Synthesis and application of thiol-reactive zwitterionic copolymers

Abstract

In recent years, zwitterionic polymeric materials have gained attention thanks to their ultra-hydrophilicity due to the equimolar number of evenly distributed anionic and cationic moieties that they contain along their polymer chains while still preserving their overall charge neutrality. Moreover, zwitterionic polymers are typically regarded as an alternative to the popular poly(ethylene glycol) (PEG) polymers for anti- biofouling applications to prevent nonspecific protein adsorption and to reduce bacterial or mammalian cell adhesion. Due to its potential uses in interdisciplinary fields, including biomaterials, material science, and targeted delivery, the synthesis of zwitterionic polymers with reactive functional groups is a popular area of research. Polymers with reactive maleimide units as functional groups at the side chains can be obtained by a copolymerization technique using zwitterionic monomers and maleimide-containing monomers. In the thesis, the functionalization of zwitterionic structures was done by copolymerization with an acrylate-based 'latent- reactive' monomer in which maleimide is masked with furan by the Diels-Alder reaction to protect the double bond of the maleimide moiety. By using the advantage of the thermo- responsive behavior of the cycloadduct, the thiol-reactive maleimide unit was activated by the retro DA reaction. To show the effectiveness of the maleimide unit, the thiol-containing hydrophobic dye was conjugated to the linear polymeric structure by the 'click' reaction. Since the hydrophobic dye can become soluble in water when attached to the designed zwitterionic polymer, the methodology serves as a model of drug conjugation.