Unveiling Solubilization Mechanisms of Natural Deep Eutectic Solvents in Triazole Fungicides: COSMO-RS Calculations and Screening for Eco-Friendly, High-Efficiency Pesticide Systems

Enhancing the dissolution of lipophilic agrochemicals is paramount for addressing agricultural environmental pollution and improving utilization efficiency. This study introduced a novel methodology to enhance pesticide solubility by integrating theoretical calculations, targeted design, and high-throughput screening for the development of sustainable solvents. Natural deep eutectic solvents (NADESs) optimized for pesticide formulation were systematically designed and selectively filtered from 1768 species, exhibiting exceptional solubility for triazole fungicides identified through the conductor-like screening model for real solvents (COSMO-RS). Experimental results demonstrated a significant increase in solubility relative to water, ranging from 2.8 to 3.6 × 105 times. Molecular dynamics simulations, quantitative calculations, and property measurements elucidated van der Waals and hydrogen bonding interactions as the dominant roles of the solubilization mechanisms. Furthermore, the novel eco-friendly pesticide system, integrating triadimefon with three NADESs, exhibited a 0.87 times increase in inhibitory activity against Fusarium graminearum, accompanied by a 15.6% reduction in equilibrium surface tension and a 58.1% decrease in contact angle on wheat leaves compared to commercial emulsifiable concentrate (EC). These findings underscore the potential of NADESs-based formulations to enhance pesticide utilization efficiency with minimal impact on wheat growth indicators, higher cell survival, and increased biocompatibility, thus providing innovative strategies for sustainable agricultural design.