Studies of the reactions of S-nitroso-N-acetylcysteine

Abstract

The discovery of the many important roles of nitric oxide in vivo has prompted a large research effort, in recent times, into the chemistry of nitric oxide and of nitric oxide donors. The chemical and biological aspects of NO and S-nitrosothiols (thionitrites RSNO) are reviewed in Chapter 1. It is known that RSNO decomposition is Cu(^+) catalysed, while formation by S-nitrosation of thiols ensures the presence of some thiolate ion in solutions of RSNO generally. The extent of free thiolate ion in solutions of S-nitroso-N-acetylcysteine (SNAG) has been determined by the Ellman procedure. The effects of added Cu(^2+), thiolate ion and ascorbic acid on the reactivity of SNAG have been determined experimentally, and conditions established where the thiolate ion acts either primarily as a reducing agent or a complexing agent for Gu(^2+). UV spectral evidence is produced for the intermediacy of Cu(^+), by the observation of its complex with neocuproine, a specific chelator for Cu(^+) Finally the results of the reactions of SNAG with both ascorbate and thiolate ion at significantly higher added concentrations have confirmed the existence of other reaction pathways, yielding ammonia from thiolate ion and nitric oxide from ascorbate in reactions which do not involve copper ions. Reaction pathways consistent with the results are presented.