High-throughput screening of a chalcone library identifies a naked-eye "traffic light" chemosensor for the discrimination of Cu2+ and Ni2+ in aqueous media.

High-throughput screening (HTS) of a 32-membered chalcone library identified C28 as a dual colorimetric and fluorometric chemosensor for Zn2+, Cd2+, Cu2+ and Ni2+ in MeCN. Critically, C28 differentiates Cu2+ from Ni2+ in aqueous media via a naked-eye "traffic light" response, with limits of detection of 0.032 µM and 0.198 µM, both below the recommended maximum daily intake levels. Solid-state validation using a dipstick format confirms suitability for portable, instrument-free deployment, with particular relevance to resource-limited or off-grid settings where rapid water quality assessment is required but currently absent. A systematic structure-activity relationship (SAR) study from over 384 datapoints identified the structural requirements for optimum sensor activity unlocking a second-generation library with enhanced performance.