期刊
NEW JOURNAL OF CHEMISTRY
卷 45, 期 3, 页码 1626-1633出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0nj04113k
关键词
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资金
- Heilongjiang Provincial Health and Family Planning Research Projects [2018492]
- Joint Guidance Project of Natural Science Foundation of Heilongjiang Province [LH2019H059]
This study explores the role of hydroxyl in the synthesis of pharmaceutical cocrystals and the impact on physicochemical properties of flavonoids by combining dihydroflavonols with 4,4'-bipyridine. Two new pharmaceutical cocrystals were synthesized and characterized, showing different structures and solubilities due to the intermolecular hydrogen bonds formed by hydroxyl groups. The study indicates that hydroxyl groups play a crucial role in the self-assembly process of flavonoid pharmaceutical cocrystals, affecting the properties of active pharmaceutical ingredients.
In order to further explore the role of hydroxyl in the synthesis of pharmaceutical cocrystals and with a view to improving physicochemical properties of flavonoids, two dihydroflavonols in which 3-OH is exposed and cross-conjugated system is destroyed (dihydroquercetin (DHQ) and dihydromyricetin (DMY)) were selected to combine with 4,4 '-bipyridine (BPY) to explore the role of 3-OH of dihydroflavonol in synthetic processes of pharmaceutical cocrystals of dihydroflavonol. As a result, two new pharmaceutical cocrystals of dihydroflavonol with BPY (2(C15H12O7)center dot 3(C10H8N2), DHQ center dot BPY); and (C15H12O8 center dot 2.5(C10H8N2), DMY center dot BPY) have been synthesized and characterized. Structure analysis revealed that in DHQ center dot BPY the intermolecular hydrogen bond formed by 3-OH of DHQ with BPY participated in the formation of motifs R-6(6)(44) to form the cocrystal with helical structure. In DMY center dot BPY, the intermolecular hydrogen bond formed by 3-OH of DMY with BPY connects adjacent motifs R-4(4)(38) to form the cocrystal with layered structure. The solubility of DHQ center dot BPY is lower than that of pure DHQ, possibly because the helical structure of DHQ center dot BPY is tighter than that of nonplanar DHQ, which limits the entry of water molecules. Compared with nonplanar DMY, DMY center dot BPY with layered structure is more likely to allow water molecules to enter, which leads to the solubility of DMY center dot BPY being higher than that of pure DMY. The hygroscopic stabilities of DHQ center dot BPY and DMY center dot BPY are better than that of their corresponding parent APIs. It is possible that in DHQ center dot BPY and DMY center dot BPY, most of the hydroxyls in the A, B and C rings of DHQ and DMY are involved in the formation of intermolecular hydrogen bonds, which means the hydroxyls of DHQ center dot BPY and DMY center dot BPY are difficult to combine with moisture. This work shows that 3-OH of nonplanar dihydroflavonol can form hydrogen bonds with BPY after the destruction of the cross-conjugated system, and then form cocrystals with helical structure and layered structure, thereby having an effect on the properties of APIs. This successful study implies that the role of 3-OH in the self-assembly process of flavonoid pharmaceutical cocrystals and improving the physicochemical properties of flavonoid APIs should not be neglected in the future.
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