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Title

Analytical Approaches to the Characterization and Investigation on Novel Synthetic Ion Transporter Families

Date of Award

Summer 8-15-2009

Author's School

Graduate School of Arts and Sciences

Author's Department

Chemistry

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Living cells are usually surrounded by lipid bilayers, which exhibit remarkable structural variety. Further, they incorporate integral proteins, receptors, transporters and various small molecules such as sterols, sphingomyelin, ceramide, etc. The ion transport across bilayer membrane is essential for biological activity and to vitality. The natural transporters, carriers or channels that regulate ion flow within cellular systems are very complex and have prompted the exploration of synthetic transporter systems. The compounds that have emerged from such studies are often simple compounds that can be prepared in a straightforward fashion, and that exhibit a range of functions including ion selective transport. As a result of the work reported here, several families of synthetic ion channels have been designed, synthesized and characterized by multiple analytical techniques. Their function has been assayed by a range of techniques, but especially by the planar lipid bilayer voltage clamp experiment (BLM), which is an in vitro technique used to study the behavior of ion channels within a bilayer membrane. A series of synthetic anion transporters (SATs) that had the same heptapeptide sequence but differed in structure at both the N- and C-termini were assayed by several ion release experiments, by molecular modeling and by ESI-MS. Significant differences in complexation and transport were documented. A family of structurally distinct amphiphiles that we have named “aplosspans” was designed for extreme simplicity but showed classic open-close gating behavior and modest cation-selective transport. A third family of ion transporters was developed from copper-seamed pyrogallarene capsules, which were also shown to function as cation-selective ion channels in bilayer membrane. Study with related pyrogallarenes gave large-conductance pores, probably resulting from self-assembly in the bilayer. These results provide a unique way to predict the supramolecular structures of self-assembled molecules in solution or membrane phase.

Language

English (en)

Chair and Committee

George W. Gokel

Committee Members

John-Stephen A. Taylor, Carolyn J. Anderson, Vladimir B. Birman, Katherine Henzler-Wildman, Kevin D. Moeller

Comments

Permanent URL: https://doi.org/10.7936/K7KW5CZG

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