EXPLOITING THE FLUOROUS EFFECT TO CREATE SUPRAMOLECULAR FLUOROPEPTIDE MATERIALS
Open Access
- Author:
- Sloand, Janna
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 01, 2021
- Committee Members:
- William Hancock, Major Field Member
Justin Brown, Major Field Member
Scott Medina, Chair & Dissertation Advisor
Daniel Hayes, Major Field Member
Julianna Simon, Outside Unit & Field Member
Daniel Hayes, Program Head/Chair - Keywords:
- Fluorous Effect
Perfluorocarbons
Peptides
Self-Assembly
Templated Assembly
Protein Delivery
Ultrasound - Abstract:
- Organofluorine compounds possess unique structural, chemical, and thermodynamic properties that have encouraged their use in an array of biomedical applications. Synthetic organofluorination strategies have expanded from use as refrigerants toward biomaterials in the last century from observing unique and bioinert characteristics of fluorous materials. Imparted by fluorine’s high electronegativity, the unnatural attributes of fluorous molecules are exclusive to the unique properties of fluorine and the carbon-fluorine (C-F) bond. The preferential organization or solubilization of fluorinated species with other fluorinated species is termed “the fluorous effect”. Exploiting the fluorous effect is a unique tool to engineer biomolecules, and subsequent hierarchical materials, with augmented properties (e.g. the ‘non-stick’ coated cookware via Teflon). Here, I exploit the fluorous effect to guide the supramolecular organization of fluorine-containing peptide building blocks into hierarchical architectures at highly fluorous liquid interfaces. When carbon-fluorine bonds are incorporated into amino acids, or appended to peptide scaffolds, an emergence of an entirely new class of biopolymers are established with unusual bioactivities and structural states compared to their non- fluorinated counterparts. Interestingly, organofluorine peptides have not yet been explored at fluorous liquid interfaces for templated assembly. In light of this, I converge the two fluorous materials – fluorinated amino acid-based building blocks and specifically liquid perfluorocarbons – for the development of functional materials. Importantly, the liquid perfluorocarbon template, volatile but bioinert, has high fluorophilic character imparting them with a particularly unique fluorous liquid phase and interfaces critical for supramolecular organization. First in this dissertation, I use the non-canonical amino acid, Fmoc-pentafluoro-L-phenylalanine (Fmoc-F5-Phe), to fundamentally understand templated assembly at the fluorous-water interface; the resultant architecture developed into organelle-like, mechanomorphogenic films with selective perfluoroalkyl permeability. Structure-activity insights gained from this work led to the design of de novo fluorine-containing peptide sequences with varying F5-Phe content and preferential assembly at liquid perfluorocarbon interfaces into nanoemulsions. I demonstrate that nanoemulsions can be tuned for acoustic sensitivity driven by the fluoropeptide emulsifier’s fluorine content for use as ultrasound (US) contrast agents for real-time imaging of venous clots, as an exemplary application. Expanding upon this work, I employ these US-sensitive nanoemulsions for spatiotemporal intracellular protein delivery. For this, I developed a novel methodology of 'fluoro- masking' proteins for dispersion into the highly fluorous liquid core of nanoemulsions, ultimately affording direct cytosolic therapeutic antibody delivery in vivo. Collectively, a deeper understanding of fluorinated building block interaction with the fluorous phase and at the fluorous interface was realized resulting in unprecedented biomaterials for a broad range of applications, endowed with functionalities otherwise inaccessible without fluorine’s unique character.