# Glutathione-activatable synthetic channel for hopping-mediated anion transport

## TL;DR

Researchers created a synthetic ion channel that activates in response to glutathione, enabling selective anion transport across membranes.

## Contribution

A glutathione-activatable synthetic anion channel is introduced, which self-assembles upon activation to enable selective anion transport.

## Key findings

- The protransporter 1c′ lacks ion channel activity due to poor self-assembly.
- Glutathione activation generates a functional anion channel with preferential chloride selectivity.

## Abstract

Controlled transport of ions across the cellular membrane is an essential process. While nature employs stimuli-gated transmembrane proteins to facilitate the appropriate transport of essential ions or molecules across cellular membranes, the endeavor to create a stimuli-controlled synthetic analogue presents considerable challenges. Herein, we introduced isophthalamide-based synthetic ion transporters 1a–1e and a protransporter 1c′. Transport studies divulged that even though the protransporter 1c′ cannot transport the anions, the glutathione-based activation generates a self-assembled anion channel 1c in the membrane and turns ON the anion transport with preferential selectivity towards the chloride anion. Detailed mechanistic studies validated that the transport of anions occurs via the antiport mechanism. An electrophysiological experiment divulged that the protransporter is inefficient in forming stable channels in the membrane. In contrast, the addition of the GSH releases the compound 1c, which forms a stable channel in the membrane with an average diameter of 4.7 ± 0.3 Å. The calculated single-channel conductance is 165 ± 1 pS, and the average PCl−/PK+ = 5.0 ± 1.3. A dodecameric assembly of the monomeric rosette of 1c and [(1c)12 + Cl−] was geometrically optimized to understand the ion channel formation and investigate the responsible channel–ion interactions for the ion transport process.

A glutathione-activatable synthetic anion channel is reported. The doubly 2,4-dinitrobenzene-protected form lacks ion channel activity due to poor self-assembly. Activation with glutathione restores self-assembly and turns ON ion channel activity.