Synthesis of multifunctional ABC stars with a reduction-labile arm by consecutive ROP, RAFT and ATRP processes

This study aims at versatile synthesis of 3-arm ABC-type (A=poly(epsilon-caprolactone), PCL; B=poly(N-isopropylacrylamide), PNIPAM; C=poly(tert-butyl acrylate), PtBA, or poly(acrylic acid), PAA) miktoarm star copolymers with a reducible disulfide linkage. Using 2-((2-((2-hydroxymethyl-2-((2-bromo-2-methyl)propionyloxy)methyl)propionyloxy)ethyl)disulfanyl)ethyl 4-cyano-4-(phenylcarbonothioylthio)pentanoate (HBCP) as a heterotrifunctional initiator, consecutive ring-opening polymerization (ROP) of epsilon-caprolactone (CL), reversible addition-fragmentation chain transfer (RAFT) polymerization of N-isopropylacrylamide (NIPAM) and atom transfer radical polymerization (ATRP) of tert-butyl acrylate (tBA) afforded ABC(1) star, and followed by a subsequent hydrolysis to give ABC(2) star. H-1 nuclear magnetic resonance (H-1 NMR) and gel permeation chromatography (GPC) analyses revealed the desired stars and their precursors had well-controlled molecular weight and relatively low polydispersity (PDI <= 1.12). As confirmed by GPC analysis, the disulfide linkage in ABC(1) star could be efficiently cleaved upon reductive stimulus, during which the topology was converted from star terpolymer to mixtures of homopolymer (B) and diblock copolymer (AC(1)). In addition to acting as nanocarriers for stimuli-triggered drug delivery systems, ABC stars with terminal bromide, dithiobenzoate and hydroxyl functionalities are expected to form other reduction-cleavable multicomponent copolymers such as (BC-graft-A)(m) and dendritic graft copolymers via postpolymerization modification. Our research affords a straightforward core-first method to construct multifunctional star terpolymers with stimuli-responsive arms and reduction-labile linkage.