| Flavonoids are found in a wide variety of plants and have a variety of biological activities,including antibacterial,anti-inflammatory,antioxidant,etc.Most flavonoids are insoluble or non-soluble in water,making them difficult to be absorbed by organisms,resulting in biological activity that is difficult to fully exploit.As a result,improving the solubility of insoluble flavonoids in water has become a research hotspot,with cyclodextrin inclusion techniques being one of the commonly used means.In this study,the inclusion complex of beta-cyclodextrin(β-CD),2,6-dimethyl-beta-cyclodextrin(DM-β-CD),2-hydroxypropyl beta-cyclodextrin(HP-β-CD)and different small molecular compounds of flavonoids was prepared by the inclusion method of cyclodextrin(CDs).Based on the structure-activity relationship of the inclusion complex,the interaction and inclusion mechanisms between the owner and the contained object have been quantitatively studied by combining multiple molecular simulations.The study mainly consists of the following three sections:(1)In Chapter 3,the inclusion mechanism of three clathrates formed by β-CD,DM-β-CD,HP-β-CD and rutin was studied by molecular simulation and experiment.The model of inclusion complex was obtained by molecular docking.The microstructure parameters of β-CD,DM-β-CD,HP-β-CD and rutin inclusion complex were calculated by molecular dynamics(MD)simulation,including solubility parameters,binding energy,root mean square displacement,hydrogen bond and radial distribution function.The simulation results showed that all three kinds of cyclodextrins had good compatibility with Rutin,the interaction between Rutin and DM-β-CD was the strongest,and the stability of the inclusion complex was the strongest.Then,the inclusion complexes of rutin and three kinds of cyclodextrin were prepared by freeze-drying method.Fourier transform infrared analysis(FT-IR),X-ray diffraction spectroscopy(XRD),differential scanning calorimetry(DSC),ultraviolet visible spectroscopy(UV-vis)was carried out,and the phase solubility experiments were carried out,and the inclusion stability constant of the inclusion complexes was calculated.The results showed that the inclusion complexes were formed between Rutin and three kinds of cyclodextrins.The inclusion ratio was 1:1 according to the phase dissolution diagram,and the inclusion stability constant proved that the inclusion complexes of Rutin and DM-β-CD were the most stable.The simulation agrees with the experimental results.(2)In Chapter 4,a screening mechanism for guest small molecules is established through molecular simulation.From 16 kinds of flavonoids,curcumin was selected as the most suitable guest small molecule for inclusion with cyclodextrin.Then,the inclusion mechanism of curcumin and three kinds of cyclodextrin was studied by molecular simulation and experiment.The inclusion complexes of three cyclodextrins and curcumin were established by molecular docking,and the parameters of molecular dynamics simulation were calculated.Three inclusion complexes of cyclodextrin and curcumin were prepared and characterized by freeze-drying method.The characterization results showed that curcumin and three kinds of cyclodextrins were successfully included,and the curcumin/2,6-dimethyl-β-cyclodextrin(CUR/DM-β-CD)inclusion complex was the most stable.(3)In Chapter 5,luteolin was selected as the most suitable small molecule for inclusion with cyclodextrin from 10 kinds of polyphenols by molecular screening mechanism,and the inclusion mechanism of luteolin and three kinds of cyclodextrin was simulated and experimentally studied.The solubility parameters,binding energy,mean square displacement,hydrogen bond,radial distribution function and oxygen permeability coefficient were calculated.The permeability trajectories of oxygen in the inclusion complex system were extracted and the displacement difference before and after each displacement of oxygen molecules was calculated.In the experimental part,FT-IR,XRD,DSC,UV-vis and phase solubility tests were carried out,followed by the oxidation resistance test.The antioxidant activity of the inclusion complex was studied by molecular simulation and experiment.It was proved that the inclusion of luteolin with cyclodextrin did not lose its antioxidant activity,and the antioxidant activity of luteolin/cyclodextrin inclusion complex was stronger than that of free luteolin. |
