Synthesis of Functionalized and Biodegradable Hyperbranched Polymers from Novel AB2 Macromonomers Prepared by RAFT Polymerization

A straightforward synthetic approach to the preparation of disulfide linked hyperbranched polymers with peripheral pyridyl disulfide functionalities is described. The hyperbranched polymers were obtained by the condensation of novel AB(2) macromonomers bearing alpha-dithobenzoate and omega-double pyridyl disulfide end-groups. These AB(2) macromonomers were prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization of styrene or N-(2-hydroxypropyl) methacrylamide (HPMA) using a novel RAFT agent, N,N'-bis(2-(4-(2-pyridyldisulfide) ethyl butyric-1-carbonyloxo)ethyl) cyanopentanoic amide dithiobenzoate. After polymerization the alpha-dithobenzoate functionality was aminolyzed to yield thiol that was simultaneously subjected to an exchange reaction with pyridyl disulfide, resulting in the formation of hyperbranched structures. The primary chains of the hyperbranched polymers possessed well-defined molecular weights and low polydispersities, The linkages between primary chains consisted of biodegradable disulfide bonds, as confirmed by their reduction in the presence of DL-dithiothereitol(DTT), resulting in the destruction of the hyperbranched structure. The hyperbranched architectures were designed as carriers bearing excess pyridyl disulfide groups for potential reactions with my thiol-bearing biomolecule (e.g., cysteine residue in proteins, or -SH terminal nucleotides).