Heresy, The Synthesis And Characterization Of Telechelic Polyethylene Glycol

Poly(ethylene glycol)(PEG) is a polyether polymer that has wide applications in biomedicine fields due to its good biocompatibility and biological safety, special water hydration ability and anti-immunogenicity. Hetero telechelic PEG containing two different functional groups can be used to build multi-functional biomedical devices or drug-loaded systems by the selectivity of end groups in chemical reactions, and thereby is a highly valuable material.In this thesis a series of hetero telechelic PEGs with different functional groups were prepared via direct ring-opening polymerization and/or end group modification. The chemical structures and weight average molecular weights of the resultant products were characterized by1H-NMR and GPC, and the utility of the PEG with terminal hydroxyl and carboxyl groups was explored in a preliminary study.Firstly, mono-methoxy-PEG with high yield and narrow molecular weight distribution was synthesized via ring-opening polymerization of ethylene oxide using methanol as initiator and naphthalene potassium as ionization reagent. It was found that the residue water contained in the reaction system played a significant role in the ring-opening polymerizaton of ethylene oxide. When its content in the solvent was high than80ppm, the catalyst lost the initiation activity, while below20ppm, high purity product was achieved.Secondly, three hetero telechelic PEGs were prepared by direct ring-opening polymerization of ethylene oxide using2-(benzyloxy)-ethanol,2-(tetrahydro-2H-pyran-2-yloxy)-ethanol,2-allyloxy-ethanol as initiators, respectively.1H-NMR and GPC results showed that the three alcohols were highly reactive initiators, and by the change of monomer/initiator ratio, the molecular weight of the products could be effectively controlled and high purity products with narrow molecular weight distribution were acquired.Thirdly, two hetero telechelic PEGs with terminal carboxyl and hydroxyl groups, and terminal amino and hydroxyl groups, were prepared through the conversion of functional end group using the PEG with benzyl ether protecting group on one end and hydroxyl on the other end as the starting material. Furthermore, based on the PEG with propenyl and hydroxyl end groups, the hetero telechelic PEG with terminal amino and hydroxyl groups was also synthesized by the technique of "click" reaction between propenyl and thiol groups.1H-NMR and GPC results showed that all the three hetero bifunctional PEGs are practically useful due to the narrow molecular weight and high purity of the products.Finally, di-block copolymer of COOH-PEG-b-PLA was prepared by the ring-opening polymerization of D, L-lactide using the hetero telechelic COOH-PEG-OH as initiator and stannous octoate as catalyst. This copolymer could self-assemble into nano-micelles in aqueous water with the particle size ranging from50-200nm and average particle size of120run, which are suitable for injectable use. The carboxyl group on the surface of the nano-micelles is useful to link with target peptide and construct drug delivery nano-systems with targeting function.