A mitochondria-targeted deep-red cyclometalated iridium(III)-based probe for detection of hypochlorite in traumatic brain injury

Acute traumatic brain injury (TBI) is often accompanied by excessive mitochondrial hypochlorite (ClO−) production, which contributes to neuroinflammation and secondary damage. However, deep-red mitochondria-targeted probes validated for in vivo imaging in TBI models remain limited. In this study, we developed a mitochondria-targeted deep-red cyclometalated iridium(III) phosphorescent probe, Mito-Ir-HClO, for ClO− detection. The probe showed good photostability and long-lived luminescence, responded to ClO− within 3 min, and achieved a detection limit of 0.45 μM with satisfactory selectivity. Theoretical calculations combined with spectroscopic studies elucidate the sensing mechanism: the selective oxidation of the imine bond (CN) by ClO⁻ activates phosphorescence. Mito-Ir-HClO enabled imaging of mitochondrial ClO− in microglia (BV-2 and HMC3). Mito-Ir-HClO was further applied to in vivo imaging in a TBI mouse model, allowing dynamic visualization of mitochondrial ClO− changes during neuroinflammation. These results provide a useful strategy for the design of ClO− probes and support the application of this probe in visualizing ClO−-related changes in TBI.