目的 以水溶性磷酸盐柱[6]芳烃（phosphate salt pillar[6]arene，PP6A）作为芫花素的药物载体即主体分子，天然药芫花素为客体分子，构筑了一种新型的芫花素/PP6A（genkwanin/PP6A，GK/PP6A）超分子主客体包合物，对其进行表征和性能分析，进一步对包合机制进行研究。方法 采用饱和水溶液法制备芫花素与PP6A的超分子包合物；以包合物的包合率为指标，选用物质的量比、包合温度、包合时间和甲醇与水的体积比4个因素，每个因素3个水平，以L₉(3⁴)设计正交试验，对GK/PP6A包合物的制备工艺进行优化筛选。采用紫外可见吸收光谱法、傅里叶变换红外光谱、X射线粉末衍射、扫描电子显微镜和差示扫描量热等分析方法对芫花素和PP6A包合前后的理化性质进行研究分析；通过半经验分子轨道法、分子对接和核磁共振波谱法揭示了芫花素与PP6A最稳定的包合模式。结果 GK/PP6A包合物的最优制备工艺为PP6A与芫花素的物质的量比为1∶1，包合温度为50 ℃，包合时间8 h，甲醇与超纯水体积比为1∶8，GK/PP6A包合物的包合率为89.93%；芫花素和PP6A以物质的量比1∶1形成超分子包合物，其络合常数为49 488 L/mol；半经验分子轨道法与分子对接揭示的包合机制与二维核磁共振氢谱推断的主客体可能的包合模式相互吻合；芫花素包合前后的水溶解性和稳定性显著提高，其中水溶解性由3.5 μg/mL提升至540.5 μg/mL，约提高了155倍。结论 PP6A是芫花素的良好宿主，芫花素与PP6A形成包合物后，芫花素的水溶性和稳定性得到显著提高，疏水作用和氢键作用为包合物形成的主要驱动力。

Objective A novel supramolecular host-guest inclusion complex of genkwanin/phosphate salt pillar[6]arene (GK/PP6A) was constructed with water-soluble phosphate salt pillar[6]arene (PP6A) as the drug carrier (as the host) and the natural medicine genkwanin (GK) as the guest molecule. The characterization and performance analysis were carried out, and the formation mechanism of inclusion complex was studied. Methods The inclusion complex of GK/PP6A was prepared by saturated solution, the preparation process of GK/PP6A inclusion compound was optimized and screened. The orthogonal experiment was designed with L₉(3⁴), using four factors, including molar ratio, inclusion temperature, inclusion time and volume ratio of methanol to water, with three levels for each factor. The physico-chemical properties of genkwanin and PP6A before and after inclusion were studied by ultraviolet-visible spectroscopy, infrared spectroscopy, X-ray powder diffraction, scanning electron microscope and differential scanning calorimeter, and the most stable inclusion modes of genkwanin and PP6A were revealed by semi-empirical molecular orbital method, molecular docking and nuclear magnetic resonance spectroscopy. Results The optimal preparation process of GK/PP6A inclusion complex was that the molar ratio of PP6A to genkwanin is 1:1, 50 ℃ for the temperature, 8 h for the time, and 1:8 for the volume ratio of ethanol to water, the inclusion rate of GK/PP6A inclusion complex was 89.93%. The experimental results showed that genkwanin and PP6A form supramolecular inclusion complex with a molar ratio of 1:1, and the inclusion complex constant was calculated to be 49 488 L/mol. The inclusion mechanism revealed by semi-empirical molecular orbital method and molecular docking was in agreement with the possible inclusion model of host and guest inferred by two-dimensional hydrogen magnetic resonance spectroscopy. The stability and water solubility of genkwanin before and after inclusion complex were significantly improved, and the water solubility was increased from 3.5 μg/mL to 540.5 μg/mL, about 155 times. Conclusion PP6A is a good host of genkwanin. The water solubility and stability of genkwanin were significantly improved after genkwanin formed inclusion complex with PP6A. Hydrophobicity and hydrogen bonding are the main driving forces for inclusion complex formation.

国家自然科学基金资助项目（21762051）；云南省兴滇英才支持计划（教学名师专项）；云南省高校科技创新团队项目；云南省教育厅科学研究基金项目（2023Y0519）；研究生基金资助项目（2022SKY031）