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论文类型：期刊论文

发表时间：2015-03-01

发表刊物：CHEMICAL RESEARCH IN TOXICOLOGY

收录刊物：SCIE、PubMed、Scopus

卷号：28

期号：3,SI

页面范围：482-489

ISSN号：0893-228X

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.