Clickable Poly(ethylene glycol)‐Based Copolymers Using Azide–Alkyne Click Cycloaddition‐Mediated Step‐Growth Polymerization

Abstract

The design, synthesis, and post‐polymerization functionalization of linear poly(ethylene glycol) (PEG)‐based polytriazole copolymers containing thiol‐reactive maleimide functional groups as pendant side chains are described. A copper(I)‐catalyzed Huisgen‐type 1,3‐dipolar cycloaddition reaction is utilized to prepare copolymers through a combination of diazide‐ and dialkyne‐functionalized triethylene glycol derivatives, along with a dialkyne‐functionalized furan‐protected maleimide‐containing monomer. After the polymerization, a microwave‐assisted retro‐Diels–Alder reaction is utilized to unmask the pendant maleimide groups by removal of the furan moieties. Post‐polymerization modifications of these PEG‐based copolymers containing the furan‐protected maleimide group are accomplished using a photoinitiated radical thiol‐ene reaction, whereas polymers containing the reactive maleimide group are functionalized using the Diels–Alder and nucleophilic thiol‐ene reactions. The nucleophilic thiol‐ene reaction is utilized to fabricate hydrogels by treatment of the maleimide‐containing PEG polymers with dithiol‐containing crosslinkers. Facile functionalization of thus‐obtained hydrogels under mild conditions is demonstrated through the treatment of the residual maleimide groups within the hydrogel with a thiol‐containing fluorescent dye. image