Synthesis Of Amphiphilic Diblock Copolymer MPEG-PtBA By Atom Transfer Radical Polymerization

Amphiphilic block copolymers are winning more and more extensive application in thedrug delivery system(DDS) because they are prone to form micelles via self-assembly andhave high thermodynamic stability and low critical micelle concentration(CMC). So it issignificant to design and synthesize the amphiphilic block copolymers with specific structurefor obtaining the drug-loaded micelles that have proper particle size, uniform distribution ofparticle size and stable structure. Atom transfer radical polymerization(ATRP) is one of themost effective methods to synthesize the amphiphilic block copolymers with controllingmolecular weight, narrow molecular weight distribution and well-defined structure. Becauseof its fast reaction rate and convenient reaction conditions, ATRP plays a more and moreimportant role in synthesis of the novel polymers especiallythe amphiphilic block copolymerswith specific structure. Proposed in this paper, an amphiphilic diblock copolymer wassynthesized byATRP.The amphiphilic copolymer monomethoxy poly(ethylene glycol)-b-poly(tert-butylacrylate) (mPEG-PtBA) was synthesized by the traditional ATRPmethod using biocompatiblemonomethoxy polyethylene glycol as the hydrophilic chain and the poly(tert-butyl acrylate)as the hydrophobic one. The macroinitiator mPEG-Br was prepared by acylation, and then thecopolymer mPEG-PtBA was synthesized using CuBr/PMDETA as catalyst and mPEG-Br asmacroinitiator in the mixed solvent of anisole and tetrahydrofuran. The macroinitiatormPEG-Br and copolymer mPEG-PtBA were characterized by the FT-IR, 1HNMR and GPC.The results showed that mPEG-Br and mPEG-PtBAwere synthesized successfully.The influences of process conditions, such as the molar ratio of the monomer tomacroinitiator, reaction time, reaction temperature and the molar ratio of catalyst to ligand onmolecular weight and molecular weight distribution were evaluated. The optimum conditionsare as follows: the molar ratio of the monomer to macroinitiator is 200, the reaction time is 24h, reaction temperature is 80℃and the molar ratio of catalyst to ligand is 1. Besides, thedynamic behavior and the relationship between the conversion, reaction time and molecularweight of the copolymer were investigated. The plot of molecular weight of copolymer vstime is linear, and the polymerization is a first-order process, which indicates that the processis the living and well-controlled radical polymerization.It is usually difficult to remove the large amount of catalyst used in the traditional ATRPmethod, so the novel method of activators regenerated by electron transfer for atom transfer radical polymerization(ARGET ATRP) was used to synthesize the copolymer mPEG-PtBA.Reducing agents tin(II) 2-ethylhexanoate is employed to continuously reduce a deactivatorCu(II) to an activator Cu(I) species. So the excess Cu(II) deactivator formed in terminationreactions is continuously regenerated to the original active Cu(I) state by an excess ofreducing agent. It has been demonstrated that the small amount of copper catalyst not onlyleads to an environmentally benign polymerization process, but also drastically suppressesside reactions between the chain end and the catalyst, enabling desired molecular weightpolymers with low polydispersity.