Preparation And Properties Of End-functional Polymers

Gene therapy is one of the most promising for the treatment of major diseases in the21stcentury, as the main carrier of the gene therapy, polymer gene vectors have caused extensiveattention by researchers due to their safe, simple to prepare and reusable. Polylysine is acommonly used polymer gene carrier. Lysine which will be produced by degradation ofpolylysine is necessary for the body. Therefore polylysine has been approved by the FDA as asafety and non-toxic polymer material which can be used in the human body, linear polylysinehas no buffering capacity substantially under physiological conditions, it is difficult to releasethe DNA which it carried, resulting in low transfection efficiency, but compared with otherpolymeric carrier, such as PEI and PAMAM, polylysine has the advantages,such as ease tosynthesis, structure and molecular weight is easy to control.In this essay, PHEMA was synthesized by RAFT radical polymerization. Then wesynthesized polymer PHEMA-co-PHEMA-Boc-L-lysine with the protected primary aminogroup by using esterification. We used strong acid to deprotect PHEMA-co-PHEMA-Boc-L-lysine to PHEMA-co-PHEMA-L-lysine. Then we use GSH to modify PHEMA-co-PHEMA-Boc-L-lysine and got PHEMA-co-PHEMA-Boc-L-lysine-GSH. The polymers werecharacterized by fourier transform infrared (FTIR), nuclear magnetic resonance (~1HNMR),GPC, and differential scanning calorimeter (DSC). And we use some polymer to interact withDNA, PHEMA-co-PHEMA-L-lysine and PHEMA-co-PHEMA-Boc-L-lysine-GSH havegood composite effect of DNA, and when the ratio of N/P is6:1, the composite effect is better.GSH mercapto group at the end of the formation will have a disulfide bond with the mercaptogroup at the end of the other segment, which will cause a partially crosslinked complexes, andtherefore will have a better composite effect of PHEMA-co-PHEMA-L-lysine-GSH DNA. Inthe presence of hydroxyl group in HEMA structure, resulting certain uncontrollable during thepolymerization process, no matter how to change the amount of monomer content of the chaintransfer agent, or the reaction temperature, the molecular weight of the homopolymer is hardto control and molecular weight distribution is large.Therefore, using RAFT polymerization which is regulated by xanthate to synthesis PVAc-CTA had a narrow PDI. Then based on hydrogen bonding and electrostatic interaction ofpolymer and DNA formed a complex, we choose NVA as a functional monomer. Blockcopolymer PVAc-b-PNVA was obtained by RAFT polymerization. Then study the process ofVAc and NVA, it is found that the polymerization process meet the characteristics of RAFTliving polymerization. The structure and performance of the diblock copolymerPVAc-b-PNVA were characterized by fourier transform infrared (FTIR), nuclear magneticresonance (~1HNMR), GPC and differential scanning calorimeter (DSC). It is found that themolecular weight gradually increases with the amount of NVA increased and the distributionof molecular weight (Mw/Mn) lesses than1.5. The amphiphilic diblock copolymers couldaggregate into micelles in selective solution. In the study on the self-assembly ofPVAc-b-PNVA polymer, we found with PVAc-b-PNVA hydrophilic chain segment contentincreased, critical water content (CMC) increases, the formation of micelle diameter becomes larger, with the increased proportion of hydrophilic segments, micelle morphology changed.In the process of block copolymer PVAc-b-PNVA self-assembly to form micelles, it isfound that the copolymers exhibit a unique phenomenon. We analysis block copolymerPVAc-b-PNVA in different solvents such as ethanol and THF solutions’ conformations. Tthestructural characteristics and morphology of PVAc-b-PNVA in ethanol solution and the THFsolution of the polymer were studied by infrared and NMR characterization. We found blockcopolymer PVAc-b-PNVA in ethanol formed β-folding. For comparison, VAc the NVArandom copolymer has been synthesized, Random copolymer in the ethanol solution had arandom coil form. Measured by UV, optical microscopy and electron microscopy, we foundthat dropwise water into the THF solution of PVAc-b-PNVA, it has been carried out theprocess from the solution of the polymer micelle and formation of reverse micelles; in theethanol solution it has been carried out the process that the ethanol-induced formation ofhydrogen bonds to form β-folding conformation, and can be self-assembled into hydrogenbond-based multilayer film.Hydrophilic block copolymer which the side groups are hydroxyl group and primaryamine group can be formed by hydrolysis of PVAc-b-PNVA block copolymer. Then thiolatedon the end of the block copolymer to obtain PVAc-b-PNVA-SH, studies on the synthesis oftype mercapto group reducing sensitivity, and whether the formation of disulfide bonds of thepolymer/DNA complex can have a stabilizing effect. The polymerization process is relativelysimple and efficient, synthesis and properties of this synthetic amino acid structure of theblock copolymer PVAc-b-PNVA can be used to guide the synthesis and properties ofpoly-lysine derivatives.