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.
Jiang et al. (2026) studied this question.