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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
Source PublicationCHEMICAL RESEARCH IN TOXICOLOGY
2015-03-01
DOI10.1021/tx500470f
Volume28Issue:3Pages:482-489
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Physical Sciences
WOS SubjectChemistry, Medicinal ; Chemistry, Multidisciplinary ; Toxicology
WOS Research AreaPharmacology & Pharmacy ; Chemistry ; Toxicology
WOS KeywordFLUORINATED ORGANIC-COMPOUNDS ; ISOTOPE EFFECT PROFILES ; SPRAGUE-DAWLEY RATS ; PERFLUORINATED COMPOUNDS ; HUMAN EXPOSURE ; SUBSTITUTED N,N-DIMETHYLANILINES ; SULFONATE PRECURSORS ; INITIATED OXIDATION ; LIVER-MICROSOMES ; CYTOCHROME-P450
AbstractAs 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.
Language英语
WOS IDWOS:000351326400023
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/146092
Collection中国科学院大连化学物理研究所
Affiliation1.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
Recommended Citation
GB/T 7714
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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