BIOTRANSFORMATION OF 1,2-DIHYDRONAPHTHALENE AND 1,2-DIHYDROANTHRACENEBY RAT-LIVER MICROSOMES AND PURIFIED CYTOCHROMES P-450 - FORMATION OFARENE HYDRATES OF NAPHTHALENE AND ANTHRACENE

Both 1,2-dihydroanaphthalene and 1,2-dihydroanthracene were hydroxylat ed at the benzylic (1-) or the allylic (2-) position by rat liver micr osomes and purified cytochrome E-450 enzymes to yield ''arene hydrates ''. Two other classes of metabolites were formed, the dehydrogenation products naphthalene and anthracene, and trans-1,2-dihydroxy-1,2,3,4-t etrahydronaphthalene and its anthracene analog as products of the clas sical epoxide pathway. Regioselectivity (hydroxylation at benzylic or allylic positions) and stereoselectivity (hydroxylation at pro-R or pr o-S hydrogen atoms) during metabolism of dihydroarenes to yield arene hydrates were found to be dependent upon the nature of the inducing ag ents used during pretreatment of the rats and thus the level of partic ular P-450 enzymes. This selectivity was more pronounced for anthracen e than for naphthalene. Naphthalene and anthracene were formed enzymat ically by direct dehydrogenation of the dihydro compounds rather than by dehydration of the arene hydrate metabolites. A general mechanism i nvolving the intermediacy of benzylic and resonance-stabilized allylic carbon radicals can account for the formation of both enzyme-catalyze d hydroxylation (arene hydrate) and dehydrogenation (arene) metabolite s of dihydroarene substrates.