Rational polymorph design to enhance isoxaflutole herbicidal performance and enable dosage reduction

Abstract BACKGROUND Improving herbicidal efficiency while avoiding excessive application remains a long‐standing challenge for reducing the environmental footprint of modern agrochemicals. Isoxaflutole (IFT), a highly effective herbicide increasingly used with IFT‐tolerant crops, has raised concerns because both IFT and its primary metabolite diketonitrile (DKN) have been detected in surface waters approaching regulatory thresholds. Here, we report a crystal chemistry strategy that intrinsically improves IFT performance without incorporating additional chemical components. RESULTS A novel polymorph, designated as Form II, was developed through rational crystal‐structure design guided by systematic analysis of the physicochemical and solid‐state factors governing IFT behavior. Accessed via a solvent‐free melt crystallization process, Form II exhibits greater chemical stability, aqueous solubility, and lipophilicity than the commercial Form I, collectively contributing to reduced environmental losses and enhanced plant uptake. Structural analysis reveals that the absence of intermolecular C–H···N contacts and lower lattice energy in Form II underpin its superior chemical stability and solubility. Bioassays against Echinochloa crus‐galli (L.) P. Beauv. demonstrate that Form II achieves two‐fold higher efficacy in soil application (median effective dose (ED 50 ): 3.00 versus 5.88 g AI ha −1 ) and six‐fold higher efficacy in foliar application (ED 50 : 0.17 versus 1.11 g AI ha −1 ) relative to Form I. CONCLUSION These findings highlight rational polymorph design as an effective, preventive, and atom‐economic strategy to enhance herbicide efficiency, thereby reducing IFT usage and minimizing environmental impact. © 2026 Society of Chemical Industry.