REACTIONS OF PEROXYNITRITE WITH GAMMA-TOCOPHEROL

The reaction of peroxynitrite with gamma-tocopherol (gamma-TH) in a me thanol/potassium phosphate buffer solution results in the formation of four major products, which were identified as thyl-2-(4,8,12-trimethy ldecyl)-5-nitro-6-chromanol (NGT), methyl-2-(4,8,12-trimethyldecyl)-5, 6-chromaquinone (tocored), and two diastereomers of 8a-(hydroxy)-gamma -tocopherone. NGT was the major product formed in these reactions, and its formation was modestly increased by increasing amounts of Fe3+-ED TA. Tocored and NGT also were formed when gamma-TH was exposed to 3-mo rpholinosydnonimine (SIN-1), a compound that decomposes to form peroxy nitrite. When gamma-TH reacted with the nitrating agent NO2+BF4- in ac etonitrile or methanol/potassium phosphate buffer, NGT and tocored als o were formed, but the major product detected was gamma-tocopherol qui none(gamma-TQ). This product was not detected in reactions involving p eroxynitrite. Oxidation of gamma-TH by peroxynitrite involves nitratio n and electron transfer reactions. Since the product distribution in o xidations with NO2+BF4- differed substantially from that in oxidations with peroxynitrite and SIN-1, NO2+ appeared not to be the principal s pecies involved in NGT formation. Nitration of gamma-TH may involve ei ther peroxynitrite or some peroxynitrite-derived oxidant other than NO 2+. Because of its stability and formation as a novel product of the r eaction between gamma-TH with peroxynitrite, NGT may be a useful in vi vo marker for peroxynitrite interactions with lipid structures that co ntain gamma-TH.