Synthesis of pH‐Responsive Hyperbranched Polyesters by Thiol‐Acrylate Michael Addition Reaction and Versatile Post‐Polymerization Functionalization

Thiol-acrylate Michael addition reaction has been utilized as for the synthesis of hyperbranched polyesters with a sulfur atom located at the β-position of the ester carbonyl group, through the A2+B3 addition approach from a dithiol (A2) and tri-acrylate (B3) monomer. This reaction occurs at room temperature, it is 100% atom efficient and produces well-defined hyperbranched polymer (HP) with a degree of branching ≈0.52. Unreacted acrylate groups were utilized for highly efficient post-polymerization functionalization with different functional thiols, producing new HPs with amphiphilic character and different peripheral functional groups. Size exclusion chromatography studies with one representative polymer revealed Mark-Houwink coefficient (α) 0.38, indicating a compact structure, as expected for a typical HP. The presence of the β-thiopropionate ester group in the backbone makes these polymers degradable under mild acidic conditions. Studies with model compounds confirm the slow hydrolysis of the ester linkage by neighboring group participation by the sulfur atom. Glucose functionalized HP, derived by post-polymerization functionalization, produces micelle-like nanoparticles in water with hydrophobic guest encapsulation ability and exhibits sustained release under mild acidic conditions. Such glyco-polymer aggregates show excellent glyco-cluster effect with Concanavaline A (K_a ≈5 × 10⁴ m^-1).