Study on Structure, Stability, and Phase Transformation of Dufulin Polymorphs

Although plant virus disease is destructive for economic losses of agricultural production, few studies focus on the field of solid state of pesticides. Dufulin (DFL) is a novel plant antiviral agent with high efficiency but low solubility and is easy to agglomerate during the process of crystallization. In this paper, the polymorphism behavior of DFL was systematically studied. Five polymorphs (Forms I–IV and VI), a solvate (Form V) and an amorphous form were discovered and characterized by powder X-ray diffraction and thermal analytical methods. Single crystals of Forms I, III, IV, V, and VI were obtained and their structures were identified by single-crystal X-ray diffraction. Based on the results of stability experiments (solid-state stability and solvent-mediated transition), thermal analysis methods, solubility studies and powder dissolution experiments, Form I appeared to be the thermodynamically most stable phase with the lowest solubility under ambient conditions, closely followed by Form III. In addition, the relative stability of the different crystal forms was simulated by density functional theory. As the result, the thermodynamic order of different forms was as follows: I > III > II > IV > VI > V. It is the first time that seven crystalline forms of DFL are reported, which fills the blank of DFL in the crystal engineering field and prompts the development of the formulation.