3d-Qsar-Based Molecular Design and One-Step Dialysis Self-Assembled Synthesis of Amphiphilic-Balance Phenylpyrazole Amide Nano-Micelles for Reducing the Toxicities, Enhancing Bioactivity and Natural Sunlight Degradation Properties

Abstract

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. Amphiphilic-balance nano-micelles obtained by noncovalent interactions improve the mobility of plant phloem and directly controlled pests without using surfactants. The biological activity test indicated nano-micelles didn’t affect the cocoon cultivation rate of silkworms and enhance the control effect of silkworm belly parasitic fly. The LC50 of PE5 NMs to silkworms was lower 24.8 times that of fipronil and the toxicity to non-target organisms and silkworms was greatly reduced with good ecological compatibility. The insecticidal activity of PE5 and PE5 NMs against P. xylostella was 2.15 times and 5.2 times that of fipronil respectively. Under simulated natural sunlight irradiation, nano-micelles exhibited good photo-self-degradation properties and converted into phenylpyrazole parent fragments, thereby improving biological activity and reducing residues and environmental pollution. Reversed-phase HPLC confirmed the introduction of amide units improved the lipophilic properties, which formed a balance between hydrophilic and lipophilic properties after self-assembly, 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 were preliminarily verified. Thereby, nano self-assembly technology promotes modern pesticide development for reducing the toxicities and residues to ecology and environment.

Keywords: amphiphilic balanced nano-micelles pesticides, one-step dialysis self-assemble, 3D-QSAR, phenylpyrazole amide derivatives, bioactivity, natural sunlight degradation properties