Transition Metal High‐Entropy Nanozyme: Multi‐Site Orbital Coupling Modulated High‐Efficiency Peroxidase Mimics

Strong substrate affinity and high catalytic efficiency are persistently pursued to generate high‐performance nanozymes. Herein, with unique surface atomic configurations and distinct d‐orbital coupling features of different metal components, a class of highly efficient MnFeCoNiCu transition metal high‐entropy nanozymes (HEzymes) is prepared for the first time. Density functional theory calculations demonstrate that improved d‐orbital coupling between different metals increases the electron density near the Fermi energy level (EF) and shifts the position of the overall d‐band center with respect to EF, thereby boosting the efficiency of site‐to‐site electron transfer while also enhancing the adsorption of oxygen intermediates during catalysis. As such, the proposed HEzymes exhibit superior substrate affinities and catalytic efficiencies comparable to that of natural horseradish peroxidase (HRP). Finally, HEzymes with superb peroxidase (POD)‐like activity are used in biosensing and antibacterial applications. These results suggest that HEzymes have great potential as new‐generation nanozymes. Limited catalytic efficiency and poor selectivity are bottlenecks in the development of nanozymes. This work integrates state‐of‐the‐art high‐entropy alloys with currently reported intrinsic enzyme activity sites to design a class of high‐efficiency transition metal nanozymes. This unique design strategy advances the systematic understanding of the structure‐performance relationship between the electronic structure and catalytic activity of nanozymes.