Ferromagnetic Coupling in Dual‐Atom Nanozymes Enables Spin‐Favorable Catalase‐Like Catalysis for Rheumatoid Arthritis Therapy

ABSTRACT Iron dual‐atom (Fe DA) nanozymes, structurally analogous to natural catalase, exhibit promising catalase‐like (CAT‐like) activity, yet further improving their catalytic performance and elucidating the underlying mechanism remain major challenges. Herein, we developed a cascade strategy integrating vacancy induction and electrostatic adsorption to construct two representative Fe DA nanozymes, pr‐Fe‐DA and py‐Fe‐DA, with coordination environments dominated by pyrrolic‐N and pyridinic‐N, respectively. The resulting py‐Fe‐DA exhibits an exceptionally high CAT‐like activity of 100 U mg −1 , which is 2.4 times that of pr‐Fe‐DA (42 U mg −1 ), representing the highest value reported to date. Mechanistic studies and density functional theory calculations reveal that modulating the nitrogen coordination environment from pyrrolic‐N to pyridinic‐N promotes an antiferromagnetic‐to‐ferromagnetic transition in the magnetic coupling between Fe sites. This transition enables spin‐favorable H 2 O 2 activation through parallel spin alignment of the oxygen atoms in adsorbed H 2 O 2 , thereby accelerating O─H bond cleavage and O 2 generation while decreasing the Gibbs free energy change of the rate‐determining step from 0.84 to 0.08 eV. Moreover, py‐Fe‐DA effectively alleviates oxidative stress and inflammation in rheumatoid arthritis models. These findings identify magnetic coupling as a key descriptor of CAT‐like activity and establish magnetic‐coupling engineering as a powerful strategy for designing high‐performance nanozymes.