The Molecular Recognition Behavior Ofβ-Cyclodextrins With Anticancer Drugs

Cyclodextrins and their derivatives have been widely used as molecular receptor, artificial enzyme models and drug carriers in various field, such as:life science and technology, because of their particular structure and characteristics. The hydrophobic cavity of CDs gives them inclusion capacity with a variety of guest molecules by non-covalent bond interaction to form a "Molecule Capsules". Which can usually improve the physical and chemical properties of the encapsulated natural drugs. To further research the molecular recognition mechanism between cyclodextrins and antineoplastic drugs and the mechanism of drug action between cyclodextrins inclusion complexes and cancer cell, the inclusion complexation behavior and binding ability of scutellarin, scutellarein with hydroxypropyl-β-cyclodextrin and the stability and water solubility of inclusion complex are studied. Moveover, four kinds of anthracene anthryl-modified β-cyclodextrins were prepared and the inclusion complexation behavior of5-fluorouracil with them are also be studied, this phenomenon can provide a material basis of how to determine the interaction between encapsulated drug and cancer cell.This dissertation was mainly constituted of three sections as follows:1. Four amino modified β-cyclodextrin derivatives were obtained:mono-6-(amino)-6-deoxy-β-cyclodextrin(NH2-(3-CD), mono-6-(ethylene-diamino)-6-deoxy-(3-cyclodextrin(EN-β-CD), mono-6-(diethylenetriamine)-6-deoxy-β-cyclodextrin(DETA-β-CD), mono-6-(triethylene tetramine)-6-deoxy-β-cyclodextrin(TETA-β-CD) and all of their structures were charactered by1H NMR.2. The inclusion complexation behavior of scutellarin and scutellarein with hydroxypropyl-β-cyclodextrin has been investigated by phase-solubility diagram in solution. According to the phase-solubility diagram and the calculation formula, we could obtain the inclusion ratio and stability constant(Ks); Moreover, the inclusion complexes were characterized by means of ’H NMR, XRD and DSC. Through the analysis of2D NMR and phase-solubility diagram, we speculated the possible inclusion mode. The measurement of solubility and stability of the inclusion complexes in water will be potentially useful for improving their bioavailability.3. The fluorescence β-cyclodextrins with different chain lengths were prepared through using condensation agent, their structures and conformation were charactered by1H NMR,2D NMR and mass spectrum. The inclusion behavior of anthracene modified β-cyclodextrins and5-fluorouracil in aqueous solution were demonstrated by fluorescence spectroscopy and their binding ability has also been analyzed. In addition, the solid inclusion system were prepared by suspension method, and the formation of anthracene modified (β-cyclodextrins/5-fluorouracil inclusion complexes were confirmed by1H NMR, XRD and DSC, and the inclusion mode was concluded by2D NMR.