Wang Zhongyu, Fu Zhiqiang, Yu Qi, Chen Jingwen
Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, China.
Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, China.
J Environ Sci (China). 2017 Dec;62:11-21. doi: 10.1016/j.jes.2017.08.001. Epub 2017 Aug 12.
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.
由于对多溴二苯醚（PBDEs）使用的限制，替代性溴化阻燃剂（BFRs）已变得普遍。为了对这些替代品进行风险评估，需要了解它们通过细胞色素P450酶的代谢情况。我们之前已经证明密度泛函理论（DFT）能够通过揭示分子机制来预测PBDEs的代谢。在当前研究中，研究了1,2 - 双（2,4,6 - 三溴苯氧基）乙烷及结构相似的化学品与代表P450酶活性位点的化合物I模型的反应活性。DFT计算描绘了反应途径，这些途径为湿实验检测到的产物提供了合理的解释，同时还提出了无法确定的中间体。结果表明，烷基氢的夺取会导致双（2,4,6 - 三溴苯氧基）乙醇，其可能会发生水解生成2,4,6 - 三溴苯酚，一种神经毒性化合物。此外，在几种模型化合物中观察到了关于2,4,6 - 三溴苯基部分的氧化反应活性的一般模式。我们的研究为方便评估其他结构相似的BFRs的代谢提供了见解。
