Main content area

Transformation pathways of MeO-PBDEs catalyzed by active center of P450 enzymes: A DFT investigation employing 6-MeO-BDE-47 as a case

Wang, Xingbao, Chen, Jingwen, Wang, Yong, Xie, Hongbin, Fu, Zhiqiang
Chemosphere 2015 v.120 pp. 631-636
biochemical pathways, biotransformation, chemical bonding, chemical elements, cytochrome P-450, energy, enzymes, hydroxylation, in vitro studies, models, polybrominated diphenyl ethers, toxicity, xenobiotics
Recent in vivo and in vitro experiments indicated that methoxylated polybrominated diphenyl ethers (MeO-PBDEs) can be biotransformed into hydroxylated PBDEs (HO-PBDEs) that are more toxic than PBDEs and MeO-PBDEs. Nevertheless, the enzymatic transformation mechanism is not clear. We hypothesized that cytochrome P450 enzymes (CYPs) play a key role in the transformation and employed the density functional theory calculations to unveil the mechanism. The transformation of a model compound, 6-MeO-BDE-47, catalyzed by the active center of CYPs (Compound I), was computed. For the first time, our results show that the energy barriers for the addition of Compound I to the C atoms on the phenyl of 6-MeO-BDE-47 are much higher than that for hydroxylation of the methoxyl, indicating that O-demethylation is a dominating metabolic pathway. This is in line with experimental observations performed by others. The pathways for the transformation of 6-MeO-BDE-47 catalyzed by Compound I were clarified. A C–H bond of the methoxyl is activated by Compound I, followed by radical rebound to form carbinol intermediates, then the carbinols decompose to form 6-HO-BDE-47 with the assistance of water molecules. The computational method can be potentially employed to develop models that predict biotransformation of xenobiotics catalyzed by CYPs.