Controlled Synthesis of Amino Acid-Based pH-Responsive Chiral Polymers and Self-Assembly of Their Block Copolymers

Abstract

Leucine/isoleucine side chain polymers are of interest due to their hydrophobicity and reported role in the formation of α-helical structures. The synthesis and reversible addition-fragmentation chain transfer (RAFT) polymerization of amino acid-based chiral monomers, namely Boc-L-leucine methacryloyloxyethyl ester (Boc-L-Leu-HEMA, 1a), Boc-L-leucine acryloyloxyethyl ester (Boc-L-Leu-HEA, 1b), Boc-L-isoleucine methacryloyloxyethyl ester (Boc-L-Ile-HEMA, 1c), and Boc-L-isoleucine acryloyloxyethyl ester (Boc-L-Ile-HEA, 1d), are reported. The controlled nature of the polymerization of the said chiral monomers in N, N-dimethylformamide (DMF) at 70 °C is evident from the formation of narrow polydisperse polymers, the molecular weight controlled by the monomer/chain transfer agent (CTA) molar ratio and the linear relationship between molecular weight and monomer conversion. The resulting well-defined polymers were used as macro-CTAs to prepare corresponding diblock copolymers by RAFT polymerization of methyl (meth)acrylate monomers. Deprotection of Boc groups in the homopolymers and block copolymers under acidic conditions produced cationic, pH-responsive polymers with primary amine moieties at the side chains. The optical activity of the homopolymers and block copolymers were studied using circular dichroism (CD) spectroscopy and specific rotation measurements. The self-assembling nature of the block copolymers to produce highly ordered structures was illustrated through dynamic light scattering (DLS) and atomic force microscopy (AFM) studies. The side chain amine functionality instills pH-responsive behavior, which makes these cationic polymers attractive candidates for drug delivery applications, as well as for conjugation of biomolecules.