Stimuli-responsive polymers based on L-phenylalanine residues: the protonation thermodynamics of free polymers and cross-linked hydrogels

ABSTRACT: 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 (-¢H°) changes in relation to R (degree of protonation) showed an abrupt drop at R ) 0.5. This was ascribed to the formation of hydrogen bonds between the protonated and the ionized neighboring COOgroups. The process was driven by the side-chain aromatic rings that improved hydrophobic interactions. The entropy (¢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.