Study On PAMAM Dendrimer: Folic Acid Modification And Synthesis Of Non-ethylenediamine-core Structure

Dendrimers, which emerged from1970s, have attracted many interests invarious research fields due to their structural advantages such as thespherical appearance, nano-sized molecule, and highly symmetricalstructure. Dendrimers are widely used in template materials for nanoparticlesynthesis, catalyst supports, self-assembly based on host-guest chemistry,and biomedical applications. Thanks to the diversity of synthetic methodsand the various choices of dendrimer core, A large amount of dendrimerstructures have been reported in literatures. The related contents includingthe history and the synthetic method of dendrimers, the structural type andfeatures of dendrimers, and their potential applications are generallydescribed in this thesis.As a targeting molecule for folic acid receptor (FR) overexpressed tumorcells, folic acid is of significance for improving the antitumor activity ofmedicines. Due to its water solubility, monodispersity of nano-sizedmolecule and outstanding performance in controlled drug release, dendrimermolecule is particularly suitable as a carrier for anti-cancer drugs deliveryand imaging application. In this thesis, ethylenediamine-core PAMAMdendrimer were synthesized and folic acid was grafted at the end of thedendrimer molecules by two consecutive steps. The PAMAM-FA structureswere characterized by1H-NMR and FT-IR. The aqueous solution of thesecompounds with different concentrations and different generations wereprepared at room temperature and investigated using UV spectrometer. Withthe help of standard absroption curve of folic acid, the grafting ratio of folicacid on the dendrimers is determined.In order to improve the structure and performance of traditionalethylenediamine-core PAMAM dendrimer, several trials on the synthesis ofnon-ethylenediamine-core dendrimers were also explored. First, diethanolamine-core dendrimers of unilateral divergent structure weresynthesized and characterized with1HNMR and FT-IR. These fan-shapeddendrimers possess two hydroxyl groups at one end, which are expected tobe modified according to the future application of drug delivery and genetransfer. Furthermore, tris(2-aminoethyl)amine was used as the starting unitto synthesize larger dendrimer core, in order to obtain more flexibledendrimer molecules based on it. Moreover, an azide-containing compoundwas synthesized. The azide group can be conversed to primary amine bycatalytic hydrogenation and this compound is expect to be used as thestructural unit in the divergent-convergent synthesis of dendrimers.