Stereoselective metabolism of 8‐and 9‐fluorobenzo[a]pyrene by rat liver microsomes: Absolute configurations of trans‐dihydrodiol metabolites

Abstract

Rat liver microsomal metabolism of 8‐fluorobenzo[a]pyrene (8‐fluoro‐BaP) generated 3‐hydroxy‐8‐fluora‐BaP, 8‐fluoro‐BaP trans‐4,5‐dihydrodiol, and 8‐fluoro‐BaP, 3,6‐quinone as major products. A minor metabolite of 8‐fluoro‐BaP was tentatively assigned as 8‐fluoro‐BaP 9,10‐dihydrodiol. Metabolism of 9‐fluorobenzo[a] pyrene (9‐fluoro‐BaP) gave 3‐hydroxy‐9‐fluoro‐BaP, 9‐fluoro‐BaP trans‐4,5‐dihydrodiol, 9‐fluoro‐BaP trans‐7,8‐dihydrodiol, and 9‐fluoro‐BaP 3,6‐quinone. All three dihydrodiol metabolites were optically active. Comparison of the circular dichroism spectra of BaP 4R,5R‐dihydrodiol, 6‐bromo‐BaP 7R,8R‐dihydrodiol, and 6‐fluoro‐BaP 7R,8R‐dihydrodiol with those of the respective dihydrodiol metabolites allowed assignments of an R,R absolute configuration to the major enantiomers of the three dihydrodiol metabolites.