阳离子型环糊精对甘草素的超分子包合行为及增溶作用  

Supramolecular Binding Behavior and Solubilization of Cationic Cyclodextrins towards Liquiritigenin

作　　者：邓颖慧[1,2] 张东京 王海琨 陈加兴 宋爽 杨波 廖霞俐[1] DENG Ying-Hui;ZHANG Dong-Jing;WANG Hai-Kun;CHEN Jia-Xing;SONG Shuang;YANG Bo;LIAO Xia-Li(Faculty of Life Science and Technology,Kunming University of Science and Technology,Kunming 650500,China;School of Pharmacy,Qujing Medical College,Qujing 655000,China)

机构地区：[1]昆明理工大学生命科学与技术学院,昆明650500 [2]曲靖医学高等专科学校药学院,曲靖655000

出　　处：《分析化学》2025年第2期289-299,共11页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金项目(No.22061023);云南省教育厅基金教师类项目(No.2018JS627)资助。

摘　　要：甘草素(LG)是一种具有多种药理活性的黄酮类化合物,但水溶性极低,限制了其在生物医药领域的应用潜力。LG在水溶液中可发生部分解离形成酚氧负离子,因此,利用阳离子型环糊精(CCDs)对其进行包合可望达到更好的主客体包合和增溶效果。本研究合成了4种在第一面(小口端)上用不同长度氨基链进行单修饰的CCDs,并用饱和溶液法制备了其与LG的固体包合物。利用扫描电镜和X-射线粉末衍射对固体包合物进行了表征,证实了包合物的形成。进一步利用多种技术手段对包合物在溶液状态下的超分子包合行为进行了研究,测定了Job曲线并确定包合比均为1∶1,随后通过紫外滴定实验测得包合稳定常数Ks分别为2862.77、3494.70、6521.85和9599.48 L/mol,相比于β-环糊精本身(Ks=236.79 L/mol)有明显提升,表明CCDs通过氨基链提供的阴阳离子相互作用,对LG的包合能力显著增强。利用核磁共振氢谱和二维ROESY谱等并结合分子对接技术对包合模式分别进行了解析。包合物水溶性的测试结果表明,LG的溶解度最高可提升至4.9 mg/mL,提高了约70倍。本研究可为阳离子型大环化合物的设计及其对酚类物质如黄酮的超分子包合行为和增溶作用研究提供有益的借鉴。Liquiritigenin(LG)is a flavone of pharmacological importance,however,its application potential is severely limited due to its poor water solubility.LG could be disassociated slightly in water to form phenolate anion,therefore,better solubilization effect is expected by inclusion with cationic cyclodextrins(CCDs).In this work,four kinds of CCDs modified with amino groups at the primary face were synthesized,and their solid inclusion complexes with LG were successfully prepared by preparing their saturated solutions.The formation of the solid inclusion complexes was confirmed by scanning electron microscopy(SEM)and powder X-ray diffraction(PXRD),and their supramolecular binding behavior in solution was studied using multiple techniques.A 1∶1 inclusion stoichiometry of inclusion complexation was defined using Job plot by ultraviolet-visible(UV-vis)spectroscopy,and their binding stability constants(Ks)were determined as 2862.77,3494.70,6521.85 and 9599.48 L/mol using UV-vis spectroscopic titration,far more superior to that of nativeβ-CD(Ks=236.79 L/mol).This indicated that the amino side chains on CCDs could actively participate in the inclusion complexation through anion-cation interactions,significantly strengthening the host-guest binding between CCDs and LG.The inclusion modes were further elucidated based on proton and two-dimensional rotating-frame overhauser enhancement spectroscopy(2DROESY)nuclear magnetic resonance(NMR)experiments and molecular docking.Water solubility of LG was dramatically promoted up to 4.9 mg/mL,which was 70-fold higher than that of native LG.This study could draw inspiration for the binding and solubilization of phenols such as flavones by design of cationic macrocyclic molecules.

关 键 词：甘草素 阳离子型环糊精 包合行为 氨基链 增溶作用 

分 类 号：TQ4[化学工程]