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 Al³⁺ 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 Al³⁺ 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.

有机磷酸酯化合物 (OP) 的神经毒性可通过抑制乙酰胆碱酯酶 (AChE) 的表达来灾难性地导致神经系统损伤。尽管已经开发出用于间接神经保护的人工系统，但它们仅限于解离 PO 键以消除 OP。然而，这些系统未能克服 AChE 失活的问题。在此，我们报告了我们的发现，将 Al ³⁺设计到金属有机骨架的节点上，合成了具有增强路易斯酸度的 MOF-808-Al。所得MOF-808-Al有效模仿AChE的催化行为，并具有打破OPs活性抑制的自卫能力。机理研究表明，具有强极化效应的Al ³⁺路易斯酸位点将高负电性的–OH基团结合在一起，形成类酶催化中心，从而产生优异的底物活化和亲核攻击能力，活性提高了2.7倍。多功能MOF-808-Al具有良好的生物安全性，可有效降低神经毒性作用并预防神经组织损伤。