Wang Ying, Paidi Vinod K, Wang Weizhen, Wang Yong, Jia Guangri, Yan Tingyu, Cui Xiaoqiang, Cai Songhua, Zhao Jingxiang, Lee Kug-Seung, Lee Lawrence Yoon Suk, Wong Kwok-Yin
State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
European Synchrotron Radiation Facility, 71 Avenue des Martyrs, Grenoble, 38043, Cedex 9, France.
Nat Commun. 2024 Mar 12;15(1):2239. doi: 10.1038/s41467-024-46528-w.
The precise design of single-atom nanozymes (SAzymes) and understanding of their biocatalytic mechanisms hold great promise for developing ideal bio-enzyme substitutes. While considerable efforts have been directed towards mimicking partial bio-inspired structures, the integration of heterogeneous SAzymes configurations and homogeneous enzyme-like mechanism remains an enormous challenge. Here, we show a spatial engineering strategy to fabricate dual-sites SAzymes with atomic Fe active center and adjacent Cu sites. Compared to planar Fe-Cu dual-atomic sites, vertically stacked Fe-Cu geometry in FePc@2D-Cu-N-C possesses highly optimized scaffolds, favorable substrate affinity, and fast electron transfer. These characteristics of FePc@2D-Cu-N-C SAzyme induces biomimetic O activation through homogenous enzymatic pathway, resembling functional and mechanistic similarity to natural cytochrome c oxidase. Furthermore, it presents an appealing alternative of cytochrome P450 3A4 for drug metabolism and drug-drug interaction. These findings are expected to deepen the fundamental understanding of atomic-level design in next-generation bio-inspired nanozymes.
单原子纳米酶（SAzymes）的精确设计及其生物催化机制的理解对于开发理想的生物酶替代品具有巨大潜力。尽管人们已经付出了相当大的努力来模仿部分受生物启发的结构，但将异质SAzymes构型与类似酶的均相机制相结合仍然是一个巨大的挑战。在此，我们展示了一种空间工程策略，用于制备具有原子铁活性中心和相邻铜位点的双位点SAzymes。与平面铁-铜双原子位点相比，FePc@2D-Cu-N-C中垂直堆叠的铁-铜几何结构具有高度优化的支架、良好的底物亲和力和快速的电子转移。FePc@2D-Cu-N-C SAzyme的这些特性通过均相酶促途径诱导仿生氧活化，类似于天然细胞色素c氧化酶的功能和机制相似性。此外，它为药物代谢和药物-药物相互作用提供了一种有吸引力的细胞色素P450 3A4替代物。这些发现有望加深对下一代受生物启发的纳米酶原子水平设计的基本理解。
