Facile Synthesis of H₂O₂-Cleavable Poly(ester-amide)s by Passerini Multicomponent Polymerization

Abstract

We report the straightforward synthesis of two types of H 2 O 2 -cleavable poly(ester-amide)s ( P1 and P2 ) via the Passerini multicomponent polymerization (P-MCP) of 4-formylbenzeneboronic acid pinacol ester with 1,6-diisocyanohexane and 1,6-hexanedioic acid or a polyethylene glycol (PEG) dicarboxylic acid. The H 2 O 2 -cleavable phenylboronic acid ester was integrated into the polymer backbone by the in situ formed benzyl ester bond. GPC and 1 H NMR confirmed the complete H 2 O 2 -triggered degradation of these polymers in aqueous medium by a mechanism of sequential oxidation of phenylboronic acid ester and self-immolative elimination. Compared with the hydrophobic polymer P1, the PEG-based water-soluble polymer P2 degraded much faster even at a lower H 2 O 2 concentration. Cytocompatible nanoparticles of polymer P1 loaded with fluorescent Nile red were fabricated, and controlled release of Nile red in response to H 2 O 2 was achieved, thus, demonstrating the utility of these polymers as potential H 2 O 2 -responsive delivery vehicles.