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

• Published in: Journal of molecular structure Vol. 1320; p. 139719
• Main Authors: Zhu, Yujing, Wang, Lin, Li, Jiangying, Shi, Xiaoju, Deng, Zongwu, Zhang, Hailu
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15-01-2025
• Subjects: Crystal structure; Hesperetin; Pharmaceutical cocrystal; Polymorphism; Thermodynamic relationship; Thermodynamic relationship; Pharmaceutical cocrystal; Hesperetin; Polymorphism; Crystal structure
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.139719

•A novel flavonoid–BPY cocrystal polymorphic system was obtained.•Rotatable C—C bonds lead to distinct chain structures in the two crystalline forms.•The two cocrystals are in monotropic relationship and Form Ⅱ is more thermodynamically stable than Form Ⅰ.
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···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.
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