Cocrystal Engineering of Low-Melting-Point Pesticides for Replacement of Emulsifiable Concentrates: A Scalable Strategy to Reduce Pesticide-Derived Volatile Organic Compound Emissions

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.