Gold nanoclusters-based fluorescence turn off/on probe for sensing of calcium ion and daptomycin

Yellow-green fluorescent AuNCs are synthesized by using 2-mercapto-1,3,4-thiadiazole (MTD) as a template. • Fluorescent MTD-AuNCs could be quenched by Ca 2+ via electrostatic interactions and sulfur coordination. • Daptomycin could restore the fluorescence of MTD-AuNCs by competitive Ca 2+ sequestration. • MTD-AuNCs can be applied as a fluorescence turn-off/on probe for sensing of Ca 2+ and daptomycin. • The limit detection of Ca 2+ and daptomycin are found to be 3.6 and 0.96 μM, respectively. Daptomycin's calcium-dependent antibacterial activity and significant pharmacokinetic variability necessitate therapeutic drug monitoring, yet current methods cannot simultaneously quantify pharmacodynamically critical Ca 2+ and daptomycin. To address this limitation, we developed fluorescent gold nanoclusters functionalized with 2-mercapto-1,3,4-thiadiazole (MTD-AuNCs) via a facile one-pot synthesis. The obtained MTD-AuNCs exhibit bright yellow-green fluorescence (quantum yield = 8.85%, emission at 545 nm) and exceptional stability. Crucially, they demonstrate a reversible fluorescence response: Ca 2+ induces quenching through aggregation caused by electrostatic interactions and sulfur coordination, while subsequent daptomycin addition triggers fluorescence recovery via competitive Ca 2+ sequestration. This dual-response enables sensitive detection of Ca 2+ and daptomycin with excellent selectivity over biological interferents. The assay was successfully validated in human urine samples, showing high accuracy and statistical equivalence to reference methods. This work presents the first nanocluster-based sensor for simultaneous Ca 2+ and daptomycin monitoring, offering a rapid, cost-effective platform for pharmacodynamically-informed antimicrobial therapy optimization. Download: Download high-res image (62KB) Download: Download full-size image