Direct Synthesis of Poly(2-hydroxyethylacrylamide) Copolymers with Pendant Allyl Groups by Coamidation of Polymethyl Acrylate As a Platform for Tunable Hydrogels by Thiol–Ene Coupling

Hydrophilic N -substituted polyacrylamides are interesting materials for biocompatible and tunable hydrogels. However, synthesizing functional N -substituted polyacrylamide hydrogels or hydrogel precursors via copolymerization of respective functional monomers may lead to variations in monomer composition and dispersity or even undesired cross-linking due to incompatibility with various polymerization processes. Moreover, very few functional acrylamide monomers are commercially available. Hence, traditional postpolymerization modification strategies such as amidation of activated esters have successfully been developed for the preparation of functional polyacrylamides. However, challenges remain in terms of atom economy, the need for specialized monomers, and the susceptibility to hydrolysis. In this work, we report the direct TBD-catalyzed coamidation of poly(methyl acrylate) (PMA) with allylamine and ethanolamine to synthesize multifunctional poly[( N -hydroxyethyl acrylamide)- co -( N -allyl acrylamide)] (P(HEAAm- co -AllAAm)) copolymers containing pendant alkene groups, making them suitable as precursors for hydrogel preparation via thiol–ene click chemistry. By systematically varying the ratio of the two amines, we achieved controlled incorporation of the reactive allyl and hydroxyl groups without adversely affecting dispersity, albeit with preferential incorporation of the more-reactive ethanolamine. Subsequently, the synthesized copolymers were successfully cross-linked via radical-mediated thiol–ene coupling using dithiothreitol as a model cross-linker, to fabricate hydrogels with tunable gelation kinetics, mechanical strength, and swelling behavior. The results demonstrate that increasing the cross-linking density and polymer chain length accelerates gelation and enhances the storage modulus. In addition, successful postgelation thiol–ene modification of the hydrogel by attachment of a fluorescent label confirms the potential of this platform for further functionalization.