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.