2018 Theses Doctoral

Bringing Cyclopropenium to Life

Brucks, Spencer D.

Burgeoning fields of nanomedicine and theranostics are propelled forward by the creative and systematic design of synthetic polymers. Cationic polyelectrolytes, comprising covalently-linked cations within each repeat unit, have drawn particular interest for their ability to bind nucleic acids and permeate cell membranes. Expanding the design space of these systems, we introduced a new family of polyelectrolytes based on the carbon-centered cyclopropenium cation. Cyclopropenium is a modular, aromatic building block with unique structural and electronic properties and, when coupled with modern living polymerization techniques, can be incorporated into macromolecules with precise size, shape, and composition. This thesis describes the translation of cationic polyelectrolytes based on cyclopropenium to biomedical applications and is structured into three parts. The first part evaluates cyclopropenium polymers as candidate non- viral vectors for gene therapy and demonstrates that some derivatives are both biocompatible and efficacious transfection agents. In the second part, nanoparticles comprising cyclopropenium are exploited as live-cell image contrast agents and evolved into potentially theranostic tools. The final part describes a facile route to a novel class of cyclopropenium-based polymers. Together, this thesis illustrates that cyclopropenium is a versatile component of polyelectrolytes, poised to address leading biological challenges.