Unusual Hypochlorous Acid (HClO) Recognition Mechanism Based on Chlorine–Oxygen Bond (Cl−O) Formation

One of the most important endogenous reactive oxygen species, hypochlorous acid (HClO), is involved in numerous pathological and physiological processes. Herein, a near‐infrared fluorescence probe (CyHR) was designed and synthesized for ultrafast (within 0.2 s), sensitive (limit of detection=39.44 nm), and selective response to HClO. The reaction mechanism was systematically analyzed by MS, 1H NMR spectroscopy, HPLC‐MS techniques, and theoretical calculations. The results indicated that HClO can be recognized by CyHR, which is based on chlorine–oxygen (Cl−O) bond formation. To the best of our knowledge, this study is the first to find Cl−O bonds among organic aromatic compounds, given that Cl−O bonds are common among inorganics. Through biological experiments, CyHR was successfully applied to image exogenous and endogenous HClO in macrophage cells (RAW 264.7). Thus, CyHR is a promising tool for HClO‐related physiological and pathological studies and may provide a means for designing HClO‐specific fluorescence probes. Detecting HClO: A highly selective and sensitive probe (CyHR) for detecting HClO was developed. The probe mechanism is based on the electrophilic addition of Cl+ (from the decomposition of HClO) to the phenolic hydroxyl of CyHR. The reaction process was systematically analyzed by MS, NMR spectroscopy, HPLC‐MS techniques, and theoretical calculations. All analysis results suggest the formation of a Cl−O bond.