Mechanistic investigations of the S-nitrosothiol, peroxynitrous acid and thiol system

Abstract

S-Nitrosothiols have been found to undergo nucleophilic attack by the hydroperoxide anion to effect electrophilic nitrosation of the nucleophile. Peroxynitrite anion is formed in almost quantitative yields and the kinetics of the reaction examined, confirming attack through the deprotonated form of hydrogen peroxide. Conversely, under slightly acidic conditions peroxynitrous acid, the neutral form of peroxynitrite, has been shown to nitrosate an excess of thiol in an indirect pathway. Initially two moles of thiol are oxidised to the corresponding disulfide with the concomitant production of nitrite. Under mildly acidic conditions nitrous acid is formed which can then nitrosate excess thiol present. The reaction of a 2;1 excess of thiol over peroxynitrous acid has been shown to generate nitrous acid, which remains relatively stable, as there is no thiol remaining due to its oxidation to the disulfide. At higher acidities an additional source of nitrosation is uncovered which is explained in the terms of the formation of a protonated from of peroxynitrous acid with analogies toward the nitrous acidium ion. A comparison of the antioxidant potential of S-nitrosothiols versus thiols has also been examined using the powerful oxidant potassium bromate. Complex kinetic traces were generated but evidence was obtained which showed that S-nitrosothiols have enhanced antioxidant potential over thiols due to the nitroso moiety. The alkaline hydrolysis of S-nitrosothiols was also investigated with attack of the hydroxide ion postulated to proceed via nucleophilic attack on the sulfur atom of S-nitrosothiols. Also the reaction between S-nitrosothiols and phenolic compounds was found to proceed through different mechanisms depending on the ring substituents on the phenol.