Development of S-Fluxametamide for Bioactivity Improvement and Risk Reduction: Systemic Evaluation of the Novel Insecticide Fluxametamide at the Enantiomeric Level

Increasing numbers of novel pesticides have been applied in agriculture. However, traditional evaluation of pesticides does not distinguish between their enantiomers, which may lead to inaccurate results. In this study, systematic research on the chiral insecticide fluxametamide was conducted at the enantiomeric level. The methods for enantioseparation and semipreparative separation of fluxametamide enantiomers were developed. The optical rotation and absolute configuration of two enantiomers were determined, and their stability was verified in solvents and soils. Enantioselective bioactivities against four target pests (Plutella xylostella, Spodoptera exigua, Aphis gossypii, and Tetranychus cinnabarinus) were tested. Acute toxicities of fluxametamide enantiomers toward honeybees were also evaluated. S-(+)-Isomer exhibited 52.1-304.4 times and 2.5-3.7 times higher bioactivity than R-(-)-isomer and rac-fluxametamide, respectively. Meanwhile, rac-fluxametamide was more toxic than S/R-isomer, and S-(+)-isomer showed >30-fold higher acute toxicity than R-(-)-isomer. Molecular docking studies were performed with γ-aminobutyric acid receptor (GABAR) to monitor the mechanism of stereoselective bioactivity. The better Grid score of S-(+)-fluxametamide (-60.12 kcal/mol) than R-(-)-enantiomer (-56.59 kcal/mol) indicated higher bioactivity of S-(+)-isomer than of R-(-)-isomer. The dissipation of fluxametamide in cabbage, Chinese cabbage, and soil was nonenantioselective under field conditions. Development of S-(+)-fluxametamide could maintain the high-efficacy and low-risk properties, which should attract attention of producers, applicators, and managers of pesticides.