Date of Award

Summer 8-15-2015

Author's School

Graduate School of Arts and Sciences

Author's Department

Chemistry

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

The utilization of electron transfer reactions has allowed the transformation of a variety of substrates from polymer surfaces to highly functionalized organic molecules. The intricacies of these electron transfer reactions have been utilized to develop a new platform for building and studying addressable molecular libraries as they interact with biological targets. As a low cost, reusable alternative to other methods of these studying binding interactions, microelectrode arrays are beginning to gain traction with the scientific community as we continually push the limits of their potential. Additionally, the electron transfer techniques used to build the molecular libraries can be expanded to the preparative-scale synthesis of complex molecules. The goal of this thesis is to demonstrate the significance of the advancements made towards these areas.

First, we discuss the development of a tunable polymer surface by taking advantage of a rapid ligand exchange on a boronic ester polymer. This allows us to reversibly modify the surface of an electrode for pacification towards any biological system being monitored. This is followed by the development of a copper-mediated, chemoselective coupling of peptides to the surface of the polymer-coated electrode. This method builds a molecular library with a selective orientation, which is critical for understanding structure-activity relationships of molecule coupled to a surface. Additionally, we demonstrate the ability to directly couple peptides that contain common bioorthogonal functionalities such as an azide and acetylene for “click” chemistry. These techniques further expand our extensive synthetic toolbox for building molecular libraries.

This work of building molecules and selectively modifying electrode surfaces comes to fruition with the analysis of a cyclic peptide, v107 against a vascular endothelial growth factor protein that has been difficult to detect by other analytical techniques. This exciting work helps cement the efforts made by our group over the last several years in developing the microelectrode array-based binding studies as a viable alternative.

Finally, the utility of electron transfer reactions is shifted towards preparative-scale synthesis of highly functionalized ring system. After the improved synthesis of a widely-used ligand, we apply photoredox catalysis to our previous work on anodic oxidation chemistry to better understand the mechanism of radical cyclizations.

Language

English (en)

Chair and Committee

Kevin D Moeller

Committee Members

Suzanne E Lapi, Liviu M Mirica, John-Stephen A Taylor, Timothy A Wencewicz,

Comments

Permanent URL: https://doi.org/10.7936/K7F47MB7

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