Peroxyl radical oxidation of beta-carotene: formation of beta-carotene epoxides.

A chemical model system was used to study peroxyl radical trapping reactions of beta-carotene (1) that may contribute to its antioxidant action in biological systems. Peroxyl radicals generated in hexane by thermolysis of azobis(2,4-dimethylvaleronitrile) (AMVN) at 37 degrees C oxidized 1 to 5,6-epoxy-beta,beta-carotene (2) and a previously unreported product, 15,15'-epoxy-beta,beta-carotene (6), in addition to several unidentified polar products. The epoxide products were purified by high-performance liquid chromatography and characterized by UV-vis spectroscopy, mass spectrometry, and 1H NMR. Epoxides 2 and 6 and the polar products were formed together from the initial stages of the reaction. As the reaction progressed, the epoxides were oxidized further to more polar products. Although epoxides 2 and 6 were formed at similar rates, 2 was oxidized more rapidly than 6. Incubations with [14C]-1 indicate that at their maximum concentrations 2 and 6 account for approximately 20% of the radiolabeled oxidation products. Epoxide formation may result from peroxyl radical addition to the polyene chain to form a resonance-stabilized peroxyl radical adduct. Peroxide bond scission would yield the epoxide and release an alkoxyl radical. Although this two-step sequence produces no net radical trapping, it could produce a kinetically significant inhibition of peroxyl radical propagation and account, in part, for the antioxidant properties of 1. Epoxides 2 and 6 are structurally distinct from retinoids, which are the metabolic products of 1, and therefore may be useful biochemical markers for its antioxidant actions.