Reactions of Peroxynitrite with γ-Tocopherol

Abstract

The reaction of peroxynitrite with γ-tocopherol (γ-TH) in a methanol/potassium phosphate buffer solution results in the formation of four major products, which were identified as 2,7,8-trimethyl-2-(4,8,12-trimethyldecyl)-5-nitro-6-chromanol (NGT), 2,7,8-trimethyl-2-(4,8,12-trimethyldecyl)-5,6-chromaquinone (tocored), and two diastereomers of 8a-(hydroxy)-γ-tocopherone. NGT was the major product formed in these reactions, and its formation was modestly increased by increasing amounts of Fe³⁺−EDTA. Tocored and NGT also were formed when γ-TH was exposed to 3-morpholinosydnonimine (SIN-1), a compound that decomposes to form peroxynitrite. When γ-TH reacted with the nitrating agent NO₂⁺BF₄^- in acetonitrile or methanol/potassium phosphate buffer, NGT and tocored also were formed, but the major product detected was γ-tocopherol quinone (γ-TQ). This product was not detected in reactions involving peroxynitrite. Oxidation of γ-TH by peroxynitrite involves nitration and electron transfer reactions. Since the product distribution in oxidations with NO₂⁺BF₄^- differed substantially from that in oxidations with peroxynitrite and SIN-1, NO₂⁺ appeared not to be the principal species involved in NGT formation. Nitration of γ-TH may involve either peroxynitrite or some peroxynitrite-derived oxidant other than NO₂⁺. Because of its stability and formation as a novel product of the reaction between γ-TH with peroxynitrite, NGT may be a useful in vivo marker for peroxynitrite interactions with lipid structures that contain γ-TH.