The mechanism of the reductive dehalogenation of polyhalogenated compounds by microsomal cytochrome P450

Polyhalogenated ethanes are metabolized by reductive dehalogenation under anaerobic and also hypoxic conditions in vitro in the presence of NADPH and hepatic microsomal cytochrome P450. The cytochrome P450 dependence was shown by induction and inhibition experiments using microsomal fractions from livers of rats receiving various pretreatments. The main products of the in vitro metabolism of hexa- and pentachloroethane were tetra- and trichloroethene, respectively. Minor products were penta- (0.5%) and 1.1.2.2.-tetrachloroethane (4%). The stoichiometry of NADPH-oxidation and product formation was 1:1. From these results and earlier investigations on polyhalogenated methanes, a reaction scheme is proposed. The reductive dehalogenation probably proceeds by two sequential one electron reductions forming first a radical and then a carbanion. The carbanion may undergo protonation, alpha-, or beta-elimination forming a monodehalogenated haloalkane, an olefin or a carbene, respectively.