Proton Driving Mechanism Revealed in Sulfur‐Doped Single‐Atom FeN2O2 Carbon Dots for Superior Peroxidase Activity

Heteroatom‐doped single‐atom nanozymes (SAEs) hold great promise as enzyme mimics, yet their catalytic mechanisms remain unclear. This study reveals that the proton driving mechanism induced by sulfur doping in single‐atom FeN2O2 carbon dots (S‐FeCDs) significantly enhances peroxidase (POD)‐like activity. Synthesized via low‐temperature carbonization, S‐FeCDs exhibit FeN2O2 coordination with sulfur in the second shell, as confirmed by XAFS and AC‐STEM. The POD‐specific activity of S‐FeCDs reached 295 U/mg, which is 11.2‐fold higher than that of sulfur‐free FeCDs, with natural enzyme‐like kinetics. In situ experiments, kinetic and mechanistic studies revealed that sulfur doping promotes H2O dissociation, enhances H+ adsorption, reduces the ΔG for H2O2‐to‐·OH conversion. DFT revealed a lowered energy barrier for the rate‐determining step (2*OH → *O+*H2O) from 2.50 eV to 1.62 eV. In vivo, S‐FeCDs demonstrated broad pH efficacy in MRSA‐infected wound models, achieving near‐complete healing within 7 days. The proton driving mechanism was further validated through nitro compound reduction, demonstrating accelerated N‐H bond activation. This work highlights the critical role of sulfur‐induced proton dynamics in enhancing SAEs performance, providing a rational strategy for designing multifunctional nanozymes in biomedical and catalytic applications.