The Mechanism of Photochemical Release of Nitric Oxide from S‐Nitrosoglutathione

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Abstract— Laser flash photolysis of S‐nitroso complexes of glutathione (GSNO) and bovine serum albumin (BSANO) via excitation at 355 nm has been used to investigate the photogeneration of nitric oxide (NO) and subsequent radical reactions. In the case of GSNO, liberation of NO was confirmed by its oxidation of oxyhemoglobin to met hemoglobin. Initial NO release is via homolytic cleavage of the S‐N bond to produce the glutathione thiyl radical, GS, which can subsequently react with (a) ground‐state GSNO (k= 1.7 × 109M−1/i> s−1) to yield additional NO and oxidized glutathione, GSSG; and (b) oxygen (k= 3.0 × 109M−1 s−1) to give the glutathione peroxy radical, GSOO, which subsequently reacts with ground‐state GSNO (k= 3.8 × 108M−1 s−1), also producing additional NO and GSSG. The relative concentrations of oxygen and GSNO in the system determine the major pathway for removal of G'. These secondary reactions occur at such high rates that they preclude radical recombination under low‐intensity irradiation conditions. The quantum yield of overall loss of GSNO thus varies with both GSNO and oxygen concentrations; a value of 0.66 was determined for an aerated solution of GSNO (0.86 mM). In the case of GSNO, therefore, generation of NO is not due solely to homolysis of the S‐N bond; secondary reactions of the radicals formed lead to further NO liberation. In rationalizing the known phototoxicity of GSNO, possible contributions from thiyl and thiyl‐derived radicals should be considered. In contrast to GSNO, direct excitation of BSANO (containing one bound NO group per molecule) led to photodecomposition with a quantum yield of 0.09 but no evidence was obtained for liberation of NO into the bulk medium.