Synthesis Of Several Novel Cyclodextrin Derivatives And Their Study On PPT Supramolecular System

20(S)-Protopanaxatriol(PPT) separation from ginseng, notoginseng, or American ginseng and other medicinal plants separation have been the one of the four ginsenosides, and ginseng saponin has the same physiological activity, application prospect is a cancer cell differentiation inducer. But given the PPT water-soluble low alcohol, bioavailability is not high, as in the further development and application of antitumor drug candidates. Using cyclodextrin and its derivatives(CDs) special structure and unique amphiphilic to improve the properties of drug solubilization and the study of supramolecular chemistry has became a research hotspot. Drug molecules combined with serum albumin on drug absorption, transport, distribution and maintenance of blood drug concentration has the vital significance. Therefore, in recent years the research of drug molecules interact with proteins has became one of hot point in the field of chemistry and life science. In this article, 6 kinds of modified cyclodextrins were syntheticed, nine supramolecular systems were constructed with several kinds of modified cyclodextrins and PPT. The supramolecular systems had been characterized. And then the knot patterns were speculated. Moreover, fluorescence spectrometry was used to study the interaction between supramolecular system and bovine serum albumin(BSA).The major reseach works of this thesis are as follows:1. Supramolecular systems of the guest PPT with three kinds of modified cyclodextrins(CDs) had been prepared and characterized by means of 1H NMR, XRD, SEM and IR. Supramolecular systems stability constants and inclusion ratios of three kinds of CDs with PPT were determined by means of phase solubility. Phase solubility diagram showed that the apparent solubility of PPT increased with the addition of SBE-β-CD and HP-β-CD. And phase solubility diagrams indicated are type AL, CDs and PPT package ratio of 1:1. DM-β-CD phase solubility curve of the AN type, both package ratio not than 1:1 and 2:1. The K values for the supramolecular systems of CDs with PPT increased in the following order: KSBE-β-CD/RZK > KDM-β-CD/RZK > KHP-β-CD/RZK. Three possible binding modes of CDs with PPT were analyzed by 2D ROESY. Saturated water solution method experiments showed that after the formation of supramolecular system PPT water soluble increased 735, 609, 460 times, respectively. SBE-β-CD solubilization effect is the best. Studied on the interaction mechanism between SBE-β-CD/PPT supramolecular system and BSA by fluorescence spectrometry. The results showed that a strong fluorescence quenching was observed and the quenching mechanism was considered as static quenching. Hydrogen bonding and van der Waals force as the main driving force to form 1:1 compounds. Meanwhile, the addition of supramolecular system led to the conformation of BSA changed significantly. Further, using the electrochemical impedance(EIS) method to verify the BSA-SBE-β-CD/PPT new compounds were generated.2. Designed and synthesized of the three kinds momo-β-CDs(H4-6) and the three new bis-β-CDs(H7-9), were characterized by its 1H NMR, and optimized the synthetic conditions and separation methods.3. Supramolecular systems of the guest PPT with three new kinds of mono-β-CDs had been prepared and characterized by means of 1H NMR, XRD, SEM and IR. Supramolecular systems stability constants and inclusion ratios of CDs with PPT were determined by means of phase solubility. Phase solubility diagram showed that the apparent solubility of increased with the addition of CDs. And phase solubility diagrams showed that they were type AL, AN and AL. The K values for the supramolecular systems of CDs with PPT increased in following the order: KH6/PPT> KH4/PPT>KH5/PPT. Three possible binding modes of CDs with PPT were analyzed by 2D ROESY. Water soluble experiments showed that after PPT was packaged by CDs, the guest of water soluble increased 83, 49, 122 times, respectively. Among the three CDs, H6 solubilization effect is the best. The interaction mechanism between supramolecular system H5/PPT and BSA was investigated by fluorescence spectrometry. The results showed that H5/PPT could significantly quench the intrinsic fluorescence of BSA by static quenching. The combined process of electrostatic forces as the main driving force to form the 1:1 compounds. Because of the addition of supramolecular system has influenced on the conformation of BSA.4. Supramolecular systems of the guest PPT with three new kinds of bis-β-CDs had been prepared and characterized by means of 1H NMR, XRD, SEM and IR. Supramolecular systems stability constants and inclusion ratios of three kinds of CDs with PPT are determined by means of 1H NMR, The ratios were 1:1. Three possible binding modes of CDs with PPT were analyzed by 2D ROESY. The water soluble experiments show that after PPT form the supramolecular system by CDs, water soluble increased 265, 254, 395 times, respectively. In comparison H9 showed the strongest ability of solubilization for PPT. Further, interaction mechanism was studied by fluorescence spectrometry to H8/PPT with BSA. It was found that the addition of H8/PPT can significantly quenched fluorescence of BSA by static quenching type. The main driving force was hydrogen bonding and van der Waals force. Supramolecular system with BSA by 1:1 type combined to form new compounds. H8/PPT exists had some influence on the conformation of BSA.