Synthesis and Properties of Mono- or Diamine-Initiated Imidazolium-Based Cationic Polypeptides.

A series of cationic polypeptide imidazolium conjugates were prepared by ring-opening polymerization (ROP) of γ-4-(3-chloropropoxycarbonyl)benzyl-L- glutamic acid-based N-carboxyanhydride (CPBLG-NCA) initiated by various mono- or diamine initiators and subsequent side-chain modification with high grafting efficiency. Rapid and controlled ROP was achieved by polymerizing CPBLG-NCA in a dichloromethane/NaHCO3/H2O solvent mixture with the amine initiators. The resulting polypeptides bearing imidazolium iodide pendants showed reversible upper critical solution temperature (UCST)-type thermoresponsive properties in both ethanol and DI water while the polypeptides with tetrafluoroborate counter-anions showed a UCST in phosphate buffer saline (PBS). The cloud point temperature (Tcp) in ethanol and aqueous solutions can be tuned by both molecular weight and the end- or linkage-groups in the main chain. The cationic polypeptides showed good antibacterial activity against Staphylococcus aureus and low hemolysis. Our results provide a facile and rapid ROP strategy to develop new families of stimuli-responsive polypeptides with tunable properties as well as antibacterial polypeptides with optimized selectivity.