title: Cytochrome P-450-catalyzed rearrangement of a peroxyquinol derived from butylated hydroxytoluene. Involvement of radical and cationic intermediates.
abstract: The p-peroxyquinol derived from butylated hydroxytoluene, 2,6-di-t-butyl-4-hydroperoxy-4-methyl-2,5-cyclohexadienone, was degraded by the ferric form of rat liver cytochrome P-450, and the resulting products and their mechanisms of formation were investigated. Quinoxy radical BO. from homolysis of the O-O bond reacted by competing pathways; beta-scission yielded 2,6-di-t-butyl-p-benzoquinone, and rearrangement with ring-expansion produced an oxacycloheptadienone free radical (X(.)). This rearranged radical was stabilized by the captodative effect that facilitated competitive interactions with the P-450 iron-oxo complexes formed during O-O bond scission. Approximately 15% of X(.) was captured by oxygen rebound with a hydroxyl radical from the P-450 complex (FeOH)3+ to form a hemiketal, that led to the ring-contracted product 2,5-di-t-butyl-5-(2'-oxopropyl)-4-oxa-2-cyclopentenone by spontaneous rearrangement. The major fraction of X(.), however, underwent electron transfer oxidation to form the corresponding cation. Hydration of this cation produced the ring-contracted product, and proton elimination (or, alternatively, direct H(.) removal from X(.) led to the product 2,7-di-t-butyl-4-methylene-5-oxacyclohepta-2,6-dienone. The findings indicate that cytochrome P-450 intermediate complexes are mainly responsible for oxidation of X(.). The results complement our previous study with 2,6-di-t-butyl-4-hydroperoxy-4-methyl-2,5-cyclohexadienone (Thompson, J. A., and Wand, M. D. (1985) J. Biol. Chem. 260, 10637-10644), demonstrating competitive heterolytic and homolytic mechanisms of O-O bond cleavage, and competitive rebound and oxidation processes when a substrate-derived radical interacts with P-450 complexes.
mesh_terms: D000818:Animals; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008433:Mathematics; D010545:Peroxides / Q000378:metabolism*; D011809:Quinones; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005609:Free Radicals; D010545:Peroxides; D011809:Quinones; D002084:Butylated Hydroxytoluene; C046508:2,6-di-tert-butyl-4-hydroperoxy-4-methyl-2,5-cyclohexadienone; D003577:Cytochrome P-450 Enzyme System