RAFT Copolymerization of DMAEA and AETAC Toward Charge‐Shifting Copolymers With Tunable Heparin Complexation

Charge-shifting polycations based on poly(2-(N,N-dimethylamino)ethyl acrylate) (PDMAEA) are promising materials for forming polyelectrolyte complexes relevant to biomedicine. Their complexation behavior can be tuned by incorporating a controlled fraction of permanently charged quaternary ammonium units. This strategy relies on the homogeneous distribution of these units while maintaining charge-shifting properties of PDMAEA. Herein, we report the reversible addition-fragmentation chain-transfer copolymerization of 2-(N,N-dimethylamino)ethyl acrylate (DMAEA) and 2-acryloxyethyltrimethylammonium chloride (AETAC). Optimized conditions afford copolymers with molecular weights of 26 000-130 000 g/mol and dispersities below 1.1, with good agreement between theoretical and experimental compositions. Reactivity ratios close to unity indicate near-statistical copolymerization and a homogeneous distribution of AETAC units along the chains. Hydrolysis studies showed that incorporating up to 40 mol% AETAC negligibly influenced the rate of DMAEA hydrolysis. In contrast, isothermal titration calorimetry revealed that increasing the AETAC content resulted in three times more heparin molecules bound per copolymer chain for copolymers between 10 and 40 mol% AETAC, while reducing the number of binding contacts per heparin molecule. The results demonstrate that the precise compositional control achieved under the proposed polymerization conditions enables tuning of the complexation behavior of DMAEA-based copolymers, which may be useful for the design of biomedical polyelectrolyte platforms.