Selective partial hydrolysis of amphiphilic copoly(2-oxazoline)s as basis for temperature and pH responsive micelles

The acidic and basic hydrolyses of gradient and diblock copolymers based on 2-methyl-2-oxazoline (MeOx) and 2-phenyl-2-oxazoline (PhOx) were investigated. Various reaction times were examined revealing polymers with varying ratios of PMeOx, PPhOx and poly(ethylene imine) (PEI). It could be shown that under acidic conditions, PMeOx as well as PPhOx are readily cleaved while under basic conditions PPhOx was almost not hydrolyzed leading to higher selectivity. However, partial degradation of the polymers occurred under basic conditions as evidenced by SEC. Thermal investigations of the polymers cleaved under acidic conditions revealed that most obtained copolymers exhibited a melting temperature due to the large PEI content. Self-assembly studies revealed that the partially hydrolyzed copolymers formed micelles at both ambient and elevated temperatures in acidic medium due to protonation of the ethylene imine units leading to good solubility. In contrast, the copolymers were insoluble at ambient temperature in water or basic medium, but self-assembled into spherical micelles at elevated temperatures as evidenced by transmission electron microscopy and dynamic light scattering. As such, these novel PEI–PPhOx copolymers exhibit thermoresponsive micellization behavior based on the crystallization induced phase separation of linear PEI at lower temperatures. Moreover, the copolymer consisting of 84 ethylene imine repeat units, 16 PPhOx groups also revealed pH responsive micellization due to increased solubility of the ethylene imine units upon protonation in acidic solution.