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

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 × 10⁷ L mol^-1 s^-1 at 285.4 K for 3,1.66 × 10⁷ L mol^-1 s^-1 at 293.2 K for 4, and 5.2 × 10⁶ 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 × 10⁵ L mol^-1 s^-1 at 293.5 K for 3, 3.34 × 10⁵ L mol^-1 s^-1 at 293.2 K for 4, and 7.64 × 10³ 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 × 10² L mol^-1 s^-1) and slow (6.62 × 10¹ L mol^-1 s^-1) reactions are many orders-of-magnitude less than observed for the tellurium analogues.