Chemical and enzymatic oxidation of alkylated benzo[a]pyrenes

The chemical and enzymatic oxidations of 6-, 7- and 10-methylbenzoa]pyrenes, 6,10- and 7,10-dimethylbenzoa]pyrenes and benzoa]pyrene (BP) itself have been investigated to study the effects of alkyl substitution on the pathways of oxidation. The chemical oxidizing systems employed were Fenton's reagent ($\text{FeSO}{}_4\text{H}{}_2\text{O}{}_2$); trifluoroacetic acid-hydrogen peroxide (TFA/H₂O₂); thallium tristrifluoracetate in trifluoroacetic acid (TTFA/TFA) and H₂SO₄. The enzymatic systems were horseradish peroxidase (HRP/H₂O₂) and rat liver microsomes. The oxidations were investigated by electron paramagnetic resonance (EPR) spectroscopy to detect radical intermediates and by high performance liquid chromatography (HPLC) to separate the products. All the compounds studied produced radicals, identified as cationic species, in both H₂SO₄ and TTFA/TFA. In addition the 7-methyl-, 10-methyl- and 7,10-dimethyl-BP's produced 6-oxy radicals in some or all of the remaining oxidizing systems. Both chemically and enzymatically these same three compounds were observed to produce quinones as stable products. Microsomal oxidations gave the broadest range of products exhibiting HPLC peaks in the diol, quinone and phenol regions of the chromatograms, however, there were considerable differences between products from the individual derivatives and those from the parent molecule. 6-Methyl and 6,10-dimethyl-BP's showed no evidence of oxy radical intermediates or quinones under any set of conditions, the 6-substituent effectively blocking this oxidation pathway. The observations are consistent with the expected effects of alkyl substituents at particular positions and indicate that studies such as this one are potentially useful in better understanding oxidation and possible activation pathways of polycyclic aromatic hydrocarbons.