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Transformation Pathways of Isomeric Perfluorooctanesulfonate Precursors Catalyzed by the Active Species of P450 Enzymes: In Silico Investigation
Fu, Zhiqiang1,2; Wang, Yong2; Wang, Zhongyu1; Xie, Hongbin1; Chen, Jingwen1
刊名CHEMICAL RESEARCH IN TOXICOLOGY
2015-03-01
DOI10.1021/tx500470f
28期:3页:482-489
收录类别SCI
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine ; Physical Sciences
类目[WOS]Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Toxicology
研究领域[WOS]Pharmacology & Pharmacy ; Chemistry ; Toxicology
关键词[WOS]FLUORINATED ORGANIC-COMPOUNDS ; ISOTOPE EFFECT PROFILES ; SPRAGUE-DAWLEY RATS ; PERFLUORINATED COMPOUNDS ; HUMAN EXPOSURE ; SUBSTITUTED N,N-DIMETHYLANILINES ; SULFONATE PRECURSORS ; INITIATED OXIDATION ; LIVER-MICROSOMES ; CYTOCHROME-P450
英文摘要As evidenced from various in vitro and in vivo studies, metabolism of perfluorooctanesulfonate (PFOS) precursors by cytochrome P450 enzymes. (CYPs) acts as an -important indirect pathway for mammal PFOS exposure. NeVertheless, the mechanism of this transformation remains largely unclarified. In this study, in silieo investigations adopting density functional theory (DFT) were performed to reveal the biotransformation of a typical PFOS precursor, N-ethyl perfluorooctane sulfonamide (N-EtPFOSA), catalyzed by the active species, of CYPs (Compound I). Results unveil that in the enzymatic environment, N-EtPFOSA is hydroxylated feasibly (reaction energy barriers Delta E = 11.4-14.5 kcal/mol) with a H atom transfer (HAT) from the ethyl C alpha to Compound I. The HAT derived C alpha radical then barrierlessly combines With the OH radical to produce a ferric-ethanolarnine intermediate. Subsequently, the ethanolamine nonenzymatically with the assistance of water molecules. The rate-limiting O-addition (Delta E = 21.2-34.0 kcal/mol) of Compound I to PFOSA initiated a novel deamination pathway that comprises O-S bond formation and S-N bond cleavage. The resulting hydroxylamine is then hydrolyzed to PFOS. In addition, the results reveal that both the N-deallcylation and deamination pathways are isomeric-specific, which is cOnsistent with experimental observations. Accordingly, DFT calculations may help uncover possible toxicological effects by predicting the biotransformation mechanisms and products of xenobioticsi by CYPs.
语种英语
WOS记录号WOS:000351326400023
引用统计
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/146092
专题中国科学院大连化学物理研究所
作者单位1.Dalian Univ Technol, Sch Environm Sci & Technol, Key Lab Ind Ecol & Environm Engn MOE, Dalian 116024, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China
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Fu, Zhiqiang,Wang, Yong,Wang, Zhongyu,et al. Transformation Pathways of Isomeric Perfluorooctanesulfonate Precursors Catalyzed by the Active Species of P450 Enzymes: In Silico Investigation[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2015,28(3):482-489.
APA Fu, Zhiqiang,Wang, Yong,Wang, Zhongyu,Xie, Hongbin,&Chen, Jingwen.(2015).Transformation Pathways of Isomeric Perfluorooctanesulfonate Precursors Catalyzed by the Active Species of P450 Enzymes: In Silico Investigation.CHEMICAL RESEARCH IN TOXICOLOGY,28(3),482-489.
MLA Fu, Zhiqiang,et al."Transformation Pathways of Isomeric Perfluorooctanesulfonate Precursors Catalyzed by the Active Species of P450 Enzymes: In Silico Investigation".CHEMICAL RESEARCH IN TOXICOLOGY 28.3(2015):482-489.
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