Catalytically Potent and Selective Clusterzymes for Modulation of Neuroinflammation Through Single-Atom Substitutions
Emerging artificial enzymes with reprogrammed and augmented catalytic activity and substrate selectivity have long been pursued with sustained efforts. The majority of current candidates rely on noble metals or transition metal oxides with rather poor catalytic activity compared with natural molecules. To tackle this limitation, we strategically designed a novel artificial enzyme based on a structurally well-defined Au25 cluster, namely clusterzyme, which is endowed with intrinsic high catalytic activity and selectivity driven by single-atom substitutions with modulated bond lengths. The 3-mercaptopropionic acid (MPA)-stabilized Au24Cu1 and Au24Cd1 clusterzymes exhibit 137 and 160 times higher antioxidant capacities than the natural trolox, respectively. Meanwhile, the clusterzymes each demonstrate preferential enzyme-mimicking catalytic activities with compelling selectivity: Au25 exhibits superior glutathione peroxidase-like (GPx-like) activity; Au24Cu1 shows a distinct advantage towards catalase-like (CAT-like) activity by its Cu single active site; Au24Cd1 preferably acts as a superoxide dismutase-like (SOD-like) enzyme via the Cd single active site. This unique diversified catalytic landscape manifests distinctive reactions against inflammation in brain. Au24Cu1 behaves as an endogenous multi-enzyme mimic that directly decreases peroxide in injured brain via catalytic reactions, while Au24Cd1, catalyzes superoxide and nitrogenous signal molecules by preference, and significantly decreases inflammation factors such as IL-1\b{eta}, IL-6, and TNFα, indicative of an important role in mitigating neuroinflammation.