Author's School

Graduate School of Arts & Sciences

Author's Department/Program



English (en)

Date of Award

January 2010

Degree Type


Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

George Gokel


The study of proteins and natural molecules that transport cations and anions across biological membranes has been a major focus of biochemistry and cellular biology for more than a century. The function of ion transporters is vital for all known forms of life. Natural and synthetic transporters can have applications as antimicrobial agents, in nerve impulse transduction and cell signaling. The current work was performed to further the understanding of a diverse array of novel and previously-studied synthetic molecules as membrane-active ion transporters. In the process, important facets such as ion binding capacity, aggregation behavior, ion transport functionality, and antimicrobial activity are investigated. While these studies yield structural and mechanistic insights into our own research group's synthetic systems, they may also aid in understanding both other synthetic ion transporters as well as natural ion carriers and channels. Among the studies that are performed, is the design, synthesis and characterization of members of the dipicolinic dianilide class of compounds as synthetic chloride channels. In originating this project, an array of both known and novel synthetic chloride receptors were modeled computationally. These compounds were selected for their synthetic accessibility and potential use as a chloride transporter. While some of the dipicolinic dianilides or closely-related isophthalic dianilides have been previously reported, few have been investigated for chloride-binding activity and none for chloride transport activity. Chloride binding and transport activity were correlated to the structural variations within the family, which entailed variation of aromatic substituents. This class of molecules are made in a one step synthesis from commercially-available materials. Some members elicit rapid chloride transport activity: over 80% in 10 minutes or less) at low micromolar concentrations. At least one of these select members displays channel functionality in planar bilayers--one of the smallest family of compounds known to do so. Molecular modeling and monitoring aggregation formation by fluorescence spectroscopy reveals that a stack of transporter monomers presents a geometric arrangement conducive of transmembrane pore formation. This class of compounds, among others, is investigated for antimicrobial activity in Gram negative E. coli. While no activity is present for these chloride transporters, co-application with a known antimicrobial cation transporter diminishes the antimicrobial activity of the latter in Gram positive S. epidermidis.


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