Zhang Zhaoyang, Wang Sheng, Wang Qianlei, Ye Qian, Wang Wenjuan
Center for Scientific Research of Anhui Medical University, Hefei, 230032, China.
School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
AAPS PharmSciTech. 2025 Feb 10;26(2):60. doi: 10.1208/s12249-025-03049-z.
Ion pairs represent a robust molecular force arising from the union of oppositely charged ions, held together by Coulomb attraction. Daidzein (Dai), categorized as a BCS IV drug, faces limitations in clinical application due to its relatively low solubility. To enhance the drug's solubility, a Dai ion pair was prepared, and the mechanism underlying ion-pair formation was investigated. A comprehensive approach, combining experimental techniques and theoretical calculations, such as scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, X-ray Photoelectron Spectroscopy, and computational simulation was employed to explore the ion-pair formation mechanism. The findings indicate a significant improvement in Dai solubility through the preparation of Arg and Lys ion-pair compounds. The results revealed that the Dai-Lys ion pair exhibited more short hydrogen bonds and fewer long hydrogen bonds than did the Dai-Arg ion pair, strengthening the intermolecular interactions and improving crystal structure stability. This study effectively enhanced the solubility of Dai and offers valuable insights into the mechanisms underlying ion pair formation in ionizable drugs.
离子对是由带相反电荷的离子结合而成的一种强大的分子力，通过库仑引力结合在一起。大豆苷元（Dai）属于BCS IV类药物，由于其溶解度相对较低，在临床应用中面临局限性。为提高该药物的溶解度，制备了大豆苷元离子对，并对离子对形成的机制进行了研究。采用了一种综合方法，结合扫描电子显微镜、粉末X射线衍射、差示扫描量热法、傅里叶变换红外光谱、质子核磁共振光谱、X射线光电子能谱等实验技术和理论计算以及计算模拟来探索离子对形成机制。研究结果表明，通过制备精氨酸和赖氨酸离子对化合物，大豆苷元的溶解度有显著提高。结果显示，与大豆苷元-精氨酸离子对相比，大豆苷元-赖氨酸离子对表现出更多的短氢键和更少的长氢键，增强了分子间相互作用并提高了晶体结构稳定性。本研究有效地提高了大豆苷元的溶解度，并为可电离药物中离子对形成的机制提供了有价值的见解。
