Mechanisms of hydroxylation by cytochrome P-450: metabolism of monohalobenzenes by phenobarbital-induced microsomes.

作者：Leo T. Burka, T M Plucinski, Timothy L. Macdonald · 发表于：Proceedings of the National Academy of Sciences · 年份：1983 · DOI：10.1073/pnas.80.21.6680 · 被引用次数：53 · 研究领域：Pharmacogenetics and Drug Metabolism、Chemical Reactions and Isotopes、Eicosanoids and Hypertension Pharmacology

The monohydroxylation of halobenzenes by phenobarbital-induced rat liver microsomes was studied. The p-halophenol was found to be the major metabolite from all four halobenzenes; o-halophenol formation decreased as the halogen atom size increased. Vmax for total hydroxylation (ortho and para products) correlated well with the sigma + Hammett constant with a negative rho value. This implies a positively charged intermediate in the rate-determining step. Vmax for either ortho or para hydroxylation alone did not correlate with a Hammett constant, implying that the product-determining step occurs after the rate-determining step. Rate-determining formation of a radical cation intermediate is postulated to explain this data.