Preparation, Characterization and Molecular Modeling Studies of Inclusion Complex of Vincamine With Water-Soluble Phosphate Salt Pillar[6]Arene

A novel host-guest inclusion complex MAA/PP6A was constructed by the saturated solution method with water-soluble phosphate salt pillar[6]arene (PP6A) as the host and the natural medicine maackiain (MAA) as the guest. The preparation process of MAA/PP6A clathrate was screened by orthogonal test with the drug loading of clathrate as an index. The inclusion complex MAA/PP6A was characterized by fluorescence spectroscopy, scanning electron microscope (SEM), X-ray powder diffraction (XRD), and infrared spectroscopy (FT-IR). The inclusion mode of MAA and PP6A inclusion complex was studied by nuclear magnetic resonance spectroscopy (NMR) and molecular simulation docking semi-empirical molecular orbital methods. The results of orthogonal experiments showed that the optimal conditions for the preparation of the inclusion complex were as follows: the mass ratio of PP6A to MAA was 2:1, the volume ratio of ethanol to water was 1:1, and reaction at 50 degrees C for 8 h. Fluorescence spectroscopic titration experiment showed that the inclusion ratio between MAA and PP6A was 1:1 and there was a strong interaction between the host and the guest. The host-guest complex constant was calculated to be 2.458x104 L/mol by the non-linear least squares curve fitting method. Analytical test results showed that the inclusion complex was successfully prepared. The water solubility of MAA increased from 0.3463 to 6.123 mg/mL after the formation of the inclusion complex between MAA and PP6A, which effectively improved the water solubility of MAA. Semi-empirical molecular orbital method and molecular docking calculations indicated that there was no hydrogen bond formed between the host and guest. MAA could enter the cavity of PP6A and formed a conformationally stable inclusion complex. PP6A was a good host for MAA, and the optimal mode was consistent with the NMR results.