Single-cluster catalysts (SCCs) have become a research hotspot due to their abundant active sites and tunable interatomic electronic structure, demonstrating excellent catalytic properties. However, the diversity of metal species in SCCs leads to unclear intrinsic activity toward metals and interaction between different metal species. In this manuscript, the impact of a series of precious metal-based (Ru, Rh, Pd, Ag, Os, Ir, Pt, and Au) trimetallic SCCs loaded on graphdiyne (UxVyWz@GDY) on the performance of the oxygen reduction reaction (ORR) is investigated using first-principles. The results show that the 18 holes of graphdiyne (GDY) efficiently achieve uniform doping of trimetallic clusters. In the UxVyWz@GDY structure, Pt3@GDY, Pt2Pd@GDY, and AuPdPt@GDY displayed high thermodynamic limit potentials near the top of the volcano plot at 0.79 eV, 0.80 eV, and 0.82 eV, respectively. These catalysts also show low overpotentials of 0.44 V, 0.43 V and 0.50 V, respectively. Deeper scrutiny of the interaction mechanism between *OH and the catalytic sites on Pt3@GDY, Pt2Pd@GDY, and AuPdPt@GDY unveils the pivotal role of electron transfer and intermetallic interactions in modulating the d-band center. Notably, the observed left shift of the d-band center in these catalysts, leading to the generation of more electron-deficient centers, effectively mitigates the issue of over-absorption between *OH and metal active sites, thereby significantly enhancing *OH desorption. This work provides inspiration for the efficient design of trimetallic SCCs.
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