Electronic Theses and Dissertations

Date

2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Chemistry

Committee Chair

Daniel Baker

Committee Member

Abby Parrill-Baker

Committee Member

Charles Garner

Committee Member

Jessica Jennings

Committee Member

Tomoko Fujiwara

Abstract

Biofilms are composed of biomolecules, bacteria, and sometimes fungi and are considered the leading cause of antibiotic resistance. Biofilm formation and dispersion is regulated in part by signaling molecules called diffusible signal factors (DSF) through a process termed quorum sensing. However, the mechanism of action behind quorum sensing remains poorly understood. Chapter 1 focuses on the structure activity relationship (SAR) of DSF. DSF are medium chain fatty acids with an alkene at the C2-C3 carbon position. Tail length, branching, and cis/trans configuration all significantly affect antibiofilm action; these affects are also microbe specific. The chapter concludes with a discussion on future considerations for the discipline. This group previously synthesized a DSF analog which showed promising antibiofilm activity for Gram (-) and Gram (+) bacteria. The original studies used a racemic mixture. Often for biologically active compounds with stereocenters, one stereochemical configuration is active while the other is inactive. Chapter 2 describes work to further elaborate on DSF SAR through the separation, characterization, and biological analysis of each enantiomer to determine bioactivity levels. Chapter 3 discusses synthesis of chemical tools for further elaboration on the SAR from chapter 2. The goal was to synthesize a modular compound series to study the effects that ring sizes, tail length, branching, and stereochemistry have on antibiofilm activity. Starting materials for all ring sizes were commercially available and all reactions and product purifications were optimized. Chemical characterization confirmed the desired compounds were successfully made. Chapter 4 summarizes the current knowledge of the field, the research presented herein, and describes potential next steps for these two projects along with future directions for the discipline as a whole. Specifically, additional relevant microbes are proposed to test synthetic DSF bioactivity against. Long term goals for the modular compound series could involve biological testing and coupling to different delivery systems; details are discussed. One appendix is included. It contains all chemical characterization of intermediates and final products with fully annotated spectra and with key features and noteworthy comments added.

Comments

Data is provided by the student.”

Library Comment

Dissertation or thesis originally submitted to ProQuest.

Notes

Embargoed until 12-19-2025

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Available for download on Friday, December 19, 2025

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