Radical-triggered ring-opening of aminocyclopropane for detection of hydroxyl radicals in living cells†

Abstract

Hydroxyl radicals (˙OH), highly reactive oxygen species involved in oxidative stress and cancer therapy, are challenging to detect intracellularly due to their short lifetime, low concentration, and high reactivity. To address this, a novel ˙OH-specific fluorescent probe, CC-7, was developed by integrating an aminocyclopropane group into a coumarin derivative. This design was inspired by the radical-mediated ring-opening of aminocyclopropanes in synthetic chemistry. The ring-opening reaction triggered by ˙OH in CC-7 produces a significant “Fluorescence-ON” response with a 10-fold increase in intensity, demonstrating high selectivity for ˙OH over other reactive oxygen species. CC-7 effectively visualized intracellular ˙OH, distinguished between normal (HEK-293T) and cancer cells (4T1), and monitored ˙OH generated by chemotherapeutic agents like doxorubicin and cisplatin. This study highlights CC-7 as a powerful tool for selectively detecting ˙OH in living cells, with potential applications in investigating oxidative stress-related diseases and monitoring cancer therapy.