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 have rather poor catalytic activity compared with natural molecules. To tackle this limitation, we design artificial enzymes based on a structurally well-defined Au-25 cluster, namely clusterzymes, which are endowed with intrinsic high catalytic activity and selectivity driven by single-atom substitutions with modulated bond lengths. Au24Cu1 and Au24Cd1 clusterzymes exhibit 137 and 160 times higher antioxidant capacities than natural trolox, respectively. Meanwhile, the clusterzymes demonstrate preferential enzyme-mimicking catalytic activities, with Au-25, Au24Cu1 and Au24Cd1 displaying compelling selectivity in glutathione peroxidase-like (GPx-like), catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) activities, respectively. Au24Cu1 decreases peroxide in injured brain via catalytic reactions, while Au24Cd1 preferentially uses superoxide and nitrogenous signal molecules as substrates, and significantly decreases inflammation factors, indicative of an important role in mitigating neuroinflammation. Artificial enzymes with reprogrammed and augmented catalytic activity and substrate selectivity have emerged to tackle limitations of noble metals or transition metal oxides. Here, the authors report Au-25 clusterzymes which are endowed with high catalytic activity and selectivity in a range of enzyme-mimicking reactions.

Automated summary

Clusterzymes based on Au-25 clusters exhibit high catalytic activity and selectivity in enzyme-mimicking reactions, such as GPx-like, CAT-like, and SOD-like activities. They can effectively decrease oxidative stress and inflammation in injured brain, showing promise in mitigating neuroinflammation.