Bioinspired Chemosensor with Configuration-Dependent Affinity for Localized Tracking of Labile Zn²⁺ during Neuronal Differentiation

Homeostasis and transportation of labile Zn 2+ across neuronal membranes are of great importance for biological functions, in which molecular tools are urgently demanded to understand the mechanism of actions in depth. Here, we report a zinc-specific fluorescence-switchable chemosensor ( trans T–P) for the targetable tracing of labile Zn 2+ in live nerve cells. The molecular design was inspired by the coordination structure in the catalytic centers of metalloenzymes. The strong coordination and response to Zn 2+ were demonstrated to be stereochemistry-sensitive, in which only the trans conformer has ultrahigh affinity, selectivity, and sensitivity. Benefited from its amphiphilic and phosphate-bearing molecular structure, trans T–P is readily cell membrane permeable and achieves preferential accumulation in the near-membrane region, enabling regionally specific localization and imaging of labile Zn 2+ at the intracellular side of plasma membranes. Provided with these unique properties, trans T–P achieved an in situ visualization of labile Zn 2+ fluctuations during neuronal differentiation. The targeted sorting and tracking highlight the prominence of trans T–P in monitoring Zn 2+ spatiotemporal dynamics for understanding the actions of labile Zn 2+ in nerve functions and development.