New Salts And Cocrystals Of Pymetrozine With Improvements On Solubility And Humidity Stability: Experimental And Theoretical Study

For the purpose of enhancing the solubility and humidity stability of pymetrozine (PMZ), a highly active but nonbiocidal pesticide, new multicomponent crystals were developed based on the connotation of crystal engineering. In the coformer screening process, a combined method, the Conductor-like Screening Model for Realistic Solvents (COSMO-RS) approach together with Cambridge Structural Database (CSD) analysis, was employed to shorten the screening process. Further, seven single crystals of PMZ's new multicomponent solids were obtained including three cocrystals and four salts. Single-crystal X-ray diffraction together with Hirshfeld surface analysis clarified the detailed structure and the molecular interactions in these new crystals. Thermodynamic properties and spectral data were characterized by thermogravi-metric analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. Hygroscopicity and solubility of the seven cocrystals/salts were investigated by dynamic vapor sorption and equilibrium solubility measurement, respectively. Multicomponent crystals not only exhibit better stability against humidity and but also higher water solubility than PMZ. Meanwhile, the insecticidal activity of PMZ was preserved during the formation of cocrystals/salts. On this basis, we conducted the atoms-in-molecules (AIM) analysis and the molecular electrostatic potential surfaces (MEPs) analysis to assess the strength of hydrogen bonds and reveal the origins of salt/cocrystal formation. So, the variations and origins of these physicochemical properties were rationalized and explained on the atomic scale. On the whole, the efficiency of the novel combined coformers screening method was verified and new multicomponent crystalline forms of PMZ were successfully obtained to prevent the parent compound from hydrating transformation.