nitrosothiol, giving nitric oxide and disulfide as the ultimate products. The reaction requires only small quantities of ascorbic acid, and is catalytic in copper. The second pathway requires higher concentrations of ascorbic acid, the stoichiometry being one mole of ascorbic acid to two moles of nitrosothiol. The products are nitric oxide and thiol, and the reaction has been interpreted in terms of rate limiting nucleophihc attack by ascorbate at the nitroso nitrogen, followed by decomposition of the 0-nitroso ascorbate formed to nitric oxide and dehydroascorbic acid. The rate equation is first order in both the nitrosothiol and ascorbic acid, and the entropy of activation is significantly negative. pH - rate profiles reveal the ascorbate dianion is much more reactive than the monoanion, and that the neutral form has negligible reactivity. Nitrosation of thione-containing nitrogen heterocycles by nitrous acid leads to the equilibrium formation of =SNO(^+) species; large equilibrium constants are observed. The reactions exhibit many of the features generally observed in nitrosation, including catalysis by halides and thiocyanate, and some participation by dinitrogen trioxide as a nitrosating agent. The nitrosation rate constants are large, approaching values representing the encounter-controlled limit. The =SNO(^+) species are generally unstable, decomposing under acidic conditions to nitric oxide and a disulfide. Decomposition of S-nitrosated 4-thiopyridine showed hydrolysis occurs at pH 7.4, re-forming the thione. The nitroso species reacts rapidly with ascorbate, forming nitric oxide and thione.