Oxidation reactivity of 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) by Compound I model of cytochrome P450s

Alternative brominated flame retardants (BFRs) have become prevalent as a consequence of restrictions on the use of polybrominated diphenyl ethers (PBDEs). For risk assessment of these alternatives, knowledge of their metabolism via cytochrome P450 enzymes is needed. We have previously proved that density functional theory (DFT) is able to predict the metabolism of PBDEs by revealing the molecular mechanisms. In the current study, the reactivity of 1,2-bis(2,4,6-tribromophenoxy)ethane and structurally similar chemicals with the Compound I model representing the active site of P450 enzymes was investigated. The DFT calculations delineated reaction pathways which lead to reasonable explanations for products that were detected by wet experiments, meanwhile intermediates which cannot be determined were also proposed. Results showed that alkyl hydrogen abstraction will lead to bis(2,4,6-tribromophenoxy)ethanol, which may undergo hydrolysis yielding 2,4,6-tribromophenol, a neurotoxic compound. In addition, a general pattern of oxidation reactivity regarding the 2,4,6-tribromophenyl moiety was observed among several model compounds. Our study has provided insights for convenient evaluation of the metabolism of other structurally similar BFRs.