Stimuli-responsive poly(ampholyte)s containing L-histidine residues: synthesis and protonation thermodynamics of methacrylic polymers in the free and in the cross-linked gel forms

Methacrylate-structured poly(ampholyte)s were synthesized in the homopolymer and copolymer forms starting from the N-methacryloyl-L-histidine (MHist) and the N-isopropylacrylamide (NIPAAm). They were also obtained in the cross-linked (hydrogel) form, showing a close thermodynamic behaviour as that shown by the corresponding soluble free polymer analogues. Viscometric data revealed that the minimum hydrodynamic volume of the polymer at its isoelectric point (pH 5) shifted to lower pHs as the NIPAAm content increased, and beyond a critical low MHist content the reduced viscosity decreased, even at low pHs. The phenomenon was attributed to hydrophobic forces between the isopropyl groups outweighing the repulsive electrostatic interactions of the polymer in the positively charged form. A similar behaviour was shown by the corresponding hydrogel. The latter also revealed a different phase transition phenomenon induced by external stimuli (temperature, pH, ionic strength, electric current) when compared to the acrylate-structured analogues. The polyMHist, as well as the corresponding monomer, was found for two days to be non toxic against the mouse osteoblasts (MC3T3-E1).