Zhang, Yu-nan, Zhang, Yan-fei, Liu, Li-xin, Zhang, Da-jun, Wang, Zhe, Zhang, Yu, Feng, Yan-ru, Wu, Li-li, Zhang, Lei, Liu, Ying-li, Zhang, Yun-jie, Zou, Dong-yu, Chang, Liang, Su, Xin, Cheng, Guang-dong, and Zhang, Xue-song
In order to further explore the role of Charge-assisted hydrogen bonds (CAHBs) recognition in the formation of tetrahydroberberine (THB) pharmaceutical salt/cocrystal, based on the analysis of the molecular interactions in forming unit pharmaceutical salts/cocrystal of THB and sulfophenyl acids, we speculate that hydroxyl group of sulfamic acid (SA) may cocrystallize with N atom on the quinoline ring of THB via CAHBs. Consequently, an unreported pharmaceutical salt (C 20 H 22 NO 4 ·NH 2 SO 3 , THB-SA) of the THB was designed and synthesized. The THB-SA was characterized by single crystal X-ray diffraction, XRPD and TG methods. As expected, structure analysis of the THB-SA revealed that the THB molecule binds to the SA molecule precisely through CAHBs (N+-H···O−) between the N atom on the quinoline ring and sulfonic acid group of SA in asymmetric unit of THB-SA. This successfully implemented work implies that in the preparation of THB pharmaceutical salts/cocrystals, cocrystal formers (CCFs) that can form CAHBs with THB should be selected, which will provide a facilitate way to prepare THB pharmaceutical salts/cocrystals. Image 1 • The successful preparation of THB-SA pharmaceutical salt has been verified that the formation mechanism of CAHBs in tetrahydroberberine and sulfamic acid is basically consistent with the formation mechanism of CAHBs in tetrahydroberberine and organic acids. [ABSTRACT FROM AUTHOR]