Synthesis of three-arm poly(ethylene glycol) by combination of controlled anionic polymerization and 'click' chemistry

Poly(ethylene glycol) (PEG) is an important water-soluble polymer, which is widely used in the biomedical field because of its good biodegradability, biocompatibility and permeability. It is usually synthesized by anionic polymerization of ethylene oxide but side reactions lead to the formation of some oligomers. High molecular weight PEG can be obtained, however, through coordinated anionic polymerization. Recently a novel controlled anionic polymerization based on the initiating system ammonium bromide/trialkylaluminium was reported. Related studies have shown that the controlled anionic polymerization allows the synthesis of linear polyethers with low dispersity in a wide range of molecular weights at ambient temperature. Unfortunately, so far this controlled anionic polymerization has not been used to synthesize polymers with complex architectures. In the work reported here, controlled anionic polymerization was combined with 'click' chemistry for the first time to synthesize polyethers with multiple arms. Firstly, controlled anionic polymerization was employed to synthesize a linear bromine-terminated PEG (PEG-Br) using ethylene oxide as the monomer and tetraoctylammonium bromide/triisobutylaluminium as the initiating system at room temperature. The terminal bromine in the PEG thus synthesized was then converted into an azide group by the reaction of PEG-Br and sodium azide. A trifunctional linking agent was also prepared by the reaction of trimethylolpropane and propiolic acid. By using 'click' chemistry,a three-arm PEG was finally obtained through the reaction of the azide-terminated PEG and the trifunctional linking agent. The chemical structure of the polymer thus synthesized was characterized using infrared spectroscopy, NMR spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and size-exclusion chromatography with multi-angle laser light scattering. It was found that the synthesized polyether possesses the designed structure. Considering the wide applicability of controlled anionic polymerization and 'click' chemistry, their combination is a valuable way to synthesize various polyethers with multiple arms. (C) 2009 Society of Chemical Industry