Coordination Number Regulation of Iron Single‐Atom Nanozyme for Enhancing H ₂ O ₂ Activation and Selectively Eliminating Cephalosporin Antibiotics

Abstract Nanozymes present promising alternatives to natural enzymes, but controlling nanozymes' performance and employing them for selectively removing antibiotics are extremely challenging. Employing theoretical calculations to design the coordination environments of mental and coordination atoms for directing single‐atom nanozymes synthesis emerges as a promising strategy to enhance their efficiency and selectivity in antibiotic elimination. In this study, the peroxidase‐like specificity of iron single‐atom nanozymes (Fe _SA ‐N _x , x = 2,3, and 4) with specific Fe–N coordination numbers is demonstrated based on theoretical calculations. These calculations guide the synthesis of corresponding ultra‐thin Fe _SA ‐N _x , achieving a high degree of consistency between theoretical predictions and experimental results. Fe _SA ‐N ₃ with a Fe─N3 coordination number proves to be the most effective. The efficient electron transfer from Fe─N3 site to H ₂ O ₂ reduces the free energy required for •OH generation. Quantitative structure‐activity relationship (QSAR) analysis reveals a strong positive correlation between degradation efficiency of cephalosporins and their electron‐donating capabilities ( R ² = 0.820–0.929), realizing selectively eliminating cephalosporins. Integration Fe _SA ‐N ₃ into ceramic membrane (Fe _SA ‐N ₃ /CM) improves hydrophilicity, achieving continuous and stable removal of cephalosporin. This study provides valuable insights into coordination number regulating nanozyme properties for selective antibiotics removal and offers novel perspectives for Fe _SA ‐N ₃ application in integrated systems.