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Indexed by:期刊论文

Date of Publication:2015-02-01

Journal:CHEMOSPHERE

Included Journals:SCIE、EI、PubMed

Volume:120

Page Number:631-636

ISSN No.:0045-6535

Key Words:P450 enzymes; Methoxylated polybrominated diphenyl ethers; Biotransformed; Density functional theory calculations

Abstract: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. (c) 2014 Elsevier Ltd. All rights reserved.