Axial Chlorination Engineering of Single-Atom Nanozyme: Fe-NCl Catalytic Sites for Efficient Peroxidase-Mimicking.

Developing axial coordination engineering of single-atom nanozymes (SAzymes), directly regulating the axial coordination environment of the catalytic site, and optimizing the axial adsorption are meaningful and challenging for boosting the enzyme-like activities. Herein, the axial chlorination engineering of SAzyme with the Fe-NCl catalytic site (Fe-NCl/CNCl) was first proposed, exhibiting superior peroxidase-like activity compared to the traditional Fe-N/CN SAzyme with Fe-N site. The maximal reaction velocity (4.73 × 10 M min), the catalytic constant (246.4 min), and the specific activity (81 U/mg) catalyzed by the Fe-NCl/CNCl SAzyme were 4.9 times, 3.9 times, and 2.7 times those of the Fe-N/CN SAzyme, revealing the enormous advantages of axial chlorination engineering of SAzymes for remarkably improving enzyme-like activities. Moreover, the Fe-NCl/CNCl SAzyme also exhibited an enhanced inhibition effect of tumor cell growth in vitro and in vivo. The density functional theory calculation revealed that the Fe-NCl site was more favorable for releasing OH radical, lowering the energy barrier of rate-determining step, and accelerating the reaction rate compared to the Fe-N site. This work demonstrated the outstanding potential of axial chlorination engineering of SAzymes for improving enzyme-like activities and practical application in tumor therapy.