A Highly Selective and Sensitive Chemiluminescent Probe for Real‐Time Monitoring of Hydrogen Peroxide in Cells and Animals

Selective and sensitive molecular probes for hydrogen peroxide (H2O2), which plays diverse roles in oxidative stress and redox signaling, are urgently needed to investigate the physiological and pathological effects of H2O2. A lack of reliable tools for in vivo imaging has hampered the development of H2O2 mediated therapeutics. By combining a specific tandem Payne/Dakin reaction with a chemiluminescent scaffold, H2O2‐CL‐510 was developed as a highly selective and sensitive probe for detection of H2O2 both in vitro and in vivo. A rapid 430‐fold enhancement of chemiluminescence was triggered directly by H2O2 without any laser excitation. Arsenic trioxide induced oxidative damage in leukemia was successfully detected. In particular, cerebral ischemia‐reperfusion injury‐induced H2O2 fluxes were visualized in rat brains using H2O2‐CL‐510, providing a new chemical tool for real‐time monitoring of H2O2 dynamics in living animals. Peroxide triggered, peroxide excited: Real‐time monitoring of hydrogen peroxide (H2O2) in rat brains has been achieved by combining a unique H2O2 sensing strategy and a peroxide bond excited chemiluminescent scaffold. This direct activation of phenoxy‐dioxetane by a tandem Payne/Dakin reaction provides a highly selective, sensitive, and rapid detection of H2O2 in chemical systems, the cellular environment, and living animals.