Cocrystal Engineering of Low-Melting-Point Pesticides for Replacement of Emulsifiable Concentrates: A Scalable...

Emulsifiable concentrates (ECs) are a major source of pesticide-derived volatile organic compound (VOC) emissions and environmental toxicity due to their reliance on hazardous organic solvents. Despite global regulatory efforts to promote water-based alternatives, ECs still account for 25% of the market, primarily due to formulation challenges associated with low-melting-point active ingredients. Here, we present a scalable crystal engineering strategy to address this bottleneck. A cocrystal of the low-melting-point fungicide difenoconazole (DZ) and thiophanate-methyl (TM) was synthesized via liquid-assisted grinding, achieving a melting point of 131 °C, 71 °C higher than that of the DZ and TM mixture. The elevated melting point ensures the thermal stability of the suspension, preventing paste-like caking during storage and enabling the formulation of stable water-based suspension concentrates (SCs) with significantly improved fluidity. The viscosity of the cocrystal SCs (105 mPa·s) was 53-fold lower than that of the physical mixture SCs (5600 mPa·s). The cocrystal also exhibits enhanced bioactivity and a 6-fold increase in foliar adhesion, improving pesticide efficiency and reducing environmental runoff. To support industrial implementation, the process was successfully scaled up to the kilogram level using simple batch crystallization under ambient conditions. As regulatory frameworks continue to tighten, this approach offers a practical and industrially feasible path to replace solvent-based formulations. If widely adopted, it could mitigate an estimated hundreds, or even thousands, of kilotons of VOC emissions annually, marking a significant step toward a sustainable agriculture system.