Predict The Retention Behavior Of Several Chiral Drugs In Chromatography And Study On The Interactions Of A Catechin With Macromolecules Or β-cyclodextrin

Protein chiral stationary phase high performance liquid chromatographic column is hard to be widely used because of its’high price and short life of limitations. The simulation method of the auxiliary primaries of the enantiomers before the separation of enantiomers in experiment may improve the utilization of the pillars and cost savings.(-)-Epigallocatechin-3-Gallate (EGCG) is an anticancer drug of great value. Studies have shown that the combination of fatty acids (FA) and human serum albumin (HSA) can change the binding properties of the drug and HSA. Therefore, it cannot be neglected the influence of FA when studying the interactions of drug and HSA. DNA is the primary target of the anticancer drug into the biological body. The research of interaction mechanism of the anti-cancer drugs and DNA helps to understand the mechanism of action of anticancer drugs at the molecular level. EGCG will immediately decompose in the body and is unable to play efficacy if taken directly.β-cyclodextrin can form inclusion complexes with a large number of small organic molecules, which will change physical and chemical properties of small molecules. The inclusion mechanism of cyclodextrins and EGCG may provide a reference and ideas about the modification of EGCG. The studies are as follows:1. Prediction of the Retention Behavior of Chiral Compounds in Protein Stationary Phase Column Using Molecular DockingThe molecular docking techniques were used for predicting the interactions of two chromatographic stationary phase proteins with four pairs chiral compounds in this paper, respectively. The results showed that the order of size of predicted binding free energies (△G) were consistent with the experimental order of chromatographic elution peaks (R-(+) and S-(-) type); the order size of the absolute value of binding free energies difference (△(△G)) of the enantiomers (R-(+) and S-(-) type) were consistent with the changing tendency of separation factor (a). These would suggest that protein’s ability to identify the different chiral compounds recognition and the elution order of compounds (R-(+) and S-(-) type) could be reflected by molecular docking.2. Interaction of (-)-Epigallocatechin-3-Gallate with the fatty acid-bound human serum albumin——flexible docking studiesIn order to understand the impact of the fatty acids (FA) to the interaction of EGCG with HSA, The interactions between ligands (EGCG and its the structural fragments (-)-Epigallocatechin (EGC) and gallic acid(GA)) and receptors (FA-bound HSA (FB-HSA) and FA-free HSA (FF-HSA)) have been predicted using the flexible docking techniques in the paper. Results show that, compared to those with not in the presence of FA, the binding affinity between EGCG and HSA is visibly weakened in the presence of FA at the site I; still that is increased dramatically at the site II and its docking pose is rotated approximately180°in situ. Meanwhile, it is found that EGC not only is the core to determine the binding mode of EGCG, but also has important contributing to the overall binding energy; GA only has important contributing to the overall binding energy.3. Studies of the Interaction between (-)-Epigallocatechin Gallate and DNA by Spectroscopic and Molecular Docking MethodsWe have made preliminary research about the mechanism of interaction of EGCG and DNA using UV and fluorescence spectroscopy, supplemented by the docking simulation. The experimental results show that EGCG can interact with DNA to form complexes which are combined with a groove mode; The formation of Complex is an spontaneous process that is mainly driven by hydrogen bonds and van der Waals forces. Simulation results were consistent with experimental results, showing that EGCG is connected in DNA G-C rich area with minor groove mode.4. Study on the Inclusion Interaction of (-)-Epigallocatechin Gallate with β-cyclodextrin by Spectrographic and Molecular Docking MethodThe inclusion mechanism of β-CD and EGCG has been studied by UV-vis, fourier transform infrared (FTIR), fluorescence spectra and molecular docking techniques. The research of UV-vis and fluorescence showed that EGCG was bound in the cavity of β-CD in a ratio of1:1at pH7.4of Tris-HCl buffer solution; The inclusion constants of inclusion complex Kc is1025L/mol at24℃; Hydro phobic is the main driving force for formation of inclusion complexes. FTIR results indicated that β-CD has encompassed the whole molecule of EGCG in its hydrophobic cavity. The docking result was in accord with the experiment and visualizes the predicted conformation.