Asymmetric Single‐Atom Catalysts Govern Diffusible and Non‐Diffusible Non‐Radical Pathways for Selective Degradation of Antibiotic Resistance Genes

To address the global health threat from antibiotic resistance genes (ARGs), non‐radical dominated advanced oxidation processes (AOPs) show promise for ARG degradation. To better understand and develop the process, a comparative study on diffusible and non‐diffusible non‐radical‐driven AOP would be of great significance. Herein, asymmetric M‐NC (M = Co, Fe) single‐atom catalysts were engineered to enable tunable switching between distinct non‐radical pathways via peroxymonosulfate (PMS) activation. The non‐diffusible electron transfer pathway (ETP)‐dominated Fe‐NC/PMS system displayed higher intrinsic reactivity toward guanine (G) but lower efficiency for ARGs degradation. Compared with diffusible 1 O 2 , non‐diffusible ETP exhibited a limited spatial accessibility to ARGs, which significantly reduces the degradation efficiency of the ETP pathway. In contrast, the diffusible 1 O 2 ‐driven Co‐NC/PMS system selectively oxidized G, achieving irreversible ARG removal with the highest degradation rate constant (2.0 min −1 ) among reported M‐NC/PMS‐based systems. Highlighting the unique advantage of diffusible 1 O 2 in ARG elimination. Moreover, this system maintained high ARG removal (>5.4 log copies/mL) under high salinity (3000 mg/L), low temperature (4°C), and over 20 consecutive cycles, demonstrating exceptional stability and environmental resilience. This study clarifies the inherent advantage of diffusible 1 O 2 over non‐diffusible ETP in elimination and delineates a clear direction for future development.