Atomic-Level Regulation of Cobalt Single-Atom Nanozymes: Engineering High-Efficiency Catalase Mimics

Nanozymes aim to mimic the highly evolved active centers of natural enzymes. Despite progress in nanozyme engineering, their catalytic performance is much less favorable compared with natural enzymes. This study shows that precise control over the atomic configuration of the active centers of Co single-atom nanozymes (SAzymes) enables the rational regulation of their catalase-like performance guided by theorical calculations. The constructed Co-N₃PS SAzyme exhibits an excellent catalase-like activity and kinetics, exceeding the representative controls of Co-based SAzymes with different atomic configurations. Moreover, we developed an ordered structure-oriented coordination design strategy for rationally engineering SAzymes and established a correlation between the structure and enzyme-like performance. This work demonstrates that precise control over the active centers of SAzymes is an efficient strategy to mimic the highly evolved active sites of natural enzymes.     

Atomic engineering of single-atom nanozymes for enzyme-like catalysis

Enzyme mimics, especially nanozymes, play a crucial role in replacing natural enzymes for diverse applications related to bioanalysis, therapeutics and other enzyme-like catalysis. Nanozymes are catalytic nanomaterials with enzyme-like properties, which currently face formidable challenges with respect to their intricate structure, properties and mechanism in comparison with enzymes. The latest emergence of single-atom nanozymes (SAzymes) undoubtedly promoted the nanozyme technologies to the atomic level and provided new opportunities to break through their inherent limitations. In this perspective, we discuss key aspects of SAzymes, including the advantages of the single-site structure, and the derived synergetic enhancements of enzyme-like activity, catalytic selectivity and the mechanism, as well as the superiority in biological and catalytic applications, and then highlight challenges that SAzymes face and provide relevant guidelines from our point of view for the rational design and extensive applications of SAzymes, so that SAzyme may achieve its full potential as the next-generation nanozyme.

Single-atom nanozymes with definite active centers, high catalytic activities and enzyme-like selectivities promote the nanozyme research entering a new period of atomic level.     

Tumor Microenvironment Responsive Single-Atom Nanozymes for Enhanced Antitumor Therapy

Single-atom nanozymes (SAzymes) with specific response to the unique tumor microenvironment (TME) feature providing 100 % metal atoms utilization for high-efficient enzyme-catalyzed therapy and accurate template for the study of therapeutic mechanisms. In this review, we first introduce the various synthetic strategies of SAzymes, and the TME-responsive SAzymes activities. Next, the TME-responsive enhanced antitumor therapeutic approaches based on the enzymatic activities of SAzymes are summarized, and the corresponding therapy mechanisms are elaborated. Subsequently, a concise but concentrated summary, and the challenges and opportunities for the future design and engineering of SAzyme are outlined. As a new discipline, SAzymes have vast space for development in enhanced antitumor therapy. This timely review provides guidance and constructive suggestions for the future of SAzymes.     

Non-Interacting Ni and Fe Dual-Atom Pair Sites in N-Doped Carbon Catalysts for Efficient Concentrating Solar-Driven Photothermal CO2 Reduction

Solar-to-chemical energy conversion under weak solar irradiation is generally difficult to meet the heat demand of CO₂ reduction. Herein, a new concentrated solar-driven photothermal system coupling a dual-metal single-atom catalyst (DSAC) with adjacent Ni−N₄ and Fe−N₄ pair sites is designed for boosting gas-solid CO₂ reduction with H₂O under simulated solar irradiation, even under ambient sunlight. As expected, the (Ni, Fe)−N−C DSAC exhibits a superior photothermal catalytic performance for CO₂ reduction to CO (86.16 μmol g⁻¹ h⁻¹), CH₄ (135.35 μmol g⁻¹ h⁻¹) and CH₃OH (59.81 μmol g⁻¹ h⁻¹), which are equivalent to 1.70-fold, 1.27-fold and 1.23-fold higher than those of the Fe−N−C catalyst, respectively. Based on theoretical simulations, the Fermi level and d-band center of Fe atom is efficiently regulated in non-interacting Ni and Fe dual-atom pair sites with electronic interaction through electron orbital hybridization on (Ni, Fe)−N−C DSAC. Crucially, the distance between adjacent Ni and Fe atoms of the Ni−N−N−Fe configuration means that the additional Ni atom as a new active site contributes to the main *COOH and *HCO₃ dissociation to optimize the corresponding energy barriers in the reaction process, leading to specific dual reaction pathways (COOH and HCO₃ pathways) for solar-driven photothermal CO₂ reduction to initial CO production.     

Construction of Co4 Atomic Clusters to Enable Fe−N4 Motifs with Highly Active and Durable Oxygen Reduction Performance

Fe−N−C catalysts with single-atom Fe−N₄ configurations are highly needed owing to the high activity for oxygen reduction reaction (ORR). However, the limited intrinsic activity and dissatisfactory durability have significantly restrained the practical application of proton-exchange membrane fuel cells (PEMFCs). Here, we demonstrate that constructing adjacent metal atomic clusters (ACs) is effective in boosting the ORR performance and stability of Fe−N₄ catalysts. The integration of Fe−N₄ configurations with highly uniform Co₄ ACs on the N-doped carbon substrate (Co₄@/Fe₁@NC) is realized through a “pre-constrained” strategy using Co₄ molecular clusters and Fe(acac)₃ implanted carbon precursors. The as-developed Co₄@/Fe₁@NC catalyst exhibits excellent ORR activity with a half-wave potential (E_1/2) of 0.835 V vs. RHE in acidic media and a high peak power density of 840 mW cm⁻² in a H₂−O₂ fuel cell test. First-principles calculations further clarify the ORR catalytic mechanism on the identified Fe−N₄ that modified with Co₄ ACs. This work provides a viable strategy for precisely establishing atomically dispersed polymetallic centers catalysts for efficient energy-related catalysis.     

Elucidating the Mechanism of Simultaneous Activation of CH4 and CO2 Mediated by Single Group 10 Metal Anions in Gas Phase

Quantum chemistry calculations predict that besides the reported single metal anion Pt⁻, Ni⁻ can also mediate the co-conversion of CO₂ and CH₄ to form [CH₃−M(CO₂)−H]^– complex, followed by transformation to C−C coupling product [H₃CCOO−M−H]⁻ ( A ), hydrogenation products [H₃C−M−OCOH]⁻ ( B ) and [H₃C−M−COOH]⁻. For Pd⁻, a fourth product channel leading to PdCO₂⁻…CH₄ becomes more competitive. For Ni⁻, the feed order must be CO₂ first, as the weaker donor-acceptor interaction between Ni⁻ and CH₄ increases the C−H activation barrier, which is reduced by [Ni−CO₂]⁻. For Ni⁻/Pt⁻, the highly exothermic products A and B are similarly stable with submerged barrier that favors B . The smaller barrier difference between A and B for Ni⁻ suggests the C−C coupling product is more competitive in the presence of Ni⁻ than Pt⁻. The charge redistribution from M⁻ is the driving force for product B channel. This study adds our understanding of single atomic anions to activate CH₄ and CO₂ simultaneously.     

Advances in Synchrotron Radiation‐based X‐ray Absorption Spectroscopy to Characterize the Fine Atomic Structure of Single‐atom Nanozymes

Single‐atom nanozymes (SAzymes) with high atomic utilization, excellent catalytic activities, and selectivity have recently attracted significant interest. Usually, they contain only isolated metal atoms embedded in host matrices. However, traditional measuring instruments are extremely difficult to obtain their useful structural information due to ultra‐low metal loading, amorphous structure, coordination with light‐weight surface atoms and/or co‐existing of other metal elements. Synchrotron radiation‐based X‐ray absorption fine structure spectroscopy (XAFS) has demonstrated its usefulness for this type of catalyst. In this mini‐review, we have summarized the recent progress using XAFS to characterize the fine atomic structure of these nanozymes. The synthetic strategies of SAzymes, the principle of XAFS, delicate structural information by XAFS, and the applications of SAzymes have been presented. Furthermore, the outlook and challenges in this active research field have also been discussed. We expect that the help of XAFS can offer a wealth of opportunities to design and develop more efficient SAzymes and apply them to various fields.     

One-Step Preparation of Fe/N/C Single-Atom Catalysts Containing Fe−N4 Sites from an Iron Complex Precursor with 5,6,7,8-Tetraphenyl-1,12-Diazatriphenylene Ligands

Fe/N/C single-atom catalysts containing Fe−N_x sites prepared by pyrolysis are promising cathode materials for fuel cells and metal-air batteries due to their high oxygen reduction reaction (ORR) activities. We have developed iron complexes containing N2- or N3-chelating coordination structures with preorganized aromatic rings in a 1,12-diazatriphenylene framework tethering bromo substituents as precursors to precisely construct Fe−N₄ sites in an Fe/N/C catalyst. One-step pyrolysis of the iron complex with carbon black forms atomically dispersed Fe−N₄ sites without iron aggregates. X-ray absorption spectroscopy (XAS) and electrochemical measurements revealed that the iron complex with N3-coordination is more effectively converted to Fe−N₄ sites catalyzing ORR with a TOF value of 0.21 e site⁻¹ s⁻¹ at 0.8 V vs. RHE. This indicates that the formation of Fe−N₄ sites is controlled by precise tuning of the chemical structure of the iron complex precursor.     

Vibrational Predissociation Spectra of C2N− and C3N−: Bending and Stretching Vibrations

We present infrared predissociation spectra of C₂N⁻(H₂) and C ₃N⁻(H₂) in the 300–1850 cm⁻¹ range. Measurements were performed using the FELion cryogenic ion trap end user station at the Free Electron Lasers for Infrared eXperiments (FELIX) laboratory. For C₂N⁻(H₂), we detected the CCN bending and CC−N stretching vibrations. For the C₃N⁻(H₂) system, we detected the CCN bending, the CC−CN stretching, and multiple overtones and/or combination bands. The assignment and interpretation of the presented experimental spectra is validated by calculations of anharmonic spectra within the vibrational configuration interaction (VCI) approach, based on potential energy surfaces calculated at explicitly correlated coupled cluster theory (CCSD(T)-F12/cc-pVTZ−F12). The H₂ tag acts as an innocent spectator, not significantly affecting the C_2,3N⁻ bending and stretching mode positions. The recorded infrared predissociation spectra can thus be used as a proxy for the vibrational spectra of the bare anions.     

Plasma-Assisted Coupling Reactions of Dinitrogen and Carbon Dioxide Mediated by Monometallic YB1–4−⋅Anions: Carbon−Nitrogen Bond Formation

Transition-metal catalyzed coupling to form C−N bonds is significant in chemical science. However, the inert nature of N₂ and CO₂ renders their coupling quite challenging. Herein, we report the activation of dinitrogen in the mild plasma atmosphere by the gas-phase monometallic YB_1–4⁻ anions and further coupling of CO₂ to form C−N bonds by using mass spectrometry and theoretical calculation. The observed product anions are NCNBO⁻ and N(BO)₂⁻, accompanied by the formation of neutral products YO and YB_0–2NC, respectively. We can tune the reactivity and the type of products by manipulating the number of B atoms. The B atoms in YB_1–4N₂⁻ act as electron donors in CO₂ reduction reactions, and the carbon atom originating from CO₂ serves as an electron reservoir. This is the first example of gas-phase monometallic anions, which are capable to realize the functionalization of N₂ with CO₂ through C−N bond formation and N−N and C−O bond cleavage.     

Kinetics and mechanism of the reaction of sulphur(IV) with N,N′‐ethylene‐bis(sali‐cylidiniminato)manganese‐(III) in aqueous solution

The reaction of (diaqua)(N,N′‐ethylene‐bis(salicylidiniminato)manganese(III) with aqueous sulphite buffer results in the formation of the corresponding mono sulphito complex, [Mn(Salen)(SO₃)]⁻ (S‐bonded isomer) via three distinct paths: (i) Mn(Salen)(OH₂)₂⁺ + HSO₃⁻ → (k₁); (ii) Mn(Salen)(OH₂)₂⁺ + SO₃²⁻ → (k₂); (III) Mn(Salen)(OH₂)(OH) + SO₃²⁻ → (k₃) in the stopped flow time scale. The fact that the mono sulphito complex does not undergo further anation with SO₃²⁻/HSO₃⁻ may be attributed to the strong trans‐activating influence of the S‐bonded sulphite. The values of the rate constants (10⁻²k_i/dm² mol⁻¹ s⁻¹ at 25°C, I = 0.3 mol dm⁻³), ΔH_i^#/kJ mol⁻¹ and ΔS_i^#/J K⁻¹ mol⁻¹ respectively are: 2.97 ± 0.27, 42.4 ± 0.2, −55.3 ± 0.6 (i = 1); 11.0 ± 0.8, 33 ± 3, −75 ± 10 (i = 2); 20.6 ± 1.9, 32.4 ± 0.2, −72.9 ± 0.6 (i = 3). The trend in reactivity (k₂ > k₁), a small labilizing effect of the coordinated hydroxo group (k₃/k₂ < 2), and substantially low values of ΔS^# suggest that the mechanism of aqua ligand substitution of the diaqua, and aqua‐hydroxo complexes is most likely associative interchange (I_a). No evidence for the formation of the O‐bonded sulphito complex and the ligand isomerization in the sulphito complex, (Mn^III‐OSO₂ → Mn^III‐SO₃), ensures the selectivity of the Mn^III centre toward the S‐end of the S^IV species. The monosulphito complex further undergoes slow redox reaction in the presence of excess sulphite to produce Mn^II, S₂O₆²⁻ and SO₄²⁻. The formation of dithionate is a consequence of the fast dimerization of the SO₃₋. generated in the rate determining step and also SO₄²⁻ formation is attributed to the fast scavenging of the SO₃₋. by the Mn^III species via a redox path. The internal reduction of the Mn^III centre in the monosulphito complex is insignificant. The redox reaction of the monosulphitomanganese(III) complex operates via two major paths, one involving HSO₃₋ and the other SO₃²⁻. The electron transfer is believed to be outersphere type. The substantially negative values of activation entropies (ΔS^# = −(1.3 ± 0.2) × 10² and −(1.6 ± 0.2) × 10² J K⁻¹ mol⁻¹ for the paths involving HSO₃₋ and SO₃²⁻ respectively) reflect a considerable degree of ordering of the reactants in the act of electron transfer. © 1999 John Wiley & Sons, Inc. Int J Chem Kinet 31: 627–635, 1999     

Highly dispersed Mn2O3−Co3O4 nanostructures on carbon matrix as heterogeneous Fenton-like catalyst

This work reports the synthesis of various carbon (Vulcan XC-72 R) supported metal oxide nanostructures, such as Mn₂O₃, Co₃O₄ and Mn₂O₃−Co₃O₄ as heterogeneous Fenton-like catalysts for the degradation of organic dye pollutants, namely Rhodamine B (RB) and Congo Red (CR) in wastewater. The activity results showed that the bimetallic Mn₂O₃−Co₃O₄/C catalyst exhibits much higher activity than the monometallic Mn₂O₃/C and Co₃O₄/C catalysts for the degradation of both RB and CR pollutants, due to the synergistic properties induced by the Mn−Co and/or Mn (Co)−support interactions. The degradation efficiency of RB and CR was considerably increased with an increase of reaction temperature from 25 to 45°C. Importantly, the bimetallic Mn₂O₃−Co₃O₄/C catalyst could maintain its catalytic activity up to five successive cycles, revealing its catalytic durability for wastewater purification. The structure–activity correlations demonstrated a probable mechanism for the degradation of organic dye pollutants in wastewater, involving •OH radical as well as Mn²⁺/Mn³⁺ or Co²⁺/Co³⁺ redox couple of the Mn₂O₃−Co₃O₄/C catalyst.     

Turning the Inert Element Zinc into an Active Single-Atom Catalyst for Efficient Fenton-Like Chemistry

Amongst various Fenton-like single-atom catalysts (SACs), the zinc (Zn)-related SACs have been barely reported due to the fully occupied 3d¹⁰ configuration of Zn²⁺ being inactive for the Fenton-like reaction. Herein, the inert element Zn is turned into an active single-atom catalyst (SA−Zn−NC) for Fenton-like chemistry by forming an atomic Zn−N₄ coordination structure. The SA−Zn−NC shows admirable Fenton-like activity in organic pollutant remediation, including self-oxidation and catalytic degradation by superoxide radical (O₂⋅⁻) and singlet oxygen (¹O₂). Experimental and theoretical results unveiled that the single-atomic Zn−N₄ site with electron acquisition can transfer electrons donated by electron-rich pollutants and low-concentration PMS toward dissolved oxygen (DO) to actuate DO reduction into O₂⋅⁻ and successive conversion into ¹O₂. This work inspires an exploration of efficient and stable Fenton-like SACs for sustainable and resource-saving environmental applications.     

Electron-Donors–Acceptors Interaction Enhancing Electrocatalytic Activity of Metal-Organic Polymers for Oxygen Reduction

Catalysts with metal-N_x sites have long been considered as effective electrocatalysts for oxygen reduction reaction (ORR), yet the accurate structure-property correlations of these active sites remain debatable. Report here is a proof-of-concept method to construct 1,4,8,11-tetraaza[14]annulene (TAA)-based polymer nanocomposites with well-managed electronic microenvironment via electron-donors/acceptors interaction of altering electron-withdrawing β-site substituents. DFT calculation proves the optimal −Cl substituted catalyst (CoTAA−Cl@GR) tailored the key OH* intermediate interaction with Co−N₄ sites under the d-orbital regulation, hence reaching the top of ORR performance with excellent turnover frequency (0.49 e s⁻¹ site⁻¹). The combination of in situ scanning electrochemical microscopy and variable-frequency square wave voltammetry techniques contribute the great ORR kinetics of CoTAA−Cl@GR to the relatively high accessible site density (7.71×10¹⁹ site g⁻¹) and fast electron outbound propagation mechanism. This work provides theoretical guidance for rational design of high-performance catalysts for ORR and beyond.     

Breaking Local Charge Symmetry of Iron Single Atoms for Efficient Electrocatalytic Nitrate Reduction to Ammonia

The electrochemical conversion of nitrate pollutants into value-added ammonia is a feasible way to achieve artificial nitrogen cycle. However, the development of electrocatalytic nitrate-to-ammonia reduction reaction (NO₃⁻RR) has been hampered by high overpotential and low Faradaic efficiency. Here we develop an iron single-atom catalyst coordinated with nitrogen and phosphorus on hollow carbon polyhedron (denoted as Fe−N/P−C) as a NO₃⁻RR electrocatalyst. Owing to the tuning effect of phosphorus atoms on breaking local charge symmetry of the single-Fe-atom catalyst, it facilitates the adsorption of nitrate ions and enrichment of some key reaction intermediates during the NO₃⁻RR process. The Fe−N/P−C catalyst exhibits 90.3 % ammonia Faradaic efficiency with a yield rate of 17980 μg h⁻¹ mg_cat⁻¹, greatly outperforming the reported Fe-based catalysts. Furthermore, operando SR-FTIR spectroscopy measurements reveal the reaction pathway based on key intermediates observed under different applied potentials and reaction durations. Density functional theory calculations demonstrate that the optimized free energy of NO₃⁻RR intermediates is ascribed to the asymmetric atomic interface configuration, which achieves the optimal electron density distribution. This work demonstrates the critical role of atomic-level precision modulation by heteroatom doping for the NO₃⁻RR, providing an effective strategy for improving the catalytic performance of single atom catalysts in different electrochemical reactions.     

Synthesis and Structural Characterization of Divalent Transition Metal Alkynylamidinate Complexes

A series of new alkynylamidinate complexes of selected first and second row transition metals has been synthesized and fully characterized. Treatment of MCl₂ precursors (M=Mn, Fe, Co) with 2 equiv. of the lithium alkynylamidinates Li[c-C₃H₅−C≡C−C(NR′)₂] ⋅ THF (R′=ⁱPr (2), Cy (cyclohexyl) ( 2 )) afforded a series of binuclear complexes of the type M₂[c-C₃H₅−C≡C−C(NR)₂-κN:κN′]₂[c-C₃H₅−C≡C−C(NR)₂-κ²N,N′]₂ ( 3 : M=Mn, R=Cy; 4 a : M=Fe, R=ⁱPr; 4 b : M=Fe, R=Cy; 5 : M=Co, R=ⁱPr) with no significant metal-metal bonding. In marked contrast, a similar reaction of CrCl₂ with 2 equiv. of 1 afforded the homoleptic dinuclear chromium(II) complex Cr₂[c-C₃H₅−C≡C−C(NⁱPr)₂-κN:κN′]₄ ( 6 ) which supposedly comprises a Cr−Cr quadruple bond. Complex 6 could also be prepared in a more rational way and in better yield (61 %) by using dichromium(II) tetraacetate, Cr₂(OAc)₄, as starting material. Related reactions employing dimolybdenum(II) tetraacetate, Mo₂(OAc)₄, and 2 or 3 equiv. of 1 afforded the mixed-ligand paddle wheel-type complexes trans-Mo₂(OAc-κO:κO′)₂([c-C₃H₅−C≡C−C(NⁱPr)₂-κN:κN′]₂ ( 7 ) and Mo₂(OAc-κO:κO′)([c-C₃H₅−C≡C−C(NⁱPr)₂-κN:κN′]₃ ( 8 ). All title compounds were structurally characterized through single-crystal X-ray diffraction and spectroscopic techniques (NMR, IR, Raman).     

Cooperative Catalysis of Polysulfides in Lithium-Sulfur Batteries through Adsorption Competition by Tuning Cationic Geometric Configuration of Dual-active Sites in Spinel Oxides

Fundamentally understanding the structure–property relationship is critical to design advanced electrocatalysts for lithium-sulfur (Li−S) batteries, which remains a formidable challenge. Herein, by manipulating the regulable cations in spinel oxides, their geometrical-site-dependent catalytic activity for sulfur redox is investigated. Experimental and theoretical analyses validate that the modulation essence of cooperative catalysis of lithium polysulfides (LiPSs) is dominated by LiPSs adsorption competition between Co³⁺ tetrahedral (Td) and Mn³⁺ octahedral (Oh) sites on Mn³⁺_Oh−O−Co³⁺_Td backbones. Specifically, high-spin Co³⁺_Td with stronger Co−S covalency anchors LiPSs persistently, while electron delocalized Mn³⁺_Oh with adsorptive orbital (d_z²) functions better in catalyzing specialized LiPSs conversion. This work inaugurates a universal strategy for sculpting geometrical configuration to achieve charge, spin, and orbital topological regulation in electrocatalysts for Li−S batteries.     

Metal Nanozyme with Ester Hydrolysis Activity in the Presence of Ammonia-Borane and Its Use in a Sensitive Immunosensor

Metal nanoparticle surfaces are used for peroxidase- and oxidase-like nanozymes but not for esterase-like nanozymes. It is challenging to obtain rapid catalytic hydrolysis on a metal surface and even more so without a catalytically labile substrate. Here, we report that metal nanoparticle surfaces rapidly catalyze non-redox ester hydrolysis in the presence of redox H₃N−BH₃ (AB). Metal hydrides are readily generated on a Pt nanoparticle (PtNP) from AB, and as a result the PtNP becomes electron-rich, which might assist nucleophilic attack of H₂O on the carbonyl group of an ester. The nanozyme system based on PtNP, AB, and 4-aminonaphthalene-1-yl acetate provides an electrochemical signal-to-background ratio much higher than natural enzymes, due to the rapid ester hydrolysis and redox cycling involving the hydrolysis product. The nanozyme system is applied in a sensitive electrochemical immunosensor for thyroid-stimulating hormone detection. The calculated detection limit is approximately 0.3 pg mL⁻¹, which indicates the high sensitivity of the immunosensor using the PtNP nanozyme.     

A novel one‐dimensional complex: catena‐poly­[[manganese(III)‐di‐μ‐2‐[(2‐hydroxy­ethyl)­imino­methyl]­phenolato‐κ2O1,N:κO2;κO2:κ2O1] chloride]

In the title one‐dimensional complex, {[Mn^III(C₉H₁₀NO₂)₂]Cl}_n, the Schiff base ligand 2‐[(2‐hydroxy­ethyl)­imino­methyl]­phenolate (Hsae⁻) functions as both a bridging and a chelating ligand. The Mn^III ion is six‐coordinated by two N and four O atoms from four different Hsae⁻ ligands, yielding a distorted MnO₄N₂ octahedral environment. Each [Mn^III(Hsae)₂]⁺ cationic unit has the Mn atom on an inversion centre and each [Mn^III(Hsae)₂]⁺ cation lies about another inversion centre. The chain‐like complex is further extended into a three‐dimensional network structure through Cl⋯H—O hydrogen bonds and C—H⋯π contacts involving the Hsae⁻ rings.     

Facile N≡N Bond Cleavage by Anionic Trimetallic Clusters V3−xTaxC4− (x=0–3): A DFT Study

Activation of N₂ on anionic trimetallic V_3−xTa_xC₄⁻ (x=0–3) clusters was theoretically studied employing density functional theory. For all studied clusters, initial adsorption of N₂ (end-on) on one of the metal atoms (denoted as Site 1) is transferred to an of end-on: side-on: side-on coordination on three metal atoms, prior to N₂ dissociation. The whole reaction is exothermic and has no global energy barriers, indicating that the dissociation of N₂ is facile under mild conditions. The reaction process can be divided into two processes: N₂ transfer (TRF) and N−N dissociation (DIS). For V-series clusters, which has a V atom on Site 1, the rate-determining step is DIS, while for Ta-series clusters with a Ta on Site 1, TRF may be the rate-determining step or has energy barriers similar to those of DIS. The overall energy barriers for heteronuclear V₂TaC₄⁻ and VTa₂C₄⁻ clusters are lower than those for homonuclear V₃C₄⁻ and Ta₃C₄⁻, showing that the doping effect is beneficial for the activation and dissociation of N₂. In particular, V−Ta₂C₄⁻ has low energy barriers in both TRF and DIS, and it has the highest N₂ adsorption energy and a high reaction heat release. Therefore, a trimetallic heteronuclear V-series cluster, V−Ta₂C₄⁻, is suggested to have high reactivity to N₂ activation, and may serve as a prototype for designing related catalysts at a molecular level.