Recent advances in synergetic catalysis of single-atom catalysts in biomass conversion, CO₂ reduction, and cascade reaction

Impregnation and co-impregnation method

The impregnation method through introducing active components onto the surface of the carrier within the solution, plays a significant role in fabricating SACs. In this typical process, a solution containing metal salt solution mixed with the carrier easily triggers the anchoring of atomic active sites on the surface of the support. The surface adsorption and capillary condensation would maximize the contact of main metal ions, which allows for the controlled loading of metal ions by altering the concentration and the amount of dipping solution. For instance, Gu et al.^[10] successfully prepared the Ru₁/CoO_x catalyst using impregnation, wherein Ru single atoms (Ru₁) were anchored on the CoO_x surface at an ultra-low loading of 0.5 wt% [Figure 1A]. The catalyst demonstrated exceptional efficiency in the selective electro-oxidation of 5-hydroxymethylfurfural (HMF), achieving an impressively low onset potential coupled with accelerated interfacial charge transfer kinetics. However, note that the traditional impregnation approach is often difficult in controlling the high loading of isolated, in particular, the weak interaction of post-introduced metal atoms with support easily causes the aggregation and sintering effect under high-temperature treatment. In addition, such modification would cause the randomness of the distribution of atomic species onto the support, making the precise design of active atoms difficult. Furthermore, the communication and synergy of isolated atoms become uncontrollable when the distance of the atom is large enough. In contrast, when ensuring the adjacent distance of single atoms on the same support, the interaction and electronic communication of single atoms can be released, which usually triggers the synergy effect of isolated atoms. For example, in the case of a dual-atom catalyst system, when the Au and Pd atoms were randomly dispersed on the TiO₂ surface with a relatively large average distance between them, their catalytic activity towards a specific reaction, such as the selective hydrogenation of acetylene, was only marginally better than that of the single-component SACs. However, through precise control, the isolated Au and Pd single atoms were anchored close to each other on the TiO₂ support. In this configuration, the electronic interaction between the Au and Pd atoms was enhanced, leading to an optimized electronic structure. As a result, the catalyst exhibited a significantly enhanced catalytic performance, with a much higher conversion rate and selectivity for the desired product. This demonstrated the importance of the adjacent distance and the consequent synergy effect of single atoms on the same support^[11]. The co-impregnation method, on the other hand, enables the simultaneous loading of two or more active components onto a carrier, making it ideal for preparing multi-component catalysts, which is crucial for complex multiple molecule activation reactions requiring multiple metal active sites. Ren et al.^[12] prepared the Ir-La-S/AC catalyst via co-impregnating La and Ir precursors onto activated carbon (AC) support, followed by drying and calcination [Figure 1B]. The Ir species in the catalyst were predominantly in a monodisperse state, effectively improving Ir utilization efficiency. Additionally, the sulfuric acid addition contributes to the abundant acidic sites, facilitating the rate-limiting step of CO insertion and further augmenting catalytic activity through the synergy of acid sites and Ir species, indicating the potential of the co-impregnation method in enhancing the synergy of SACs.

Figure 1. (A) Scheme of the fabrication of Ru₁/CoO_x. Adapted with permission^[10]. Copyright 2023, American Chemical Society; (B) Microscopy scheme of the fabrication of Ir-La-S/AC catalyst. Adapted with permission^[12]. Copyright 2018, Elsevier B.V.

Co-precipitation method

The co-precipitation method is capable of obtaining uniformly dispersed supported metal catalysts with different active species by simultaneously precipitating insoluble compounds from two or more soluble salts in a mixed solution. The active metal atoms can be incorporated into the support when occurring a co-hydrolysis process. However, the pH condition and concentration of the reaction solution should be controlled rigidly to avoid the individual nucleation growth of isolated atom species. Given that such control, the composition and configuration of the catalyst can be regulated. Through co-precipitation-mediated atomic substitution, Yang et al.^[13] achieved precise integration of cerium species into ZrO₂ crystalline frameworks, inducing lattice strain effects that simultaneously established multi-scale interfacial architectures and elevated oxygen defect concentrations. Systematic evaluation revealed this structural engineering strategy endowed the catalyst with superior low-temperature reduction properties and enhanced oxygen mobility rates when benchmarked against unmodified ZrO₂ and conventional impregnation-derived analogues. Sun et al.^[14] synthesized Ru₁/FeO_xSACs using co-precipitation method. Fe(NO₃)₃·9H₂O and RuCl₃·3H₂O were used as precursors for iron and ruthenium, and the amount of RuCl₃ added was adjusted to control the loading of ruthenium, achieving uniform mixing and strong interaction between single atoms Ru and FeO_x. The catalytic cycle involves synergistic coupling between hydroxyl radicals (OH^*) derived from H₂O dissociation on FeO_x substrates and CO^* intermediates adsorbed on isolated Ru sites, facilitated by interfacial electronic interactions that drive the redox transformation to CO₂ and H₂ [Figure 2]. This enhanced activity originates from the optimized electronic configuration of Ru centers that weakens CO chemisorption, combined with the defective FeO_x matrix providing abundant active oxygen species. The unique Ru-O-Fe coordination architecture not only stabilizes single-atom dispersion through strong covalent bonding but also establishes electron transfer channels that dynamically regulate oxygen vacancy formation/annihilation cycles. Furthermore, the rapid H₂ desorption kinetics at Ru sites effectively suppresses parasitic methanation pathways while maintaining high hydrogen evolution selectivity.

Figure 2. (A) MS analysis of introducing CO with temperatures on 0.18RuFe and 2.00RuFe-NP catalysts preadsorbed with 10% H₂O at 250 °C, respectively; (B) Arrhenius plots of the reaction rate vs. 1/T for the WGS reaction on 0.18RuFe and 2.00RuFe-NP catalysts, with Ea indicated in the plot. Schematic illustration of the associative mechanism with the methanation side reaction during WGS reaction over 0.18RuFe (C) and 2.00RuFe-NP (D) catalysts. Adapted with permission^[14]. Copyright 2022, Elsevier B.V. MS: Mass spectrometry; WGS: water-gas shift.

Atomic layer deposition

Atomic layer deposition (ALD) allows substances to be deposited layer by layer on the substrate surface in the form of a single atomic layer. It utilizes gas-phase precursor pulses that alternately enter the reactor, undergo chemical adsorption and reaction on the deposited substrate, and form a deposited layer. Based on the self-limitation of surface reactions in ALD, repeating this self-limiting reaction creates the desired thin film. Liu et al.^[15] explored the synthesis of single-atom platinum (SA Pt) catalysts on vertical graphene (VG) using ALD [Figure 3]. By controlling the nominal thickness of Pt at the atomic level with the self-limiting effect, and leveraging the large number of graphene edges as energy-favorable nucleation sites for SA Pt, they achieved enhanced stability. Compared with nano Pt, Pt single atoms had higher stability near the VG edge state, and their sensitivity and response speed were more than an order of magnitude higher. Song et al.^[16] selectively anchored isolated Ir single atoms onto Pt NPs through ALD, modifying the Pt NP surface. The formation of the SA-NP composite structure significantly improved the performance of the Ir_SA-Pt_NP catalyst, exhibiting excellent stability for both oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). In addition, the ALD technique has been developed to ensure the oriented deposition of atoms onto the directional crystal planes of support, which easily reaches the well-defined design of SACs to receive the interesting synergy of SACs and support. Lu et al.^[17,18] prepared Pt₁ single-atom catalysts with 4 wt% loading on cerium oxide nanorods using ALD technology. The defect sites on the CeO₂ surface, such as Ce³⁺ defects and oxygen vacancies, provided stronger metal support interactions (MSI). Such defect sites have high energy and activity, more effectively stabilizing Pt single atoms and triggering electron transfer between Pt and CeO₂. Pt single atoms at defect sites tend to form Pt²⁺ species, and compared to Pt single atoms located at the edge of CeO₂ steps, releasing the optimized electronic properties which further affects the adsorption and activation of reactants onto Pt single atoms.

Figure 3. (A) Scheme of Fabrication of ALD Pt@VG; (B) Schematic illustration of the H₂-sensing mechanism on the Pt@VG sensor with the role of the Pt catalyst in the adsorption and decomposition of H₂ molecules, followed by a charge transfer process. Inset (left): schematic diagram showing charge transfer after H is adsorbed on Pt. E_F represents the Fermi energy level and Φ_Pt represents the work function of Pt. Inset (right): schematic illustration of Pt-decorated VG grown on SiO₂/Si substrates used for H₂ sensing. Adapted with permission^[15]. Copyright 2024, American Chemical Society. ALD: Atomic layer deposition; VG: vertical graphene.

Electrochemical methods and photochemical method

Electrochemical methods are generally allowed to operate in simple two- or three-electrode systems under ambient conditions. The synthesis parameters can be adjusted by altering input techniques such as current, voltage, scan rate, and reaction time to achieve desired products. Wu et al.^[19] used electrochemical methods to embed 29 atomic transition metals into defective boron phosphide (BP) monolayers. Selecting Nb/BP and W/BP SAC as qualified electrocatalysts, they achieved high stability, low initial potential (as low as 0.25 and 0.19 V, respectively), and excellent selectivity (90.5% and 100%, respectively) for electrochemical N₂ reduction reaction (NRR). Lv et al.^[20] proposed a universal one-step electrochemical synthesis strategy to obtain various zeolite imidazolate frame-8 (ZIF-8) supported SACs by simply replacing different metal precursors [Figure 4]. Evaluating the platinum-based catalyst for electrosynthesis, it exhibited excellent activity and stability in the electrocatalytic hydrogen evolution reaction (HER). These electrochemical methods enable the in-situ generation and precise control of single-atom active sites, enhancing catalytic performance through effective synergy. Nitrogen-doped carbon-supported Pt single atom/cluster catalysts were prepared through electrochemical synthesis and subsequent pyrolysis processes Pt@NC. The active sites of Pt clusters/PtN₃ (Pt clusters and nitrogen-doped carbon carriers) are mainly located on Pt clusters. However, the Pt clusters/PtN₃ active species could further release the synergy, whose d-band center is closer to the Fermi level, which is obviously optimized compared to pure PtN₃ and Pt clusters, helping to regulate the electronic structure of Pt clusters, optimize the adsorption strength of H, and thus improve HER activity.

Figure 4. Preparation and characterizations of eZIF-Pt. (A) Schematic illustrating the synthesis of eZIF-Pt. Electrocatalytic HER performance and DFT calculations; (B) LSV curves of the 0.79-ePt@NC, 1.83-Pt@NC, commercial Pt/C, and NC; (C) The corresponding Tafel slope originated from LSV curves; (D) Comparison of overpotentials at 10 mA·cm^-2 and Tafel slopes; (E) Comparison of the HER activity for 1.83-Pt@NC with reported catalysts; (F) Mass activity and TOF values at an overpotential of 100 mV; (G) Stability test of 1.83-Pt@NC through cyclic potential scanning (inset: chronoamperometry method). Adapted with permission^[20]. Copyright 2023, Wiley-VCH GmbH. eZIF-Pt: Electrochemically synthesized zeolite imidazolate frame-8 with platinum single atoms; HER: hydrogen evolution reaction; LSV: linear sweep voltammetry; TOF: turnover frequency.

The photochemical method leverages ultraviolet (UV) light instead of electrochemical reduction, which requires the system to contain substances that can absorb UV light and release electrons. Liu et al.^[21] employed a room-temperature photochemical strategy to prepare highly stable atomic level dispersed Pd catalysts (Pd₁/TiO₂) by irradiating ultra-thin TiO₂ nanosheets stabilized with ethylene glycol (EG) through UV light. The Pd₁/TiO₂ catalyst exhibited extremely high activity in the hydrogenation reactions of C=C and C=O, nearly nine times enhancement compared to that of the Pd atoms on the surface of commercial Pd catalysts without any decay after 20 cycles. Ge et al.^[22] used photochemical reduction to reduce PdCl₄^2- on the surface of TiO₂, forming the Pd single atom PdSA/TiO₂ photocatalyst [Figure 5]. Due to the high dispersion of Pd single atoms on TiO₂ and the high density of active sites, PdSA/TiO₂ exhibited higher photocatalytic activity than Pd NPs PdNPs/TiO₂, with a photocatalytic activity (10 mol·g^-1·h^-1) much higher than that of PdNPs/TiO₂ (1.95 mol·g^-1·h^-1). This defines the synergetic promotion of Pd single atom with TiO₂ support, through the improved photocurrent response and energy gap, which contributes to the higher photocatalytic properties.

Figure 5. (A) The photocatalytic HER stability of PdSA/TiO₂ before and after the introduction of chlorpyrifos; (B) The typically photocatalytic response of PdSA/TiO₂ toward different concentrations of chlorpyrifos, 0.03, 1, 30, 200 ng·mL^-1, 1, 10 μg·mL^-1; (C) The interference assessment of other commonly used organophosphorus pesticides on chlorpyrifos determination; (D) The interference analysis of the anions and cations common in vegetable samples; (E) The principle of the PdSA/TiO_2-based sensing platform utilizing photocatalytic H₂ production. Adapted with permission^[22]. Copyright 2020, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. HER: Hydrogen evolution reaction.

Pyrolysis synthesis method

The pyrolysis synthesis method requires heat treatment of metal precursors and carrier materials at high temperatures, usually in an inert atmosphere, to prevent oxidation of metal atoms. At high temperatures, the oxidation process easily triggers the aggregation of metal atoms, because of the loss of carbon framework, which can reduce the dispersion of active sites in the catalyst, thereby lowering catalytic efficiency and potentially leading to structural damage to the material. For example, in the pyrolysis process of certain MOFs, the oxidation of metals catalyzes the graphitization of carbon, leading to the collapse of MOF structures^[23]. This is applicable for the abundant combination of various metals precursor and carrier materials, with a production scale of several kilograms per hour that can be used for large-scale production of SAC, which is of great significance for industrial applications^[24].

Jiang et al.^[25] developed high-density Fe single-atom assemblies through a carbothermal coordination-mediated synthesis strategy, utilizing graphitic carbon matrices to anchor metal complexes during pyrolysis [Figure 6A]. Through precise precursor dosage control on surface-engineered carbon matrices, the team achieved a record 7.5 wt% metal loading while maintaining atomic dispersion. Critical stabilization arises from atomic-scale chelation between Fe species and nitrogen dopants, where structural confinement effects through ordered M-N₄ coordination motifs effectively mitigate metal clustering. Systematic evaluation revealed the ORR performance enhancement follows an active-site density dependency, with catalytic currents scaling proportionally to the concentration of intact Fe-N₄ moieties. Ping et al.^[26] developed a CO₂RR catalyst (MgAl₂O₄/Ni-N-C) with abundant single Ni sites and MgAl₂O₄-NP (~14 nm) via a confinement pyrolysis strategy using NiMgAl LDHs as metal precursor [Figure 6B]. The MgAl₂O₄ NP with abundant oxygen vacancies stabilized Ni atoms and regulated the electronic structure of adjacent Ni atoms, promoting the conversion of CO₂ to ^*COOH. MgAl₂O₄/Ni-N-C has a unique three-dimensional porous structure, which helps to expose active sites and disperse Ni atoms. The MgAl₂O₄/Ni-N₄-C model exhibits a higher ^*H formation barrier than Ni-N₄-C, indicating that the competitive HER process is significantly suppressed compared to MgAl₂O₄/Ni-N₄-C. Note that the oxygen vacancy of support facilitates the trapping effect of CO₂, coupling with the existing single atom Ni to reach the synergetic catalytic conversion of CO₂^[26,27]. The pyrolysis synthesis method helps to enhance the interaction between metal atoms and the support, facilitating the formation of stable single-atom sites that contribute to improved catalytic synergy.

Figure 6. (A) Schematic illustration of the formation of xFe-SA/NPC-T samples; yellow and blue-grey balls represent melamine and the Fe-o-PD complex, respectively. Adapted with permission^[23]. Copyright 2021, Elsevier; (B) The preparation scheme of the MgAl₂O₄/Ni-N-C. Adapted with permission^[24]. Copyright 2024, Elsevier B.V. SA: Single-atom; NPC: N-doped porous carbon; T: pyrolysis temperature; o-PD: ortho-phenylenediamine.

Spray pyrolysis method

Spray pyrolysis is a scalable and versatile technique for synthesizing SACs, particularly suited for large-scale production. In this process, a precursor solution containing metal salts and support materials is atomized into fine droplets, which are rapidly dried and pyrolyzed at high temperatures. The confined environment of the droplets facilitates the uniform dispersion of metal precursors, while the fast thermal decomposition kinetics suppress metal aggregation, enabling the formation of isolated single-atom sites anchored on the support.

Recent studies highlight the efficacy of spray pyrolysis in SAC fabrication. For instance, Ding et al.^[28] demonstrated the synthesis of Fe-N-C SACs via spray pyrolysis, achieving high Fe loading (3.2 wt%) with excellent ORR activity. The method’s rapid processing and compatibility with diverse precursors (e.g., metal-organic frameworks or carbon-based supports) make it advantageous for industrial applications. Similarly, Zheng et al.^[29] utilized a modified spray pyrolysis approach to prepare Co SACs on N-doped carbon, where the synergistic interaction between Co single atoms and nitrogen defects significantly enhanced CO₂ reduction performance. These studies underscore spray pyrolysis as a robust method for tailoring SACs with precise atomic coordination and high stability.

Ball-milling method

The Ball Milling method is regarded as a mechanochemical synthesis technique, which could leverage the shearing force to tailor the size and distribution of active species and support, thereby improving the mixing, refinement, and activation of catalysts. It should be worth mentioning that the size of the support also can be further tailored to optimize the surface property. Wang et al.^[30] enabled a large-scale synthesis by ball-milling method, receiving beyond 4.7 g of Co-SNC once [Figure 7A]. The introduction of S atoms changes the charge density of the central Co atom, making the charge of Co in Co-N₄-S more negative than in Co-N₄-C. This different surface charge state endows the catalyst with different catalytic properties through the synergetic effect of S and Co. This strategy can be leveraged to construct novel dual-sites SACs without the interference of the wet chemistry method, which easily reaches great synergy in the heterogeneous catalytic reaction. Tang et al.^[31] combined mechanochemistry with SACs to prepare single atom Ni on graphitized carbon nitride (g-C₃N₄) catalyst using high-energy ball milling for photocatalytic CO₂ reduction reaction (CO₂RR) [Figure 7B] without sacrificial agents. The combined effects of impact, shear, and friction during ball milling allow Ni atoms to be highly dispersed, avoiding aggregation into clusters or NPs. The presence of single atom Ni alters the electronic structure of g-C₃N₄ and improves the separation efficiency of photogenerated charges, thus promoting the activation and reduction of CO₂. When the loading amount of Ni is 0.5 atomic percent, the photocatalyst exhibits the best photocatalytic CO₂ reduction performance. Such atomic abundance helps to stimulate more electrons to participate in photocatalytic reactions, thereby improving the efficiency of photocatalytic reactions.

Figure 7. (A) Schematic illustration of the developed ball-milling approach. Adapted with permission^[30]. Copyright 2021, Wiley-VCH GmbH; (B) Schematic diagram of Ni/CN-X synthesized via high-energy ball milling method. Enlarge diagram: a combination of impact, shear, and friction forces generated in a planetary-type ball mill. Adapted with permission^[31]. Copyright 2023, Elsevier B.V.

Chemical vapor deposition method

Chemical vapor deposition (CVD) would be available for not only obtaining the fabrication of thin films and nanomaterials but also affording the promise in the synthesis of SACs^[32]. In principle, gaseous or vaporous precursor substances would undergo chemical reactions at the gas or gas-solid interface, generating solid deposits, i.e., single-atom species onto the support. These precursors are typically composed of metal elements and ligands, which can be directly deposited onto the support with the formation of an isolated atom state by precisely altering the reaction conditions and precursor types. Shen et al.^[33] constructed Fe-N_xC moieties onto nanocellulose carbon aerogels through the synergistic application of directional freeze-casting and CVD methods. It not only substantially augmented the proportion of Fe-N_x active sites but also deftly steered the selectivity towards specific reaction pathways in four-electron ORR. Based on this approach, Han et al.^[34] developed the catalyst VSACs@1T-WS₂ for the HER, affording high catalytic activity and suitability, which is a great choice for developing efficient dual functional electrocatalysts. Single-atom vanadium (V) doped in 1T-WS₂ (tungsten disulfide) monolayer as a catalyst was synthesized through a one-step CVD strategy. After the V atom replaces the W atom, a charge depletion region will be generated around the V atom. This local charge redistribution may alter the electronic properties of 1T-WS₂ and enhance its adsorption capacity for hydrogen. V SACs have a significant impact on the hydrogen adsorption-free energy (ΔGH) at the edge sites of 1T-WS₂; the synergistic effect between V atoms and 1T-WS₂ carriers is crucial for HER activity. Even so, some challenges such as difficult precursor selection, complex control of reaction conditions, and relatively high costs still limit its widespread application^[34]. Given that, the pioneering of novel precursors and supports is believed to obtain well-defined synthesis of SACs through CVD for broader application prospects [Table 1].

Regulation of structural composition with different supports

The cornerstone in the synthesis of SACs lies in the stabilization of densely populated individual metal atoms on a befitting support. Unsaturated chemical sites present on the support surface play a dual and indispensable role during both the synthesis and catalysis process^[38,39]. Not only do they function as the physical anchors for single atoms, providing a firm footing, but they also wield the power to reshape the electronic structure of the metal centers. This electronic modulation, in turn, casts a profound catalytic or chemical influence on the overall performance of SACs^[40].

When it comes to the typical supports for SACs, they can be broadly categorized into microporous matrices, two-dimensional material, and metal-containing supports. Microporous matrices, exemplified by zeolites, MOFs, and COFs, utilize their intricate micropore networks to lock metal single atoms^[41]. Zeolites, in particular, flaunt well-developed pores replete with numerous surface hydroxyl groups. These hydroxyl-rich pores are akin to tiny cradles, effectively stabilizing a diverse array of species bearing single active sites^[42]. A case in point is the synthesis of thermally stable M-SACs^[43]. By impregnating a blend of metal salts and aqueous ethylenediamine onto modified commercial S-1 zeolites, followed by one-step pyrolysis under an argon blanket, the atomic site catalyst can be generated. XAFS and integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM) have unequivocally validated the presence of atomically dispersed transition metal atoms on the zeolite scaffold. Deeper investigations have unearthed that the dispersion of metal atoms owes its origin to the trapping prowess of silane nests. When assessing the proficiency of SACs supported on MFI-type Silicalite-1 zeolites in the conversion of CO₂, these catalysts, courtesy of their potent interactions with the zeolite walls, exhibit diminished energy barriers and tenacious resistance to aggregation and sintering. This not only safeguards the integrity of the single-atom dispersion but also promotes efficient reactant diffusion and interaction, thereby supercharging the single-atom synergistic catalytic ability.

Two-dimensional materials, such as graphene, g-C₃N₄, boron nitride (BN), etc., offer a different yet equally effective avenue for enhancing catalytic activity. In these cases, individual metal atoms form covalent bonds with their coordinating atoms (such as C, O, N, and S)^[44]. The key to unlocking their potential lies in the judicious selection of the appropriate support. When the right match is made, it triggers a cascade of changes in the electronic structure of the single-atom metal active sites [Figure 8A and B]^[45]. Taking graphene as a sample, its edges, provided they are not H-terminated, harbor C atoms with unpaired electrons. These reactive hotspots are the epicenters of activity in defect-free graphene^[46]. Graphene’s repertoire of unique traits is nothing short of impressive. Its ultra-large theoretical surface area offers an expansive playground for catalytic reactions, while its excellent conductivity ensures rapid electron shuttling. Coupled with its remarkable chemical and electrochemical stability, two-dimensional structural elegances, and highly crystalline lattice, graphene emerges as a veritable powerhouse. Moreover, its ability to finesse active sites through defect engineering and chemical doping further cements its status as an ideal support^[47]. In the context of graphene-supported single-atom transition metal catalysts for methane activation, researchers have harnessed the power of theoretical calculations, particularly those underpinned by DFT methods. By probing the activation dynamics of five magnetic transition metal atoms chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), and copper (Cu) in both adsorbed and intercalated states on graphene, a game-changing discovery has been made. Compared to their free metal methane counterparts, graphene-supported transition metal systems slash the activation energy barriers and streamline the reaction pathways, confining them to a single spin state^[48]. This eradicates the erratic polymorphic reactivity witnessed in free systems, facilitating a more coordinated and efficient catalytic process. The enhanced electron transfer and reactant adsorption capabilities, courtesy of the graphene support, galvanize the single-atom synergistic catalytic effects, driving the reaction forward with greater gusto.

Figure 8. (A) The reaction scheme to prepare PBN; (B) ACHAADF-STEM imaging of PBN-300-M (M = Fe, Co, Ni, Mn, Pd, Mo, W, Re, Ir) samples. The atomic distribution of various metal elements was evident. Adapted with permission^[45]. Copyright 2022, Wiley-VCH GmbH; (C) Schematic illustration of the preparation for the Pt-Ni(OH)₂-E; (D) Ni 2p XPS spectra; (E) XANES spectra of Ni foil, Ni(OH)₂, Pt-Ni(OH)₂-BP, and Pt-Ni(OH)₂-E at the Ni K-edge; (F) Pt 4f XPS spectra; (G) XANES spectra of Pt foil, PtO₂, Pt-Ni(OH)₂-E. Adapted with permission^[49]. Copyright 2023, Wiley-VCH GmbH. ACHAADF-STEM: Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy; PBM: pyrolytic boron nitride; XPS: X-ray photoelectron spectroscopy; XANES: X-ray absorption near-edge structure.

Metal-containing supports, including metal carbides, metal oxides, metal sulfides, and the like, bring their own set of advantages to the table. The diverse array of surface unsaturated sites on these supports is the linchpin in preventing metal agglomeration. They achieve this by forging strong chemical bonds between the metal atoms and the support surface [Figure 8C-G]^[49]. Metal compounds, in general, have emerged as the first choice for stabilizing individual metal atoms, especially in scenarios where carbon-based materials falter under high-temperature catalytic demands due to their inherent stability limitations^[35]. In SACs, the interactions between metal atoms and oxide supports are a complex web of mechanisms, including defect-mediated interactions, oxygen-stabilized couplings, spatial confinement effects, strong metal-support interactions (SMSI), and covalent metal support linkages^[50]. Consider the synthesis of SA Pt catalysts supported on nanoceria (Pt₁@CeO₂). These catalysts are fabricated through high-temperature calcination of Pt-impregnated porous ceria NPs, with a specific focus on the direct conversion of methane. A battery of advanced characterization techniques has been deployed to validate the atomic scale dispersion of Pt. The results speak for themselves, the Pt₁@CeO₂ catalyst achieves a methane conversion of 14.4% and a selectivity of 74.6% for C2 products (ethylene, ethane, and acetylene). This performance eclipses that of its NP analog by a wide margin. The secret sauce lies in the synergistic interplay between the Pt single atoms and the CeO₂ support^[51]. The support not only provides a stable anchoring point for the Pt atoms but also modulates their electronic properties, optimizing the adsorption and activation of methane. The enhanced interaction and coordination between the metal and support components turbocharge the single-atom synergistic catalytic effects, making it a force to be reckoned with in catalytic conversions.

The structural composition of supports plays a pivotal role in stabilizing SACs and modulating their electronic properties. Microporous matrices (e.g., zeolites, MOFs) confine metal atoms within well-defined pores, enabling precise spatial control and enhancing reactant diffusion. Two-dimensional materials (e.g., graphene, g-C₃N₄) leverage their large surface areas and conductive frameworks to optimize charge transfer, while metal-containing supports (e.g., CeO₂, TiO₂) utilize SMSI to prevent aggregation and tailor adsorption behavior^[42,50,52]. For instance, Pt₁@CeO₂ achieves high methane conversion (14.4%) and C₂ selectivity (74.6%) in methane activation^[51], demonstrating the synergy between isolated Pt atoms and oxygen-rich CeO₂ surfaces. The single-atom-support interaction steers the catalysis mechanism through two principal avenues: Firstly, the robust metal-support interaction, which exists between the isolated atom and its support, acts as a master tuner. It finely tunes parameters such as adsorption strength, electronic configuration, coordination environment, and binding energy. These adjustments have a direct bearing on the binding affinity of reaction intermediates at the active sites, dictating the reaction pathway and rate. Secondly, the co-catalytic interaction comes into play, where both the single atom and the support atoms actively engage and directly partake in binding the reactant species during the reaction progression^[53-59]. This synchronized participation amplifies the catalytic efficiency, unlocking the true potential of single-atom synergistic catalytic effects. The carrier enhances the synergistic catalytic effect of single atoms by intensifying the adsorption, diffusion, and activation of substrates, thereby improving the overall activity of the catalyst. These strategies are particularly valuable in industrial catalysis, where stability and selectivity under harsh conditions (e.g., high temperatures, reactive atmospheres) are critical. By selecting supports that complement the target reaction’s requirements, SACs can be engineered for scalable applications such as biomass refining and CO₂ conversion.

Regulation of defect sites

Mastering the manipulation of defect configurations on the support emerges as a highly efficacious strategy to curtail the migration of metal atoms thereon. These defects function as powerful modifiers, not only reconfiguring the coordination environment but also inducing significant alterations in the surrounding electronic structure. This, in turn, gives rise to the generation of vacancies and unsaturated coordination sites, setting the stage for enhanced catalytic performance^[59]. Concurrently, during the post-treatment phase, these very defects on the support morph into crucial anchoring points for metal precursors and subsequently, the metal atoms themselves^[60]. When embarking on the application of defect engineering strategies for the synthesis of SACs, the initial and pivotal step lies in meticulously optimizing the processing conditions [Figure 9A-C]. This optimization is geared towards guaranteeing the formation of uniformly distributed defect centers that can serve as reliable anchoring sites. By doing so, a uniform and stable dispersion of individual atoms is achieved, laying the foundation for efficient single-atom synergistic catalytic effects.

Figure 9. (A) Schematic illustration of the formation; (B) Free energy paths for Au-SA/Per-TiO₂ and Au-SA/Def-TiO₂; (C) Schematic models for the CO oxidation process. Adapted with permission^[60]. Copyright 2018, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim; (D) The schematic illustration and TEM images of morphological evolution for Fe-N₄-C_x samples when varying the amount of reactant FeCl₃; (E) LSV curves for different catalysts in 0.1 M HClO₄ electrolyte; (F) Potential dependence of J_k-specific for as-prepared various atomic Fe catalysts; (G) Comparison of E_1/2 and J_k for different testing catalysts. Adapted with permission^[63]. Copyright 2020, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. TEM: Transmission electron microscopy; LSV: linear sweep voltammetry.

Moreover, a clear identification of the defect types is of paramount importance. This knowledge empowers researchers to make informed decisions regarding the selection of appropriate metal species as precursors. Additionally, it enables the implementation of targeted measures to safeguard against the disappearance or unwanted transformation of defects during post-treatment^[61]. The size and content of defects hold the key to fine-tuning the active sites of catalysts, a crucial factor in enhancing ORR performance and paving the way for the long-term stability and practical applications of the catalysts [Figure 9D-G]^[62,63]. Through precise control of these parameters, the design of more efficient and durable catalysts becomes a tangible reality.

A prime illustration of this concept is the successful fabrication of the single-atom gold catalyst (Au-SA/Def-TiO₂). This was accomplished by deliberately introducing surface oxygen vacancy defects onto TiO₂ nanosheets. On an ideal, defect-free TiO₂ surface, gold atoms tend to form a four-center structure (Ti-Au-O-Ti) in conjunction with four Ti atoms. However, in the presence of a defective TiO₂ surface, a remarkable transformation occurs. Coordination experiments and Density Functional Theory (DFT) results converge to reveal that the oxygen vacancies trigger a profound change in the coordination environment of gold atoms. Specifically, a Ti-Au-Ti structure takes shape^[60]. This novel structure is the result of a direct interaction between the gold atom and two adjacent Ti atoms. It serves a dual purpose: firstly, it acts as a robust anchor, firmly securing individual gold atoms in place and effectively thwarting their migration and aggregation tendencies. Secondly, the presence of these defect sites works wonders for enhancing the dispersion of metal atoms on the support. It renders the gold atoms more isolated and uniformly distributed across the TiO₂ nanosheets, a prerequisite for improved catalytic activity. Notably, the d-band center of Ti atoms close to the defect sites experiences a shift, drawing nearer to the Fermi level. This shift has far-reaching implications as it can modulate the electronic state of the gold atoms. In turn, this altered electronic state exerts a direct influence on the adsorption behavior of the gold atoms towards reactants such as CO and O₂. By precisely tailoring the defect-induced changes in the electronic and coordination structures, the reaction kinetics are optimized, and the synergistic catalytic effect between single atoms and defect sites was enhanced, providing ideas for the design of highly efficient SACs.

Defect engineering is a powerful strategy to stabilize SACs and enhance their catalytic performance. Oxygen vacancies, lattice distortions, or edge defects act as anchoring sites for single atoms, reducing their surface free energy and suppressing migration. For example, Au-SA/Def-TiO₂, with Ti-Au-Ti coordination at oxygen vacancies, exhibits superior CO oxidation activity compared to defect-free counterparts^[60]. Defects also modify the electronic environment of active sites, lowering energy barriers for key intermediates (e.g., ^*COOH in CO₂ reduction). This approach is particularly advantageous in industrial processes requiring high thermal stability, such as water-gas shift reactions or syngas production. Moreover, defect-rich supports such as FeO_x with abundant oxygen vacancies enhance metal dispersion and electron transfer, enabling efficient large-scale catalysis. By precisely controlling defect density and distribution, SACs can be optimized for energy-intensive applications, including hydrogen production and pollutant degradation.

Regulation of heteroatoms

Heteroatom doping represents a strategic maneuver wherein diverse non-metal elements, such as N, S, P, etc., are deliberately incorporated into the support or coordination environment of a catalyst^[64]. This seemingly simple addition of heteroatoms wields a profound impact on the catalyst’s performance. Firstly, they act as electronic architects, restructuring the catalyst’s electronic landscape. Through p-d coupling or long-range electron delocalization, heteroatoms can tweak the metal charge at the active center. This modulation of the electronic structure is not a passive change; it is the catalyst for enhanced single-atom synergistic catalytic effects. For example, in reactions demanding acid-base catalysis, heteroatom doping, especially N doping, can transform the acid-base properties of the catalyst. N-doping has been shown to augment the alkalinity of the support, endowing it with a heightened adsorption capacity for oxygen-containing reactants. This enhanced adsorption is a linchpin in facilitating more efficient reactions, as it allows reactants to interact more favorably with the catalyst’s active sites. Moreover, heteroatom doping serves as a stabilizing force, preventing the unruly aggregation or migration of metal atoms during the reaction process. This stability is the bedrock upon which long-term catalytic efficiency is built, ensuring that the catalyst remains active and effective over extended periods.

N modification

SACs with M-N_x coordination motifs anchored on nitrogen-enriched carbon frameworks have emerged as dominant architectures in heterogeneous catalysis, demonstrating superior catalytic metrics (activity/selectivity/stability triad) that position them as viable substitutes for noble metal systems^[35]. The strategic incorporation of secondary heteroatoms (B/S/P) into M-N_x configurations enables the construction of dual-site electronic configurations, where synergistic heteroatomic pairs activate distinct reaction pathways^[9,65]. Notably, nitrogen functionalities in the carbon matrix serve dual roles as electron-donating sites that modulate reactant adsorption/desorption energetics while establishing charge-transfer networks with anchored metal centers, collectively optimizing intermediate stabilization dynamics.

Fe-N₄ monoatomic configuration catalyst system has become a strategic material system to replace platinum-based ORR catalysts because of its unique electronic regulatory properties^[66,67] [Figure 10A and B]. By regulating the electronic coordination microenvironment of pyrrole type nitrogen (PN) and graphite type nitrogen (GN) in nitrogen-doped carbon carrier, the charge distribution state of iron active center can be accurately regulated. Theoretical simulations have confirmed that PN coordination with strong electron absorption properties induces the charge polarization effect at Fe-N₄ site, induces the local electron hole state in the metal center, and then significantly improves the intrinsic activity of ORR by enhancing the interfacial electric field intensity. In typical M-N-C catalytic systems, metal-nitrogen electronegativity differences drive the formation of directional charge transfer channels, making the number of coordinated nitrogen atoms a key parameter in regulating the electronic microenvironment at the active site^[68]. Systematic DFT analysis has shown that the asymmetric tricoordination transition metal site (TM-N₃-C) exhibits more optimized adsorption free energy for oxygen-containing intermediates than the conventional tetarate configuration (TM-N₄-C)^[69]. Among them, Ni-N₃-C system is outstanding in bifunctional catalytic performance, and its ORR/OER overpotential drops to 0.29 and 0.28 V, respectively, showing a unique collaborative catalytic mechanism.

Figure 10. (A) Structure model of FeN₄-PN; (B)XPS N 1s spectra of FeN₄, FeN₄-PN, and FeN₄-GN. Adapted with permission^[66]. Copyright 2021, American Chemical Society; (C) Typical CVD procedures to synthesize the Fe(Fc)-N/S-C catalyst. Relative energy profiles for the ORR processes on (D) FeN₃S and (E) FeN₄; (F) Reaction scheme with the intermediates in the ORR process on FeN3S (O: red, C: gray, N: blue, Fe: orange, S: yellow, H: white). Adapted with permission^[75]. Copyright 2021, American Chemical Society; (G) Steps for the synthesis of the samples; SEM images of Fe-PNC at different scales; (H) Fe 2p XPS spectrum of Fe-PNC and Fe-NC; (I) P2p XPS spectrum of Fe-PNC; (J) Degradation performance of BPA in different catalytic systems; (K) The kobs values of BPA in different catalytic systems. Adapted with permission^[81]. Copyright 2024, Elsevier B.V. PN: Pyrrole type nitrogen; XPS: X-ray photoelectron spectroscopy; CVD: chemical vapor deposition; ORR: oxygen reduction reaction; SEM: scanning electron microscopy; PNC: phosphorus and nitrogen co-doped carbon; NC: nitrogen-doped carbon; BPA: bisphenol A.

Strategies for enhancing stability

Biomass conversion

As the global energy crisis and environmental pollution issues intensify, biomass, as a renewable carbon resource, has received extensive attention in research and development of conversion technologies. Biomass can be converted into various energy sources and chemicals through chemical catalytic conversion technologies, which is of great significance for reducing dependence on fossil fuels, mitigating the energy crisis, and decreasing greenhouse gas emissions^[100-102]. In biomass conversion, the isolated single atoms act as highly efficient active sites. Their unique electronic structures enable them to interact synergistically with the functional groups present in biomass-derived molecules. However, generally, the general reaction conditions of biomass conversion are harsh, and the carrier or other active center can achieve high-activity and high-stability conversion by co-catalysis with single atoms.

Photoelectrocatalytic conversion of biomass

Zhou et al.^[106] designed and synthesized a Pt single atom supported TiO₂ (PtSA-TiO₂) photocatalyst for photocatalytic methyl activation and C–C coupling reactions [Figure 11A-E]. They predicted and experimentally verified that the PtSA-TiO₂ photocatalyst can achieve methyl activation, formation of CH₃COCH₂• radicals, and production of 2,5-hexanedione (HDN) and hydrogen with a selectivity of up to 93%. Compared to other noble metal single-atom (such as Ru, Rh, Ir) or Pt NP-supported photocatalysts, PtSA-TiO₂ exhibited at least 13 times higher activity^[12,14,106]. Through in-situ attenuated total reflection infrared spectroscopy and in-situ electron spin resonance spectroscopy, it was confirmed that Pt single atoms can promote effective methyl activation and further facilitate the formation of CH₃COCH₂• radicals, which is a critical step in C–C coupling reactions. The PtSA-TiO₂ photocatalyst maintained good stability and activity during prolonged photocatalytic reactions. Xiong et al.^[107] synthesized a highly selective catalyst composed of nickel single atoms confined on the surface of titania was proposed for the conversion of glycerol into the high-value product glycolaldehyde. Driven by light, the catalyst utilizes air as a green oxidant for the reaction under ambient conditions. The optimized catalyst exhibited selectivity for glycolaldehyde exceeding 60% with a yield of 1,058 μmol·g_Cat^-1·h^-1, and the turnover number was nearly three times higher than that of NiO_x NP-modified TiO₂ photocatalysts.

Figure 11. (A) Schematic illustration of the synthesis of the Pd₁/BNC single-atom catalyst; (B) Kinetic isotope effect for reductive amination with the catalysis of Pd₁/BNC; (C) Electron density difference plots of the adsorbed isopropanol molecule at Pd₁/NC and Pd₁/BNC. The isosurface level is ± 0.01 electrons Å^-3, with blue for the accumulated electron density and pink for the depleted electron density. Adapted with permission^[105]. Copyright 2023, Wiley-VCH GmbH; (D) Reaction path of acetone dehydrogenation; (E) Pt L₃-edge XANES spectra and the corresponding k³-weighted Fourier transform (FT) spectra. Adapted with permission^[106]. Copyright 2020, American Chemical Society. Pd₁/BNC: Boron-modulated palladium single-atom architecture; Pd₁/NC: palladium single-atom architecture.

The integration of SACs into biomass conversion processes holds transformative potential for sustainable biorefineries. For instance, the Pd/ZnO/C catalyst achieves a high TON in lignocellulose depolymerization, rivaling traditional NP catalysts while minimizing metal usage and waste generation^[104]. This efficiency is critical for industrial-scale biofuel production, where cost and scalability are paramount. Such advancements align with global efforts to replace fossil-derived chemicals with renewable alternatives, particularly in sectors such as polymer manufacturing and pharmaceuticals. Future industrial adoption will depend on optimizing catalyst stability and developing continuous-flow systems to handle complex biomass feedstocks.

CO₂ reduction reaction

The system of single-atom catalysis for CO₂ reduction is frequently encountered in photocatalysis, electrocatalysis, or photoelectrocatalysis^[108]. Visible light-driven carbon dioxide (CO₂) reduction reaction (CO₂RR) into valuable chemicals and fuels is a promising strategy to utilize CO₂ as an abundant and nontoxic C1 resource while storing clean and renewable solar energy^[109]. The single atoms, often anchored on suitable supports, work in concert with the support materials. The support not only stabilizes the single atoms but also participates in the catalytic process. In the electrochemical reduction of CO₂, metal single atoms can catalyze the initial electron transfer to CO₂, while the support can provide additional binding sites and modify the local electronic density. This cooperation between the single atom and the support enhances the adsorption and activation of CO₂, steering the reaction toward the formation of valuable products such as carbon monoxide or hydrocarbons. The well-defined single-atom active sites also minimize side reactions, such as the formation of methane or carbon deposition, leading to high selectivity in CO₂ reduction.

Photocatalysis provides a sustainable avenue toward syngas with tunable CO/H₂ ratios under mild conditions^[4]. However, the photogeneration of charges occurs rapidly with an electron lifetime of several picoseconds. At the same time, the CO₂ reduction rate is relatively slow with the reaction time within milliseconds or longer, attributable to the inertness of CO₂ molecules^[110]. SACs exhibit robust catalytic active sites that can accelerate charge transfer in CO₂ reduction systems, making them highly suitable for application in CO₂RR. These catalysts are gradually enhancing their stability and activity in such systems^[111]. Many scientists have conducted explorations to address the ongoing issues in the field of CO₂RR. Various catalysts, including metal oxides, metal-organic complexes, carbon nanotubes, carbon-based materials, and COFs, have been reported in multiple literature sources to support metal single-atom active centers for use in CO₂RR^{[29,108,112,113]}.

Addressing the challenges of low catalytic efficiency and poor selectivity in CO₂RR in pure water systems, Ji et al.^[114] reported a novel atomic confinement and coordination (ACC) strategy for synthesizing rare earth erbium (Er) SACs supported on carbon nitride nanotubes (denoted as Er₁/CN-NT) [Figure 12A and B]. The synergistic catalysis between single-atom Er and the carbon nitride nanotube support is highly remarkable. During the preparation of the catalyst through the unique atom-confinement and coordination strategy, the structural characteristics of the sponge cooperate with the nitrogen atoms, urea, and the low-temperature environment of liquid nitrogen therein, successfully realizing the high dispersion of Er atoms on the support and constructing a stable and unique catalytic structure foundation. The oxidation state of Er atoms exhibits a specific variation pattern, and with the increase of the loading amount, charge redistribution is induced. Such a change in electronic properties is closely related to the catalytic activity, providing a suitable electronic environment for the catalytic reaction. The single Er atom and the support act synergistically to significantly enhance the absorption intensity of visible light. Meanwhile, in the process of charge separation, the high-density single Er atoms promote the efficient separation of charges, effectively prolong the decay lifetime of photogenerated carriers, reduce the interfacial resistance, increase the photocurrent density and carrier density, and comprehensively enhance the photoelectrochemical performance. The catalyst containing single-atom Er shows higher efficiency in catalyzing the conversion of CO₂ into CH₄ and CO compared with the support without Er. Among them, a catalyst with a high density of rare-earth single Er atoms supported on a carbon nitride nanotube (HD-Er₁/CN-NT) performs particularly outstandingly due to the higher density of single Er atoms. Moreover, through means such as CO₂-temperature-programmed desorption (TPD) measurement and electrochemical reduction measurement, the close synergistic relationship between the single atom and the support in enhancing the catalytic activity is further fully verified, providing an efficient catalytic system for the photocatalytic CO₂RR.

Figure 12. (A) Schematic process of the synthesis of single-atom Er₁/CN-NT catalysts; (B) Calculated free-energy diagram for CO₂ reduction to CO and CH₄ on the Er₁/CN-NT catalyst, as well as the adsorption configurations of key intermediates. The Er, C, H, O, and N atoms are given in yellow, brown, white, red, and blue, respectively. Adapted with permission^[114]. Copyright 2020, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim; (C and D) In situ ATR-SEIRAS spectra for the adsorption and photocatalytic activation of CO₂ on TPy-COF-Co. Adapted with permission^[111]. Copyright 2024, Wiley-VCH GmbH.

Addressing the primary issues in carbon dioxide reduction, namely the rapid recombination of photogenerated charges and the sluggish surface reduction reaction of carbon dioxide, Fu et al.^[111] constructed a unique CoN₄Cl₂ single atom site by loading Co species within a triazine-based COF [Figure 12C and D]. The triazine-based COF framework facilitates the transfer of charges to the individual CoN₄Cl₂ sites, significantly lowering the energy barrier for generating ^*COOH and thereby promoting the activation of carbon dioxide. Through this approach, the photocatalyst described in the article achieves efficient carbon dioxide reduction under visible light irradiation, producing tunable syngas with excellent stability and durability.

Regarding the issue of catalytic activity and selectivity in the CO₂RR, Cheng et al.^[112] prepared Co-N_x (x = 2, 3, 4) edge site model SACs by anchoring Co complexes with a specific number of pyridine-type ligands at the edges of carbon black (CB) via conjugated pyrazine linkers. They employed electrochemical measurements and DFT simulations to assess the catalytic performance of different Co-N_x sites. It was demonstrated that the Co-N₄ edge site is the most active site for producing CO in the CO₂RR, exhibiting a higher TOF. Furthermore, DFT simulations confirmed that the Co-N₄ site possesses a lower energy barrier for the CO₂RR and a higher energy barrier for the HER. The findings of this study provide strategies for designing efficient and selective SACs for the CO₂RR.

To explore the synergistic mechanism of SAC in CO₂RR, Jeong et al.^[115] used in situ electrochemical STM to observe the restructuring of Cu-phthalocyanine (CuPC) into Cu_xO nanoclusters during CO₂ reduction. This restructuring creates active sites where Cu single atoms interact synergistically with oxygen vacancies on the TiO₂ support, enhancing CO₂ activation and selectivity for hydrocarbons. This example illustrates how local geometric distortions and charge redistribution between single atoms and the support drive synergy.

SACs offer a promising pathway for scalable CO₂ valorization, addressing both climate change and energy storage challenges. The Er₁/CN-NT catalyst achieves a CO₂-to-CH₄ conversion rate of 105 μmol·g^-1·h^-1 under visible light, demonstrating the feasibility of solar-driven CO₂ utilization. This technology could integrate with existing carbon capture infrastructure to produce syngas (CO/H₂) or methane for industrial fuel synthesis. However, transitioning SACs from lab-scale to industrial reactors requires addressing challenges such as long-term stability under fluctuating CO₂ concentrations and scalability of synthesis methods. Partnerships with energy sectors could accelerate pilot projects, particularly in regions with abundant renewable energy for powering CO₂ electrolysis or photocatalysis.

Cascade catalysis

In cascade reactions, the strength of SACs truly comes to the fore. These reactions involve multiple sequential steps, and SACs can seamlessly guide the reaction from one stage to the next. The ability of SACs to maintain high activity and selectivity throughout the complex cascade reaction sequence is a result of their atomic-level precision. Each single atom can interact with different reactants and intermediates in a coordinated manner, ensuring that the overall reaction proceeds smoothly and efficiently toward the desired final products. Overall, SACs are revolutionizing these areas by unlocking new reaction pathways and enhancing catalytic efficiencies. SACs, endowed with unique catalytic properties due to the distinctive adsorption characteristics of their isolated active sites, exhibit exceptional activity and selectivity in cascade catalysis. This enables them to efficiently promote key reaction steps and enhance overall catalytic efficiency. Furthermore, by altering the support, ligands, or reaction conditions, the activity, selectivity, and stability of SACs can be conveniently tuned to meet the requirements of different steps in cascade catalysis. Notably, SACs typically possess high structural stability, maintaining their catalytic activity over extended reaction times, which is particularly crucial for reactions in cascade catalysis that require multiple consecutive steps.

Metal-enzyme cascade catalysis

The recent integration of chemical catalysts with biological catalysts for one-pot linear cascade reactions has garnered significant attention, particularly highlighting the advantages of noble metal-enzyme cascade catalysts in the dynamic kinetic resolution of chiral compounds^[116]. This approach not only conserves solvent and time costs but also enhances reaction efficiency. However, the incompatibility of reaction conditions between the two active centers poses challenges for achieving efficient and stable synergistic catalysis^[117]. Consequently, improving the catalytic activity of transition metals while reducing the severity of their reaction conditions can elevate the synergistic catalytic efficiency of the dual active centers^[118]. Additionally, exploring the impact of the microenvironment of immobilization carriers on enzyme structure, rigidity, and selectivity, along with conducting reaction kinetic studies, is crucial for optimizing the synergistic catalytic efficiency.

SACs and enzymes each exhibit unique advantages in their respective catalytic domains. SACs boast high catalytic activity, selectivity, and stability, while enzymes are renowned for their high biological specificity and mild reaction conditions^[119]. By combining these two, the complementary advantages of chemical and biological catalysis can be realized, offering new pathways for the synthesis of complex compounds^[120]. By designing and synthesizing combinations of SACs and enzymes with specific catalytic activities, an efficient cascade catalytic system can be constructed to achieve the selective synthesis of complex compounds. For instance, in fields such as pharmaceutical synthesis and fine chemical production, research findings on single atom and enzyme cascade catalysis hold the potential to propel the development and advancement of related industries. Professor Ge and Li et al.^[121] have conducted in-depthstudies in this regard. They synthesized a lipase-palladium single-atom composite catalyst Pd₁/CALB-Pluronic through a photochemical method and investigated its catalytic performance in the synthesis of biphenyl chiral alcohols via a bio-chemical one-pot cascade reaction [Figure 13A-D]. This composite catalyst exhibited excellent activity and good stability in C–C coupling reactions. In the Sonogashira coupling reaction between iodobenzene and phenylacetylene, the TOF value of Pd₁/CALB-Pluronic surpassed that of the homogeneous catalyst Pd(PPh₃)₄^[122], and was a remarkable 3.5 times greater than that of the commercial heterogeneous catalyst Pd/C. Remarkably, even after being reused ten times, Pd₁/CALB-Pluronic retained an impressive 97% of its initial activity, showcasing its exceptional stability and durability. This research achievement provides robust support for the co-immobilization of single atoms and enzymes in chemical-biological cascade catalysis.

Figure 13. (A) Synthesis of (R)‐1‐(4‐biphenyl)ethanol by the one‐pot chemoenzymatic reaction; (B) Conversion versus reaction time; (C) ln(A_t/A₀) versus reaction time, A_t and A₀ stand for the concentration of iodobenzene at the intervals and at the initial stage; (D) Calculated free energy profile of the Sonogashira reaction pathway catalyzed by the model catalyst for Pd₁/CALB‐P. Adapted with permission^[121]. Copyright 2022, Elsevier B.V.; (D) Schematic illustration of the Co_SA-Co_NC/CN synthesis; (E) Condensation of aldehydes and amines; (F) CHT cascade reaction; (G) Oxidation of benzyl alcohol under N₂; (H) Alcohol-amine coupling under air. Adapted with permission^[124]. Copyright 2024, American Chemical Society. CHT: Catalytic hydrogen transfer.

Other areas

In various other applications, single atoms have demonstrated remarkable potential, particularly in biomedical fields such as cancer treatment^[126]. Cai et al.^[127] reported that SACs can efficiently convert tumor-overexpressed H₂O₂ into •OH, initiating ferroptosis through the Fenton reaction and thereby achieving efficient oxidative therapy for tumors. Researchers have developed MitoCAT-g nanoamplifiers, which amplify oxidative stress in mitochondria by generating reactive oxygen species (ROS) and consuming the antioxidant glutathione (GSH), ultimately triggering cell apoptosis for cancer treatment. Moreover, single atoms find use in wound disinfection. M-N-C SACs (SAzymes), which possess structures similar to natural metalloenzymes, mimic the catalytic activity of natural enzymes, inhibiting bacterial proliferation and promoting wound regeneration. By loading hemoglobin-like single Fe atoms onto amorphous carbon structures, peroxidase-mimetic catalysis is achieved, generating •OH to inhibit the growth of both Gram-positive and Gram-negative bacteria.

Single atoms also exhibit exceptional performance in biosensing and antioxidant enzyme mimicry. In the field of biosensing, SACs have demonstrated their prowess in detecting biomolecules such as ascorbic acid (AA), H₂O₂, and glucose with high sensitivity and selectivity. By optimizing the structure and performance of SACs, researchers can achieve precise detection of these biomolecules. Furthermore, SACs can mimic the catalytic activity of antioxidant enzymes, protecting cells from oxidative stress damage. Given that natural antioxidant enzymes are prone to denaturation under harsh environmental conditions, exploring alternative catalysts to mimic their activity is of significant importance. Beyond these applications, SACs have found additional uses in the biomedical field, including drug metabolism, biomolecule recognition, and separation. By further researching and optimizing the performance and stability of SACs, we can expand their applications within the biomedical domain.

Moreover, SACs have potential applications in energy conversion and storage^[96,128]. They can enhance the efficiency of reactions such as fuel cells and water electrolysis. Additionally, they can be utilized in organic synthesis and environmental catalysis, which could trigger the oriented generation of reactive active species for contaminants degradation, offering new solutions to various challenges in these fields^[129,130]. The versatility and potential of single atoms in diverse applications make them a promising area of research for future advancements.