THE OXIDATION OF ALPHA-TOCOPHEROL AND TROLOX BY PEROXYNITRITE

Peroxynitrite reacts rapidly with alpha-tocopherol to generate a mixtu re of species. The predominant products are 8a-methoxytocopherone in m ethanol and alpha-tocopherylquinone in acetonitrile. Only a small frac tion (about 2% of original alpha-tocopherol) was detected as alpha-toc opheroxyl radical in either solvent. We propose that peroxynitrite oxi dizes alpha-tocopherol in a two-electron process yielding the alpha-to copherone cation. The two-electron oxidation may be either concerted o r sequential. The fate of the alpha-tocopherone cation is solvent depe ndent. In acetonitrile it undergoes hydrolysis, in the presence of tra ce amounts of water, to form alpha-tocopherylquinone. In methanol it u ndergoes nucleophilic addition to yield 8a-methoxytocopherone. Our dat a suggest that two-electron oxidation of alpha-tocopherol by peroxynit rite represents the major pathway, whereas one-electron oxidation to g enerate alpha-tocopheroxyl radical is a minor pathway. The biological consequences of two-electron oxidation of alpha-tocopherol are discuss ed. (C) 1994 Academic Press, Inc.