A MECHANISM FOR THE OXIDATION OF GLUTATHIONE TO GLUTATHIONE DISULFIDEWITH ORGANOTELLURIUM(IV) AND ORGANOSELENIUM(TV) COMPOUNDS - A STEPWISE PROCESS WITH IMPLICATIONS FOR PHOTODYNAMIC THERAPY AND OTHER OXIDATIVE CHEMOTHERAPY

The reactions of telluroxides or their hydrates 3-5 with glutathione t o give telluropyrylium dyes 1, 2 or diphenyl telluride, respectively, and glutathione disulfide have at least two discrete steps. A fast rea ction, which is first-order in both substrate and glutathione, is obse rved 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 glut athione, 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, a nd 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) com pound. Diphenyl selenoxide hydrate (6) displays similar behavior, alth ough 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 o rders-of-magnitude less than observed for the tellurium analogues.