Carbonylimidazole-hydroxyl coupling chemistry: Synthesis and block copolymerization of fully bio-reducible poly(carbonate-disulfide)s

Abstract

In recent years, the development of new approaches allowing for the synthesis of environment-responsive copolymers and their nanomaterials has been considered as a promising platform in materials and pharmaceutical sciences. Herein, we report a carbonylimidazole-hydroxyl coupling chemistry as a robust means to synthesize multifunctional bio-reducible poly(carbonate-disulfide)s (PCss) and their block copolymers bearing both carbonate and disulfide groups on the main chains. Our approach centers on the synthesis of a disulfide-bearing difunctional carbonylimidazole monomer for step-growth polymerization with various diols, enabling the fabrication of functional PCss with various properties. The synthesized PCss copolymers exhibit rapid and tunable degradation in a reducing environment into small hydrophilic molecules. Further, the versatility of our approach is demonstrated with block copolymerization through post-modification to synthesize an amphiphilic triblock copolymer and its nanoassemblies exhibiting dual reduction/acid-responsive degradation useful for intracellular drug delivery. These results suggest that the approach utilizing carbonyl imidazole-hydroxyl coupling chemistry opens new opportunities for the design and development of a broad range of novel main-chain-degradable polymeric nanomaterials with multifunctionalities.