Oxidation of 9-alkylanthracenes by P450 2B1, horseradish peroxidase, and iron tetraphenylporphine iodosylbenzene systems: Anaerobic and aerobic mechanisms

Variously substituted alkylanthracenes were studied as models for polycyclic hydrocarbon oxidations; 9-Methylanthracene was oxidized to 9-(hydroxymethyl)anthracene, 10-methyl-10-hydroxy-9-anthrone, and anthraquinone in several systems, including (i) NADPH- and O-2-fortified rat liver microsomes, (ii) cytochrome P450 (P450) 2B1 supported by either iodosylbenzene (PhIO) or a mixture of NADPH-P450 reductase, NADPH, and O-2, (iii) horseradish peroxidase and either H2O2 or ethyl hydroperoxide, and (iv) a mixture of iron tetraphenylporphine (FeTPP) and PhIO (in anhydrous CH2Cl2/MeOH). The microsomal system also formed dihydrodiols from 9-methyl- and 9-ethylanthracenes. The formation of the three oxidized products by the P450/NADPH/O-2 system was dependent upon O-2, label from O-18(2) was incorporated into the products, and no label from (H2O)-O-18 was incorporated. No label from O-18(2) was incorporated into the three products in the FeTPP/PhIO system. In the horseradish peroxidase/H2O2 system, the formation of the three products was decreased when O-2 was omitted, and label from both (H2O)-O-18 and O-18(2) was incorporated into all three products. The results are interpreted in terms of three mechanisms. One is used by the FeTPP and P450 systems, with all oxygen transfers coming from an FeO entity. The other two pathways are utilized by horseradish peroxidase and begin with formation of a radical cation, which can undergo reactions either with H2O or with O-2 to form the products detected here. The involvement of a 9-methylanthracene radical cation in the P450 and FeTPP pathways is a possibility, but rapid rearrangement and oxygen rebound must be invoked. Comparisons of products from various 9-alkylanthracenes do not provide evidence that one-electron oxidation is an integral part of the epoxidation process with these compounds. The significance of the lack of trapping of' radical (by (H2O)-O-18) in the P450 reactions to DNA adduct formation is considered.