Biotransformation Mechanism of Pesticides by Cytochrome P450: A DFT Study on Dieldrin | |
Chai, Lihong; Ji, Shujing; Zhang, Shubin1,5; Yu, Haiying2; Zhao, Meirong3; Ji, Li1 | |
刊名 | CHEMICAL RESEARCH IN TOXICOLOGY |
2020 | |
卷号 | 33期号:6页码:1442-1448 |
关键词 | C-H HYDROXYLATION AB-INITIO HYDROGEN ABSTRACTION HUMAN METABOLISM DRUG-METABOLISM COMPOUND-I ENZYMES POTENTIALS POPULATION PREDICTION |
ISSN号 | 0893-228X |
DOI | 10.1021/acs.chemrestox.0c00013 |
英文摘要 | Pesticide biotransformation, especially by cytochrome P450 enzymes (CYPs), may produce metabolites with substantially altered toxicological and physicochemical profiles, which has drawn great attention as a basis for environmental risk assessment. CYPs are active in the metabolism of various reactions of pesticides, and there are potentially different short-lived oxidant species in CYPs (Compound I vs Compound 0), which make elucidating their biotransformation mechanism challenging. To facilitate this task, we performed density functional theory (DFT) calculations to explore the puzzling bifurcation pathways of dieldrin by CYPs. The results show that the two-oxidant mechanism does not work, while the bifurcation pathways are within the mechanistic framework of a two-state reactivity of Compound I. Specifically, 9-hydroxy-dieldrin as a hydroxylation product is formed via H-abstraction and essentially barrierless C-9 alkyl radical rebound in the doublet state; while 3-ketone-dieldrin as a dechlorination product is formed via H-abstraction, C-9 alkyl radical cyclization, and C-3 cyclized radical rebound in the quartet state followed by HCl elimination, originating from a significant barrier for C-9 alkyl radical rebound in the quartet state to provide this radical sufficient lifetime for cyclization. Thus, the ratio [dechlorination]/[hydroxylation] can be estimated as 1:35, consistent with the experimental findings. We envision that application of computational chemistry has a great potential in revealing the complex biotransformation mechanisms of pesticides. |
学科主题 | Pharmacology & Pharmacy ; Chemistry ; Toxicology |
语种 | 英语 |
WOS记录号 | WOS:000541877700017 |
内容类型 | 期刊论文 |
源URL | [http://ir.xtbg.org.cn/handle/353005/11764] |
专题 | 西双版纳热带植物园_支撑系统 |
作者单位 | 1.Zhejiang Univ, Coll Environm & Resource Sci, MOE Key Lab Environm Remediat & Ecosyst Hlth, Hangzhou 310058, Peoples R China 2.Chinese Acad Sci, CAS Key Lab Trop Forest Ecol, Xishuangbanna Trop Bot Garden, Mengla 666303, Yunnan, Peoples R China 3.Zhejiang Normal Univ, Coll Geog & Environm Sci, Jinhua 321004, Zhejiang, Peoples R China 4.Zhejiang Univ Technol, Coll Environm, Hangzhou 310032, Peoples R China 5.Kyoto Univ, Grad Sch Agr, Kyoto 6068502, Japan |
推荐引用方式 GB/T 7714 | Chai, Lihong,Ji, Shujing,Zhang, Shubin,et al. Biotransformation Mechanism of Pesticides by Cytochrome P450: A DFT Study on Dieldrin[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2020,33(6):1442-1448. |
APA | Chai, Lihong,Ji, Shujing,Zhang, Shubin,Yu, Haiying,Zhao, Meirong,&Ji, Li.(2020).Biotransformation Mechanism of Pesticides by Cytochrome P450: A DFT Study on Dieldrin.CHEMICAL RESEARCH IN TOXICOLOGY,33(6),1442-1448. |
MLA | Chai, Lihong,et al."Biotransformation Mechanism of Pesticides by Cytochrome P450: A DFT Study on Dieldrin".CHEMICAL RESEARCH IN TOXICOLOGY 33.6(2020):1442-1448. |
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