{"title":"Quantum chemical simulations revealed the toxicokinetic mechanisms of organic phosphorus flame retardants catalyzed by P450 enzymes.","authors":"Zhiqiang Fu, Jingwen Chen, Yong Wang, Huixiao Hong, Hongbin Xie","doi":"10.1080/10590501.2018.1537564","DOIUrl":null,"url":null,"abstract":"<p><p>The metabolic fate and toxicokinetics of organic phosphorus flame retardants catalyzed by cytochrome P450 enzymes (CYPs) are here investigated by in silico simulations, leveraging an active center model to mimic the CYPs, triphenyl phosphate (TPHP), tris(2-butoxyethyl) phosphate and tris(1,3-dichloro-2-propyl) phosphate as substrates. Our calculations elucidated key main pathways and predicted products, which were corroborated by current in vitro data. Results showed that alkyl OPFRs are eliminated faster than aryl and halogenated alkyl-substituted OPFRs. In addition, we discovered a proton shuttle pathway for aryl hydroxylation of TPHP and P = O bond-assisted H-transfer mechanisms (rather than nonenzymatic hydrolysis) that lead to O-dealkylation/dearylation of phosphotriesters.</p>","PeriodicalId":51085,"journal":{"name":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","volume":"36 4","pages":"272-291"},"PeriodicalIF":0.0000,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10590501.2018.1537564","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/10590501.2018.1537564","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2018/11/20 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 2
Abstract
The metabolic fate and toxicokinetics of organic phosphorus flame retardants catalyzed by cytochrome P450 enzymes (CYPs) are here investigated by in silico simulations, leveraging an active center model to mimic the CYPs, triphenyl phosphate (TPHP), tris(2-butoxyethyl) phosphate and tris(1,3-dichloro-2-propyl) phosphate as substrates. Our calculations elucidated key main pathways and predicted products, which were corroborated by current in vitro data. Results showed that alkyl OPFRs are eliminated faster than aryl and halogenated alkyl-substituted OPFRs. In addition, we discovered a proton shuttle pathway for aryl hydroxylation of TPHP and P = O bond-assisted H-transfer mechanisms (rather than nonenzymatic hydrolysis) that lead to O-dealkylation/dearylation of phosphotriesters.
期刊介绍：
Journal of Environmental Science and Health, Part C: Environmental Carcinogenesis and Ecotoxicology Reviews aims at rapid publication of reviews on important subjects in various areas of environmental toxicology, health and carcinogenesis. Among the subjects covered are risk assessments of chemicals including nanomaterials and physical agents of environmental significance, harmful organisms found in the environment and toxic agents they produce, and food and drugs as environmental factors. It includes basic research, methodology, host susceptibility, mechanistic studies, theoretical modeling, environmental and geotechnical engineering, and environmental protection. Submission to this journal is primarily on an invitational basis. All submissions should be made through the Editorial Manager site, and are subject to peer review by independent, anonymous expert referees. Please review the instructions for authors for manuscript submission guidance.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
