Poly(2-oxazoline) termination with functional nucleophiles

Poly(2-oxazoline) (POx) represents a promising replacement for poly(ethylene glycol) in biomedical applications. For POx to readily traverse the clinical pipeline, its composition must be well characterized. While initiation and propagation have been thoroughly studied, termination is overlooked as it rarely impacts polymer molecular weight and dispersity. Here, we use a uniquely sensitive size exclusion chromatography (SEC) assay to explore termination efficiency and mechanism with five functional nucleophiles. The nucleophiles were chosen due to their ability to be further elaborated by efficient, “click-type” reactions. Termination across poly(2-phenyl-2-oxazoline), poly(2-methyl-2-oxazoline) and poly(2-nonyl-2-oxazoline) was quantified and trends based on nucleophilicity parameter ( N ) were established. Competition experiments with water revealed further differentiation. Thioacetate was the top performing terminator, displaying near quantitative conversions even in the presence of water. Overall, this work demonstrates the complexity in POx termination and suggests this step in the polymerization should not be overlooked when preparing POx for biomedical applications.