The oxidation of alpha-tocopherol and trolox by peroxynitrite

Peroxynitrite reacts rapidly with alpha-tocopherol to generate a mixture of species. The predominant products are 8a-methoxytocopherone in methanol and alpha-tocopherylquinone in acetonitrile. Only a small fraction (about 2% of original alpha-tocopherol) was detected as alpha-tocopheroxyl radical in either solvent. We propose that peroxynitrite oxidizes alpha-tocopherol in a two-electron process yielding the alpha-tocopherone cation. The two-electron oxidation may be either concerted or sequential. The fate of the alpha-tocopherone cation is solvent dependent. In acetonitrile it undergoes hydrolysis, in the presence of trace amounts of water, to form alpha-tocopherylquinone. In methanol it undergoes nucleophilic addition to yield 8a-methoxytocopherone. Our data suggest that two-electron oxidation of alpha-tocopherol by peroxynitrite represents the major pathway, whereas one-electron oxidation to generate alpha-tocopheroxyl radical is a minor pathway. The biological consequences of two-electron oxidation of alpha-tocopherol are discussed.