Mechanism and biological implications of the NO release of cis-[Ru(bpy)2L(NO)](n+) complexes: a key role of physiological thiols

Abstract

Nitric oxide (NO) has a critical role in several physiological and pathophysiological processes. In this paper, the reactions of the nitrosyl complexes of [Ru(bpy)(2)L(NO)](n+) type, where L = SO(3)(2-) and imidazole and bpy = 2,2'-bipiridine, with cysteine and glutathione were studied. The reactions with cysteine and glutathione occurred through the formation of two sequential intermediates, previously described elsewhere, [Ru(bpy)(2)L(NOSR)](n+) and [Ru(bpy)(2)L(NOSR)(2)] (SR = thiol) leading to the final products [Ru(bpy)(2)L(H(2)O)](n+) and free NO. The second order rate constant for the second step of this reaction was calculated for cysteine k(2)(SR(-))=(2.20±0.12)×10(9) M(-1) s(-1) and k(2(RSH))=(154±2) M(-1) s(-1) for L = SO(3)(2-) and k(2)(SR(-))=(1.30±0.23)×10(9) M(-1) s(-1) and k(2)(RSH)=(0.84±0.02) M(-1) s(-1) for L = imidazole; while for glutathione they were k(2)(SR(-))=(6.70±0.32)×10(8) M(-1) s(-1) and k(2)(RSH)=11.8±0.3 M(-1) s(-1) for L = SO(3)(2-) and k(2)(SR(-))=(2.50±0.36)×10(8) M(-1) s(-1) and k(2)(RSH)=0.32±0.01 M(-1) s(-1) for L = imidazole. In all reactions it was possible to detect the release of NO from the complexes, which it is remarkably distinct from other ruthenium metallocompounds described elsewhere with just N(2)O production. These results shine light on the possible key role of NO release mediated by physiological thiols in reaction with these metallonitrosyl ruthenium complexes.