2,6-二甲基-β-环糊精增溶大豆苷元的机理研究

Mechanism study of water solubility enhancement of daidzein by 2,6-di-methyl-β-cyclodextrin

采用β-环糊精、γ-环糊精、2-羟丙基-β-环糊精、2,6-二甲基-β-环糊精与6-葡萄糖基-β-环糊精作为增溶剂,研究其对大豆苷元的增溶作用。紫外-可见光谱实验结果表明,上述5种环糊精对大豆苷元都有一定的增溶效应,其中2,6-二甲基-β-环糊精的增溶作用最好。数据分析可知,环糊精是通过与大豆苷元形成的1:1型复合物实现増溶的。随后,采用傅里叶变换红外光谱法、X射线粉末衍射法等手段验证了环糊精与大豆苷元形成的复合物。为了获得可能的复合物结构,采用分子对接技术研究2,6-二甲基-β-环糊精与大豆苷元的复合过程,并对所得到的能量最低的对接结果进行了分子动力学模拟实验,发现大豆苷元的A环与C环复合在2,6-二甲基-β-环糊精空腔处,B环位于环糊精大口处,二者之间存在明显的氢键作用,而且所形成的复合物具有较强的动力学稳定性,在30 ns时间内结构稳定,未发生较大形变。主客体与复合物的RMSD变化很小。

In this paper,β-cyclodextrin,γ-cyclodextrin, 2-Hydroxypropyl-β-cyclodextrin, 2,6-di-methyl-β-cyclodextrin and 6-glucosyl-β-cyclodextrin are adopted as solubilizers for the research of solubility enhancement of daidzein. The results of UV-Vis spectroscopy show that the five cyclodextrins all have a certain hydrotropic effect on daidzein, and among them, 2,6-dimethyl-β-cyclodextrin has the best hydrotropic effect. The solubility enhancement of daidzein is achieved by forming 1∶1 complexes with cyclodextrins. Subsequently, the complexes formed by di-methyl-β-cyclodextrin and daidzein was verified by means of Fourier transform infrared spectroscopy and X-ray powder diffraction. In order to obtain the plausible complex structure, the technique of molecular docking was used to study the complexation process of 2,6-dimethyl-β-cyclodextrin and daidzein. Molecular dynamics was also applied to the lowest energy docking result. The simulation result indicates the A and C ring of daidzein are complexed in the cavity of 2,6-dimethyl-β-cyclodextrin, and the ring B is located at the large rim of the cyclodextrin. There is a hydrogen bonding interaction between the host and the guest. The formed complex has strong kinetic stability. The structure is stable in 30 ns and no large structural deformation is observed. The RMSD changes of the host, the guest and the complex are small.