Metal ion catalysis of s-nitrosothiol decompositions

Abstract

Most S-nitrosothiols (RSNO) are unstable in aqueous solution and decompose to release nitric oxide. This is catalysed by copper ions. A mechanistic study of NO formation from S-nitrosoglutathione (GSNO), the nitroso derivative of the most abundant thiol in the body, was carried out. This relatively stable S-nitrosothiol decomposed in the presence of reduced glutathione and copper ions. The products were identified as nitric oxide and oxidised glutathione, observed as a complex of copper. The role of reduced glutathione was two fold. Firstly, it reduced Cu(^2+) to produce the active Cu(^+) catalytic species and regenerated the catalyst from the oxidised glutathione complex. Spectrophotometric kinetic measurements, under pseudo first order conditions ([GSNO]»[Cu(^2+)]) showed no conventional order with respect to nitrosothiol. This was attributed to the inconstant concentration of available copper during reaction due to the ability of reduced glutathione to complex Cu(^+) and oxidised glutathione to complex Cu(^2+). An investigation of thiol induced decomposition of GSNO and other more stable nitrosothiols showed the reaction to be first order with respect to thiol and nitrosothiol. The rate equation was determined and has been explained in terms of a radical mechanism involving rate limiting attack of the thiyl radical on the RS-NO bond. The decomposition of S-nitrosothiols via the mercuric ion was also investigated. Reactions were stoichiometric rather than catalytic, and the products determined to be H(_2)NO(_2)(^+) and RSHg(^+). The rate equation was established and the reaction found to be first order in S-nitrosothiol and Hg(^2+). Second order rate constants obtained for a variety of nitrosothiols showed no dependency of the rate of the reaction on the structure of R. A mechanism was proposed involving direct attact of the Hg(^2+) ion on S of the nitroso group, reflecting the high affinity of the metal ion for the sulfur atom. Similarly, an investigation into Ag(^+) mediated S-nitrosothiol decomposition showed the reaction to be stoichiometric. Nitric oxide was not a product of this reaction.