UCLA

The ability to study and manipulate living systems in their native environment is a major goal in the field of chemical biology. The incorporation of abiotic functionality into naturally-occurring systems has facilitated the understanding of biomolecule function in vivo, the development of new drugs, and the design of biomaterials. Fluorine is an abiotic element that has seen broad use in medicinal chemistry. Fluorine’s high electronegativity and non-polarizability are further exaggerated in highly fluorinated molecules, like perfluorocarbons. This dissertation describes how the use of abiotic perfluorinated molecules can be used to study and manipulate biological systems. Highly perfluorinated saturated compounds form an orthogonal fluorous phase, distinct from both water and organic solutions. This property enables the formation of perfluorocarbon nanoemulsions, which are droplets of fluorous solvent stabilized by surfactant and suspended in water. These stable nanomaterials have been used for oxygen delivery and imaging. This dissertation reports on methods for modifying and encapsulating payloads inside these fluorous droplets for therapeutic and imaging applications.

Perfluorinated aromatic compounds are also distinct from their hydrocarbon counterparts with an inverted quadrupole moment due to fluorine’s electronegativity. These compounds have been used to modify peptides and proteins and enhance protein-protein interactions. Here, we designed macrocyclic hosts to bind perfluoroaromatics as an alternative approach to the bioorthogonal chemical reporter strategy.