Understanding the Dynamic Aggregation in Single‐Atom Catalysis

Abstract The dynamic response of single‐atom catalysts to a reactive environment is an increasingly significant topic for understanding the reaction mechanism at the molecular level. In particular, single atoms may experience dynamic aggregation into clusters or nanoparticles driven by thermodynamic or kinetic factors. Herein, the inherent mechanistic nuances that determine the dynamic profile during the reaction will be uncovered, including the intrinsic stability and site‐migration barrier of single atoms, external stimuli (temperature, voltage, and adsorbates), and the influence of catalyst support. Such dynamic aggregation can be beneficial or deleterious on the catalytic performance depending on the optimal initial state. Those examples will be highlighted where in situ formed clusters, rather than single atoms, serve as catalytically active sites for improved catalytic performance. This is followed by the introduction of operando techniques to understand the structural evolution. Finally, the emerging strategies via confinement and defect‐engineering to regulate dynamic aggregation will be briefly discussed.


Introduction
The past decade has witnessed the explosion of research on atomically dispersed metal catalysts or "single-atom catalysts (SACs)." [1,2]The interest is driven by the desire to mimic the homogeneous pathway for extremely high activity and chemoselectivity on durable, process-friendly heterogeneous supports. [3]articularly, SACs are advantageous in their maximum metal utilization efficiency and atomically precise coordination compared to other subnanometric variants (clusters/aggregates of several atoms, nanoparticles, etc.).Extensive efforts have delivered significant progress in the areas of synthesis, characterization, applications, and mechanism insights of SACs. [4,5]owever, downsizing to the single-atom level brings its own set of challenges.Conventional wisdom suggests that active DOI: 10.1002/advs.202308046metal single atoms tend to agglomerate in working conditions to minimize the surface energy, which is generally due to two mechanisms at play: site-migration and coalescence of entire nanoparticles and Ostwald ripening with the motion of atomic species from smaller to larger particles. [6,7]In both mechanisms, an emergence of larger particles will usually lead to the loss of catalytic activity and selectivity. [8]Many strategies are proposed to prevent the aggregation of SACs by regulating the metal-substrate interaction and, more recently, to reverse the aggregation by external stimuli. [5]Such reversible (dynamic) aggregation is highly desirable for the application in complex reactions that require activation of two (or more) reactants, where the single-site mechanism of SACs is inefficient compared to the dual or multi-site mechanism of clusters or nanoparticles. [3]Understanding the dynamic structural evolution of SACs is the key to establishing the structure-function relationship for subnanometric catalysts composed of single atoms and clusters. [2,9]espite its significance, monitoring the dynamic structural evolution of SACs is not easy. [10]The challenges arise from the inherent heterogeneity of supported surfaces associated with binding sites (corners, edges, and faces), defects (vacancies, terraces, and grain boundaries), and amorphous structures (hydrated layers, amorphous supports, and so on). [11]Most characterization by electron microscopy is performed ex situ for the fresh and spent catalysts to achieve atomic resolution in a nanometer-sized area. [10]Spectroscopic measurements usually provide a more comprehensive view of the entire sample in the working conditions; however, averaged information about the electronic state, local coordination environment, and vibrational modes of adsorbates are collected, resulting in insensitivity in distinguishing minor species from bulk information. [3]There is a trade-off between spatial resolution at the nanoscale and time response to dynamic conditions in the state-of-the-art operando techniques to uncover the real active sites during dynamic aggregation of SACs.
This review aims to provide a comprehensive understanding of the dynamic aggregation of single-atom catalysts in working conditions.The thermodynamics and kinetics parameters collectively contribute to the intrinsic stability of SACs, while the external conditions including temperature, voltage, and reaction intermediates, induce a reversible or irreversible structural dynamism.This will consequently affect the catalytic activity, selectivity, and stability.Typical operando techniques used for monitoring dynamic evolution will also be covered, with an  111) at different operation stages; E) Evolution of the chemical potential of Pd (μ Pd ) at different stages with reaction conditions relative to bulk Pd; F) Free energy landscape for Pd 1 activation with (p CO = 0.02 atm) and without CO at 25 °C.Reproduced with permission. [14,22,27,6] emphasis on identifying real active sites.Finally, we provide a complementary perspective on regulating dynamic aggregation by nano-confinement and defect-engineering for better catalyst designs.

The Driving Force of Dynamic Aggregation
Single metal atoms do not represent a thermodynamically stable entity on their own.The substrate supports with strong interaction to single metal atoms must be available to prevent nucleation of metal atoms to nanoparticles. [12]An ideal substrate would allow a certain degree of structural flexibility for SACs to respond to dynamic catalytic cycles while retaining their integrity for sta-ble operation. [13]In the following section, we will uncover the inherent mechanistic nuances that control the dynamic profile of SACs from the thermodynamic and kinetic viewpoints.

Intrinsic Stability of SACs
The intrinsic stability of SACs can be well explained by the thermodynamic diagram in Figure 1A,B.When the free-energy change from nanoparticles to single atoms is negative, nanoparticles can be dispersed to single atoms spontaneously, leading to the thermodynamic stability of SACs.However, even if the free-energy change is positive, single atoms can be kinetically stable when the aggregation barrier is sufficiently high to prevent sintering. [14]In this regard, the metal-substrate interaction (or binding energy of single atoms, E bind ) is a suitable descriptor to predict the thermodynamic stability of SACs.For instance, stable SACs will not be formed on the basal plane of graphene and 2H-phase MoS 2 owing to their weak interaction.The presence of defects (such as steps and vacancies), dopants, and surface terminations significantly improve the stability of single atoms via surface trapping. [2,15]18][19][20][21] Apparently, a stronger metal-support interaction (or E bind ) implies a lower mobility of atomic species on the support, but this does not truly reflect the diffusion activation barrier (E a ).This suggests that a thermodynamic metric of binding energies alone cannot explain the kinetic stability in most SAC systems.A more detailed study by Hensen et al. [22] revealed the importance of the cohesive energy of bulk metal (E c ) for the prediction of E a , which reflects the intrinsic chemical reactivity of single atoms.The diffusion activation barrier has a strong linear dependency on the ratio of (E bind ) 2 /E c for various SAC systems on reducible metal oxides (CeO 2 , TiO 2 ), stable metal oxides (MgO, ZnO), perovskite (SrTiO 3 ), and 2D materials (MoS 2 and graphene).Indeed, the ratio of E bind /E c serves as a correction factor to E bind by comparing the affinity of a single metal atom to the support surface and bulk metal.This provides a simple model for screening thermodynamics to the kinetics of metal adatom on a support. [22]

Theoretical Considerations on Site Migration
From the thermodynamics aspect, the driving force of atomic migration is generally described by this equation: [23,24] ΔG mig = ΔH mig − TΔS mig + Δ mig A (1)   where ΔG mig , ΔH mig , ΔS mig , and Δ mig are the changes in Gibbs free energy, enthalpy, entropy, and specific surface energy before and after atomic migration, respectively.A is the surface area, and T is the absolute temperature.Site migration could happen when the ΔG mig is negative and is affected by many factors, such as the concentration-induced energy difference, atomic bonding strength (mainly related to ΔH mig ), and surface energy (related to Δ mig ) in structure features of nanocatalysts. [23,25]he most well-known example is the Ostwald ripening, where large particles grow at the expense of small ones to reduce the overall surface energy. [2]The driving force (related to Δ mig ) arises from the surface energy difference owing to more exposed undercoordinated atoms on the surface of small nanoparticles.The detailed process may involve the atomic dissolution from smaller particles into electrolytes and subsequent redeposition of dissolved atoms on larger particles. [23]Similarly, the agglomeration process of nanocatalysts via initial detachment from support and subsequent coalescence with each other would be affected by the size as a consequence of the surface energy difference. [2]Apart from particle size, chemical composition (related to ΔH mig ), facet, and curvature will have a strong influence on the free energy change.
The kinetics feature of atomic migration is less studied due to the difficulty in experimental validation.In principle, it can be described by the Arrhenius equation: [23] where D mig is the migration rate constant, D 0 is the preexponential factor, E mig is the atomic migration energy barrier, and T is the absolute temperature.As mentioned above, the activation energy barrier is closely related to the metal-substrate interaction (E bind ) and the cohesive energy of bulk metal (E c ), which depends on the type of element, facet, defect, and reaction intermediate.External stimuli in working conditions, including temperature, electric field, and adsorbates, facilitate the atomic migration of single atoms. [23,25]For example, high temperature induces a larger amplitude of atomic vibration near the equilibrium position, thereby increasing the possibility to cross the migration barrier.External electrical fields can drive the atomic diffusion or migration toward specific directions and even cause the uphill diffusion behavior. [23]t should be pointed out that SACs can undergo dynamic structural transformations in both geometric (e.g., aggregation) and electronic structures in a catalytic cycle.The changes in local coordination environments (e.g., type and number of coordinated atoms) by bond dissociation and oxidation states by polarization or distortion of its electron clouds can interplay for a macroscopical behavior of structural evolution. [3]Such evolution could be progressive, irreversible, and easily detected by ex situ techniques.By contrast, it may occur discreetly and transiently under reaction conditions, requiring the use of operando methods to understand the underlying mechanism. [1]

Dynamic Response in the Single-Component Atmosphere
Subnanometric metal species can evolve after exposure to a single component atmosphere (non-reactive atmosphere), such as O 2 , H 2 , CO, and H 2 O, driven by their thermodynamic and kinetic stability. [26]A representative example would be the restructuring of Pt nanoparticles into single atoms in air at elevated temperature (800 °C) or sintering into larger particles under an inert atmosphere. [17,18]Such particle redispersion is triggered by the formation of PtO 2 (the dominant surface species) in an oxidative environment owing to the much lower evaporation free energy of PtO 2 from an oxygen pre-covered Pt(221) step compared to that of a single Pt atom from a Pt(221) step (−0.61 eV vs 4.00 eV).Therefore, it is energetically strongly unfavorable for redispersion in an inert atmosphere due to the strong covalent metalsupport interaction of Pt 1 to the surface atom. [17]In a reductive atmosphere (such as H 2 ), Pt single atoms aggregate into clusters and nanoparticles, occurring at a relatively low temperature of 200 °C on the surface of non-reducible Al 2 O 3 .The fraction of single Pt atoms decreases and eventually vanishes when raising the reduction temperature to 300 °C and 450 °C. [9]In another study, the influence of H 2 O (moisture) on the dynamic profile of the CuAl sample was carefully investigated by reoxidizing the reduced samples in dry or wet air.The H 2 reduction and dry air reoxidation promote the agglomeration of small CuO clusters and single Cu 2+ sites.In contrast, wet air reoxidation could partially recover these CuO species to their initial state, with a small number of CuO species mildly agglomerated and easily reduced. [7]herefore, pretreatment in a single-component atmosphere profoundly influences the chemical states and local coordination environment of the catalyst.

Dynamic Response to Reactive Working Conditions
Given the structural dynamism of SACs, their stability should be rigorously examined in reactive working conditions (e.g., in the presence of adsorbates).In general, SACs do not have static local coordinations but can switch from inactive to active structure (or vice versa) under reaction conditions. [26]For instance, the preferred local coordination of Rh single atoms was investigated on TiO 2 during calcination in O 2 , reduction in H 2 , CO adsorption, and reverse water gas shift (RWGS) reaction conditions. [27]heoretical and experimental studies clearly demonstrated the dynamic response of Rh single atoms in the local coordination and reactivity to various redox conditions.As shown in Figure 1C, the surface stability diagram in H 2 indicates that the preferred structure on the Rh 1 /TiO 2 (110) surface is governed by the H and O chemical potentials.Blue, light blue, and green regions denote the preferential substitution of six-coordinated surface Ti with zero, one, or two O vacancies by a Rh atom (Rh 1 @TiO 2 , Rh 1 @TiO 2-x , Rh 1 @TiO 2-2x ).Meanwhile, the supported Rh structure is favored (Rh 1 /TiO 2-x and Rh 1 /TiO 2-2× ) in the orange and pink zones, respectively. [27]It is found that hydrogen pressure stabilizes both the substitutional and the supported Rh site, but the latter is more stable in the oxygen-lean conditions.Likewise, the CO adsorption completely changes the thermodynamic site preference for the Rh, driving them to a supported site irrespective of the presence of O vacancies.This is attributed to the much stronger CO adsorption on the supported Rh (−4.89 eV for Rh 1 /TiO 2 ) than the substitutional Rh (−2.74 eV for Rh 1 @TiO 2-2x ).
Beyond its position on the support, the stability of SACs versus clustering is another crucial aspect, especially when it is potentially mobile in a reactive atmosphere.Based on Monte Carlo simulations, Myslivecek et al. demonstrated a competition for atoms between Pt single-atom sites and Pt nanoparticles.This led to dynamic evolution in the Pt nanoparticles population on the ceria surface. [12]In an oxidizing atmosphere, Pt single-atom sites provide strong bonding to single Pt atoms, and Pt nanoparticles shrink.In a reducing atmosphere, Pt single-atom sites are depopulated, and Pt nanoparticles grow.Very recently, Wang et al. demonstrated the critical roles of CO in the reversible transformations of Pd 1 /CeO 2 during methane oxidation. [6]The presence of CO destabilizes the Pd 1 single atoms via a Pd 1 -promoted interfacial reduction, mobilizes the step-Pd 1 /Pd ad, and stabilizes asformed PdO x subnanometric clusters at the doped terrace sites via a non-reductive CO adsorption.As shown in Figure 1D-F, cationic single-atom Pd 1 in a square-planar Pd 1 O 4 conformation is thermodynamically favorable over other states at elevated temperatures in an oxidative atmosphere, providing the tendency of formation and regeneration of Pd 1 single atoms in the fresh and spent catalysts. [6]Upon the exposure of CO, Pd 1 could facilitate the extraction of surface oxygen in its vicinity, leading to a reduced Pd 1 /CeO 2 interface even at room temperature.The coor-dination of Pd 1 at the terrace site remains Pd 1 O 4 , whereas step site Pd 1 is reduced to Pd 1 O 2 .This indicates that two (terrace) to three (step) O per Pd atom are extracted from the interface, leaving Pd 1 + and Pd 1 O 2 at steps and partially reduced Pd 1 O 4 at terraces.Additional CO adsorbed on step Pd 1 + serves as a diffusion promotor, substantially increasing the mobility of surface Pd compared with Pd 1 + in the absence of CO.Terrace Pd 1 remains immobile and serves as anchoring sites for CO-Pd 1 originating from step sites, leading to the formation of Pd 2 /Pd 3 and nucleation of PdO x subnanometric clusters.In contrast, the energy barrier for such nucleation is much higher in the absence of CO (2.4 vs 0.1 eV).Finally, the single-site Pd 1 /CeO 2 regenerates at high temperatures owing to its thermodynamic stability.Such reversible transformations in the Pd 1 /CeO 2 catalyst are modulated by the dynamic working conditions (temperature and atmosphere). [6]

Influence of Catalyst Support
Practically relevant host materials typically have irregular 3D morphologies and exhibit non-uniform surface structures and compositions, resulting in high polydispersity of coordination sites for SACs. [1]Therefore, several energetically favorable configurations may coexist with minimal interchange barriers.As illustrated by molecular dynamics (MD) simulations in Figure 2A, a wide range of surface and subsurface configurations of palladium atoms, dimers, and trimers were identified on the exfoliated carbon nitride (ECN) scaffold. [28]In particular, the flexible lattice of ECN enables an almost continuously variable coordination pattern of palladium to the host during the catalytic cycle of Suzuki coupling. [29]As shown in the density functional theory (DFT) calculations in Figure 2B,C, the initial catalyst of Pd 1 -ECN has a coordination number of 6 and gradually reduces to 3.2 upon the adsorption and exothermic activation of bromobenzene.The Pd atom is less coordinated to the matrix during transmetallation (2.6), elimination, and the C─C bond formation (3.0) and recovered to the initial coordination state by the endothermic removal of the product.Such adaptive coordination to the support enables high stability to deactivation by metal leaching in Suzuki coupling. [29]ikewise, reducible oxide supports such as TiO 2 , Fe 2 O 3, and CeO 2 are especially suitable for stabilizing single atoms due to the strong metal-substrate interaction. [30]The unique Ce 3+ /Ce 4+ redox properties, associated with the reversible formation of oxygen vacancies, render CeO 2 a widely used support.A theoretical analysis of platinum atoms on CeO 2 identified the possible coexistence of several well-defined and dynamically interconnected charge and oxidation states, demonstrating the oversimplification of the current static picture of electronic structures. [31]As shown in the MD simulation in Figure 2D,E, Pt single atoms can be trapped on CeO 2 (100) in the form of Pt 2+ with four O ligands owing to the inherent surface oxygen mobility.The most robust Pt 2+ -4O reduces to Pt-3O and Pt-2O with a dynamic number of Ce 3+ centers under a reductive atmosphere, leading to the co-existence of Pt 0 , Pt + , and Pt 2+ oxidation states with different lifetimes. [31]Similarly, Rousseau et al. presented ab initio molecular dynamics (AIMD) simulations of an unprecedented dynamic single-atom catalytic mechanism for CO oxidation by Reproduced with permission. [1,29,31,40] ceria-supported gold clusters.Such a mechanism results from the ability of the gold cation to strongly couple with the redox properties of the ceria in a synergistic manner, thereby lowering the energy of redox reactions.The gold cation can break away from the gold nanoparticle to catalyze CO oxidation adjacent to the metal/oxide interface and reintegrate into the nanoparticle after the reaction. [32]Such dynamic response in the local coordination environment has also been reported in the Rh 1 /TiO 2 for reverse water-gas shift reaction, [27] Pt 1 /TiO 2 for CO oxidation, [33] Cu-N-C and Ru-N-C SACs for hydrogen and oxygen evolution, respectively. [34,35]Finally, the nature of metal atoms may also affect the stability of SACs due to the self-catalytic decomposition of the substrate during the catalytic cycle.For metals with excellent catalytic activity (such as Pt), carbon-based SACs usually suffer from poor long-term stability arising from the corrosion of the carbon support, dissolution into the electrolyte, and subsequent redeposition (aggregation) of metal atoms on the surface.Harsh conditions (such as high voltage and acidic electrolyte) can also accelerate such corrosion process, calling for careful consideration of the active metal and more corrosion-resistant supports. [2]

Multimetallic and Multinuclear Systems
The stability of bimetallic and multimetallic SACs has received less attention.Besides changes in size, segregation phenomena can occur and be evaluated by DFT using the segregation and aggregation energies as descriptors of heteroatom mobility. [1]uch atomic arrangement could occur continuously toward alloying, dealloying, or segregation determined by the element type, atomic ratio, and external conditions in the phase diagram. [23,36]ith the development of SACs from monometallic to multimetallic systems, the interaction between individual atoms has received increasing attention in regulating electronic structures and catalytic reactivity. [37][39] In such an event, the bond length of the heteronuclear pair may experience dynamic changes.As shown in Figure 2F, AIMD simulations were performed to track the bond length change in a bimetallic NiZn-N 6 system during the CO 2 reduction reaction (CO2RR).It is found that the length of Ni─Zn, Ni─N, and Zn─N bonds change in a certain range with the formation of COOH * and CO * intermediates, confirming the synergistic effect of Ni─Zn bimetal sites in the kinetic pathway. [40]The adaptable coordination of individual Cu sites in the Cu g /PCN catalyst also enables a cooperative bridge-coupling pathway through dynamic Cu─Cu bonding. [41]This will be detailed in Section 3.4.

Influence of Dynamic Aggregation in the Catalytic Cycle
Dynamic aggregation can be beneficial or deleterious on catalytic performance, depending on the optimal initial state.We will highlight the influence of dynamic aggregation on catalytic activity, selectivity, and stability in the following section.Note that such structural dynamism may vary under different catalytic reactions (such as photocatalysis, electrocatalysis, and gas-phase reactions) due to variations in external driving force (Section 2.2).It should be carefully examined for a comprehensive understanding.

Catalytically Active Site: Clusters or SACs?
The determination of catalytically active sites in subnanometric metal catalysts is challenging owing to their structural dynamism. [2]Particularly, they may have completely different activities toward the same reaction.It has been reported that, in some reactions, SACs are the active species, while clusters and nanoparticles are not.In such events, a sharp increase in catalytic turnover will be observed at low metal content when the majority of metal centers become spatially isolated (Ullmann reaction in Figure 3A). [9,42]If nanoparticles can also catalyze the reaction, the activity will rise more gradually with increasing dispersion until it reaches a plateau due to the maximized atom utilization (Pt 1 /FeO x for nitrostyrene hydrogenation).For those reactions where SACs are ineffective (such as Pd 1 /Fe 3 O 4 for styrene hydrogenation), size reduction will lead to diminished activity as metal clusters are no longer present in the sample. [42]Additionally, an induction period may appear when the "real" catalyst is not initially added into the system, while transformation into inactive species results in a decline in activity in a prolonged reaction period. [2] further understand the imperative role of structural dynamism, a correlation between the coordination number of Pt-Pt and the corresponding Tafel slope in hydrogen evolution reaction (HER) was established for a series of Pt-based catalysts in Figure 3B. [43]Atomically dispersed Pt SACs possess a substantially high Tafel slope and undergo restructuring into tiny clusters due to weakened Pt-N bonding under cathodic potentials.This leads to drastically decreased Tafel slopes and a transition from the Volmer-Heyrovsky pathway to the Volmer-Tafel pathway when the particle size increases to 2 nm or even larger.Such tiny clusters are responsible for the improved HER activity and stability rather than the initial Pt SACs. [43]Likewise, the electrochemically reconstituted Cu 4 clusters from Cu 1 /CeO 2 are the real active sites for electrocatalytic urea synthesis due to favorable C-N coupling reactions and urea formation. [44]An in situ formed Cu(I)/Cu(0) mixture from the initial Cu 1 /TiO 2 can effectively promote the generation of CH 4 in the photocatalytic CO 2 reduction. [45]The breakage of the Rh-Rh bond into the mononuclear complex in supported Rh nanoparticles could be facilitated by the iodine radical and CO molecules in the working condition. [46]onversely, the redispersion of clusters into single atoms could also be beneficial.As shown in Figure 3C, the on-stream activity of 1Pt/Fe 2 O 3 nanoparticles displayed a monotonic increase in 4 h at 700 °C to reach a 65% conversion for methane oxidation.This was accompanied by the disappearance of nanoparticles and the formation of atomically dispersed Pt in the spent catalyst in Figure 3C. [17]Such phenomenon is more likely to occur in thermally stable SACs for gas-phase reactions at high temperatures, including the Pd-N 4 SAC for semihydrogenation of acetylene, [16] atomically dispersed CuO x for deNO x reactions (NO + CO or NH 3 + NO + O 2 ), [7] Ru 1 /MAFO catalysts for N 2 O decomposition, [18] and Pd 1 @CeO 2 core-shell catalysts during calcination in O 2 . [47]part from clustering, the role of SACs in heterogeneous catalysis is sometimes questioned by the distinct possibility of metal leaching in the presence of a ligand or solvent. [3]The homogeneity or heterogeneity of SAC-promoted reactions should be carefully examined by several critical criteria as previously discussed, which will not be detailed due to limited scope. [3]

Modulated Selectivity via Dynamic Aggregation
SACs are known to be chemoselective owing to the restricted adsorption configuration in contrast to the diverse binding sites on conventional heterogeneous catalysts (Figure 4A).This allows rapid replication of molecular catalysis for the synthesis of complex molecules. [3,48]However, as every coin has two sides, this could be problematic when selectivity regulation toward specific products is needed for SACs. [2]Beyond conventional strategies via modulating the electronic structure and coordination environment, (reversible) dynamic aggregation offers a distinct advantage in breaking the selectivity limitation, particularly for those reactions that require adjacent metal sites (such as CO2RR [49] and complete oxidation of hydrocarbons [6] ).
Take the CO 2 reduction reaction (CO2RR) as an example; most SAC catalysts tend to convert CO 2 into C1 products such as HCOOH, CH 3 OH, and CH 4 but fail to obtain the more profitable  [42,43,17]  C2 + hydrocarbon products (ethanol, ethene, etc.) due to the lack of nearby active sites for the C─C coupling steps between two * CO intermediates. [37,49]Combining the experimental data and DFT calculations, Xu et al. revealed the reversible transformation of Cu SACs to Cu n clusters (n = 3 and 4) under CO2RR potentials, thus achieving a CO 2 -to-ethanol Faradaic efficiency (FE) of 91% at −0.7 V and an onset potential of −0.4 V. [49] This is further validated by Karapinar et al. using operando X-ray absorption (XAS) under the working conditions of CO2RR. [50]For the gas-phase hydrogenation of CO 2 , the single-atom Cu-Zr catalyst with Cu 1 -O 3 units is the sole contributor to the desirable methanol.Meanwhile, the presence of small copper clusters or nanoparticles leads to the formation of CO by-product. [51]Similarly, such dynamic aggregation of Pt SACs to nanoparticles will induce the switching of the two-electron pathway to the fourelectron pathway in the oxygen reduction reaction (ORR), producing H 2 O instead of H 2 O 2 .The reason lies in the side-on adsorption configuration of O 2 on Pt nanoparticles, in comparison with the end-on configuration on Pt SACs with a shorter O─O bond length. [52]The change in catalytic selectivity via dynamic aggregation is universal to many reactions, whose (irreversible) progressive change with time may lead to catalyst deactivation in Section 3.3.

Catalyst Stability under Operational Condition
Despite numerous efforts, industrial deployment of SACs is still limited due to the pursuit of better activity and selectivity at the expense of stability. [2]As mentioned in Section 2.1, the instability of SACs is primarily attributed to the high surface energy of single metal atoms, prompting them to aggregate into more stable nanoparticles (sintering).Other deactivation pathways include the oxidation of carbon support, metal leaching, amorphous carbon deposition, and poisoning in operational conditions. [3]A unified framework on catalyst deactivation was established in a H) The energy levels of Cu (II)•••Cu (II) interaction with increasing proximity from infinite distance to 2.46 Å; Reproduced with permission. [3,41,53,58,57]comprehensive review by Pérez-Ramírez et al., detailing the types and approaches used to study deactivation phenomena across all catalyst types and driving forces. [8]Herein, we will highlight the influence of dynamic aggregation on the stability of SACmediated processes.
The size effect on the stability profile under working conditions is illustrated in Figure 4B,C using the Pd/TiO 2 -anatase SAC catalyzed RWGS reaction as an example. [53]A progressive, twofold increase in the RWGS rate per Pd with time-on-stream was observed in the ≤0.025 wt% Pd 1 /TiO 2 samples (purple, red, and green curves).Such increases originate from higher intrinsic activity of Pd instead of higher Pd dispersion, as Pd is already atomically dispersed on fresh Pd 1 /TiO 2 .In contrast, this was not found in less dispersed Pd/TiO 2 at higher loadings.More detailed studies revealed the partial sintering of single Pd atoms (Pd 1 ) into disordered Pd clusters (Pd n , ≈ 1 nm) by H 2 activation and the redispersion into Pd 1 in an oxidative atmosphere.Such dynamic aggregation is responsible for the increasing rate with time-on-stream, and steady-state Pd active sites are similar to the ones formed under H 2 .Meanwhile, the sintering of Pd 1 into larger crystalline Pd nanoparticles (≈5 nm) during CO treatment will deactivate the catalyst, leading to progressive activity loss in the time profile. [53]This indicates the importance of partial sintering into redispersible clusters for an optimized stability. [1,8]imilar observations were reported in the 0.17% Pt@MCM-22 for NO reduction with CO and H 2 , [54] Pd 1 /CeO 2 for methane oxidation, [6] Ni@1T-MoS 2 for hydrogen evolution, [55] Cu 1 /CeO 2 for electrocatalytic urea synthesis, [44] etc.In an extreme case, unprecedented chemical stability under hydrogenation conditions was shown in the Ni 1 Cu 2 /g-C 3 N 4 catalyst without any visible decline in either activity or selectivity for at least 350 h at 160 °C.In sharp contrast, Ni 1 /g-C 3 N 4 showed a slight activity increase approximately in the first 6 h and then rapidly deactivated with an activity loss of ≈50% in about 50 h owing to severe agglomeration of Ni atoms into Ni particles. [56]ery recently, Cargnello et al. demonstrated an opposite deactivation pathway via the decomposition of nanoparticles into inactive single atoms at high temperatures (Figure 4D), which is remarkably fast and strongly dependent on the particle density and concentration of support defect sites. [57]As shown in Figure 4E, the thermal stability of various Pd nanoparticles on Al 2 O 3 with dense, intermediate, and sparse loadings was probed in methane combustion, where the sparse one was expected to be most stable due to a lower probability of particle migration and coalescence or interparticle atomic exchange.Surprisingly, the dense Pd/Al 2 O 3 catalyst showed completely stable activity after high-temperature aging, while the sparse one rapidly deactivated with the conversion decreasing from 85% to 20%. [57]Such size dependence strongly suggests that the atomic ripening process is limited by atomic emission related to the existence of a lowest-energy Pd(OH) 2 adsorbate atop tri-coordinated Al atoms in Figure 4D rather than surface diffusion of atomic species to a nearby site.Such nanoparticle-to-single atom deactivation process is usually overlooked at low metal loadings. [57]ince the influence of dynamic aggregation on the activity, selectivity, and stability is always correlated, a radar plot charting the key catalytic descriptors allows better evaluation of various subnanometric catalysts. [58]For alkyne semi-hydrogenation, the stability could be assessed by the segregation energy (E seg ), which is the differential energy between the ground state (i.e., an alloyed metallic surface) and the system after segregating one atom toward the surface.The activity depends on the adsorption of alkyne and, more importantly, the hydrogen activation energy to split molecular hydrogen, while the selectivity depends on the adsorption energy of the alkene and the ensemble area. [58]It is found that the preferential hydrogen adsorption on Pd induces severe segregation effects in Pd 3 @C 3 N 4 or other Pd nanoparticles.Such Pd segregation or islanding is not favorable in Pd 3 S/C 3 N 4 due to the polarization of the Pd─S bond, thus out-performing all state-of-the-art catalysts in alkene formation rate and durability with no sign of segregation. [58]This phenomenon highlights multiple design criteria that need to be harmonized to develop an effective SAC.

Synergy from Correlated SACs
The switching of the single-site pathway in SACs to the multisite pathway in clusters or particles is a fundamental reason for the modulated performance during structural dynamism.Beyond dynamic clustering, it is also possible for SACs to retain spatial isolation and correlate with the adjacent sites via inter-site metal-metal interaction. [38,39,41,59]Since the number and type of the neighboring atoms in the first and second coordination shells significantly influence the local geometry and charge density of metal centers, such correlated SACs may enjoy unique structural flexibility for dynamic response under working conditions. [38]s shown in Figure 4F, Lu et al. recently developed an emerging class of SACs with paired single-atom sites in specific coordination and spatial proximity (≈4 Å).The Cu g /PCN catalyst, called geminal-atom catalysts (GACs), enables a cooperative bridge-coupling pathway through dynamic Cu─Cu bonding for diverse C-X (X = C, N, O, S) cross-couplings with a low activation barrier owing to the adaptable coordination of individual Cu sites. [41]Comprehensive theoretical calculations on the plausible mechanisms strongly support the preference of a direct coupling pathway, in which a dynamically formed Cu 2 dimer with direct Cu─Cu bonding facilitates the C─O bond formation through oxidative addition and subsequent reductive elimination in Figure 4G.The formation of such a dynamic Cu 2 dimer configuration is energetically compensated through Cu─Cu 4s─4s bonding, accompanied by a potential-energy-surface crossing from Cu II (d 9 s 0 )…Cu II (d 9 s 0 ) triplet to Cu II (d 8 s 1 )-Cu II (d 8 s 1 ) singlet states in Figure 4H.These intrinsic advantages of GACs enable the assembly of heterocycles with several coordination sites, sterically congested scaffolds, and pharmaceuticals with highly specific and stable activity. [41]Our recent studies also revealed the dynamic process of ultrahigh loading Cu 1 -C 3 N 4 SACs in the bimolecular nitrile-azide cycloaddition by operando XAS, triggering the dinuclear pathway when intermetal distance is reduced to the typical diffusion length of the reactants (<1 nm). [59]A distance threshold around 5.3 Å between adjacent Ni-N 4 and Cu-N 4 moieties is revealed to trigger effective inter-metal interaction in correlated NiCu SACs for promoted CO2RR activity and selectivity. [37]This is consistent with the findings in densely populated Fe SACs for ORR. [60]esides affecting the activity and selectivity, the distance between metal species also determines the collective properties that affect the stability by influencing the propensity towards sintering or redispersion, which will not be further detailed. [1]

Structural Dynamism in a Confined Space
Subnanometric clusters or single atoms can be restricted in the confined space of zeolite, mesoporous carbon, metal-organic frameworks (MOFs), and other porous materials using solution synthesis with inorganic salts or organo-metallic complexes. [2,61]he structural dynamism of confined SACs could be significantly different from that of conventional counterparts due to sluggish diffusion kinetics and the limited supply of available atoms in the confined space, as documented by the excellent reviews by Liu and Corma. [62,63]or instance, the dynamic structural transformation of subnanometric Pt species confined in MCM-22 zeolite (including atomically dispersed Pt and Pt clusters) was studied by in situ transmission electron microscopy (TEM) under oxidationreduction and reaction conditions. [54]Compared with conventional Pt nanoparticles, the behaviors of subnanometric Pt species are much more sensitive to the presence of reactants.Dynamic and reversible transformation between single atoms, clusters, and nanoparticles has been observed under CO and O 2 reaction conditions at different temperatures.By tuning the size and spatial distribution of Pt species in MCM-22, subnanometric Pt clusters can be stabilized under reaction conditions, even at very high temperatures (> 800 °C). [54]Likewise, the evolution of Cu cations confined in the chabazite zeolite (CHA-type zeolite) during the selective catalytic reduction (SCR) of NO x by NH 3 was studied, showing high mobility of atomically dispersed metal species under reactive conditions.It was proposed that singlesite Cu species can travel through the eight-membered-ring window of CHA supercages and form binuclear Cu species as the active sites for low-temperature NH 3 -SCR reactions. [64]The Pt particles on the external surface of MFI zeolites can disintegrate into subnanometric Pt species and get stabilized in the zeolite channels during high-temperature calcination in air, while Sn species migrate from surface to internal region during reduction at 650 °C.Dense subnanometric PtSn clusters in the sinusoidal 10MR channels could be formed in the subsequent reduction cycle, enabling highly regioselective propane dehydrogenation. [65]his suggests that understanding the confinement effect in structural dynamism is crucial for stabilizing the active sites under harsh reaction conditions and regenerating the deactivated catalyst. [63]

Monitoring the Structural Dynamism via Operando Techniques
In pursuit of the molecular level understanding of reaction mechanisms and better designs of SACs, substantial efforts have been focused on determining catalytically active sites in the dynamic catalytic cycle when interacting with substrate molecules. [9]Ex situ characterization of the fresh and spent catalysts (e.g., microscopy, spectroscopy) is generally performed to evaluate the structural and electronic changes.Due to dynamic evolution, such structural features given by these ex situ techniques may not be sufficiently reliable to describe the active sites and structureproperty relationship. [10]This necessitates monitoring structural dynamism via operando techniques in the following section.

Operando X-Ray Absorption
X-ray absorption spectroscopy (XAS) is arguably the most powerful technique in detecting the dynamic profile of SACs during the reaction course, even up to 1000 K and 100 bar. [4]In a typical XAS experiment, an atom of the measured element absorbs incident X-ray photons with energies near or above the core level binding energies of that atom.Electrons would then escape from their quantum level and carry with the excess energy as kinetic energy if the energy of X-ray is larger than electronic binding energy.The corresponding XAS spectrum is acquired by recording the X-ray energy and adsorption intensity. [23]Therefore, the change in the valence state of the active metal is reflected in the X-ray absorption near edge structure (XANES) region, while extended Xray absorption fine structure (EXAFS) provides fruitful information on the local coordination environment in the bulk materials (such as spatial distribution, bonding conditions, and coordination numbers). [3]Typically, the absorption of the incident X-ray beam is monitored by the attenuation of the transmitted photon beam or via fluorescence as the core holes decay in an operando XANES cell (with Kapton windows) for gas-phase and electrochemical measurements. [10]To prevent corrosion of organic solvent and aggressive reactant on the Kapton window, we have also customized a coin-cell type reactor with double-side Al coating for operando XAS in liquid-phase organic transformations. [59]ynamic aggregation of Cu 1 -CeO 2 SACs into Cu 4 clusters during C─N coupling was monitored by operando Cu K-edge XANES spectra in Figure 5A. [44]The formation of Cu( 0 5C.Such electrochemically reconstituted Cu 4 clusters are genuine active sites for C─N coupling and urea formation, leading to a benchmark urea yield rate of 52.84 mmol h −1 g cat −1 at -1.6 V. [44] Likewise, the dynamic profile of dual-site NiFe SACs in oxygen evolution reaction (OER) was traced by operando XAS in Figure 5D,E. [66]It was found that the single Ni sites promoted the key structural reconstruction into bridging Ni-O-Fe bonds.Upon increased voltages from 1.2 to 1.5 V, the rising-edge positions in the Ni K-edge XANES were positively shifted due to the higher oxidation state of Ni species in NiFe SACs.This was supported by a higher white line intensity.The reversibility with respect to changes in the oxidation state of Ni was confirmed by its partial recovery after the removal of voltage.Meanwhile, the Fe K-edge XANES only underwent a slight energy shift with increasing applied potentials, probably owing to the electrostatic interaction between catalyst and electrolyte or by OH − adsorption. [66]Accordingly, the distance of the first coordination shell of Ni increased at higher applied potentials due to the formation of a greater extent of Ni─O coordination.Another new peak appeared at ≈2.78 Å above 1.3 V, also reflected in the wavelet transformed (WT)-EXAFS spectra.Similarly, the local coordination of Fe centers steadily evolved at even higher potentials of >1.5 V, indicating that the new bonds are much more difficult to form at the Fe sites than those at the Ni atoms.Such newly formed Ni─O─Fe  E) Fe K-edge XAS under OER conditions.Reproduced with permission. [44,66] bonds created spin channels for electron transfer, resulting in a huge improvement in the OER activity with an overpotential of 270 mV at 10 mA cm −2 . [66]A deprotonation process to form the multiple active sites during OER and promote the O─O coupling was observed in atomic iridium stabilized on nanoporous metal phosphides for water oxidation. [67]Dynamic evolution of Cu-N 4 to Cu-N 3 and further to HO-Cu-N 2 via the Cu 2+ to Cu + redox cycle under ORR and CO2RR working conditions was also identified by operando XAS. [68,69]he use of operando XAS for dynamic aggregations of SACs is undoubtedly crucial.However, such averaging techniques cannot differentiate local inhomogeneities (polydispersity) arising from a distribution of coordination sites on the support or structural evolution under reaction conditions.This calls for careful interpretation of experimental results. [1]The spectroscopic acquisi-tion time is generally several tens of minutes in conventional XAS, which may fail to capture the fast transformation process since most reactions occur rapidly and reach a steady state in a few minutes.This urges the development of time-resolved XAS techniques to uncover the chemical state evolution of working catalysts. [23,70]

In Situ Transmission Electron Microscopy
In contrast to averaging spectroscopic methods, microscopies provide spatially resolved information on different catalyst positions in every image frame, with spatial and time resolution depending on the microscope.Transmission electron microscopy (TEM) has long been used to determine particle size distributions (histograms).Recent advances in aberration-corrected scanning transmission electron microscopy (AC-STEM), coupled with electron energy loss spectroscopy (EELS), allow the verification of the chemical identity of constituent elements with atomic resolution. [10]Visualizing SACs is also essential for understanding the formation, coordination environment, and stability of the catalyst, mainly when the catalytic performance is dominated by dynamic aggregation into other subnanometric species. [1,36]he most well-known example would be the direct observation of transforming nanoparticles into thermally stable SACs via in situ environmental TEM (ETEM), which utilizes a series of apertures and differential pumping to have sections of gradually changing vacuum while protecting the electron gun.Alternatively, it can be achieved with the micro-electromechanical system (MEMS) based specialty holders to provide stimuli such as heat, gas, light, or strain (or a combination) at the microscale. [13]s shown in the representative images acquired at different temperatures and times in Figure 6A, Li et al. provided solid and direct evidence of the evolution from Pd nanoparticles to Pd SACs in a zeolite imidazolate framework-8 (ZIF-8) derived nitrogendoped carbon substrate via in situ ETEM observations. [16]Owing to the coexistence of two competitive atomization and agglomeration processes, initial sintering will occur, leading to a steady increase in the diameter of Pd nanoparticles from room temperature to 900 °C.However, these nanoparticles would eventually transform into single atoms to minimize the ΔG of the system.Once the temperature increased to 1000 °C, agglomeration and atomization accelerated.Small Pd nanoparticles vanished in situ at 1000 °C after 36 s (Figure 6A) due to the capture of mobile Pd atoms by N defects on the substrate.Meanwhile, the sintered Pd nanoparticle (6.5 nm in diameter) underwent thermal motions within the substrate and downsized to 4.0 nm at 136 s and 1.9 nm at 150 s by Pd coordination with the N defects before final atomization to single atoms at 162 s. [16] This was supported by the highly exothermic (−3.96 eV) process for forming a Pd-N 4 SAC from the decomposition of the Pd 10 cluster in Figure 6B.Such transformation required a moderate energy barrier of 1.47 eV to be overcome, which was much higher than the diffusion energy of a single Pd cluster for sintering (0.58 eV).Hence, sintering was dominant at relatively low temperatures, and atomization dominated at high temperatures (900-1000 °C). [16,19]imilarly, the dynamic and reversible transformation between carbon-supported single Pt atoms and their agglomerates under redox conditions was monitored by in situ TEM. [54]In another report, the dynamic process of nanoporous Au to catalyze methane pyrolysis was monitored by in situ TEM, demonstrating the release of Au single atoms by partial disintegration of nanoporous Au surfaces. [71]DeRita et al. also systematically investigated the movement of Pt SACs dispersed on anatase TiO 2 under different reducing and oxidizing conditions via in situ AC-STEM.The variation in local coordination strongly influenced the chemical reactivity for CO oxidation. [33]We should point out that in situ TEM observation under vacuum is only suitable for certain reactions, primarily pyrolysis of SAC precursors and gas-phase reactions.A complete picture of a catalyst should include operating conditions and investigations into degradation.However, replicating the catalytic environment poses challenges in losing spatial resolution or scattered electrons due to equipment limitations. [13]he spatial resolution of in situ TEM is usually around 100 nm, far from the atomic scale.Technical problems such as bubble formation in a liquid environment and electron beam damage need to be solved. [23] typical challenge lies in the TEM observation of SACs in a liquid environment, which is more valuable for applications in (photo)electrochemical and organic catalysis.Conventional liquid cells are made with silicon nitride (SiN x ) windows and are only suitable for observation in nanoparticle formation, dissolution, and shape changes.[13] Graphene liquid cells may induce a much thinner liquid layer and less scattering from the windows to achieve atomic resolution in in situ liquid phase imaging.Very recently, Haigh et al. developed a double graphene liquid cell for the monitoring of the dynamics of platinum adatoms on the monolayer in an aqueous salt solution with atomic resolution.[72] As shown in Figure 6C,D, a modified adsorption site distribution and higher diffusivities for the adatoms in the liquid phase were found compared with those in vacuum by imaging more than 70 000 single adatom adsorption sites.Most single Pt adatoms are mobile, as demonstrated in the trajectories of several representative Pt adatoms over a sustained period.The high mobility of Pt atoms is consistent with the predominant adatoms located on the surface rather than substituted in the MoS 2 lattice.[72] In summary, microscopy always encounters questions of whether these observations are representative of the whole sample.It should be cross-referenced by other spectroscopic techniques to exclude the influence of artifacts and beam-induced damage generated by the experimental conditions.Parameters such as the acceleration voltage, beam current, and pixel dwell time must be optimized to minimize beam-induced damage and sample drift due to thermal instability or charging.Knock-on damage and ionization/radiolysis are two major forms of beam damage.[13] At higher acceleration voltages, knock-on damage is more prominent and induces sputtering from the surface, atomic deformation, and defects.Lowering the acceleration voltage below twice the threshold for atomic displacement can effectively reduce such damage.For covalent and weakly ionic compounds at lower acceleration voltages, the principal form of damage is radiolysis due to inelastic scattering, which can readily disrupt the chemical bond and shape.6]

Operando DRIFTS
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. [10,30]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. [13]s shown in Figure 7A-C, the dispersion, oxidation state, and CO oxidation activity of Pt/-Al 2 O 3 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. [73]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. [73]ikewise, CO-DRIFTS was conducted to probe the evolution of surface Pd species in methane oxidation (Figure 7D,E). [6]After initial saturation of CO on isolated Pd 1 + and Pd 2+ at 2134 and 2145 cm −1 in the first 5 min, peaks from linear CO adsorption on Pd 0 gradually appear at 2098 and 2068 cm −1 , indicating the nucleation of highly dispersed PdO x clusters containing mixed Pd 2+ /Pd 0 oxidation states.The presence of highly dispersed Pd species such as Pd 2 or Pd 3 is suggested by another weak peak at 1905 cm −1 from the CO adsorption on either bridge sites (CO-Pd 2 ) in an isolated state or three-fold sites (CO-Pd 3 ) on an extended Pd surface.The peak from CO adsorbed on Pd 2+ slowly  [73,6,30,77]  decreases after 10 mins, accompanied by the formation of a new peak at ≈1980 cm −1 from CO adsorption on Pd 2 in a compressed state.This suggests the progressive change of Pd 1 single atoms in larger PdO x clusters. [6]Similar phenomena were observed in the CO-DRIFTS for quantifying the relative populations of Pd 1 , Pd n, and Pd p 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 triple-bonded 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 . [30,74]art 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 Pt 1 -MoS 2 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- (bidentate) configuration) on the Pt nanoparticles.This leads to an extraordinary chemoselectivity of 99% toward 3-aminostyrene. [75]In situ DRIFTS of C 2 H 2 hydrogenation on the spent Ni 1 Cu 2 /g-C 3 N 4 catalyst confirms an identical result with the fresh sample, validating the excellent stability. [56].4.Near-Ambient Pressure X-Ray Photoelectron Spectroscopy Near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) is an emerging operando method due to its inherent surface sensitivity resulting from the small inelastic mean path of the photoelectrons.It can be applied to monitor structural evolution in adsorption, segregation, alloying, and coking during ongoing reactions in the few mbar pressure range.[10] For example, PdO (or PdO x ) was believed to be the active phase for methane combustion on Pd/Al 2 O 3 from the ex situ studies.However, operando NAP-XPS suggests a new surface phase of PdO seeds on a Pd 5 O 4 surface oxide, governed by a delicate balance of seed formation and methane reduction.Such PdO decomposes, and the reaction proceeds on metallic Pd at 350 °C and above, but with its near-surface region saturated by dissolved oxygen.[6,10] Since the photoelectrons can only travel a few millimeters at mbar pressure, the nozzle of the electron energy pre-lens has to be very close to the sample (e.g., a pressed catalyst pellet mounted on a sapphire holder) in a typical NAP-XAS setup.The gas pressure is then reduced by 10 9 using strong differential pumping until the electrons reach the hemispherical electron energy analyzer.[10] As shown in Figure 7F, the surface electronic structure of the working catalysts was followed by in situ NAP-XPS.Conventional Pd 1 /CeO 2 catalyst contains two oxidation states during CO oxidation at 50 °C in the Pd 3d core-level spectrum.The more intense component at 337.8 eV corresponds to the atomically dispersed Pd 2+ ions covalently bonded to CeO 2 .In comparison, the second one, located at ≈336 eV, is attributed to small PdO x clusters, indicating the susceptibility of Pd SACs to reduction and agglomeration even under mild reaction conditions.Almost half of the Pd converts into metallic (335.4 eV) and semi-oxidized (≈ 336 eV) states at 300 °C.On the contrary, the corresponding NAP-XPS spectra for high-surface-area Pd 1 /CeO 2 SACs using flame spray pyrolysis only contain the Pd 2+ oxidation state, independent of the CO oxidation reaction conditions.[30] The agglomeration of Ir atoms on Fe 3 O 4 at 960 K during CO oxidation and watergas shift reaction was validated by in situ XPS. [76]The dynamic evolution of CuO during the reduction/oxidation treatments in deNO x reactions was also traced by in situ XPS.Complete reduction of CuO to metallic Cu occurred in H 2 reduction, leading to the shift of the typical Cu 2+ peak at 934.0 eV to a lower binding energy.The recovery in the XPS profile to its initial state after re-oxidation in wet air confirmed good reversibility.[7] The excellent stability of Ni 1 Cu 2 /g-C 3 N 4 catalyst in hydrogenation could be verified by in situ XPS, where the Cu 2p 3/2 binding energy was invariant at 933.2 eV for the +1 oxidation state, irrespective of the treatments.[56] Nevertheless, most NAP-XPS studies are conducted in the quasi-operando conditions in gas-phase, calling for the development of adapting the XPS technique into or close to practical reaction conditions, particularly for electrochemical or liquid-phase reactions.[23]

Operando FTIR and Raman
Apart from DRIFTS, operando FTIR and Raman in the liquid phase are valuable vibrational spectroscopy techniques for revealing the active species, phases, and mechanisms.From a funda-mental aspect, infrared spectroscopy reflects the change of dipole moment of molecules, while Raman corresponds to the variation in polarizability.Hence, Raman is more frequently employed than FTIR in the structural profiling of inorganic electrocatalysts due to the limitation of infrared energy. [10,23]Depending on the transmissivity of the samples, various operando cells, including transmission, diffuse reflectance, and attenuated total reflection (ATR), are commercially available using KBr or CaF 2 windows and ZnSe or Ge ATR crystals.For transmission and diffuse reflectance, catalyst powders are usually pressed into pellets or small crucibles, while the crystals are coated with thin catalyst films for ATR. [10]or instance, operando synchrotron Fourier transform infrared spectroscopies (SR-FTIR) were performed to uncover the atomic-level dynamics of active site evolution at the solid-liquid electrochemical interfaces associated with the reactive intermediates proceeding over a Ni 1 -NC SAC during ORR. [77]As shown in Figure 7G,H, a new absorption band from the surface * O intermediate over the Ni 1 -N 2 active site at 908 cm −1 appears at 0.85 V. Isotope labeling was then performed to clarify the origin of such intermediate.The isotope exchange of 16 O/ 18 O in singlet oxygen ( * O) leads to a redshift of the vibrational band from 908 to 894 cm −1 when 16 O 2 gas is replaced by 18 O 2 , confirming the potentialdriven chemical coupling between the * O 2 precursor adsorbed on Ni 1 -N 2 site and an assisted water molecule adsorbed on adjacent N and C sites.This leads to the formation of crucial * O intermediates and the accumulation of O-H species on the catalyst surface, bypassing the conventional, rate-determining step of O-O dissociation in ORR. [77]tructural fingerprints and the metal-substrate interaction in carbon or oxide-supported SACs could be derived from operando Raman. [4]The strong interaction between isolated Pd 1 and CeO 2 support is verified by an apparent redshift from 465 to 453 cm −1 in the F 2g peak of Pd 1 /CeO 2 in the Raman spectra, originating from the defect-sensitive, symmetrical stretching vibration of O 2− around Ce 4+ .Notably, the F 2g peak suddenly blueshifts to 461 cm −1 upon RT-CO treatment in 5 mins, which is attributed to rapid oxygen extraction and nucleation of PdO x clusters at the Pd/CeO 2 interface. [6]In separate work, a broad peak attributed to an I-H vibration band at 1460 cm −1 is seen in the in situ Raman for single-atom iodine stabilized on nickel hydroxide when the potential was more negative than the thermodynamic potential of HER. [78]][81] A good example lies in the geminal-atom catalysis for the well-designed combination of experimental and theoretical approaches. [41]Note that probes such as high energy electrons and X-rays can damage catalysts; conducting low-dosage and control experiments is essential to minimize the interference (artifacts). (A-E) Copyright 2023, Springer Nature.

Regulation of the Dynamic Aggregation
Given the complexity of dynamic profile in a catalytic cycle, precise fabrication of active sites with controlled atomicity and composition is ever-more fascinating but incredibly complex to achieve.Such catalyst discovery often relies on empirical screening guided by the influence of variations of the synthetic parameters on performance, which is time-consuming and unable to predict the catalyst response to a reactive environment. [1]This calls for reliable methods to regulate the dynamic transformation between subnanometric species.The understanding of cluster chemistry, including their structure, formation pathway, and reactivity, has also made significant processes. [82,83]The transformation chemistry between different cluster species has been extensively studied, especially by mass spectrometry as well as other techniques. [84]The cluster chemistry knowledge may potentially benefit the regulation of dynamic aggregation.
Recalling the driving force in Section 2.1, the island growth mode (Volmer-Weber growth) is the primary mechanism for nanoparticle formation due to more favorable enthalpic interaction within the metal itself than with the substrate. [85]A trivial solution lies in the thermodynamic regulation of the metalsubstrate interaction to prevent nanoparticle formation (i.e., sta-ble SACs).This often leaves too few metal sites available for reactant binding and catalysis, and sintering may still occur when exposed to sufficiently harsh conditions; [86] A nontrivial solution is to tune the supply or diffusion kinetics of free atoms via confinement or defect-engineering, which allows some degrees of freedom for dynamic response and prevents irreversible sintering into large particles. [12,25,87]o this end, Liu et al. proposed a "nanoglue" strategy via confining atomically dispersed metal atoms on tiny oxide clusters. [87]s shown in Figure 8A,B, isolated and defective CeO x nanoglue islands with a size of less than 2 nm were grafted on high-surfacearea SiO 2 as the host for one Pt atom.In contrast to conventional sintering, such Pt SACs remain highly stable under oxidizing and reducing environments at high temperatures and exhibit markedly increased activity for CO oxidation in Figure 8C.This is attributed to the mobility of the Pt atom on each CeO 2 nanoglue island while preventing inter-island movement for coalescence.Such a strategy can produce various robust SACs and cluster catalysts. [87]Similarly, the confined space in non-collapse metalorganic frameworks prevents the excessive aggregation of Cu single atom under cathodic potentials, yielding ultrasmall clusters (≈4 nm) for a benchmark performance in ammonia electrosynthesis via nitrate reduction. [88]imicking the homogeneous catalyst through a reversible opening and closing of the metal-ligand coordination sphere in the catalytic cycle is another emerging approach to achieving controllable dynamism.As shown in Figure 8D, Xu et al. proposed a possible mechanism in a heterogeneous Cu 1 /CeO 2 SAC for CO oxidation, where the metal center can migrate from a fully coordinated site (the closed state) to a defective site (the open state) on the support.The activation of the reactant is facilitated in the open state in the first half of the catalytic cycle (i-iv), while the release of the product is facilitated when the active center is transformed back to the closed state in steps v to viii in Figure 8E.The changes in metal-support coordination are accompanied by the changes in the valence of Cu, i.e., open for Cu(I) and closed for Cu(II). [89]Reaction product-driven restructuring and assisted stabilization at the atomic scale during steam reforming of methane was also observed in the Rh-on-ceria catalyst. [90]The introduction of such reversible coordination in heterogenous catalysis provides a new perspective for tuning the structural dynamism of SACs.

Conclusion
Dynamic aggregation into other subnanometric species is a universal behavior in single atom catalysts (SACs) to respond to reactive environments, regardless of their thermodynamic or kinetic stability on support materials.Fundamentally, this is driven by many factors, including changes in the energetics due to interactions with reactants or intermediates and structural transformations of the support.Such aggregation could be progressive and irreversible, leading to a perpetual change in catalytic performance as suggested by conventional wisdom (catalyst deactivation by sintering).By contrast, it may occur discreetly and transiently under reaction conditions, generating redispersible tiny clusters and nanoparticles as the real active sites for various reactions.The restructuring of SACs could be uncovered by combining operando studies using X-ray absorption spectroscopy, in situ transmission electron microscopy, near-ambient pressure X-ray photoelectron spectroscopy, and operando vibrational spectroscopies.In many cases, this is more reliable than those ex situ techniques to describe the active sites and structureproperty relationship due to the complexity of the dynamic profile.It is also crucial to regulate the dynamic transformation between subnanometric species via emerging strategies such as confinement and defect engineering.Such knowledge provides a new paradigm for designing intelligent SACs for practical applications.

Figure 1 .
Figure 1.Dynamic aggregation induced by surface migration.A) Schematic illustration of free-energy diagram of sintering and dispersion processes between Au nanoparticles and single atoms; B) Four types of single atoms on oxide support; C) Surface stability diagram for Rh single atom on TiO 2 (110) in the presence of H 2 .Axes represent the H and O chemical potentials (noted Δμ(H) and Δμ(O) in eV); D) DFT computed atomic structures of the favored Pd states on Pd-doped CeO 2 (111) at different operation stages; E) Evolution of the chemical potential of Pd (μ Pd ) at different stages with reaction conditions relative to bulk Pd; F) Free energy landscape for Pd 1 activation with (p CO = 0.02 atm) and without CO at 25 °C.Reproduced with permission.[14,22,27,6](A, B) Copyright 2018, Oxford Academic.(C-F) Copyright 2019 and 2023, Springer Nature.
Figure 1.Dynamic aggregation induced by surface migration.A) Schematic illustration of free-energy diagram of sintering and dispersion processes between Au nanoparticles and single atoms; B) Four types of single atoms on oxide support; C) Surface stability diagram for Rh single atom on TiO 2 (110) in the presence of H 2 .Axes represent the H and O chemical potentials (noted Δμ(H) and Δμ(O) in eV); D) DFT computed atomic structures of the favored Pd states on Pd-doped CeO 2 (111) at different operation stages; E) Evolution of the chemical potential of Pd (μ Pd ) at different stages with reaction conditions relative to bulk Pd; F) Free energy landscape for Pd 1 activation with (p CO = 0.02 atm) and without CO at 25 °C.Reproduced with permission.[14,22,27,6](A, B) Copyright 2018, Oxford Academic.(C-F) Copyright 2019 and 2023, Springer Nature.

Figure 2 .
Figure 2. Adaptive coordination environment in SACs.A) Snapshots of molecular dynamics simulations of palladium dimers and trimers stabilized on g-C 3 N 4 , illustrating distinct possible configurations; B) Contour plot of the interatomic Pd-N distances for each N-coordination site at each of the intermediate and transition states; C) The transmetallation step (A2 → A3) for Pd-ECN; D) Coordination environment of Pt-2O, where two O atoms are acting as ligands; E) Time evolution at 600 K of the atom-resolved oxidation states of the Pt and surface Ce atoms for Pt-2O; F) AIMD calculations of the structure of the *CO step of the catalytic process with respect to the change in the NiZn-N 6 -C, Ni-N 4 -C, and Zn-N 4 -C bond lengths with time.Reproduced with permission.[1,29,31,40](A-E) Copyright 2018, 2021, 2023.Springer Nature.(F) Copyright 2021, Wiley-VCH.
Figure 2. Adaptive coordination environment in SACs.A) Snapshots of molecular dynamics simulations of palladium dimers and trimers stabilized on g-C 3 N 4 , illustrating distinct possible configurations; B) Contour plot of the interatomic Pd-N distances for each N-coordination site at each of the intermediate and transition states; C) The transmetallation step (A2 → A3) for Pd-ECN; D) Coordination environment of Pt-2O, where two O atoms are acting as ligands; E) Time evolution at 600 K of the atom-resolved oxidation states of the Pt and surface Ce atoms for Pt-2O; F) AIMD calculations of the structure of the *CO step of the catalytic process with respect to the change in the NiZn-N 6 -C, Ni-N 4 -C, and Zn-N 4 -C bond lengths with time.Reproduced with permission.[1,29,31,40](A-E) Copyright 2018, 2021, 2023.Springer Nature.(F) Copyright 2021, Wiley-VCH.

Figure 3 .
Figure 3. Influence of dynamic aggregation on catalytic activity.A) Trends in relative TOF upon reducing the atomic population of metal nanoparticles and SACs; B) Quantitative correlation between the first-shell Pt-Pt coordination numbers of various Pt catalysts and corresponding Tafel slope for the HER; C) Dynamic formation of a Pt SAC during methane oxidation.Light-off curve of 1Pt/Fe 2 O 3 -NP for methane oxidation.STEM images of catalyst before (left) and after (right) reaction.Scale bars, 2 nm.Reproduced with permission.[42,43,17](A) Copyright 2018, Wiley-VCH.(B) Copyright 2021, Wiley-VCH.(C) Copyright 2019, Springer Nature.
Figure 3. Influence of dynamic aggregation on catalytic activity.A) Trends in relative TOF upon reducing the atomic population of metal nanoparticles and SACs; B) Quantitative correlation between the first-shell Pt-Pt coordination numbers of various Pt catalysts and corresponding Tafel slope for the HER; C) Dynamic formation of a Pt SAC during methane oxidation.Light-off curve of 1Pt/Fe 2 O 3 -NP for methane oxidation.STEM images of catalyst before (left) and after (right) reaction.Scale bars, 2 nm.Reproduced with permission.[42,43,17](A) Copyright 2018, Wiley-VCH.(B) Copyright 2021, Wiley-VCH.(C) Copyright 2019, Springer Nature.

Figure 4 .
Figure 4. Influence of dynamic aggregation on selectivity and stability.A) The relationships of possible adsorption configuration of reactants and reaction selectivity per metal atom on a traditional supporting substrate with metal size; B) Variations in the RWGS rate per Pd with TOS at 400 °C for Pd/TiO 2 catalysts at various Pd loadings; C) 0.0125 wt% Pd 1 /TiO 2 at various temperatures; D) Statistical mechanics model of density-dependent particle decomposition; E) CH 4 conversion profiles for Pd/Al 2 O 3 catalysts with different nanoparticle loadings following the temperature profile; F) STM characterization of Cu g /PCN at 370 K; G) Schematic illustration of the dynamic coordination of geminal Cu active centers for C-O coupling over Cu g /PCN;H) The energy levels of Cu (II)•••Cu (II) interaction with increasing proximity from infinite distance to 2.46 Å; Reproduced with permission.[3,41,53,58,57](A) Copyright 2021, Wiley-VCH.(B, C) Copyright 2023, ACS.(D, E) Copyright 2019, Springer Nature.(F-H) Copyright 2023, Springer Nature.
Figure 4. Influence of dynamic aggregation on selectivity and stability.A) The relationships of possible adsorption configuration of reactants and reaction selectivity per metal atom on a traditional supporting substrate with metal size; B) Variations in the RWGS rate per Pd with TOS at 400 °C for Pd/TiO 2 catalysts at various Pd loadings; C) 0.0125 wt% Pd 1 /TiO 2 at various temperatures; D) Statistical mechanics model of density-dependent particle decomposition; E) CH 4 conversion profiles for Pd/Al 2 O 3 catalysts with different nanoparticle loadings following the temperature profile; F) STM characterization of Cu g /PCN at 370 K; G) Schematic illustration of the dynamic coordination of geminal Cu active centers for C-O coupling over Cu g /PCN;H) The energy levels of Cu (II)•••Cu (II) interaction with increasing proximity from infinite distance to 2.46 Å; Reproduced with permission.[3,41,53,58,57](A) Copyright 2021, Wiley-VCH.(B, C) Copyright 2023, ACS.(D, E) Copyright 2019, Springer Nature.(F-H) Copyright 2023, Springer Nature.
) and Cu(I) species at different cathodic potentials was validated by the absorption signals located at lower energy edges than those of Cu 1 -CeO 2 under open circuit voltage.Further analysis by the EX-AFS spectra in Figure 5B confirmed the evolution of first-shell coordination from Cu-O in the Cu 1 -CeO 2 SAC to mainly Cu─Cu bonding in Cu 4 clusters.The Cu─Cu bonding was strengthened at more negative voltages (−1.6 V) to a coordination number of 7.Even extending the duration at -1.6 V to 50 mins, atomically dispersed copper can only aggregate to Cu 4 clusters, not copper nanoparticles.The reversible transformation of Cu 4 to Cu 1 configurations occurred after the removal of voltage, as depicted in Figure

Figure 5 .
Figure 5. Operando EXAFS for dynamic structural evolution.A) Cu K-edge XANES spectra and B) R-space EXAFS spectra of Cu 1 -CeO 2 recorded at different cathodic potentials during C-N coupling; C) Schematic diagram of reconstitution of copper single-atoms to clusters suggested by the operando XAS measurements; D) FT-EXAFS and wavelet transform spectra of NiFe-CNG for Ni andE) Fe K-edge XAS under OER conditions.Reproduced with permission.[44,66](A-C) Copyright 2023, Wiley-VCH.(D, E) Copyright 2021, Springer Nature.
Figure 5. Operando EXAFS for dynamic structural evolution.A) Cu K-edge XANES spectra and B) R-space EXAFS spectra of Cu 1 -CeO 2 recorded at different cathodic potentials during C-N coupling; C) Schematic diagram of reconstitution of copper single-atoms to clusters suggested by the operando XAS measurements; D) FT-EXAFS and wavelet transform spectra of NiFe-CNG for Ni andE) Fe K-edge XAS under OER conditions.Reproduced with permission.[44,66](A-C) Copyright 2023, Wiley-VCH.(D, E) Copyright 2021, Springer Nature.

Figure 6 .
Figure 6.Operando microscopy for dynamic structural evolution.A) Frames acquired at various temperatures and times of Pd-NPs@ZIF-8 pyrolyzed in situ with ETEM under an Ar atmosphere.Scale bar: 50 nm; B) Calculated energies along the stretching pathway of the Pd atom from the Pd 10 cluster to Pd-N 4 defect by CI-NEB, and the corresponding initial and final configurations; C) A single Pt adatom trajectory from a 134 s video in the graphene double liquid cell; D) Trajectories of an ensemble of Pt atoms in the liquid cell, colored according to the elapsed time.Reproduced with permission. [16,72](A, B) Copyright 2018, Springer Nature.(C, D) Copyright 2022, Springer Nature.

Figure 7 .
Figure 7. Operando spectroscopies for dynamic structural evolution.A) DRIFTS color maps showing the evolution of the  C−O absorption band(s) in the Pt carbonyl wavenumber region during postreduction and B) postcalcination reaction steps; C) Schematic illustration of the dynamic structural evolution process; D) In situ DRIFTS during RT-CO activation; E) CH 4 oxidation on Pd 1 /CeO 2 after RT-CO activation for 1-30 min; F) In situ NAP-XPS of the Pd 3d core line as a function of the reaction conditions for 1PdRods (left) and 1PdFSP (right); G) Operando SR-FTIR measurements in the range of 600−1400 cm −1 under various potentials for Ni 1 −NC during the ORR process and H) the corresponding isotope-labeling experiment.Reproduced with permission.[73,6,30,77](A-C) Copyright 2019, ACS.(D, E) Copyright 2023, Springer Nature.(F) Copyright 2021, Springer Nature.(G, H) Copyright 2020, ACS.
Figure 7. Operando spectroscopies for dynamic structural evolution.A) DRIFTS color maps showing the evolution of the  C−O absorption band(s) in the Pt carbonyl wavenumber region during postreduction and B) postcalcination reaction steps; C) Schematic illustration of the dynamic structural evolution process; D) In situ DRIFTS during RT-CO activation; E) CH 4 oxidation on Pd 1 /CeO 2 after RT-CO activation for 1-30 min; F) In situ NAP-XPS of the Pd 3d core line as a function of the reaction conditions for 1PdRods (left) and 1PdFSP (right); G) Operando SR-FTIR measurements in the range of 600−1400 cm −1 under various potentials for Ni 1 −NC during the ORR process and H) the corresponding isotope-labeling experiment.Reproduced with permission.[73,6,30,77](A-C) Copyright 2019, ACS.(D, E) Copyright 2023, Springer Nature.(F) Copyright 2021, Springer Nature.(G, H) Copyright 2020, ACS.

Figure 8 .
Figure 8. Emerging strategies for controlling the dynamic aggregation.A) Fabrication processes of functional CeO x nanoglue islands and CeO x /SiO 2supported Pt 1 single-atom catalysts; B) Atomic-resolution HAADF-STEM image of crystalline CeO x clusters; C) Evaluation of low-temperature CO oxidation activity and stability; D) Possible mechanism with hemilabile coordination in Cu 1 /CeO 2 , where the metal center can migrate from a full metalsupport coordination site (the closed state) to a defect site (the open state); E) Optimized structures for Cu 1 /CeO 2(111) in the catalytic cycle with the hemilabile metal-support coordination.Reproduced with permission.[87,89](A-E) Copyright 2023, Springer Nature.