单原子纳米酶（SANZs）由原子间分散的单个金属原子构成，与其纳米级对应物相比，其催化活性和选择性更优秀，最近在生物医学领域取得了突破性进展。调制其协同结构可以提高SANZs的催化性能。因此，调整活性中心金属原子的协同数量是增强催化治疗效果的一种潜在方法。本研究合成了多种具有不同氮配位数的原子间分散Co纳米酶，用于过氧化物酶（POD）类单原子催化抗菌治疗。在具有氮配位数3（SACNZs-N3-C）和4（SACNZs-N4-C）的单原子Co纳米酶中，配位数为2（SACNZs-N2-C）的单原子Co纳米酶具有最高的POD类催化活性。动力学分析和密度泛函理论（DFT）计算表明，降低配位数可以降低单原子Co纳米酶的反应能垒，从而提高其催化性能。体外和体内抗菌实验表明，SACNZs-N2-C具有最佳的抗菌效果。该研究提出了通过调节协同数来增强单原子催化治疗的概念证明，为肿瘤治疗和伤口消毒等各种生物医学应用提供了指导思路。重要性声明：单原子催化位点的纳米酶已被证明可以通过表现类过氧化物酶活性有效促进细菌感染创伤的愈合。催化位点的同质协同环境与高抗菌活性相关联，这提供了设计新型活性结构并了解其作用机制的见解。本研究通过切割Co-N键和修饰聚乙烯吡咯烷酮（PVP）设计了一系列具有不同协同环境的钴单原子纳米酶（PSACNZs-Nx-C）。合成的PSACNZs-Nx-C对革兰氏阳性和阴性细菌株都具有增强的抗菌活性，并在体内和体外实验中表现出良好的生物相容性。版权所有 © 2023 Elsevier Ltd.

Single-atomic nanozymes (SANZs) characterized by atomically dispersed single metal atoms have recently contributed to breakthroughs in biomedicine due to their satisfactory catalytic activity and superior selectivity compared to their nanoscale counterparts. The catalytic performance of SANZs can be improved by modulating their coordination structure. Therefore, adjusting the coordination number of the metal atoms in the active center is a potential method for enhancing the catalytic therapy effect. In this study, we synthesized various atomically dispersed Co nanozymes with different nitrogen coordination numbers for peroxidase (POD)-mimicking single-atomic catalytic antibacterial therapy. Among the single-atomic Co nanozymes with nitrogen coordination numbers of 3 (SACNZs-N3-C) and 4 (SACNZs-N4-C), single-atomic Co nanozymes with a coordination number of 2 (SACNZs-N2-C) had the highest POD-like catalytic activity. Kinetic assays and Density functional theory (DFT) calculations indicated that reducing the coordination number can lower the reaction energy barrier of single-atomic Co nanozymes (SACNZs-Nx-C), thereby increasing their catalytic performance. In vitro and in vivo antibacterial assays demonstrated that SACNZs-N2-C had the best antibacterial effect. This study provides proof of concept for enhancing single-atomic catalytic therapy by regulating the coordination number for various biomedical applications, such as tumor therapy and wound disinfection. STATEMENT OF SIGNIFICANCE: The use of nanozymes that contain single-atomic catalytic sites has been shown to effectively promote the healing of bacteria-infected wounds by exhibiting peroxidase-like activity. The homogeneous coordination environment of the catalytic site has been associated with high antimicrobial activity, which provides insight into designing new active structures and understanding their mechanisms of action. In this study, we designed a series of cobalt single-atomic nanozymes (PSACNZs-Nx-C) with different coordination environments by shearing the Co-N bond and modifying polyvinylpyrrolidone (PVP). The synthesized PSACNZs-Nx-C demonstrated enhanced antibacterial activity against both Gram-positive and Gram-negative bacterial strains, and showed good biocompatibility in both in vivo and in vitro experiments.Copyright © 2023. Published by Elsevier Ltd.