THE REACTION OF S-NITROSOTHIOLS WITH THIOLS AT HIGH THIOL CONCENTRATION

Reactions of S-nitrosothiols (RSNO) with their corresponding thiols (R SH) present in a large excess (>20-fold) proceed readily to give the d isulfide. Ammonia is formed together with some nitrite anion, and thes e constitute >90% of the ''nitrogen'' products. This is in marked cont rast with the reaction at low thiol concentration, where nitric oxide is the major initial ''nitrogen'' product, which is rapidly converted in the presence of oxygen in water to nitrite anion. Also in marked co ntrast to the ''low thiol concentration'' reaction, the reaction at hi gh thiol concentration is not affected by added Cu2+, nor by the metal -ion scavenger EDTA. Kinetically all reactions were excellent first-or der processes, and the reactions were also strictly first order in thi ol concentration. A large range of nitrosothiols were studied and the generality of the reaction established. Some reactions of RSNO with ot her thiols (R'SH) were examined and the results readily interpreted in terms of a prior rapid equilibrium transnitrosation. The pH dependenc e for the reaction of S-nitrosocysteine with cysteine clearly showed t hat the reactive species is the cysteine thiolate anion. The results a re discussed along with those of two other recent reports of these rea ctions, in terms of thiolate attack initially at the nitroso nitrogen atom, and subsequently at sulfur atoms, eliminating RSSR and yielding hydroxylamine, which is rapidly reduced by thiolate ion to ammonia. Th e results are also discussed in connection with the release of NO from nitrosothiols and with the important biological consequences, both fo r the in vivo reactions of NO and for the potential of nitrosothiols a s NO-releasing drugs for medical use.