MP8-dependent oxidative dehalogenation: evidence for the direct formation of 1,4-benzoquinone from 4-fluorophenol by a peroxidase-type of reaction pathway.

The present study shows that MP8 in the presence of H2O2 is able to catalyze the rupture of the stable carbon-fluorine bond of 4-fluorophenol, used as a model substrate for the oxidative dehalogenation reaction. 1,4-Benzoquinone was shown to be the primary reaction product. It is also demonstrated that there was significant [18O] incorporation into the product, 1,4-benzoquinone, from 18O-labelled H2(18)O but not from H2(18)O2. This implies that water participates in the reaction mechanism, and acts as a source for the oxygen atom inserted into the product. It also suggests that the reaction is not a result of direct oxygen transfer from H2O2 through the heme catalyst to the product. Furthermore, ascorbic acid, known to efficiently block MP8-catalyzed peroxidase-type conversions, inhibits the MP8-dependent dehalogenation reaction, most likely because of its ability to reduce the phenoxy radical back to the parent substrate. This observation together with the above-mentioned incorporation of oxygen from the solvent into the benzoquinone product indicates that MP8 dehalogenates 4-fluorophenol and converts it to 1,4-benzoquinone in a peroxidase- and not a P-450-type of reaction mechanism. Overall, our results indicate that the oxidative dehalo genation of para-halogenated phenols, resulting in the formation of benzoquinones, is not specific only for cytochrome P-450 enzymes. Hemoproteins exhibiting peroxidase activity could also play a role in the metabolism of these xenobiotics, resulting in the formation of electrophilic reactive benzoquinone type metabolites.