Atomically precise metal nanoclusters, particularly Au25 and Pt38, have emerged as model catalysts for CO oxidation due to their well-defined structures and tunable electronic properties. These nanoclusters bridge the gap between homogeneous and heterogeneous catalysis, offering atomic-level control over active sites. Their ultrasmall size, typically below 2 nm, results in discrete energy levels and quantum confinement effects that influence catalytic performance. The ability to synthesize these clusters with exact atom counts allows systematic studies of structure-activity relationships, making them ideal for probing mechanistic details of CO oxidation.

Size-dependent activity thresholds play a critical role in the catalytic behavior of these nanoclusters. For Au25, experimental studies show that the intact cluster exhibits negligible CO oxidation activity below 150°C due to strong ligand protection and electronic stabilization. However, partial removal of thiolate ligands activates the cluster, with optimal activity observed when approximately 60-70% of ligands are eliminated. The remaining ligands stabilize the cluster structure while exposing active gold sites. In contrast, Pt38 demonstrates higher intrinsic activity, with CO oxidation initiating at temperatures as low as 50°C. The smaller HOMO-LUMO gap of Pt38 compared to Au25 facilitates electron transfer during the reaction, explaining its superior performance. Both clusters exhibit a sharp activity threshold where decreasing the size below 25 atoms leads to instability under reaction conditions, while increasing beyond 50 atoms results in bulk-like behavior with diminished activity.

Ligand removal strategies are essential for activating these nanoclusters while maintaining their structural integrity. Thermal treatment remains the most widely used method, with optimal temperatures ranging from 200-250°C for Au25 and 150-200°C for Pt38. Excessive heating leads to aggregation, while insufficient treatment leaves the clusters inactive. Oxidative treatments using ozone or oxygen plasma provide alternative activation pathways, often achieving complete ligand removal at lower temperatures than thermal methods. Recent developments include photocatalytic ligand stripping using UV irradiation in the presence of TiO2, which selectively removes ligands while preserving the metal core. The choice of activation method significantly impacts the cluster's surface charge and coordination environment, directly influencing CO adsorption strength and O2 activation capability.

In-situ characterization techniques have provided unprecedented insights into the working mechanisms of these catalysts. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) reveals distinct CO adsorption bands at 2100-2120 cm-1 for Au25 and 2060-2080 cm-1 for Pt38, corresponding to linear CO binding at corner sites. The red shift observed for Pt38 indicates stronger back-donation into the CO π* orbital, consistent with its higher activity. Ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) tracks the oxidation state dynamics during reaction conditions, showing that active Au25 clusters maintain a mixed Au0/Au+ state, while Pt38 predominantly remains metallic. These techniques have identified reaction-induced restructuring phenomena where clusters transiently expand their metal-metal bonds by 5-8% during CO oxidation before returning to their ground state configuration.

Cluster-support interactions profoundly influence the catalytic performance, with CeO2 and TiO2 being the most studied substrates. On CeO2, strong electronic coupling occurs between Au25 and oxygen vacancies, leading to charge transfer that creates active Auδ+ sites. The reducibility of CeO2 facilitates oxygen activation, with studies showing that clusters anchored near Ce3+ sites exhibit turnover frequencies 3-5 times higher than those on stoichiometric surfaces. For Pt38/CeO2 systems, the support stabilizes partially oxidized Ptδ+ species that act as preferential CO oxidation sites. TiO2 supports interact differently, primarily through metal-support charge transfer that modifies the cluster's work function. Anatase TiO2 provides optimal interactions for Au25, creating an electron-deficient cluster surface that enhances O2 adsorption. Rutile TiO2 tends to over-stabilize the clusters, reducing their activity. The interfacial perimeter between cluster and support constitutes the most active zone, accounting for approximately 70% of the total activity in optimized systems.

The reaction mechanism on these nanoclusters proceeds through a Langmuir-Hinshelwood pathway where co-adsorbed CO and O2 react at adjacent sites. Kinetic studies reveal that the rate-determining step shifts from O2 activation on fully ligand-protected clusters to CO oxidation on activated systems. Isotopic labeling experiments using 18O2 demonstrate that support oxygen participates in the reaction for CeO2-supported clusters but remains inert for TiO2-supported systems. The unique electronic structure of these nanoclusters enables simultaneous CO and O2 adsorption at room temperature, a feature rarely observed in conventional nanoparticles.

Stability under reaction conditions remains a challenge, with Au25 maintaining its structure for over 50 hours at 200°C, while Pt38 shows signs of sintering after 20 hours. Advanced stabilization strategies include doping the clusters with heteroatoms such as Ag or Pd, which increases the sintering resistance by 30-40% without compromising activity. Encapsulation within porous oxides represents another promising approach, where the porous matrix confines the clusters while allowing reactant access.

Future developments in this field will likely focus on precisely controlling the cluster-support interface at the atomic level and developing operando characterization techniques with higher spatial and temporal resolution. The fundamental insights gained from these model systems are already informing the design of more efficient industrial catalysts for CO removal applications. The combination of atomic precision in synthesis, advanced characterization, and theoretical modeling positions metal nanoclusters as indispensable tools for unraveling the complexities of heterogeneous catalysis at the molecular level.