The Design of Sulfobetaine Polymers with Thermoresponsiveness under Physiological Salt Conditions

Thermoresponsive polymers are attractive in terms of basics and applications because of the phase separation in aqueous solution. Some sulfobetaine polymers are known for their antifouling biocompatibility and upper critical solution temperature (UCST) type thermoresponsiveness; however, thermoresponsiveness disappears in aliphatic sulfobetaine polymers in physiological salt conditions. Aromatic cation-containing sulfobetaine polymers are not responded because of the strong intermolecular interactions. In this study, new sulfobetaine methacrylamides with a pyridinium cation, 3-(4-(2-methacrylamido)alkyl pyridinio-1-yl)propane-1-sulfonates, (PySMAAm)s, are designed and then prepared the homopolymers using aqueous reversible addition-fragmentation chain transfer polymerization. The P(PySMAAm)s exhibited UCST-type thermoresponsiveness that is induced by substitution of the dipole-dipole interaction between the interpolymer side chain to an ion-dipole interaction in physiological salt conditions. The thermoresponsiveness is affected by the molecular weight and structure of the side chains. Such sulfobetaine polymers can be promising tools as biomaterials especially for drug delivery and regenerative medicine.