3D-QSAR-based molecular design and one-step dialysis self-assembled synthesis of amphiphilic-balance phenylpyrazole amide nano-micelles for enhancing bioactivity and degradation properties

Abstract

Pesticide nano-preparation is an effective way to improve the utilization efficiency and reduce the environmental pollution. As a broad-spectrum and efficient insecticide acting on GABA receptors, fipronil is strictly limited due to its high toxicity to non-targets. To pursue novel nano-insecticides with high activity and unique mode of action on GABA receptor, under 3D-QSAR guide, a series of phenylpyrazole amide derivatives were synthesized by one-pot solvothermal method and three amphiphilic-balance phenylpyrazole amide nano-micelles were fabricated by dialysis self-assembly method. The nano-micelles improve the mobility of plant phloem and directly controlled pests without using surfactants. Bioassays demonstrated the nano-micelles preserved silkworm cocooning rates while enhanced parasitic fly control. The LC₅₀ of PE₅ NMs to silkworm was 24.8 times lower than that of fipronil, indicating markedly reduced non-target toxicity and superior ecological safety. The insecticidal activity of PE₅ and PE₅ NMs against P. xylostella respectively was 2.15 times and 5.2 times that of fipronil. Under simulated natural sunlight irradiation, PAs, PBs and PEs exhibited good photo-self-degradation properties and converted into phenylpyrazole parent fragments, enhancing bioactivity while reducing residues and environmental impact. Reversed-phase HPLC confirmed the introduction of amide units improved the lipophilic properties, improving phloem mobility. Due to its low surface tension, low PDI, strong negative charge and excellent stability, nano-micelles increase the wettability of pesticides and improve the effective utilization rate. Through molecular stacking, molecular docking, and Hirshfeld surface analysis, the intermolecular interaction and strong interaction with GABA receptor of P. xylostella preliminarily verified.

Keywords: 3D-QSAR; Amphiphilic balanced nano-micelles pesticides; Bioactivity; Natural sunlight degradation properties; One-step dialysis self-assemble; Phenylpyrazole amide derivatives.