School of Chemistry and Chemical Engineering, Shenyang Normal University, Shenyang 110034, China.
Experimental Center, Shenyang Normal University, Shenyang 110034, China.
Int J Mol Sci. 2020 Jan 24;21(3):766. doi: 10.3390/ijms21030766.
Four cyclodextrins (CD) including β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), heptakis--(2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), and heptakis--(2, 6-di--methyl)-β-cyclodextrin (DM-β-CD) were used as solubilizer to study the solubility enhancement of myricetin. The results of the phase solubility study showed that the presence of CDs could enhance the solubility of myricetin by forming 1:1 complexes. Among all CDs, HP-β-CD had the highest solubilization effect to myricetin. The concentration of myricetin could be 1.60 × 10 moL/L when the presence of HP-β-CD reached 1.00 × 10 moL/L, which was 31.45 times higher than myricetin's aqueous solubility. Subsequently, the HP-β-CD:myricetin complex was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). In order to get an insight of the plausible structure of the complex, molecular docking was used to study the complexation process of HP-β-CD and myricetin. In the complex, the A ring and C ring of myricetin were complexed into the hydrophobic cavity of HP-β-CD, while the ring B was located at the wide rim of HP-β-CD. Four hydrogen bonding interactions were found between HP-β-CD and -OH groups of the guest in the HP-β-CD: myricetin complex. The complexation energy (△E) for the host-guest interactions was calculated with a negative sign, indicating the formation of the complex was an exergonic process. A 30-ns molecular dynamics simulation was conducted to the HP-β-CD: myricetin complex. Calculation results showed that no large structural deformation or position change were observed during the whole simulation time span. The average root-mean-square deviation (RMSD) changes of the host and guest were 2.444 and 1.145 Å, respectively, indicating the complex had excellent stability.
四种环糊精（CD），包括β-环糊精（β-CD）、γ-环糊精（γ-CD）、七（2-羟丙基）-β-环糊精（HP-β-CD）和七（2,6-二甲基）-β-环糊精（DM-β-CD），被用作增溶剂来研究杨梅素的溶解度增强。相溶解度研究的结果表明，CD 的存在可以通过形成 1:1 配合物来提高杨梅素的溶解度。在所有 CD 中，HP-β-CD 对杨梅素的增溶效果最高。当 HP-β-CD 的浓度达到 1.00×10-2mol/L 时，杨梅素的浓度可以达到 1.60×10-2mol/L，是杨梅素在水中溶解度的 31.45 倍。随后，通过傅里叶变换红外光谱（FT-IR）、X 射线衍射（XRD）和热重分析（TGA）对 HP-β-CD：杨梅素配合物进行了表征。为了深入了解配合物的可能结构，使用分子对接研究了 HP-β-CD 和杨梅素的配合过程。在配合物中，杨梅素的 A 环和 C 环被包合到 HP-β-CD 的疏水性腔内，而 B 环位于 HP-β-CD 的宽边缘。在 HP-β-CD：杨梅素配合物中发现了四个氢键相互作用，HP-β-CD 和客体的-OH 基团之间存在氢键相互作用。用负号计算了主体-客体相互作用的配合能（△E），表明配合物的形成是一个放能过程。对 HP-β-CD：杨梅素配合物进行了 30ns 的分子动力学模拟。计算结果表明，在整个模拟时间范围内，没有观察到主体和客体的大结构变形或位置变化。主体和客体的平均均方根偏差（RMSD）变化分别为 2.444 和 1.145Å，表明配合物具有优异的稳定性。
