Hesperetin-4,4′-bipyridine cocrystal: Polymorphism, crystal structures, and thermodynamic relationship

The investigation of cocrystal polymorphism remains relatively limited compared to that of single-component crystals. This study focuses on the cocrystallization of hesperetin (HES), a typical flavonoid substance, with 4,4 '-bipyridine (BPY), resulting in the formation of two distinct 1:1 cocrystal phases. Single crystal X-ray diffraction analysis reveals that the O-H<middle dot><middle dot><middle dot>N hydrogen interaction serves as the hetero-synthon of the cocrystals, driving the formation of featured 1D molecular chains in both structures. The presence of rotatable C-C bonds in both HES and BPY introduces the possibility of the molecular conformational variations, contributing to differing molecular stacking arrangements between the two structures. Thermal analysis, solvent-mediated polymorphic transformation, and theoretical calculations confirm a monotropic relationship between the two cocrystals.