A mechanism for the oxidation of glutathione to glutathione disulfide with organotellurium(IV) and organoselenium(IV) compounds. A stepwise process with implications for photodynamic therapy and other oxidative chemotherapy

Abstract

The reactions of telluroxides or their hydrates 3-5 with glutathione to give telluropyrylium dyes 1, 2 or diphenyl telluride, respectively, and glutathione disulfide have at least two discrete steps. A fast reaction, which is first-order in both substrate and glutathione, is observed with second-order rate constants of 2.30 x 10(7) L mol(-1) s(-1) at 285.4 K for 3, 1.66 x 10(7) L mol(-1) s(-1) at 293.2 K for 4, and 5.2 x 10(6) L mol(-1) s(-1) at 285.5 K for 5. This reaction is followed by a slower reaction, which is first-order in both substrate and glutathione, with second-order rate constants of 2.65 x 10(5) L mol(-1) s(-1) at 293.5 K for 3, 3.34 x 10(5) L mol(-1) s(-1) at 293.2 K for 4, and 7.64 x 10(3) L mol(-1) s(-1) at 285.5 K for 5. The slow reaction is accompanied by the generation of the corresponding tellurium-(II) compound. Diphenyl selenoxide hydrate (6) displays similar behavior, although the rate constants associated with the fast (2.26 x 10(2) L mol(-1) s(-1)) and slow (6.62 x 10(1) L mol(-1) s(-1)) reactions are many orders-of-magnitude less than observed for the tellurium analogues.