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

作者：Xing, Linfeng; Wang, Bin; Li, Jin; Guo, Xinjian; Lu, Xicun; Chen, Xiaohua; Sun, Haitao; Sun, Zhenrong; Luo, Xiao^*; Qi, Suhua^*; Qian, Xuhong^*; Yang, Youjun^*

来源：Journal of the American Chemical Society, 2022, 144(5): 2114-2119.

DOI：10.1021/jacs.2c00094

• IN-SITU
• PEROXYNITRITE
• THERAPEUTICS
• IDENTIFICATION
• ANTIOXIDANTS
• COMBINATION
• MECHANISMS
• LIGHT

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.

• 单位
  华东理工大学