Issue 19, 2023

Halogen bonding relay and mobile anion transporters with kinetically controlled chloride selectivity

Abstract

Selective transmembrane transport of chloride over competing proton or hydroxide transport is key for the therapeutic application of anionophores, but remains a significant challenge. Current approaches rely on enhancing chloride anion encapsulation within synthetic anionophores. Here we report the first example of a halogen bonding ion relay in which transport is facilitated by the exchange of ions between lipid-anchored receptors on opposite sides of the membrane. The system exhibits non-protonophoric chloride selectivity, uniquely arising from the lower kinetic barrier to chloride exchange between transporters within the membrane, compared to hydroxide, with selectivity maintained across membranes with different hydrophobic thicknesses. In contrast, we demonstrate that for a range of mobile carriers with known high chloride over hydroxide/proton selectivity, the discrimination is strongly dependent on membrane thickness. These results demonstrate that the selectivity of non-protonophoric mobile carriers does not arise from ion binding discrimination at the interface, but rather through a kinetic bias in transport rates, arising from differing membrane translocation rates of the anion–transporter complexes.

Graphical abstract: Halogen bonding relay and mobile anion transporters with kinetically controlled chloride selectivity

Supplementary files

Article information

Article type
Edge Article
Submitted
03 mars 2023
Accepted
03 avr. 2023
First published
04 avr. 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2023,14, 5006-5013

Halogen bonding relay and mobile anion transporters with kinetically controlled chloride selectivity

T. G. Johnson, A. Docker, A. Sadeghi-Kelishadi and M. J. Langton, Chem. Sci., 2023, 14, 5006 DOI: 10.1039/D3SC01170D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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