CATALYSIS BY CU2+ OF NITRIC-OXIDE RELEASE FROM S-NITROSOTHIOLS (RSNO)

The decomposition of a range of S-nitrosothiols (thionitrites) RSNO, based on cysteine derivatives, yields in water at pH 7.4 nitrite ion quantitatively. If oxygen is rigorously excluded then no nitrite ion is formed and nitric oxide can be detected using an NO-probe. The reaction is catalysed by trace quantities of Cu2+ (there is often enough present in distilled water samples) and also to a lesser extent by Fe2+, but not by Zn2+, Cu2+, Mg2+, Ni2+, Co2+, Mn2+, Cr3+ Or Fe3+. The rate equation (measuring the disappearance of the absorption at ca. 350 nm due to RSNO) was established as v = k[RSNO].[Cu2+] + k' over a range of [Cu2+] typically 5-50 mu mol dm(-3). The constant term k' represents the component of the rate due to residual Cu2+ the solvent and buffer components, together with the spontaneous thermal reaction. Decomposition can be virtually halted by the addition of EDTA. Reactions carried out in the presence of N-methylaniline gave a quantitative yield of N-methyl-N-nitrosoaniline, but a negligible yield when oxygen was rigorously excluded. Values of the second-order rate constant k were obtained for a range of S-nitrosothiols. Reactivity is highest for the S-nitrosothiols derived from cysteamine and penicillamine, when Cu2+ can be complexed both with the nitrogen atom of the nitroso group and the nitrogen atom of the amino group, via a six-membered ring intermediate. If there is no amino (or other electron donating group) present, reaction is very slow (as for RSNO derived from tert-butyl sulfide). N-Acetylation of the amino group reduces the reactivity drastically as does the introduction of another CH2 group in the chain. There is evidence of a significant gem-dimethyl effect. Kinetic results using the S-nitrosothiols derived from mercaptoacetic, thiolactic and thiomalic acids suggests that coordination can also occur via one of the oxygen atoms of the carboxylate group. EPR experiments which examined the Cu2+ Signal showed no spectral change during the reaction suggesting that the mechanism does not involve oxidation and reduction with Cu(2+)reversible arrow Cu+ interconversion.