Complex formation of pendant lysine residue-containing zwitterionic random copolymer with copper (II)

Excess copper accumulation in the body can lead to various health complications including Parkinson’s disease, Alzheimer’s disease, gastrointestinal disorders, liver damage, and hemolytic anemia. As such, the development of effective strategies to remove excess copper is critical for preventing these adverse health outcomes. In this study, a copolymer (P(MPC/LysA)) comprising 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) and l-lysinylacrylamide (LysA) was synthesized via reversible addition–fragmentation chain transfer (RAFT) radical polymerization. Under different pH conditions, the pendant primary amine (–NH³⁺) and carboxy groups (–COOH) of LysA underwent protonation and deprotonation, resulting in cationic, zwitterionic, and anionic structures. The copolymer exhibited a zwitterionic structure under physiological conditions due to the pH-independent neutral charge of MPC. The LysA residues formed a complex with copper (II) ions (Cu²⁺) under neutral-basic conditions, with two pendant l-lysine residues forming a complex with one Cu²⁺ molecule. The addition of Cu²⁺ to an aqueous solution of P(MPC/LysA) at pH 7.4 resulted in the formation of interpolymer aggregates due to Cu²⁺/LysA complex formation. Overall, this study reveals that P(MPC/LysA) has potential for use in removing excess Cu²⁺ in the body by forming water-soluble aggregates with Cu²⁺ at physiological pH.