Document Type



Doctor of Philosophy


Chemistry, Organic

Date of Defense


Graduate Advisor

George Gokel, Ph.D.


James K. Bashkin

Michael R. Nichols

Christopher D. Spilling


Amphiphiles are molecules that contain both water-soluble and water-insoluble components. The dual nature of these molecules engenders remarkable properties including the ability to self-assemble into ordered structures. Cell membranes are composed of amphiphilic phospholipids that organize into a bilayer motif. Synthetic amphiphiles can interact with natural membranes and influence the transport of molecules across the cell membrane. The work elaborated in this report employs amphiphiles to co-assemble with DNA and transport the genetic material across cell membranes. First, a simplified method for interacting DNA with amphiphiles was developed. Second, a series of known ion-transporting compounds were assayed for their interaction with DNA. Finally, a new class of DNA-binding molecules was designed and characterized. The findings have application in biological research and potentially in gene therapy to cure disease. In addition, some of the molecules designed in this study were found to have antimicrobial properties. These compounds were shown to reverse antimicrobial resistance when co-administered with another antibiotic. Mechanistic studies suggest that the compounds are membrane-active, which implies a more general strategy for combating antibiotic resistance. Together, this work represents a structure-based approach to the understanding of how amphiphilic small molecules interact within biologically relevant systems.

Included in

Chemistry Commons