Insight into the Formation of Cocrystals of Flavonoids and 4,4′-Vinylenedipyridine: Heteromolecular Hydrogen Bonds, Molar Ratio, and Structural Analysis

Cocrystals offer an opportunity to modulate the properties of active pharmaceutical ingredients (APIs). The formation of heteromolecular hydrogen bonds is important in the prediction and formation of cocrystals. In this article, ten cocrystals of flavonoids and 4,4'-vinylenedipyridine (VDP) were synthesized and characterized. By calculating the molecular electrostatic potential surfaces (MEPS) of flavonoids and VDP, the possible heteromolecular hydrogen bonds and API/CCF ratio in the cocrystals were predicted. Single crystals of the ten cocrystals were all obtained, and their crystal structures were elaborated. After analyzing the computational data and the experimental results, it was found that the predicted results matched well with the actual situations in cocrystals when the potential number of intermolecular hydrogen-bond donors in the flavonoids are no more than two. In other cases, the situation of heteromolecular hydrogen bonds will be more complex.

Automated summary

Cocrystals offer a way to modify the properties of active pharmaceutical ingredients, with heterogeneous hydrogen bonds playing a crucial role in their prediction and formation. This study synthesized and characterized ten cocrystals of flavonoids and VDP, successfully predicting the presence of heteromolecular hydrogen bonds based on computational data and experimental results. It was found that the predicted outcomes align well with the actual situations in cocrystals, particularly when the number of intermolecular hydrogen-bond donors in the flavonoids is limited to two.