Study On The Binding Behavior Of β-Cyclodextrin And Selected Isomeric Compounds

Molecular recognition investigations on macrocyclic sugars called cyclodextrin have attracted extensive attention in supramolecular chemistry. It is well known that cyclodextrins can include a wide variety of guest molecules into their cavities to form supramolecular inclusion complexes, so they have been successfully employed in pharmaceutical application in order to enhance the solubility, stability and bioavailability of drug molecules and develop reaction rate and its molar conversion of bioconversion of drug molecules. However, the inclusion mechanisms are still complicated, which limits their uses in pharmaceutical formulations. In order to reveal the influence of the position of the substituent group and molecular chirality of the guest molecules on the binding behavior, in this thesis a series of inclusion complexes of P-cyclodextrin with isomeric compounds and6-modified β-cyclodextrin, were synthesized and characterized by means of some modern techniques.The major contents are as follows.(1) A series of inclusion complexes of cyclodextrin and selected isomeric compounds were synthesized and their inclusion behavior was studied by means of X-ray crystallography, TG-DTA, DSC, SEM, FTIR and NMR spectroscopy in both aqueous solution and the solid state. The inclusion behavior was discussed from the viewpoints of size/shape-fit, geometric matching, etc. The results obtained show that the steric effects play a key role in the inclusion complexation, namely the positional change of nitro group on aromatic ring gives rise to the difference of the stoichiometric ratio of host-guest and the position and orientation of the substituent group in the β-cyclodextrin cavities. On the other hand, the chirality has no significant effects on the inclusion compounds of β-cyclodextrin with cinchonidine and cinchonine. Furthermore, Phase-solubility studies indicate the solubility enhancement of guests in aqueous solution.(2) The mono-modified β-cyclodextrin,6-deoxy-6-(2-pyrimidinethio)-β-cyclodextrin, was synthesized and characterized. Its conformation was measured by x-ray crystallographic analysis, AFM and NMR in both solution and the solid state. The crystal structure shows that the pyrimidine group penetrates deeply into the hydrophobic cavity of the adjacent β-cyclodextrin from the second side, and the molecules are stacked along the twofold screw axis to form a head-to-tail helical columnar superstructure. The results indicate that the intramolecular/intermolecular interactions are a critical factor in determining the self-assembly behavior. Further NMR studies on the self-assembly behavior of the compound in aqueous solution shows that the binding behavior is in good agreement with the solid state. The aggregation number reveals that the dimerization step is the key to the formation of linear polymeric supramolecular architecture.