OXIDATION OF THIOLS BY COPPER(II)

Thiols were oxidized by Cu(II) in a reaction that had two phases. Ther e was an immediate reaction between thiol and Cu(II) with loss of thio l, measured by its reaction with 5,5'-dithio-bis(2-nitrobenzoic acid), and formation of Cu(I), measured by its reaction with bathocuproinedi sulfonic acid. With equal molar concentrations of thiols and Cu(II), o nly the first phase was observed and thiols were oxidized in less than 15 sec. When the concentration of Cu(II) was limiting (200 mu M thiol and 10 to 160 mu M Cu(II)), the second phase of the reaction was obse rved; this phase was much slower for glutathione (GSH) than it was for cysteine and accounts for previous reports that GSH is oxidized by Cu (II) at a slower rate than cysteine. It is proposed that Cu(II) reacts with thiols to form Cu(II)-thiol complexes, Cu(lI) is reduced to Cu(I ), and the thiols are oxidized to the corresponding radicals. Two of t he radicals react to form a disulfide and Cu(I) reacts with a second t hiol to form a Cu(I)-thiol complex in which the Cu(I) is oxidized to C u(II) by oxygen. The rate of reoxidation of Cu(I) is dependent on the R group of the thiol and is the rate limiting step of the reaction.