Oxidation of 9-alkylanthracenes by cytochrome 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 O2-fortified rat liver microsomes, (ii) cytochrome P450 (P450) 2B1 Supported by either iodosylbenzene (PhIO) or a mixture of NADPH-P450 reductase, NADPH, and O2, (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/O2 system was dependent upon O2 label from 18O2 was incorporated into the products, and no label from H2(18O) was incorporated. No label from 18O2 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 O2 was omitted, and label from both H2(18)O and 18O2 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 O2 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 H2(18O) in the P450 reactions to DNA adduct formation is considered.
Anzenbacher
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P
Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232-0146, USA.
Niwa
T
T
Tolbert
L M
LM
Sirimanne
S R
SR
Guengerich
F P
FP
D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D000873:Anthracenes / Q000737:chemistry / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000378:metabolism*; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011083:Polycyclic Compounds / Q000737:chemistry / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism*; D051381:Rats; D013250:Steroid Hydroxylases / Q000378:metabolism*
D000873:Anthracenes; D011083:Polycyclic Compounds; D011166:Porphyrins; C016136:tetraphenylporphine sulfonate; D003577:Cytochrome P-450 Enzyme System; D006735:Horseradish Peroxidase; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C025619:steroid 16-beta-hydroxylase