Transmembrane anion transport: investigating mechanism and selectivity

Abstract

In the last decade, the development of synthetic anion transporters has attracted much attention. A variety of small molecules have been established to facilitate the transport of biologically relevant anions such as chloride, bicarbonate and sulfate across lipid bilayers. This interest has been piqued due to their potential as therapeutics for ‘channelopathies’ such as cystic fibrosis and in some cases their anion transport has been linked to anti-cancer activity in cells.

This thesis explores a new series of chloride transporters which possessed high binding affinity for oxo-anions such as phosphate and bicarbonate. They were found to transport via an antiport mechanism, with a preference for Cl-/NO3- over Cl-/HCO3-. The series also exhibited some self-association characteristics, which appeared detrimental to their transport activity.
The transmembrane transport of fluoride was also investigated using a series of strapped calix[4]pyrroles. The fluoride transport was monitored directly using ion selective electrode and NMR techniques. The length of the strap was found to modulate the fluoride over chloride selectivity, showing fluoride selectivity for the shortest strapped calix[4]pyrroles.

Furthermore the fundamental transport mechanism of these calix[4]pyrroles was elucidated as electrogenic by extending the series and employing cationophore coupling techniques. The smallest strapped receptor showed unprecedented Cl- selectivity even in the presence of fatty acid. Additional studies showed the rest of the series’ halide and nitrate selectivity follows an anti-Hofmeister bias.

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Identifiers

ORCID for Philip Gale: orcid.org/0000-0001-9751-4910

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