Zwitterionic Amino-Acid-Derived Polyacrylamides with a Betaine Twist – Synthesis and Characterization

Abstract

Amino-acid-derived polyzwitterions and polybetaines (PBs) are two promising alternatives to non-ionic polymers, for example, to increase tumor permeability. In this study, amino-acid-derived polyzwitterions are synthesized and a strategy to quarternize the amine in the side chain functional group is developed to combine the advantages of both types. The functional monomer is polymerized via reversible addition−fragmentation chain-transfer polymerization for which a kinetic study is performed. Further, the impact of the permanent positive charge on amino-acid-derived polyzwitterions is studied based on two zwitterionic polymers obtained via post-polymerization modification (PPM) of Poly(N-acryloxysuccinimide) to allow good comparison between methylated and non-methylated polymers. Circular dichroism shows that the stereocenter remains intact during PPM. pH titration and ζ-potential measurements show that the methylated polymer has a negative ζ-potential over the measured pH range and, therefore, the polymer remains zwitterionic over a broader pH range than its non-methylated equivalent. Both polymers are well tolerated by mammalian cells up to concentrations of 1 mg mL⁻¹. The study introduces a path to a new polymer class that combines the advantages of both PBs and amino-acid-derived polyzwitterions and highlights the impact a permanent charge has on the physiochemical properties.