Stimuli-Responsive Polymers Based on l -Phenylalanine Residues: Protonation Thermodynamics of Free Polymers and Cross-Linked Hydrogels

Vinyl polymers carrying l -phenylalanine residues were synthesized in the free and in the cross-linked hydrogel form, as homo- and copolymers with N -isopropylacrylamide (NIPAAm). The protonation reaction thermodynamics of the COO - group were studied in aqueous media, at different temperatures and at increased concentrations of sodium chloride, mainly by potentiometry and solution calorimetry. The soluble polymer, namely poly( N -acryloyl- l -phenylalanine), and its copolymers with low NIPAAm content displayed characteristic features. Their basicity constants (log K ), as well as the enthalpy (−Δ H °) changes in relation to α (degree of protonation) showed an abrupt drop at α = 0.5. This was ascribed to the formation of hydrogen bonds between the protonated and the ionized neighboring COO - groups. The process was driven by the side-chain aromatic rings that improved hydrophobic interactions. The entropy (Δ S °) changes sharply increased as a result of the increased macromolecular conformational freedom and the release of water molecules surrounding the hydrophilic groups of the polymer. The corresponding cross-linked polymers formed hydrogels that were responsive to pH, temperature, and ionic strength. The two hydrogels, P9 (homopolymer with 9 mol% cross-links) and CP2 (copolymer with 90 mol% of NIPAAm and 2 mol% cross-links), were characterized for their pH- and temperature-responsive behavior by equilibrium and oscillatory swelling studies. They demonstrated a strong pH-dependent volume phase-transition and an unusual sodium chloride phase-transition phenomenon. Moreover, the hydrogel CP2 exhibited a temperature-dependent volume phase-transition (LCST, lower critical solution temperature) behavior in aqueous solution, where the LCST decreased by lowering the pH. It was nontoxic against the RAW264 cell line.