Carboxylic acid α-end-functionalized poly(2-oxazoline)s synthesized through benzylic CROP initiators

Abstract

The increasing significance of poly(2-oxazoline)s (POx) as a replacement for poly(ethylene glycol) in biomedical applications has triggered a need for end-functionalized building blocks that can be functionalized with components such as targeting ligands, labels, or other polymers. In the present study, we introduce methyl esters at the α-chain end of hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) as well as hydrophobic poly(2-n-nonyl-2-oxazoline) (PNonOx) through the utilization of two bromomethylbenzoates as initiators for the cationic ring-opening polymerization (CROP) of the corresponding monomers. Kinetic studies revealed that the meta-substituted compound was superior to the para-substituted compound as it enabled faster initiation of the CROP. Detailed studies of the end-group fidelity by NMR spectroscopy, matrix-assisted laser desorption ionization mass spectrometry and high-performance liquid chromatography revealed that PEtOx obtained through CROP at 140 °C contained >20% proton-initiated chains lacking the end group of interest due to the occurrence of chain transfer reactions. The chain transfer was almost absent when the CROP was performed at 85 °C in acetonitrile. Methyl-3-(bromomethyl)benzoate was further applied to obtain block copolymers comprising PEtOx and PNonOx, as well as heterotelechelic PEtOx through termination of the CROP with triethylammonium acetate and sodium azide, respectively. Hydrolysis using aqueous NaOH yielded PEtOx with carboxylic acid α- and azide or hydroxyl ω-end groups. As high end-group fidelities were achieved, the simple commercial initiator opens a new and straightforward route towards various building blocks for advanced POx architectures, in particular with respect to the orthogonal reactivity of carboxylic acid or methyl ester and azide end groups.