Halogen Bonding Relay and Mobile Anion Transporters with Kinetically Controlled Chloride Selectivity

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2023 May 19

PMID 37206385

Authors

Toby G Johnson

Andrew Docker

Amir Sadeghi-Kelishadi

Matthew J Langton

Affiliations

Soon will be listed here.

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.

Citing Articles

Anion transporters based on halogen, chalcogen, and pnictogen bonds: towards biological applications.

Singh A, Torres-Huerta A, Meyer F, Valkenier H Chem Sci. 2024; .

PMID: 39268212 PMC: 11385378. DOI: 10.1039/d4sc04644g.

Molecular Machines For The Control Of Transmembrane Transport.

Johnson T, Langton M J Am Chem Soc. 2023; 145(50):27167-27184.

PMID: 38062763 PMC: 10740008. DOI: 10.1021/jacs.3c08877.

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