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

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 H2O2 activation through parallel spin alignment of the oxygen atoms in adsorbed H2O2, thereby accelerating O─H bond cleavage and O2 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.