In situ functionalization of thermoresponsive polymeric micelles using the "click" cycloaddition of azides and alkynes

Abstract

Well-defined surfactants, composed of a hydrophobic cholesterol moiety and a hydrophilic polymer segment, were synthesized via the atom transfer radical copolymerization of various oligo(ethylene glycol) (meth)acrylates initiated by Cholesteryl-2-Bromoisobutyrate (CBI). After polymerization, the bromine ω-end-groups of the surfactants were transformed into an azide function by nucleophilic substitution. Depending on their hydrophilic-hydrophobic balance, these novel surfactants lead to different types of structures in pure deionized water. For instance, surfactants with a hydrophilic block based on Oligo(Ethylene Glycol) Methyl Ether Acrylate (OEGA) repeat units were found to be molecularly soluble in pure water, even for very short hydrophilic segments. On the other hand, surfactants based on copolymers of OEGA with the more hydrophobic monomer 2-(2-Ethoxyethoxy)Ethyl Acrylate (EEO2A) formed defined micellar aggregates (Dh∼100 nm) in aqueous solution. These aggregates were found to be thermoresponsive and exhibited a lower critical solution temperature in water at approximately 45°C. Moreover, the outer-corona of these micellar assemblies could be successfully functionalized in situ using the copper-catalyzed "click" cycloaddition of azides and alkynes. For instance, the azide functions of the surfactants could be efficiently "clicked" to propargyl alcohol at room temperature and in dilute aqueous solutions. FTIR and 1H NMR measurements indicated that the yield of click cycloaddition was in most cases above 95%. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.