Rui Li,Yanqing Zhang,Yanhong Li,Zihao Chen,Zhen Wang,Minghua Wang
As a chiral piperidine fungicide, fenpropidin has been widely used to control plant diseases. However, there are rare studies that have investigated fenpropidin at the enantiomer level. In this study, the single-factor analysis combined with a Box-Behnken design was used to obtain the optimal enantio-separation parameters of the fenpropidin enantiomers on ultra-performance liquid chromatography-tandem mass spectrometry. The absolute configuration of two fenpropidin enantiomers was confirmed for the first time using electron circular dichroism and optical activity. On the Lux cellulose-3 column,S-(-)-fenpropidin flowed out beforeR-(+)-fenpropidin. The enantio-separation mechanism was revealed by molecular docking. A modified QuEChERS method was developed for the trace determination of the fenpropidin enantiomers in seven food and environmental substrates. The average recoveries were 71.5–106.1% with the intra-day and inter-day relative standard deviations of 0.3–8.9% and 0.5–8.0%. The method was successfully verified by enantioselective dissipation of fenpropidin in soil under the field.R-(+)-fenpropidin dissipated faster thanS-(-)-fenpropidin, and the half-lives were 19.8 d and 22.4 d. This study established a brand-new effective chiral analysis method for the fenpropidin enantiomers, providing a basis for accurate residue monitoring and the risk assessment of fenpropidin.Keywords:fenpropidin;enantio-separation;absolute configuration;Box-Behnken design;enantioselective dissipation;molecular docking
Rui Li,Yingying Wu,Nuanhui Wen,Wenjie Wei,Wei Zhao,Yanhong Li,Liangliang Zhou,Minghua Wang
Fenpropidin (FPD), a widely employed chiral fungicide, is frequently detected in diverse environments. In an in vitro rat liver microsomes cultivation (RLMs), the metabolism exhibited the order of R -FPD > S -FPD, with respective half-lives of 10.42 ± 0.11 and 12.06 ± 0.15 min, aligning with kinetic analysis results. CYP3A2 has been demonstrated to be the most significant oxidative enzyme through CYP450 enzyme inhibition experiments. Molecular dynamics simulations unveiled the enantioselective metabolic mechanism, demonstrating that R -FPD forms hydrogen bonds with the CYP3A2 protein, resulting in a higher binding affinity (−6.58 kcal mol −1 ) than S -FPD. Seven new metabolites were identified by Liquid chromatography time-of-flight high-resolution mass spectrometry, which were mainly generated through oxidation, reduction, hydroxylation, and N-dealkylation reactions. The toxicity of the major metabolites predicted by the TEST procedure was found to be stronger than the predicted toxicity of FPD. Moreover, the enantioselective fate of FPD was studied by examining its degradation in three soils with varying physical and chemical properties under aerobic, anaerobic, and sterile conditions. Enantioselective degradation of FPD occurred in soils without enantiomeric transformation, displaying a preference for R -FPD degradation. R -FPD is a low-risk stereoisomer both in the environment and in mammals. The research presented a systematic and comprehensive method for analyzing the metabolic and degradation system of FPD enantiomers. This approach aids in understanding the behavior of FPD in the environment and provides valuable insights into their potential risks to human health.
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