A Copper‐Incorporated meso‐(N’‐acetyl‐hydrizide)‐BODIPY as a “Off‐On” Fluorescent Probe for Histidine

Abstract We present a highly sensitive and selective fluorescence “turn‐on” sensor for l ‐histidine (His) detection in aqueous solutions utilizing a 1‐Cu 2+ complex. This sensing platform employs a fluorescence‐based ligand displacement approach, featuring a meso ‐( N ’‐acetyl‐hydrizide)‐based BODIPY derivative ( 1 ) complexed with Cu 2+ . Initially highly fluorescent, compound 1 is selectively quenched by Cu 2+ ions, forming the 1‐Cu 2+ complex. The high affinity between His and Cu 2+ effectively displaces 1 from the complex, restoring fluorescence. The system exhibits rapid response (within 5 minutes), excellent sensitivity (detection limit of 78 nM), operational simplicity, and a large fluorescence “turn‐on” signal. It demonstrates remarkable selectivity for His over other amino acids, with maleimide masking cysteine interference. Notably stable in complex biological matrices, the sensor has successfully quantified His in artificial urine samples. Its practical applicability extends to paper‐based test strips, offering portability and potential for real‐time His monitoring in clinical diagnostics and biological systems.