Inclusion Study Of Dihydroartemisinin Ester Derivatives And Construction Of Multiple Recognition Polypseudotaxane

Molecular recognition and self-assembly are the basic phenomena to maintain life.Thereinto,molecular recognition is the basis of molecular assembly.One of aims of supramolecular chemistry is to form supramolecular functional system by molecular assembly.Due to the hydrophobic cavity and hydrophilic surface of cyclodextrins,it can be used as the host to combine with inorganic,organic and biological molecules generating host-guest compounds,reflecting the recognition of cyclodextrins on the guest molecule.Moreover,by clathration with the linear polymer,cyclodextrins can form supramolecualr assembly such as polyrotaxane,which has extensive application prospect.In this paper,we have chosen three kinds of cyclodextrins(?-CD,HP-?-CD and SBE-?-CD)to form the host-guest inclusion complexes with dihydroartemisinin ester derivatives,and performance characterization,which is aimed at exploring the inclusion behavior.On the other hand,prepared targeted mediated molecules modified cyclodextrin as macrocyclic molecular,synthesized triblock cationic copolymer as linear polymer,we can construct multiple recognizable polypseuorotaxane non-viral vector together with them for gene therapy.Specific work can be divided into four parts as follow:1.Preparation of cyclodextrin chemistry derivatives:mono-6-deoxy-6-(p-tolylsulfonyl)-?-cyclodextrin(TsO-?-p CD);mono-6-deoxy-6 ?amino-?-cyclodextrin(NH2-p-CD);mono-6-deoxy-6-ethylenediamino-?-cyclodextr in(EN-p-CD);mono-6-deoxy-6-diethylenetriamino-?-cyclodextrin(Dien-?-CD);mono-6-deoxy-6-triethylenetetraamino-?-cyclodextrin(Trien-?-CD).Above compounds were characterized to confirm structures by 1H NMR.2.Artesunate was used as the host,p-CD,HP-P-CD and SBE-?-CD were used as the guest,we have prepared solid inclusion complexes by saturated aqueous solution method.Through UV-vis spectra,NMR,thermal analysis,and X-ray powder diffraction,inclusion complexes were characterized in liquid and solid to confirm the formation and the stoichiometric ratio,then we can calculate the stability constant(KS)and make the proper deduction about the inclusion mode.In addition,the result of solubility test suggested that solubility of encapsulated artesunate was significantly improved,and data of cell activity test in vitro show a potential anti-cancer activity.3.With 1-adamantane carboxylic acid as raw material,we attempted to synthesize the dihydroartemi sinin ester by chloride esterification and Steglich esterification,respectively.Then,prepared the inclusion complexes similar to the artesunate,and characterized by 1H NMR to confirm structure.4.With polyethylene glycol 3000(PEG 3000)as raw material,we firstly synthesized the PEG-bis(tosylate)as a macroinitiator,then obtained the PMeOZO-PEG-PMeOZO triblock copolymer by cationic polymerization using 2-methyl-2-oxazaline(MeOZO).After hydrolysis,PEI-PEG-PEI triblock copolymers were synthesized.Above compounds were characterized to confirm structures by 1H NMR.