Oxygen-Binding\nSites of Enriched Gold Nanoclusters\nfor Capturing Mitochondrial Reverse Electrons

Reverse electron\ntransfer (RET), an abnormal backward\nflow of electrons\nfrom complexes III/IV to II/I of mitochondria, causes the overproduction\nof a reduced-type CoQ to boost downstream production of mitochondrial\nsuperoxide anions that leads to ischemia-reperfusion injury (IRI)\nto organs. Herein, we studied low-coordinated gold nanoclusters (AuNCs)\nwith abundant oxygen-binding sites to form an electron-demanding trapper\nthat allowed rapid capture of electrons to compensate for the CoQ/CoQH<sub>2</sub> imbalance during RET. The AuNCs were composed of only eight\ngold atoms that formed a Cs-symmetrical configuration with all gold\natoms exposed on the edge site. The geometry and atomic configuration\nenhance oxygen intercalation to attain a d-band electron deficiency\nin frontier orbitals, forming an unusually high oxidation state for\nrapid mitochondrial reverse electron capture under a transient imbalance\nof CoQ/CoQH<sub>2</sub> redox cycles. Using hepatic IRI cells/animals,\nwe corroborated that the CoQ-like AuNCs prevent inflammation and liver\ndamage from IRI via recovery of the mitochondrial function.