Oxidation-responsive poly(amino ester)s containing arylboronic ester and self-immolative motif: Synthesis and degradation study

摘要

We report the synthesis of a new type of amphiphilic poly(amino ester)s which can be completely degraded in aqueous media via H_2O_2 oxidation. The polymers were prepared by the controlled Michael-type addition polymerization of a phenylboronic pinacol ester-containing diacrylate and N-aminoethylpiperazine, followed by postmodification with mPEG5K-succinimide ester. Upon oxidation, the side chain phenylboronic esters will be transformed into phenol groups which can trigger the sequential self-immolative process to degrade the polymer main chain. Meanwhile, the amino groups on the polymer main chain are capable of trapping the highly active quinone methides generated in situ during the oxidative degradation of the polymers. Based on the detailed oxidation kinetics and products of several model compounds, the H _2O_2-triggered degradation of nanoparticles of these copolymers was investigated by NMR spectroscopy, GPC, and Nile red fluorescence probe. The results demonstrate that the poly(amino ester) backbones were completely degraded by H_2O_2, resulting in the dissociation of nanoparticles. Oxidative degradation rates of the nanoparticles could be accelerated by increasing the concentration of H_2O_2, the PEGylation degree, or the pH of the buffer. Interestingly, the in situ formed quinone methides could be captured by secondary amines due to their higher nucleophilicity than H_2O. Of potential importance, these amphiphilic oxidation-responsive copolymers are sensitive to stimulation of 200 μM H _2O_2; therefore, they may find application in the field of intelligent drug/gene delivery systems.