Impact of Zwitterions on the Acidity Constant and Glucose Sensitivity of Block Copolymers with Phenylboronic Acid

Abstract

Molecular assemblies that transform in response to pH and saccharide concentration are promising nanomaterials in the field of biomedicine, and polymeric micelles of amphiphilic polymers with phenylboronic acids (PBAs) have been studied. Herein, we report the impact of zwitterions on the acidity constant for the collapse and the glucose sensitivity of a polymeric micelle produced from a diblock copolymer comprising polyacrylamides with PBA and zwitterionic carboxybetaine (PAEBB-b-PCBAAm). The diblock copolymer was synthesized through reversible addition−fragmentation chain-transfer polymerization followed by deprotection. PAEBB-b-PCBAAm produced micellar aggregates in aqueous solutions at a neutral pH, and the polymeric micelles collapsed at a pH of 11.0 because the PBA transformed into a hydroxyboronate anion. The pK a decreased in the presence of glucose owing to boronate ester formation. The PCBAAm chain significantly increased the pH at which the molecular assemblies dissociated. This is probably because the pK a of boronic acid increased through the dipolar interaction of zwitterions, and/or the zwitterionic polymer corona is valid for screening of PBA ionization and electrostatic repulsion of boronate anions. This study on the modulation of pK a through the zwitterionic interaction can facilitate the molecular design of pH-and saccharide-responsive biomaterials.