Diffuse reflectance infrared Fourier-transform spectroscopy (DRIFTS) using CO or another adsorbate as a probe molecule is a versatile operando method to characterize the electronic structure and nuclearity of the surface metal species in working catalysts. Specifically, CO has a strong binding to many metal centers, whose site-specific vibrational fingerprint in 1800 ~ 2200 cm -1 depends on the metal oxidation state and local coordination. For instance, the different binding modes (e.g., linear, bridged, and geminal) of CO induce changes in the vibrational frequency, thus providing structural information about the adsorption site. As shown in Figures 7A ~ 7C, the dispersion, oxidation state, and CO oxidation activity of Pt/γ-Al2O3 SAC were simultaneously monitored by operando XAS and DRIFTS, which confirmed the dynamically aggregated Pt clusters from single atoms as the active sites for CO oxidation. The main peak of CO-DRIFTS at 2100 ~ 2106 cm -1 is ascribed to the linearly adsorbed CO on single atoms, while the shoulder at 2070 ~ 2090 cm -1 present in heating and cooling profile can be ascribed to adsorption on partially oxidized Pt clusters. Single Pt atoms can hardly accommodate CO and oxygen, and the adsorption competition is favorable to oxygen at low temperatures and CO at higher temperatures, which may prevent the SACs from catalyzing the reaction. As the clusters are more active than the single atoms, their formation during the reaction increases CO oxidation activity. Likewise, CO-DRIFTS was conducted to probe the evolution of surface Pd species in methane oxidation (Figures &). After initial saturation of CO on isolated Pd1 δ+ and Pd 2+ at 2134 and 2145 cm -1 in the first 5 mins, peaks from linear CO adsorption on Pd 0 gradually appear at 2098 and 2068 cm -1 , indicating the nucleation of highly dispersed PdOx clusters containing mixed Pd 2+ /Pd 0 states. The presence of highly dispersed Pd species such as Pd2 or Pd3 is suggested by another weak peak at 1905 cm - 1 from the CO adsorption on either bridge sites (CO-Pd2) in an isolated state or three-fold sites (CO-Pd3) on an extended Pd surface. The peak from CO adsorbed on Pd 2+ slowly decreases after 10 mins, accompanied by the formation of a new peak at ~ 1,980 cm -1 from CO adsorption on Pd2 in a compressed state. This suggests the progressive change of Pd1 single atoms in larger PdOx clusters. Similar phenomena were observed in the CO-DRIFTS for quantifying the relative populations of Pd1, Pdn, and Pdp within different catalysts. The singular 2040 and 2060 cm -1 peaks are assignable to linearly bonded CO on Pd clusters and particles, while the broad bands at lower-frequency regions (< 2000 cm -1 ) are related to the bridge-bonded or triplebonded CO on continuous palladium ensembles. The coexistence of Pd1 in these samples is confirmed by the linearly bonded CO at 2080 and 2120 cm -1 . Apart from the CO probe, the adsorption configuration of other reactant(s) on SAC is also somewhat different than that on surfaces of metal nanoparticles. For instance, our Pt1-MoS2 prefers a monodentate "end-on" adsorption of the nitro functionality in 3-nitrostyrene in the in situ DRIFTS measurements, compared to the planar binding configuration of the alkene groups (such as ethylidyne (tridentate) or di-σ (bidentate) configuration) on the Pt nanoparticles. This leads to an extraordinary chemoselectivity of 99% toward 3-aminostyrene. In situ DRIFTS of C2H2 hydrogenation on the spent Ni1Cu2/g-C3N4 catalyst confirms an identical result with the fresh sample, validating the excellent stability. 56