Amine-containing diblock terpolymers via AROP: a versatile method for the generation of multifunctional micelles

Abstract

We herein report the synthesis, characterization and block copolymerization via AROP of three different glycidyl amines, piperidinyl(glycidyl amine) (PiGA), N-octylpiperazinyl(glycidyl amine) (OPGA), and N-methylpiperazinyl(glycidyl amine) (MPGA). We synthesized diblock terpolymers of the general structure allyl-poly(ethylene oxide)-block-poly(glycidyl amine-co-furfuryl glycidyl ether) (PEO-b-P(GA-co-FGE)), which include, besides the mentioned glycidyl amine monomers, both the possibility to functionalize or crosslink the hydrophobic block via Diels–Alder reaction of furfuryl glycidyl ether with a maleimide, and to end-functionalize the polymer via thiol–ene click reaction. Diblock terpolymers containing PiGA and OPGA as main monomer of the hydrophobic block self-assemble into micelles of different morphologies in aqueous solution and show pH-dependent disassembly or structural changes. In contrast, MPGA-containing diblock terpolymers can form micelles via complexation of small anionic molecules at low pH values. Further, the amine groups incorporated in the micellar core can be oxidized to the corresponding N-oxides in the presence of H₂O₂ in aqueous solution. Depending on the type of amine-containing repeating unit, this can lead to the disassembly of the micellar structures. The possibility to encapsulate hydrophobic small molecules into the core of the presented micelles and release them upon a specific external trigger emerges PiGA and OPGA as suitable monomers for the synthesis of block copolymers for drug delivery applications. Micelles formed by complexation of MPGA-containing diblock terpolymers with anionic substances can be used to transfer the latter into hydrophobic environments.