Quasi-isostructural order–disorder phase transitions and anisotropic thermal expansions in polymorphic crystals of a biologically active molecule with distinct solubility and dissolution rate

Abstract

Order–disorder phase transitions are common in inorganic and hybrid materials but are rare in single-component purely organic molecular crystals and are even scarcer in polymorphic crystals of biologically active molecules. Herein, we report the discovery of two polymorphic forms of a quinolone-amide-based biologically active molecule that undergo isosymmetric reversible order–disorder phase transitions at low temperatures, adopting crystal structures with low-to-high Z′ values and exhibiting anisotropic thermal expansions. These studies were supported by variable-temperature X-ray diffraction experiments on single-crystals and powders of the dimorphs and by differential scanning calorimetry experiments. While the triclinic form undergoes a dynamic order–disorder phase transition at 150 K with a thermal hysteresis of ∼10 K, the monoclinic form undergoes a similar transition at 170 K without thermal hysteresis. The molecules also experience a unique pedal-like motion. A detailed analysis of the molecular packing and energy frameworks establishes their distinctive identities, thereby describing these transitions as quasi-isostructural. The underlying mechanisms of the phase transition, molecular motion, and unusual thermal expansions are understood by examining nine sets of single-crystal X-ray diffraction data collected from 298 to 100 K for both polymorphs. Interestingly, the dimorphs display distinct equilibrium solubilities and intrinsic dissolution rates. This study offers valuable insights for establishing structure–property relationships in biologically active molecules and designing advanced materials with tunable biological and thermal properties.