Computational Study on the Peroxidase-like Catalytic Activity of Ligand-Regulated Au ₂₅ Nanoclusters

Atomically precise Au₂₅ nanoclusters are ideal catalyst models for unraveling the nanozyme structure-activity relationship due to their well-defined structures and tunable electronic properties. Herein, ab initio molecular dynamics (AIMD) simulations combined with density functional theory (DFT) calculations were employed to systematically investigate the ligand removal behavior and peroxidase (POD)-like catalytic activity of Au₂₅ nanoclusters modified with phosphine (PR), thiol (SR), alkynyl (C≡CR), and N-heterocyclic carbene (NHC) ligands. Constrained AIMD (cAIMD) simulations revealed that all clusters preferentially remove halogen ligands (Cl/Br) with free energy barriers below 0.25 eV, while NHC and phosphine ligands exhibit stronger binding stability with the Au core. The exposed low-coordination gold sites upon halogen removal display excellent POD-like activity, wherein the second *OH reduction (or the second TMB oxidation) is determined to be the rate-determining step (RDS). Among them, [Au₂₅(NHC)₁₀(Br)₆]²⁺-top (removal of Br at the top coordination site) exhibits the most optimal activity with a moderate RDS barrier (0.83 eV) owing to its isolated active site and higher d-band center that balance *OH adsorption and the catalytic activity. This study clarifies the structure-activity relationship of atomically precise Au₂₅ nanoclusters in the peroxidase-like catalysis, providing a quantitative basis for high-efficiency Au-based nanozyme design.