A Fluorogenic ONOO–-Triggered Carbon Monoxide Donor for Mitigating Brain Ischemic Damage

Ischemia-reperfusion (I/R) injuries are from the secondary radicals of ONOO^-. Direct radical scavenging is difficult because of their high reactivity. ONOO^- is longer-lived than the radicals in the biological milieu. Scavenging ONOO^- suppresses radical generation preventively. CO is neuroprotective during ischemia. With the scaffold of carbon-caged xanthene, we designed an OONO^--triggered CO donor (PCOD585). Notably, PCOD585 exhibited a concomitant fluorescence turn-on upon ONOO^-detection, facilitating microscopic monitoring. PCOD585 was cytoprotective in oxygen-glucose deprivation (OGD)-insulted PC-12 cells. It was permeable to the blood-brain barrier and further exhibited neuroprotective effects to MCAO rats by reducing infarction volume, cell apoptosis, and brain edema.