Catalytically potent and selective clusterzymes for modulation of neuroinflammation through single-atom substitutions

• Published in: Nature communications 2021-01, Vol.12 (1), p.114-14, Article 114
• Main Authors: Liu, Haile, Li, Yonghui, Sun, Si, Xin, Qi, Liu, Shuhu, Mu, Xiaoyu, Yuan, Xun, Chen, Ke, Wang, Hao, Varga, Kalman, Mi, Wenbo, Yang, Jiang, Zhang, Xiao-Dong
• Format: Article
• Language: English
• Subjects: 631/378/371; 631/45/173; 631/92/607; 639/638/77/603; 639/638/911/406; Animals; Antioxidants; Brain - enzymology; Catalase; Catalysis; Catalytic activity; Cell Line; Enzymes; Enzymes - chemistry; Glutathione; Glutathione peroxidase; Glutathione Peroxidase - chemistry; Humanities and Social Sciences; Inflammation; Male; Metals; Metals - chemistry; Mice; Mice, Inbred C57BL; Mimicry; Models, Molecular; multidisciplinary; Neuromodulation; Neurons - enzymology; Neurons - immunology; Noble metals; Organometallic Compounds - chemistry; Peroxidase; Peroxide; Science; Science (multidisciplinary); Selectivity; Substrates; Superoxide dismutase; Superoxide Dismutase - chemistry; Superoxides; Transition metal oxides; Vitamin E
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20275-0

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. Au 24 Cu 1 and Au 24 Cd 1 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 , Au 24 Cu 1 and Au 24 Cd 1 displaying compelling selectivity in glutathione peroxidase-like (GPx-like), catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) activities, respectively. Au 24 Cu 1 decreases peroxide in injured brain via catalytic reactions, while Au 24 Cd 1 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.