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Thiosquaramides: pH switchable anion transporters
Journal article   Open access

Thiosquaramides: pH switchable anion transporters

Nathalie Busschaert, Robert B. P Elmes, Dawid D Czech, Xin Wu, Isabelle L Kirby, Evan M Peck, Kevin D Hendzel, Scott K Shaw, Bun Chan, Bradley D Smith, …
Chemical science (Cambridge), Vol.5(9), pp.3617-3626
09/01/2014
DOI: 10.1039/C4SC01629G
PMCID: PMC4486358
PMID: 26146535
url
https://doi.org/10.1039/C4SC01629GView
Published (Version of record) Open Access

Abstract

The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small series of thiosquaramides was synthesised and their pH-dependent chloride binding and anion transport behaviour was investigated using 1 H NMR titrations, single crystal X-ray diffraction and a variety of vesicle-based techniques. Spectrophotometric titrations and DFT calculations revealed that the thiosquaramides are significantly more acidic than their oxosquaramide analogues, with p K a values between 4.0 and 9.0. This led to the observation that at pH 7.2 the anion transport ability of the thiosquaramides is fully switched OFF due to deprotonation of the receptor, but is completely switched ON at lower pH.

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