How PBDEs Are Transformed into Dihydroxylated and Dioxin Metabolites Catalyzed by the Active Center of Cytochrome P450s: A DFT Study | |
Department | OSSO国家重点实验室 |
Fu, Zhiqiang1; Wang Y(王永)2; Chen, Jingwen1; Wang, Zhongyu1; Wang, Xingbao3 | |
2016 | |
Source Publication | Environmental Science and Technology |
ISSN | 0013-936X |
Volume | 50Issue:15Pages:8155-8163 |
Abstract | Predicting metabolism of chemicals and potential toxicities of relevant metabolites remains a vital and difficult task in risk assessment. Recent findings suggested that polybrominated diphenyl ethers (PBDEs) can be transformed into dihydroxylated and dioxin metabolites catalyzed by cytochrome P450 enzymes (CYPs), whereas the mechanisms pertinent to these transformations remain largely unknown. Here, by means of density functional theory (DFT) calculations, we probed the metabolic pathways of 2,2′,4,4′-tetraBDE (BDE-47) using the active center model of CYPs (Compound I). Results show that BDE-47 is first oxidized to monohydroxylated products (HO-BDEs), wherein a keto–enol tautomerism is identified for rearrangement of the cyclohexenone intermediate. Dihydroxylation with HO-BDEs as precursors, has a unique phenolic H-abstraction and hydroxyl rebound pathway that is distinct from that for monohydroxylation, which accounts for the absence of epoxides in in vitro studies. Furthermore, we found only dihydroxylated PBDEs with heterophenyl −OH substituents ortho- and meta- to the ether bond serve as precursors for dioxins, which are evolved from aryl biradical coupling of diketone intermediates that are produced from dehydrogenation of the dihydroxylated PBDEs by Compound I. This study may enlighten the development of computational models that afford mechanism-based prediction of the xenobiotic biotransformation catalyzed by CYPs. |
Subject Area | 物理化学与绿色催化 |
DOI | 10.1021/acs.est.6b00524 |
Funding Organization | the National Basic Research Program (2013CB430403);the National Natural Science Foundation of China (21137001;21325729;21173211) |
Indexed By | SCI |
If | 6.198 |
Language | 英语 |
compositor | 第二作者单位 |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.licp.cn/handle/362003/20311 |
Collection | 羰基合成与选择氧化国家重点实验室(OSSO) |
Corresponding Author | Chen, Jingwen |
Affiliation | 1.Dalian Univ Technol, Sch Environm Sci & Technol, Key Lab Ind Ecol & Environm Engn MOE, Dalian 116024, Peoples R China 2.Chinese Acad Sci, LICP, Suzhou Res Inst, State Key Lab Oxo Synth & Select Oxidat, Lanzhou 730000, Peoples R China 3.Dalian Univ Technol, Sch Pharmaceut Sci & Technol, State Key Lab Fine Chem, Dalian 116024, Peoples R China |
Recommended Citation GB/T 7714 | Fu, Zhiqiang,Wang Y,Chen, Jingwen,et al. How PBDEs Are Transformed into Dihydroxylated and Dioxin Metabolites Catalyzed by the Active Center of Cytochrome P450s: A DFT Study[J]. Environmental Science and Technology,2016,50(15):8155-8163. |
APA | Fu, Zhiqiang,Wang Y,Chen, Jingwen,Wang, Zhongyu,&Wang, Xingbao.(2016).How PBDEs Are Transformed into Dihydroxylated and Dioxin Metabolites Catalyzed by the Active Center of Cytochrome P450s: A DFT Study.Environmental Science and Technology,50(15),8155-8163. |
MLA | Fu, Zhiqiang,et al."How PBDEs Are Transformed into Dihydroxylated and Dioxin Metabolites Catalyzed by the Active Center of Cytochrome P450s: A DFT Study".Environmental Science and Technology 50.15(2016):8155-8163. |
Files in This Item: | ||||||
File Name/Size | DocType | Version | Access | License | ||
acs.est.6b00524.pdf(2322KB) | 期刊论文 | 作者接受稿 | 开放获取 | CC BY-NC-SA | View Application Full Text |
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment