Recent Advances in the ESIPT-based Responsive Probes for the Detection of Bio-Active Molecules CO, NO and H₂S

Excited-state intramolecular proton transfer (ESIPT)-based fluorescent probes have emerged as powerful tools for bioimaging and chemical sensing owing to their large Stokes shifts, dual-emission characteristics, high sensitivity, and reduced self-absorption effects. These unique photophysical properties have facilitated the development of advanced fluorescent probes for the detection of biologically important gasotransmitters, including carbon monoxide (CO), nitric oxide (NO), and hydrogen sulfide (H₂S), which play crucial roles in numerous physiological and pathological processes. This review provides a comprehensive overview of ESIPT-based fluorescent probes reported for the detection of these gasotransmitters, with emphasis on their molecular design strategies, sensing mechanisms, photophysical properties, and biological applications. The reported systems are systematically classified according to their recognition units and analyte-triggered transformations, highlighting the mechanisms responsible for ESIPT modulation and fluorescence signal generation. Particular attention is given to representative fluorophore platforms, including benzothiazole, quinoline, flavone, and related derivatives, as well as the integration of ESIPT with intramolecular charge transfer (ICT), aggregation-induced emission (AIE), and near-infrared (NIR) fluorescence for enhanced analytical performance. Comparative analysis of the reported probes reveals the advantages and limitations of different sensing strategies with respect to sensitivity, selectivity, response kinetics, and biological applicability. Current challenges, including probe toxicity, interference from competing species, and limited in vivo applicability, are critically discussed. Finally, future perspectives toward metal-free systems, multimodal sensing platforms, NIR-emissive probes, and clinically relevant bioimaging applications are presented. This review aims to provide a systematic understanding of ESIPT-based gasotransmitter probes and to offer insights for the rational design of next-generation fluorescent sensing platforms.