Alternative to Poly(2-isopropyl-2-oxazoline) with a Reduced Ability to Crystallize and Physiological LCST.

In this work, we sought to examine whether the presence of alkyl substituents randomly distributed within the main chain of a 2-isopropyl-2-oxazoline-based copolymer will decrease its ability to crystallize when compared to its homopolymer. At the same time, we aimed to ensure an appropriate hydrophilic/lipophilic balance in the copolymer and maintain the phase transition in the vicinity of the human body temperature. For this reason, copolymers of 2-ethyl-4-methyl-2-oxazoline and 2-isopropyl-2-oxazoline were synthesized. The thermoresponsive behavior of the copolymers in water, the influence of salt on the cloud point, the presence of hysteresis of the phase transition and the crystallization ability in a water solution under long-term heating conditions were studied by turbidimetry. The ability of the copolymers to crystallize in the solid state, and their thermal properties, were analyzed by differential scanning calorimetry and X-ray diffractometry. A cytotoxicity assay was used to estimate the viability of human fibroblasts in the presence of the obtained polymers. The results allowed us to demonstrate a nontoxic alternative to poly(2-isopropyl-2-oxazoline) (PiPrOx) with a physiological phase transition temperature (LCST) and a greatly reduced tendency to crystallize. The synthesis of 2-oxazoline polymers with such well-defined properties is important for future biomedical applications.