# Redox-Controlled Chalcogen Bonding as a Modulator of ZnCl2 Chelation and Transport

## TL;DR

This paper introduces a redox-controlled transporter for Zn2+ ions that adjusts its activity based on chalcogen bonding.

## Contribution

A novel redox-responsive Zn2+ transporter using N–Te chalcogen bonding to modulate ion transport.

## Key findings

- Oxidation of the tellurium center reduces Zn2+ affinity due to strengthened N–Te bonding.
- The transporter enables stimulus-responsive Zn2+ transport across phospholipid bilayers.
- Glutathione can trigger transport by reducing the tellurium center in situ.

## Abstract

Zinc is a ubiquitous metal in biological systems where
an elaborate
array of zinc transporters is involved in maintaining its homeostatic
levels. Because toggling these levels may define new therapeutic approaches,
strategies for the selective transport of Zn2+ ions are
becoming increasingly coveted. Here, we describe a unique stimulus-responsive
Zn2+ transporter, the activity of which can be adjusted
by a redox-controlled intramolecular chalcogen bonding motif positioned
at the heart of the construct. This system features a dipicolylamine
(DPA) zinc chelator engaged, through its amino group, in a N–Te
chalcogen bond with an adjacent diaryl tellurium moiety. Our work
shows that oxidation of the tellurium center to the tetravalent state
decreases the Zn2+ affinity of the DPA unit because of
strengthened N–Te chalcogen bonding. We exploited this property
for the differentiated transport of Zn2+ ions across phospholipid
bilayers while also demonstrating the stimulus-responsive nature of
this system in a set of experiments where transport is initiated in situ through reduction of the TeIV form of
the transporter into its divalent counterpart using glutathione.