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

Article abstract of DOI:10.1021/jo00105a049

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 2.30E7 L mol^-1 s^-1 at 285.4 K for 3, 1.66E7 L mol^-1 s^-1 at 293.2 K for 4, and 5.2E6 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 2.65E5 L mol^-1 s^-1 at 293.5 K for 3, 3.34E5 L mol^-1 s^-1 at 293.2 K for 4, and 7.64E3 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 (2.26E2 L mol^-1 s^-1) and slow (6.62E1 L mol^-1 s^-1) reactions are many orders-of-magnitude less than observed for the tellurium analogues.