Effect of Solvent Properties on the Critical Solution Temperature of Thermoresponsive Polymers

The ability of thermoresponsive polymers to respond to temperature with a reversible conformational change makes them promising 'smart' materials for solutions in medical and biotechnological applications. In this work, two such polymers and structural isomers were studied: poly(N-isopropyl acrylamide) (PNiPAm) and poly(2-isopropyl-2-oxazoline) (PiPOx). We compare the critical solution temperatures (CST) of these polymers in D₂O and H₂O in the presence of Hofmeister series salts, as results obtained under these different solvent conditions are often compared. D₂O has a higher dipole moment and electronegativity than H₂O, which could significantly alter the CST transition. We used two complementary methods to measure the CST, dynamic light scattering (DLS) and differential scanning calorimetry (DSC) and found that the CST decreased significantly in D₂O compared to H₂O. In the presence of highly concentrated kosmotropes, the CST of both polymers decreased in both solvents. The influence of the kosmotropic anions was smaller than the water isotope effect at low ionic strengths but considerably higher at physiological ionic strengths. However, the Hofmeister anion effect was quantitatively different in H₂O than in D₂O, with the largest relative differences observed for Cl^-, where the CSTs in D₂O decreased more than in H₂O measured by DLS but less by DSC. PiPOx was more sensitive than PNiPAm to the presence of chaotropes. It exhibited much higher transition enthalpies and multistep transitions, especially in aqueous solutions. Our results highlight that measurements of thermoresponsive polymer properties in D₂O cannot be compared directly or quantitatively to application conditions or even measurements performed in H₂O.