Generation of superoxide radicals by copper–glutathione complexes: Redox-consequences associated with their interaction with reduced glutathione

Cu(I)–[GSH] 2 reacts with oxygen forming superoxide radicals. Upon removal of such radicals Cu(II)–GSSG is formed. Subsequent addition of GSH regenerates the Cu(I)–[GSH] 2 complex. Redox implications of these interactions are discussed. The interaction between Cu 2+ ions and GSH molecules leads to the swift formation of the physiologically occurring Cu(I)–[GSH] 2 complex. Recently, we reported that this complex is able to reduce molecular oxygen into superoxide in a reversible reaction. In the present study, by means of fluorescence, luminescence, EPR and NMR techniques, we investigated the superoxide-generating capacity of the Cu(I)–[GSH] 2 complex, demonstrated the occurrence and characterized the chemical nature of the oxidized complex which is formed upon removing of superoxide radicals from the former reaction, and addressed some of the redox consequences associated with the interaction between the Cu(I)–[GSH] 2 complex, its oxidized complex form, and an in-excess of GSH molecules. The interaction between Cu(I)–[GSH] 2 and added GSH molecules led to an substantial exacerbation of the ability of the former to generate superoxide anions. Removal of superoxide from a solution containing the Cu(I)–[GSH] 2 complex, by addition of Tempol, led to the formation and accumulation of Cu(II)–GSSG. Interaction between the latter complex and GSH molecules permitted the re-generation of the Cu(I)–[GSH] 2 complex and led to a concomitant recovery of its superoxide-generating capacity. Some of the potential redox and biological implications arising from these interactions are discussed.