An Edaravone-Guided Design of a Rhodamine-Based Turn-on Fluorescent Probe for Detecting Hydroxyl Radicals in Living Systems.

The hydroxyl radical (·OH), one of the reactive oxygen species (ROS) in biosystems, is found to be involved in many physiological and pathological processes. However, specifically detecting endogenous ·OH remains an outstanding challenge owing to the high reactivity and short lifetime of this radical. Herein, inspired by the scavenging mechanism of a neuroprotective drug edaravone toward ·OH, we developed a new ·OH-specific fluorescent probe . is a hybrid of rhodamine and edaravone and exploits a ·OH-specific 3-methyl-pyrazolone moiety to control its fluorescence behavior. itself is almost nonfluorescent in physiological conditions, which was attributed to the formation of a twisted intramolecular charge transfer (TICT) state upon photoexcitation and the acylation of its rhodamine nitrogen at the 3' position. However, upon a treatment with ·OH, its edaravone subunit was converted to the corresponding 2-oxo-3-(phenylhydrazono)-butanoic acid (OPB) derivative (to afford ), thus leading to a significant fluorescence increase (ca. 195-fold). shows a high sensitivity and selectivity to ·OH without interference from other ROS. has been utilized for imaging endogenous ·OH production in living cells and zebrafishes under different stimuli. Moreover, allows a high-contrast discrimination of cancer cells from normal ones by monitoring their different ·OH levels upon stimulation with β-Lapachone (β-Lap), an effective ROS-generating anticancer therapeutic agent. The present study provides a promising methodology for the construction of probes through a drug-guided approach.