Biomimetic single Al-OH site with high acetylcholinesterase-like activity and self-defense ability for neuroprotection

• Published in: Nature communications Vol. 14; no. 1; pp. 6064 - 10
• Main Authors: Xu, Weiqing, Cai, Xiaoli, Wu, Yu, Wen, Yating, Su, Rina, Zhang, Yu, Huang, Yuteng, Zheng, Qihui, Hu, Liuyong, Cui, Xiaowen, Zheng, Lirong, Zhang, Shipeng, Gu, Wenling, Song, Weiyu, Guo, Shaojun, Zhu, Chengzhou
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.09.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 119/118; 14/10; 14/19; 14/34; 631/45/603; 639/301/54/989; 639/638/298/921; Acetylcholinesterase; Acidity; Aluminum; Biomimetics; Damage prevention; Deactivation; Electronegativity; Humanities and Social Sciences; Lewis acid; Metal-organic frameworks; multidisciplinary; Nervous system; Neuroprotection; Neurotoxicity; Organophosphates; Science; Science (multidisciplinary); Self defense; Substrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-41765-x

Neurotoxicity of organophosphate compounds (OPs) can catastrophically cause nervous system injury by inhibiting acetylcholinesterase (AChE) expression. Although artificial systems have been developed for indirect neuroprotection, they are limited to dissociating P-O bonds for eliminating OPs. However, these systems have failed to overcome the deactivation of AChE. Herein, we report our finding that Al 3+ is engineered onto the nodes of metal–organic framework to synthesize MOF-808-Al with enhanced Lewis acidity. The resultant MOF-808-Al efficiently mimics the catalytic behavior of AChE and has a self-defense ability to break the activity inhibition by OPs. Mechanism investigations elucidate that Al 3+ Lewis acid sites with a strong polarization effect unite the highly electronegative –OH groups to form the enzyme-like catalytic center, resulting in superior substrate activation and nucleophilic attack ability with a 2.7-fold activity improvement. The multifunctional MOF-808-Al, which has satisfactory biosafety, is efficient in reducing neurotoxic effects and preventing neuronal tissue damage. The neurotoxicity of organophosphate compounds damages nerve system by inhibiting acetylcholinesterase (AChE) expression, but it is difficult to overcome the deactivation of AChE. Here, the authors report the design of Lewis acid sites in metal-organic frameworks as AChE mimics for effective neuroprotection.