On the nature of the thermoresponsiveness of poly(2-isopropyl-2-oxazoline) in aqueous solution

Poly(2-oxazoline)s (POAs) are a class of biocompatible polymers, that is gaining a prominent role in biomedical field due to its thermoresponsiveness at temperatures compatible with physiologically relevant ones. This work represents the first extensive molecular dynamics simulation study of poly(2-isopropyl-2-oxazoline) (PiPOx) - that is amongst the simplest thermoresponsive POAs - both at infinite dilution as well as finite concentration, aimed at unveiling the thermoresponsive nature of this macromolecular class. Benchmarking simulations against experimental data obtained from specifically synthesized PiPOx's with controlled degree of polymerisation, we can explore the nature of thermoresponsive behaviour. This appears to be dominated by intermolecular interactions that lead to the experimentally observed liquid-liquid phase separation (LLPS). By means of a combined atomistic and coarse-grained approach, we could characterise the polymer rich phase formed upon LLPS, finding average properties of the solution, such as the average distance between polymer chains, that are reminiscent of the experimental lattice pitch measured on crystalline phases. At last, we can hint at the presence of a Liquid Crystalline phase in the polymer rich region at high temperatures