Sequential-chain coupling over hierarchical click-sites enables highly selective urea electrosynthesis

Domain: neuroscience
Published: 2026-02-05
Editorial outcome: major_revision

Abstract
Electrochemical C−N coupling is an appealing approach for sustainable urea synthesis, while it is technically challenging due to the complex reaction mechanism and the spatiotemporal mismatch between C- and N- intermediates. Here, inspired by click chemistry, we design a hierarchical click-site catalyst (Se−InO x) that enables an efficient sequential-chain coupling pathway for urea electrosynthesis, achieving a urea yield rate of 254.94 mmol h−1 g−1, Faradaic efficiency of 78.61%, >85% N urea-selectivity and 100% C urea-selectivity. Mechanistic studies reveal that Se−InO x as the first click-site can selectively adsorb NO 3 − and hydrogenate it to stable *NO 2, while inhibiting CO 2 adsorption at this stage. The surface-anchored *NO 2 then acts as the second click-site to click couple with CO 2, forming the key *CO 2NO 2 intermediate. This sequential-chain coupling strategy effectively resolves the spatiotemporal mismatch between N- and C- intermediates, thereby maximizing the suppression of side-reactions and enhancing C−N coupling selectivity. Techno-economic analysis and scalable synthesis validate the feasibility of this approach, providing a blueprint for high-selectivity multicomponent electrosynthesis.

Introduction
Urea (CO(NH 2) 2), with annual production exceeding 180 million tons, is an indispensable nitrogen-based fertilizer and a key intermediate in pharmaceuticals and fine chemicals 1–4. Its industrial production via the Haber−Bosch (350−550°C, 150−350 bar) and Bosch−Meiser (150−200°C, 150−250 bar) processes is highly energy-intensive 5–8, consuming 1–2% of global energy and emitting over 200 million tons of CO 2 annually (equivalent to 1.2 tons of CO 2 emissions per ton of urea, Fig. 1a) 9–11. Electrochemical urea synthesis (urea electrosynthesis) from waste-derived nitrate (NO 3 −) and anthropogenic CO 2 under ambient conditions offers a sustainable alternative to fossil-dependent thermochemical processes, with the potential for net-negative carbon emissions (up to −0.6 tons of CO 2 per ton of urea, Fig. 1b) 3,8,9,12–21. However, this route is technically limited by low activity and selectivity.

Recent advances in urea electrosynthesis have demonstrated promising improvements in activity and selectivity through the design of synergistic catalytic strategies 9,14–16,22–27 such as bonded Fe−Ni pairs 15, alternating CuWO 4 dual-metal sites 16 and heterostructured Cu−Bi bimetallics 22. While these studies underscore the immense promise of sustainable urea production, major challenges remain as follows: (i) a complex 16-electron transfer involving two C−N coupling steps results in broad product distributions 16,17,23; (ii) spatial separation of active sites leads to spatiotemporal mismatches between C- and N- intermediates (Fig. 1c) 19,22; and (iii) insufficient regulation over the cross-adsorption of NO 3 −, CO 2 and their corresponding N- and C- intermediates causes undesired cross-contamination 14,28. These factors collectively promote undesired CO 2 reduction (CO 2RR) and nitrate reduction (NO 3RR) side-reactions that suppress C−N coupling and limit urea selectivity 9,12,15,18. These challenges underscore the urgent need for new catalytic strategies capable of orchestrating C−N coupling with high precision and selectivity.

Click chemistry, awarded the 2022 Nobel Prize in Chemistry, offers a highly modular and selective framework for assembling complex molecules under mild conditions with high efficiency and minimal by-products 29–31. Inspired by its ability to precisely stitch together small molecular units, we propose a hierarchical click-site strategy for urea electrosynthesis, in which two reactants, NO 3 − and CO 2, undergo sequential-chain coupling. The first click-site selectively anchors and activates either NO 3 − or CO 2 while excluding the other, followed by a second click-site that promotes targeted coupling with the remaining reactant via a nucleophilic attack on the surface-bound intermediate. This hierarchical click-site strategy, inspired by click chemistry, enables precise sequential-chain adsorption of NO 3 − and CO 2 on a single active site, addressing key challenges in C−N coupling selectivity by mitigating (i) competitive intermediate adsorption, (ii) spatiotemporal mismatches, and (iii) interfacial cross-contamination.

Despite its conceptual promise, this approach remains unexplored in urea electrosynthesis due to two major challenges: (i) the difficulty of achieving selective adsorption of only one feedstock at the first click-site, given the comparable affinity of most catalysts for both NO 3 − and CO 2; and (ii) the instability of the second click-site, which is often over-hydrogenated or prematurely desorbed.

To overcome these challenges, we systematically screened representative catalysts from CO 2RR, NO 3RR and C−N coupling, identifying InO x as a promising base due to its weak CO 2 adsorption via O-terminal (*OCO) configurations, disfavoring *CO formation while preferentially adsorbing and stabilizing nitrate-derived *NO 2 (Supplementary Fig. 1) 32–37. Guided by molecular orbital theory (Supplementary Fig. 2) 38, substituting lattice oxygen with a larger and less electronegative element is expected to increase electron density at the active centers and induce moderate lattice distortion, thereby making CO 2 adsorption thermodynamically unfavorable. Following this rationale, we replaced lattice O with Se, yielding a Se-modulated InO x catalyst (Se−InO x) with enhanced *NO 2 stabilization and fully suppressed CO 2 binding. In this system, Se−InO x (Fig. 1c) serves as the first click site, selectively adsorbing NO 3 − and converting it to stable *NO 2 without interacting with CO 2, while suppressing undesired NO 3RR and CO 2RR. The surface-bound *NO 2 then functions as second click site, facilitating the selective nucleophilic attack of CO 2 at the N site of *NO 2 to form the key *CO 2NO 2 intermediate. This sequential-chain coupling aligns C- and N- intermediates both spatially and temporally, enabling precise C−N bond formation while minimizing cross-contamination and by-product generation. Overall, the hierarchical click-site concept enables selective and sustainable urea electrosynthesis, establishing a generalizable framework for high-selectivity multicomponent electrosynthesis.

Results
Design of hierarchical click-site catalysts
Effective implementation of hierarchical click catalysis requires sequential and selective adsorption of CO 2 and NO 3 −, wherein CO 2 adsorption is selectively suppressed while NO 3 − is preferentially adsorbed and subsequently transformed into a stable *NO 2 during the first click step. To identify suitable host for this function, we initially screened several metals commonly employed in CO 2RR. Metals such as Cu, Fe, Zn, and Ag exhibited strong CO 2 adsorption via carbon-terminal (*COO) modes (Fig. 2a), leading to complex intermediates and products, such as methane, methanol, ethylene, and ethanol, etc. 32,33. Conversely, metals such as Bi, Sn, and particularly In, exhibit weaker CO 2 adsorption via the oxygen-terminal (*OCO) mode, predominantly yielding formate (HCOOH) 34. Among these, In-based catalysts, represented by InO x, exhibit the weakest CO 2 affinity 35–37. Meanwhile, the intrinsically high activation barrier from *NO 2 to *NOOH in NO 3RR favors the stabilization of *NO 2 (Supplementary Fig. 1), positioning InO x as a promising candidate for hierarchical click-site design. However, pristine InO x still retains measurable CO 2RR activity, necessitating further electronic modification to completely suppress undesired CO 2 adsorption 36,37. Based on molecular orbital theory (Supplementary Fig. 2) 38, enhancing the local electron density around In centers can weaken interactions with the electrophilic CO 2 molecule. To this end, we substituted lattice oxygen with larger and less electronegative anions (S, Se) to modulate the local electronic environment of the InO x. Electron localization function (ELF) analysis confirmed the enhanced electron density around In atoms upon doping with S and Se (Fig. 2b). This result is quantitatively supported by charge redistribution analysis (Fig. 2c and Supplementary Figs. 3 and 4), manifesting as an increase in electron density around In atoms from 1.24 (InO x) to 1.83 (Se−InO x). Structural distortion indices (Di) further revealed progressive lattice distortion from InO x (Di=0.014) to S−InO x (Di=0.039) and Se−InO x (Di=0.048, Fig. 2d). These distortions shift electronic states toward the Fermi level (Fig. 2e), weakening intrinsic In−O covalent bonds, thus enabling selective adsorption and minimizing undesired side-reactions.

Density functional theory (DFT) calculations were conducted to validate the modulation of surface adsorption behavior. Substitution of lattice oxygen with S or Se rendered CO 2 adsorption thermodynamically unfavorable, with the adsorption energy shifting from −0.26 eV (InO x) to +0.17 eV (S−InO x) and +0.27 eV (Se−InO x), respectively (Fig. 2f). Integrated crystal orbital Hamilton population (ICOHP) analyses revealed decreased In−O CO2 bonding strength on Se−InO x surfaces, confirming the suppression of CO 2 adsorption (Fig. 2g and Supplementary Fig. 5-7). In contrast, NO 3 − adsorption progressively strengthened from InO x to S−InO x and Se−InO x, as indicated by increased covalency in In−O NO3− interactions observed via ICOHP analysis, projected density of states (PDOS), and differential charge density mapping (Fig. 2h, i and Supplementary Figs. 8–10). As expected, the Se−InO x displayed the strongest *NO 2 adsorption and the highest hydrogenation barrier toward *NOOH formation (Supplementary Fig. 11), effectively preventing the over-reduction to NH 3 by-product. Collectively, these results indicate that Se−InO x acts as an efficient hierarchical click-site, selectively adsorbing NO 3 − and stabilizing it as *NO 2, while completely suppressing CO 2 adsorption and thereby minimizing undesired side-reactions (Fig. 2j, k).

Characterization of hierarchical click-site catalysts
The Se−InO x catalyst was synthesized via a two-step pyrolysis process. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed that Se−InO x consisted of porous nanoparticles with an average diameter of ~30 nm, comparable to InO x and S−InO x (Fig. 3a and Supplementary Figs. 12–17). Powder X-ray diffraction (XRD) analysis (Fig. 3a) confirmed retention of the cubic In 2O 3 phase (PDF#71-2195) after S or Se incorporation. High-resolution aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (AC HAADF-STEM) demonstrated distinct lattice fringes of 0.25 nm indexed to the (040) and (004) planes along the [100] zone axis (Fig. 3b, c), in agreement with simulated HR-TEM and electron diffraction patterns (Supplementary Figs. 18–21). Atomic-resolution STEM-energy dispersive X-ray spectroscopy (STEM-EDS) mapping distinctly revealed atomically dispersed Se uniformly substituting for O atoms around In sites (Fig. 3d), corroborated by X-ray photoelectron spectroscopy (XPS, Supplementary Figs. 22 and 23). Elemental analysis determined the Se content as ~2.92 at%, comparable to metal single-atom concentrations corresponding to a near-stoichiometric atomic dispersion 39,40. Similar substitution levels were observed for S–InO x (Supplementary Table 1). Complementary integrated differential phase contrast (iDPC) imaging revealed local lattice distortions arising from the substitution of larger-radius Se atoms in place of smaller O atoms within the InO x lattice (Fig. 3e and Supplementary Figs. 24–26), consistent with previous distortion analysis and further confirmed by geometric phase analysis (GPA) strain (Supplementary Fig. 27) 41. Based on these findings, an atomic model was constructed (Fig. 3f), highlighting how Se substitution at O lattice sites induced lattice rearrangements, modifying the local electronic environment of the In active sites and thereby influencing catalytic performance. We performed X-ray Absorption Near Edge Structure (XANES) and Extended X-ray Absorption Fine Structure (EXAFS) measurements at the In K-edge to examine local coordination and oxidation state changes on the InO x, S−InO x, and Se−InO x catalysts (Supplementary Fig. 28−31 and Supplementary Table 3). The XANES spectra (Supplementary Fig. 30a) show that the absorption edges of three samples lie between those of metallic In and In 2O 3, and are close to that of In 2O 3, suggesting the oxidation state is slightly below +3 in all samples. Notably, with the incorporation of S and Se, a gradual redshift of the edge was observed, indicating a gradual reduction in the In oxidation state. This trend is attributed to the larger atomic radii and lower electronegativities of S and Se, which promote electron localization around In centers and reduce the symmetry of In−O coordination, thereby enhancing electronic back-donation to In atoms. The non-phase-corrected FT-EXAFS spectra (Supplementary Fig. 30b) display a sharp first-shell peak for pristine InO x, whereas broader and more asymmetric peaks appear in S−InO x and Se−InO x, indicating increased local disorder and the presence of additional In−S or In−Se bonds. This interpretation is further supported by wavelet transform (WT) analysis (Supplementary Fig. 31), where the maximum intensity for Se−InO x (~4.60 Å−1) exceeds that of S−InO x (~4.20 Å−1) and InOx (~4.00 Å−1), reflecting contributions from heavier scatterers. EXAFS fitting (Supplementary Table 3) reveal that all three samples maintain a similar In coordination number (N≈6), with partial substitution of In−O by In−S or In−Se (N≈0.6) in the doped catalysts. These comparable coordination environments establish a solid basis for subsequent structure-property analysis. Collectively, these findings confirm that S and Se incorporation induces subtle local distortions and partially modulates the In oxidation state, without drastically altering the overall coordination geometry.

Subsequently, in-situ attenuated total reflection infrared (ATR-SEIRAS) spectroscopy under CO 2-saturated conditions showed pronounced CO 2 adsorption on InO x but negligible signals on Se−InO x (Fig. 3g and Supplementary Fig. 32), consistent with theoretical predictions of suppressed CO 2 affinity (Fig. 2f, g). In contrast, under conditions with only NO 3 − present, Se–InO x exhibited markedly enhanced adsorption and stabilization of *NO 2 species. Notably, simultaneous introduction of CO 2 and NO 3 − resulted in the detection of a red-shifted CO 2 adsorption peak and a blue-shifted *NO 2 signal on the Se−InO x surface (Fig. 3g and Supplementary Fig. 33), suggesting direct interaction and electron transfer between adsorbed CO 2 and *NO 2, thus forming the crucial *CO 2NO 2 intermediate. Electron paramagnetic resonance (EPR) spectroscopy confirmed signals for *CO 2NO 2 and *CONH x intermediates (Fig. 3h), further supporting direct C−N coupling on Se−InO x. Complementary electrochemical characterization reinforced the spectroscopic findings (Fig. 3i). Based on these results, we propose a hierarchical click-site catalytic mechanism proceeding via a sequential-chain coupling pathway (Fig. 3j): (i) Se doping activates adjacent In sites as first click-sites, which selectively adsorb NO 3 − and rapidly convert it into stable *NO 2 without interacting with CO 2. (ii) These *NO 2 species then function as second click-sites, selectively coupling with CO 2 at the N-center to generate the pivotal *CO 2NO 2 intermediate. This sequential-chain design effectively suppresses side-reactions associated with CO 2RR and NO 3RR, thereby overcoming the intrinsic challenges of competitive adsorption and spatiotemporal mismatch (Supplementary Fig. 34).

Enhanced urea selectivity on hierarchical click-site catalysts
The urea electrosynthesis performance of hierarchical click-site catalysts was evaluated using gas-diffusion electrodes loaded with catalysts in a flow electrolysis cell with CO 2-saturated 0.1 M KHCO 3 + 0.1 M KNO 3 electrolyte (Supplementary Fig. 35). Se−InO x with 2.92 at% Se displayed the highest urea FE, yield rate and J urea among samples with varying Se contents (1.16, 2.92 and 6.77 at%) and was thus selected for subsequent evaluation (Supplementary Figs. 36–44 and Table 2). As shown in Fig. 4a, b, urea yield rate and FE increased progressively with S and Se incorporation, particularly Se−InO x achieved a competitive urea yield rate and FE at −0.4 V (vs. RHE) with 69.29±7.48 mmol h−1 g−1 and 62.44±2.85%, surpassing S−InO x (49.45±6.51 mmol h−1 g−1 and 44.15±3.50%) and significantly outperforming InO x (14.85±2.11 mmol h−1 g−1 and 10.02±1.12%, Supplementary Tables 4–6). In addition, the S/Se co-doped sample (S 1.16Se 1.64−InO x) exhibited intermediate urea electrosynthesis activity between that of S−InO x and Se−InO x, further corroborating the electronic modulation effect of Se doping on the In active sites (Supplementary Figs. 45–49 and Table 1). Full product analysis showed similarly low NH 3 and NO 2 − yield rates among the three catalysts, while HCOOH production predominated on InO x but was strongly suppressed on Se−InO x with enhanced urea performance (Supplementary Figs. 50, 51 and Tables 7–9). These observations, supported by partial current densities (J product) and Tafel slopes (Supplementary Figs. 52–58), are consistent with theoretical and in-situ spectroscopic evidences showing that Se introduction promotes C−N coupling while suppressing CO 2RR and NO 3RR side-reactions. Control experiments confirmed that urea formation required the co-presence of CO 2 and NO 3 − (Fig. 4c), affirming that urea arose from their co-electroreduction. Moreover, Se−InO x exhibited stable electrochemical performance over 10 consecutive cycles (Fig. 4d), with negligible variation in urea yield rate, J urea, and FE. Post-reaction characterizations (XRD, HAADF-STEM, STEM mapping, diffraction, and XPS, Supplementary Figs. 59–62 and Table 1) confirmed that the atomic-scale structural integrity, homogeneous elemental distribution, and original electronic configuration after prolonged electrochemical operation of Se−InO x, suggesting good electrochemical durability and structural stability.

The first click-site requires sufficient NO 3 − to generate adequate *NO 2 on the catalyst surface, while the second click-site necessitates a comparable amount of CO 2 to effectively couple with *NO 2. Further, optimized urea selectivity was achieved by balancing NO 3 − and CO 2 availability at the catalytic interface through controlled adjustment of NO 3 − concentrations (c(NO 3 −)) and CO 2 flow rate. At c(NO 3 −) below 0.15 M (0.05 and 0.10 M), HCOOH and H 2 were detected as the main by-product alongside urea, with minor amounts of NO 2 − and NH 3 (Fig. 4e). Increasing the c(NO 3 −) to 0.15 M resulted in the highest urea FE of 78.61%, with HCOOH undetected and minimal production NO 2 −, NH 3 and H 2 production (Fig. 4e), indicating an optimal dynamic balance of NO 3 − and CO 2 at the catalyst surface. Further increasing c(NO 3 −) resulted in increased NO 2 − and NH 3 formation, suggesting over-hydrogenation to NH 3 by-product, consistent with a concurrent decrease in H 2 evolution. We further evaluated the effect of CO 2 flow rate at fixed c(NO 3 −) = 0.15 M (Supplementary Fig. 63). At low flow rates (≤40 mL min−1), urea FE decreased markedly, while NO 3RR by-products became dominant, likely due to limited CO 2 accessibility at the catalyst-electrolyte interface. This imbalance led to *NO 2 accumulation, followed by desorption or over-hydrogenation to NH 3. Increasing the flow rate to 80 mL min−1 significantly enhanced urea FE and suppressed NO 2 − and NH 3 formation, thereby mitigating side reactions (Supplementary Fig. 63). Notably, HCOOH remained undetectable throughout. These findings define 0.15 M NO 3 − and 80 mL min−1 CO 2 as the optimal conditions for achieving high urea selectivity on hierarchical click-site catalysts. Even under optimal interfacial conditions, InO x favored CO 2RR (FE HCOOH = 41.28%, C HCOOH-selectivity = 94.42%, Fig. 4f–h and Supplementary Figs. 64 and 65) over NORR (FE NH3+NO2- = 20.85%, N NH3+NO2--selectivity = 73.38%) and C−N coupling (FE urea = 19.52%, N urea-selectivity = 26.62%, C urea-selectivity = 5.58%). Conversely, S−InO x and Se−InO x notably suppressed CO 2RR and NORR side-reactions. Notably, Se−InO x achieved a urea FE of 78.61%, N urea-selectivity of 85.32%, and C urea-selectivity of 100% (Figs. 4f–h and Supplementary Figs. 64 and 65), alongside significantly reduced NH 3 formation (FE NH3 = 0.53%, N NH3-selectivity = 0.58%) and completely inhibits HCOOH formation (FE HCOOH = 0.00%, N HCOOH-selectivity = 0.00%). Thus, hierarchical click-site engineering endowed Se−InO x with competitive urea yield rate, FE, J urea, and N urea/C urea-selectivities (Fig. 4i), demonstrating promising performance among reported electrocatalysts (Fig. 4j and Supplementary Table 10).

Mechanistic verification
To elucidate the underlying mechanism of urea electrosynthesis, DFT calculations (Figs. 5a–f, Supplementary Fig. 66, Data 1 and Table 11) and in-situ spectroscopic analyses were conducted (Fig. 5g–j). As shown in Fig. 5b, two major uphill steps dominate the urea formation pathway, i.e., the initial *NO 2 and CO 2 coupling to form *CO 2NO 2 (*NO 2 + CO 2 → *CO 2NO 2), identified as the likely rate-determining step (RDS), and the subsequent protonation of *CO 2NH 2 to *COOHNH 2. Notably, the second coupling step occurred spontaneously. Se incorporation significantly lowered the energy barrier for *CO 2NO 2 formation from 0.98 eV (InO x) to 0.55 eV (Se−InO x), and for *CO 2NH 2 protonation from 0.72 to 0.45 eV, suggesting a more favorable energy landscape. All catalysts also showed a thermodynamic preference for *NO 2 + CO 2 → *CO 2NO 2 over *OCHO + H → *OCHOH and *NO 2 + H → *NOOH (Fig. 5d–f and Supplementary Figs. 67–69), with Se−InO x showing the largest energy gap (0.87 and 2.78 eV), compared to S−InO x (0.20 and 2.59 eV) and InO x (0.04 and 1.37 eV), which may help reduce HCOOH and NH 3 by-products. CI-NEB calculations suggest that CO 2 diffusion and subsequent coupling with anchored *NO 2 proceeds with reduced barriers of 0.87, 0.66, and 0.48 eV for InO x, S−InO x, and Se−InO x, respectively (Supplementary Fig. 70). The resulting *CO 2NO 2 intermediates are predicted to exhibit progressively shorter C−N bond lengths (1.81 to 1.61 Å) and higher ICOHP values (2.08 to 3.50; Supplementary Figs. 71a and 72), implying stronger C−N covalent bonding upon Se doping. COHP analysis further reveals an upward shift of the antibonding orbital, which may enhance bond stability (Supplementary Fig. 71b). The negligible role of *NH 2- and *NH 2OH-based coupling with CO 2 highlights the efficiency and specificity of the *NO 2 + CO 2 pathway (Supplementary Fig. 73). Additionally, Se−InO x showed the lowest H 2O dissociation barrier, which could facilitate proton supply for subsequent hydrogenation of *CO 2NO 2 to urea (Supplementary Figs. 74–80).

In-situ ATR-SEIRAS further confirmed these insights (Fig. 5g–i). On InO x surface (Fig. 5g), strong *HCOO signals at ~1650 cm−1 was increased with negative potential, consistent with dominant CO 2RR 42. Concurrently, a *NO 2 signal at ~1200 cm−1 diminished with increasing potential, suggesting poor *NO 2 stability on InO x 43. The absence of *COOHNH 2 and *C−N signals implies that *NO 2 conversion led primarily to NH 3, as evidenced by the increasing *NH x signal 18. Therefore, CO 2RR and NO 3RR are independent and dominant on the InO x surface. For S−InO x, *HCOO signals are suppressed, while *NH x/*NH 2 and NH 2OH bands are enhanced, indicating improved NO 3 − adsorption and conversion to NH 3 compared to InO x (Fig. 5h) 17. Notably, the *NO 2 signal decreased at −0.3 V (vs. RHE) and gradually transformed into *CO 2NO 2, accompanied by minor *COOHNH 2 and *C−N signals, suggesting improved urea electrosynthesis. Se−InO x showed no *HCOO signal, and negligible *NH x, *NH 2, and NH 2OH signals, indicating complete suppression of CO 2RR and significant inhibition of NO 3RR. Instead, a clear transformation of *NO 2 to *CO 2NO 2 at −0.2 V (vs. RHE) was observed (Fig. 5i), with rapid growth of the *CO 2NO 2 signal and accompanying *C−N and *COOHNH 2 signals, indicating a preference for C−N coupling reactions on Se−InO x 11,44. These findings were further supported by a series of control experiments, demonstrating sequential-chain coupling pathways at hierarchical click-sites (Supplementary Fig. 81).

In-situ EPR spectra further provided additional support for the sequential-chain coupling pathway on Se−InO x (Fig. 5j). The signal intensity of *CO 2NO 2 increased with applied potential, in agreement with the ATR-SEIRAS findings, confirming the role of *NO 2 and CO 2 in the C−N coupling mechanism. Based on these results, we propose a hierarchical click-site catalysis mechanism via a sequential-chain coupling pathway (Fig. 5k), where Se-induced electronic modulation of In sites selectively activates of NO 3 − to form *NO 2 without CO 2 adsorption, constituting the first click step. The adsorbed *NO 2, along with the catalyst, facilitates selective coupling with CO 2 as the second click step. The resulting *CO 2NO 2 undergoes hydrogenation to urea with minimal side-reactions, aided by efficient H 2O dissociation, providing protons. To probe the catalyst behavior under operating conditions, we performed in-situ electrochemical XAS at the In K-edge on the InO x, S−InO x, and Se−InO x catalysts. As shown in Supplementary Figs. 82–87, shifting the applied potential from open-circuit potential (OCP) to −0.6 V (vs. RHE) resulted in only minor edge shifts across all samples, indicating that the In centers retain relatively stable electronic structures during operation. These subtle changes reflect moderate electron transfer between In sites and the adsorbed intermediates involved in C−N coupling, CO 2RR, and NO 3RR, without inducing significant redox transitions. Additionally, FT-EXAFS spectra show that the In−S and In−Se coordination environments in S−InO x and Se−InO x remain essentially unchanged under applied potentials (Supplementary Tables 12–14), demonstrating the structural robustness of these heteroatom-doped environments during electrocatalytic operation.

Techno-economic evaluation and scale-up of urea electrosynthesis
To enhance the economic viability of urea electrosynthesis, we increased the electrolyte concentration to CO 2-saturated 1 M KHCO 3 + 0.1 M KNO 3, leveraging the known benefits of high K+ concentration in accelerating C−N coupling via improved proton/electron transfer 11,45. This high K⁺ concentration significantly enhanced the urea yield rate and J urea, achieving peak values of 254.94 mmol h−1 g−1 and 21.87 mA cm−2 (Fig. 6a and Supplementary Fig. 88), which were 2.7 times those of low K+ concentration, respectively. A techno-economic analysis (TEA, Fig. 6b and Supplementary Table 15) showed that the minimum cost of urea production using Se−InO x is US$1.01 kg−1 at an electricity price of US$0.03 kWh−1, close to market levels but highlighting limited competitiveness at higher electricity costs. However, the production cost could be reduced to as low as US$0.16 kg−1, if electricity cost is reduced to US$0.01 kWh−1, enabled by sustainable energy sources and by-products are valorized 46. Subsequently, a financial net present value (FNPV) analysis was conducted, amortizing capital and operational costs over a 20-year lifespan. Profitability can only be achieved at electricity prices of US$0.01 kWh−1 and current densities ≥50 mA cm−2 (Fig. 6c and Supplementary Fig. 89), with payback periods decreasing substantially from 19-years at 50 mA cm−2 (FNPV=US$82,923) to just 6-years at 100 mA cm−2 (FNPV=US$7,141,881). Despite the gradual decline in FE at higher current densities, the economic value of by-products ensured cost recovery and profitability.

To provide guidelines for future development, univariate sensitivity analysis (Fig. 6d) identified key cost drivers as cell voltage, electricity price, FE, equipment, and labor cost, while water and maintenance costs had negligible impact. Specifically, reducing electrolyzer voltage to 1.5 V (e.g., via alternative anodic small molecule oxidation reactions) could lower costs by US$0.30 kg−1. Decreasing electricity costs (expansion of renewable energy) to US$0.01 kWh−1 and increasing FE to 85% (catalyst optimization based on the hierarchical click-site strategy) could further lower the cost by US$0.28 and US$0.16 kg−1 (Supplementary Figs. 90–93), respectively. Collectively, these improvements could decrease urea production costs from US$1.01 kg−1 to US$0.24 kg−1 even without considering by-product revenues. Finally, the scalability of Se−InO x was validated in 20 h continuous operation within a 5×5 cm2 flow electrolyzer under CO 2-saturated 1 M KHCO 3 + 0.1 M KNO 3 electrolyte, maintaining stable current density (Fig. 6f and Supplementary Fig. 94). The solid product, isolated by concentration, benzene extraction, and subsequent removal of benzene, yielded 1.102 g of pure urea solid, which was confirmed by 1H and 13C NMR characterization (inset of Fig. 6f) 21. Based on the mass of the isolated urea, the average urea yield rate and FE over 20 h were calculated as 183.70 mmol h−1 g−1 and 35.28%, respectively. Compared to the small-scale setup, the slightly reduced performance is attributed to increased ohmic resistance, mass transport limitations, and unavoidable losses during purification, challenges typical in scaled-up systems. Nonetheless, the Se–InO x demonstrated robust activity and selectivity under scaled conditions, affirming its promise for practical applications. The lifecycle assessment (LCA) shows that when powered by the average U.S. grid (0.12 kg CO2 MJ−1), the urea electrosynthesis route generates higher greenhouse gas (GHG) emissions (15.76 kg CO2 kg−1 urea) than the conventional Bosch−Meiser process (1.90 kg CO2 kg−1 urea), mainly due to the high electricity demand of the electrochemical cell (Supplementary Fig. 95 and Tables 16 and 17). Under low-carbon renewable electricity (0.003 kg CO2 MJ−1), the GHG intensity drops significantly to 0.63 kg CO2 kg−1 urea, which is lower than that of the conventional route under comparable renewable scenarios (1.81 kg CO2 kg−1 urea), highlighting the potential for emission reductions within a gate-to-gate boundary. In line with the conservative LCA framework adopted in this study, the results reflect process-level emissions at the plant gate and do not imply permanent CO 2 sequestration or net carbon removal. Nevertheless, the use of renewable electricity markedly enhances the environmental performance of the electrochemical pathway, supporting its promise for sustainable chemical manufacturing.

Discussion
In summary, we have developed a hierarchical click-site catalysis strategy via a sequential-chain coupling pathway to overcome the long-standing challenge of low selectivity in urea electrosynthesis from NO 3 − and CO 2. Mechanism studies demonstrate that Se−InO x, constructed by uniformly dispersed Se on CO 2-inert InO x surface, serves as the first click-site to selectively adsorb NO 3 − and stabilize it as *NO 2. This adsorbed *NO 2 together with the catalyst, then acts as the second click-site to sequential-chain coupling CO 2, forming the key *CO 2NO 2 intermediate, which undergoes rapid hydrogenation to urea. This hierarchical click-site design effectively resolves the spatiotemporal mismatch between N- and C- intermediates, achieving precise C−N coupling while effectively preventing cross-contamination and undesirable by-products. As a result, Se−InO x achieves a urea yield rate of 254.95 mmol h−1 g−1, a FE of 78.61%, >85% N urea-selectivity, and 100% C urea-selectivity, outperforming most previously reported materials. TEA and urea powder production, together with gate-to-gate LCA results under renewable electricity scenarios, suggest the feasibility of scalable, cost-effective, and lower-emission deployment. This work provides a generalizable framework for achieving high selectivity in complex electrochemical transformations and presents a promising route towards sustainable nitrogen and carbon valorization.

Methods
Chemicals
Indium(III) chloride tetrahydrate (InCl 3·4H 2O, 97%), cadmium acetate dihydrate (Cd(Ac) 2·2H 2O, ≥98%), 2,5-thiophenedicarboxylic acid (C 6H 4O 4S, 2,5-TDC, 99%), selenium powder (Se, ~100 mesh, ≥99.5%), thioacetamide (C 2H 5NS, ≥99.0%), potassium nitrate (KNO 3, ≥99.0%), isopropanol (C 3H 8O, 99.5%), diacetylmonoxime (C 4H 7NO 2, ≥99.0%), phosphoric acid (H 3PO 4, >85% in H 2O), sulfuric acid (H 2SO 4, 95%–98%), iron(III) chloride (FeCl 3, ≥99.99%), thiosemicarbazide (TSC, 99%), ethylenediaminetetraacetic acid disodium salt (EDTA, 99%), urease (~1 U/mg), potassium bicarbonate (KHCO 3, ≥99.95% trace metals basis, 99.7–100.5% dry basis), ammonium chloride (NH 4Cl, ≥99.5%), hydrochloric acid (HCl, 37%), para-(dimethylamino)benzaldehyde (C 9H 11NO, 99%), salicylic acid (C 7H 6O 3, ≥99.0%), sodum citrate dihydrate (C 6H 5Na 3O 7, ≥99.0%), sodium hypochlorite (NaClO, available chlorine 4.00–4.99%), sodium hydroxide (NaOH, 97%, powder), sodium nitroferricyanide(III) dihydrate (Na 2Fe(CN) 5NO·2H 2O, 99%), ethanol (C 2H 5OH) and Nafion 115 were purchased from Sigma-Aldrich (Singapore) and used without further purification unless otherwise noted. High-purity CO 2 (≥99.999%) and Argon (Ar, ≥99.999%) gases were purchased from Air Liquide (Singapore). All aqueous solutions were prepared with high-purity de-ionized water (DI-water, resistance 18 MΩ cm−1).

Synthesis of InO x
To synthesize InO x, an In-based metal-organic framework (In-MOF) was constructed using 2,5-TDC as the organic linker. In a representative procedure, 0.5 g of InCl 3·4H 2O and 0.5 g of Cd(Ac) 2·2H 2O were dissolved in 200 mL of ethanol and combined with 100 mL of an ethanolic solution containing 1 g of 2,5-TDC. The mixed solution was maintained at 60°C for 12 h to allow for MOF crystallization. The solid product was collected by centrifugation, sequentially washed with ethanol and deionized water to remove residual reactants, and then dried under vacuum. The resulting In-MOF precursor was thermally treated at 800°C for 4 h in a muffle furnace. Post-calcination, the material was washed with deionized water and lyophilized to obtain InO x.

Synthesis of Se-InO x
Selenium incorporation was achieved by positioning 0.3 mmol of Se powder upstream and 100 mg of InO x downstream within an alumina crucible. The system was sealed in a tubular furnace under argon and heated to 400°C at a heating rate of 20°C min−1 and kept warm for 2 h. This step was repeated three times to promote homogeneous Se dispersion across the surface. The obtained solid was purified via triple deionized water washing and drying. The final sample was labeled Se−InO x−2.92 (abbreviated as Se−InO x). Analogous procedures with adjusted selenium amounts (0.1 mmol and 1 mmol) yielded Se−InO x−1.16 and Se−InO x−6.77, respectively.

Synthesis of S-InO x
Similarly, S−InO x was synthesized by replacing Se powder with C 2H 5NS under the same experimental conditions.

Physical characterization
The morphology of the as-prepared samples was characterized using a FESEM (JEOL 7800F), TEM. High-resolution imaging was conducted using a Titan G2 60-300 HRTEM equipped with spherical and chromatic aberration correctors, and a FEI Titan G3 20-80 for HAADF-STEM analysis. Elemental composition was determined by ICP-MS (Thermo XSERIES 2), EDS, and elemental mapping (150~230 M x at 200 kV on STEM). Crystal structures were identified by XRD (Bruker D8 Advance, 9 kW, 40 kV, 40 mA) using Cu Kα radiation (λ=1.5418 Å). XPS (Thermo ESCALAB 250XI, energy range: 0−1400 eV) was employed to evaluate surface chemical states. EPR spectral signals were collected using Bruker EMX plus-9./12 spectrometer operating at X-band (9.85 GHz). FTIR spectra were recorded using a Thermo Fisher Nicolet iS50 spectrometers to detect organic functional groups. UV−vis absorption spectra were obtained with an Agilent Cary 60 spectrophotometer. Additionally, the 1H NMR spectra were obtained using a superconducting-magnet NMR spectrometer (Bruker AVANCE III HD, 600 MHz).

In-situ ATR-SEIRAS characterization
In-situ ATR-SEIRAS measurements were carried out on a Nicolet™ iS50 FT-IR spectrometer equipped with a specially designed reaction cell and a mercury cadmium telluride (MCT) detector cooled with liquid nitrogen. A 20 mm Au-coated Si hemispherical prism (MTI Corporation) was used both as the catalyst support and the internal reflection element. A Pt foil, an Ag/AgCl electrode (4 M KCl), and a CO 2-saturated 0.1 M KNO 3 + 0.1 M KHCO 3 solution served as the counter electrode, reference electrode, and electrolyte, respectively. Catalyst ink was prepared following the electrochemical protocol and drop-cast on the prism at a loading of 1 mg cm−2. In-situ ATR-FTIR spectra were recorded while scanning the working electrode potential from OCP to −0.6 V (vs. RHE) at a scan rate of 5 mV s−1. During measurements, pure CO 2 gas (99.999% purity) was continuously flowed into the reaction chamber, and spectral changes were monitored in the range of 4000−1000 cm−1.

In-situ EPR characterization
In-situ EPR measurements were conducted at room temperature using a continuous-wave (CW) Bruker EMX plus-9/12 spectrometer operating at X-band (9.85 GHz). A custom-designed quartz flat cell (Supplementary Fig. 96), comprising four ports, was employed to establish a three-electrode electrochemical configuration. The cell featured a 1 mm-thick flat window, optimized to reduce signal attenuation due to excessive solution thickness. The working electrode consisted of a flexible indium tin oxide (ITO) substrate (0.125 mm, ~10 Ω) loaded with catalyst (1 mg cm−2), precisely cut to align with the central window region. A platinum wire served as the counter electrode, while an Ag/AgCl electrode was used as the reference. The electrolyte—comprising 0.1 M KNO 3 and 0.1 M KHCO 3 supplemented with 10 mM DMPO—was purged with CO 2 for 20 min before use and continuously supplied during operation. EPR spectra were recorded using a 100 kHz modulation frequency and 10 dB microwave power, across a 200 G sweep range. Each scan lasted 60 s, and final spectra were averaged from two consecutive measurements for improved resolution. Spin-trapping experiments using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) were additionally performed on a Bruker EMX Micro EPR spectrometer under identical conditions. Spectral simulations were carried out using the EasySpin software (v6.0.0) integrated in MATLAB R2020a 49.

The X-ray absorption fine structure (XAFS) and in-situ XAFS characterization
The X-ray absorption fine structure (XAFS) spectra of the samples were collected at BL11B beamline of Shanghai Synchrotron Radiation Facility (SSRF). The SSRF is a third-generation synchrotron radiation light source composed of a 3.5 GeV electron storage ring, a full energy booster, and a 150 MeV linear accelerator. The electron-beam current during testing is 200 mA. The BL11B beamline used a bending magnet as the photon source. The experiments were performed using the double-crystal monochromator (DCM) with a Si(311) crystal. The corresponding reference samples and the samples for ex-situ experiments were collected in transmission mode. The samples for in-situ experiments were collected in fluorescence mode using a Lytle detector.
In-situ XAFS measurement was conducted with a homemade H-type cell with Nafion 115 to separate the anode and the cathode. This cell contains three electrodes with a carbon foil coated by catalyst as the working electrode, Pt mesh as the counter electrode, and Ag/AgCl as the reference electrode, respectively. The catalyst was drop-cast on the carbon foil and allowed to dry. A small window was cut out on the cathode side and sealed with Kapton film to allow fluorescence signals to pass from the electrode to the detector. The electrolyte was obtained by bubbling CO 2 into the 0.1 M KNO 3 and 0.1 M KHCO 3 aqueous solution for 30 min before testing. The XAFS spectra were collected under open-circuit potential and applied potentials. The acquired XAFS data were processed according to the standard procedures using the ATHENA module of Demeter software packages. To obtain the quantitative structural parameters around central atoms, least-squares curve parameter fitting was performed using the ARTEMIS module of Demeter software packages.
The following EXAFS equation was used:
χ(k) = Σ j (N j S 0 2 / k R j 2) exp(−2k 2σ j 2) exp(−2R j / λ(k)) sin(2kR j + φ j(k)) (1)

Electrochemical characterizations
The catalyst ink was prepared by dispersing 5 mg of the as-synthesized material and 30 μL of 5 wt% Nafion solution into 1 mL of a mixed solvent (isopropanol: deionized water = 4:1, v/v), followed by ultrasonication for 30 min to ensure homogeneity. A 40 μL of the resulting ink was transferred onto a 1.0 × 1.0 cm2 GDL, achieving a mass loading of 0.2 mg cm−2. Urea electrosynthesis from NO 3 − and CO 2 was conducted within a three-electrode flow-type electrolytic cell connected to a CHI760E electrochemical workstation under ambient laboratory conditions (25 ± 1°C). The synthesized catalyst on GDL served as the working electrode, a GDL as the counter electrode, and a saturated Ag/AgCl/KCl electrode as the reference. A Nafion 115 membrane (thickness ~127 μm, 2 × 2 cm2) was employed as the separator. Prior to use, the Nafion 115 membrane was sequentially treated in 5 wt% H 2O 2 at 80°C for 3 h, rinsed with deionized water at 80°C for 1 h, soaked in 0.5 M H 2SO 4 at 80°C for 2 h and again at 100°C for 8 h, followed by additional rinsing in deionized water at 80°C and thorough washing to ensure cleanliness. The electrolyte, consisting of KNO 3 and 0.1 M KHCO 3, was freshly prepared on the day of each experiment and used on the same day. The gas (CO 2 or Ar) and electrolyte (30 mL) were fed at rates of 80 mL and 40 min−1, respectively. Before the electrochemical test, the electrolyte was thoroughly purged with Ar or CO 2 flow for a period of 30 min. During electrolysis, the catholyte and anolyte were directed into their respective chambers, separated by the Nafion membrane, and subsequently routed into individual reservoirs. CO 2 was introduced into the cathode chamber through PTFE tubing, facilitating its interaction with the catalyst surface. The flow of the catholyte and anolyte was maintained using a peristaltic pump. Gas-phase products were analyzed using gas chromatography after flow stabilization. Chronoamperometric measurements were performed at various potentials for 1200 s, while maintaining a constant Ar or CO 2 flow within the electrochemical system. All potentials were converted to the reversible hydrogen electrode (RHE) scale using the formula: E RHE = E Ag/AgCl + 0.0592 × pH + 0.197. The Ag/AgCl (saturated KCl) reference electrode was calibrated in H 2-saturated 0.5 M H 2SO 4 using a clean Pt wire as both working and counter electrodes. The open-circuit potential was recorded and taken as 0 V (vs. RHE) after stabilization.
The resistance was measured by EIS at open circuit potential (100 kHz–0.1 Hz, 5 mV), giving an average value of 2.7 ± 0.8 Ω. Unless otherwise stated, all reported voltages are without iR compensation.
The Tafel slopes were determined using the Tafel equation: η = b log J urea + a, where η is potential (V), J urea is partial current density of urea production (mA cm−2), and b is the corresponding Tafel slope (mV dec−1). Catalyst durability was assessed over ten successive chronoamperometric cycles at −0.4 V (vs. RHE).

Large-scale electrolysis and urea isolation
Under identical conditions, electrolysis was carried out in 1 M KHCO 3 + 0.1 M KNO 3 electrolyte using a constant current method across a range of 2−100 mA cm−2. To obtain high-purity urea, a scaled-up electrolysis was performed in a 5 × 5 cm2 flow cell continuously for 20 h. The resulting electrolyte was concentrated and subjected to benzene extraction to isolate urea 3. After solvent removal, the solid urea product was obtained and confirmed by both 1H and 13C NMR spectroscopy.

Determination of urea
Method 1-Diacetylmonoxime (DAMO) colorimetry 17: Briefly, 1 mL of electrolyte was mixed with 2 mL of acid−ferric solution (comprising 100 mL concentrated phosphoric acid, 300 mL concentrated sulfuric acid, 600 mL deionized water, and 100 mg ferric chloride). Then, 1 mL of a DAMO-thiosemicarbazide (TSC) solution (5 g DAMO and 100 mg TSC in 1 L deionized water) was added. The mixture was heated to 100°C for 20 min and cooled to room temperature. Absorbance was measured at 525 nm using a UV−vis spectrophotometer, and urea concentrations were calculated based on a standard calibration curve.
Method 2-Urease enzymatic decomposition 14: 0.5 mL of a urease solution (5 mg mL−1, contained 0.1 g ethylenediaminetetraacetic acid disodium salt (EDTA) and 0.49 g K 2HPO 4 per 100 mL) was added to 4.5 mL of electrolyte, followed by incubation at 40°C for 40 min. NH 3 concentrations were determined before and after decomposition using the indophenol blue method, and urea concentration was obtained by subtracting the pre-decomposition NH 3 content from the post-reaction result.

Determination of NH 3
The concentration of NH 3 produced in the electrolyte was determined using the indophenol blue method 39. After electrolysis, 2 mL of the electrolyte was sequentially mixed with: 2 mL of 1 M NaOH containing 5 wt% sodium citrate and 5 wt% salicylic acid as solution A, 1 mL of 0.05 M NaClO as solution B, and 0.2 mL of 1 wt% sodium nitroprusside (C 5FeN 6Na 2O) as solution C. The solution was kept in the dark at ambient temperature for 2 h, followed by UV−vis absorption measurement in the range from 550 to 750 nm.

Determination of NO 2 −
NO 2 − in the electrolyte was quantified using the Griess reagent method 14. A 200 μL aliquot of Griess reagent was added to 5 mL of electrolyte, heated to 100°C for 1 min, and cooled to room temperature. The absorbance at 540 nm was recorded, and nitrite concentration was obtained by referencing a standard calibration curve.

Determination of other liquid-phase products
Liquid-phase products were analyzed by 1H NMR spectroscopy using dimethyl sulfoxide (DMSO) as the internal standard. Dimethyl sulfoxide (DMSO) was used as an internal standard, allowing for accurate determination of the liquid product yield rate.

Determination of gas-phase products
Gas-phase products were analyzed using a gas chromatograph (GC) equipped with both a thermal conductivity detector (TCD) and a flame ionization detector (FID), with Ar used as the carrier gas.

Calculaions for yield rate and FE
The detailed yield rates have been calculated by using the following equation:
Y(urea) = c(urea) × V / (t × A) (2)
Y(NH 3) = c(NH 3) × V / (t × A) (3)
Y(NO 2 −) = c(NO 2 −) × V / (t × A) (4)
Y(HCOOH) = n(HCOOH) / (t × A) (5)
The detailed FEs have been calculated as follows:
FE(urea) = 16F × c(urea) × V / (60.06 × Q) (6)
FE(NH 3) = 8F × c(NH 3) × V / (17 × Q) (7)
FE(NO 2 −) = 2F × c(NO 2 −) × V / (47 × Q) (8)
FE(HCOOH) = 2F × n(HCOOH) / Q (9)
where F is the Faradic constant (96485.3 C mol−1), c is concentration, V is the volume of electrolyte, t is the reaction time and A is the catalyst area and Q is the total charge passed through the working electrode.

Calculaions for selectivity
The C-selectivity for CO 2-to-urea and CO 2-to-HCOOH conversions was calculated as follows:
C selectivity(C-product) = n(C-product) / n(total) × 100% (10)
where n(C-product) is the number of moles of C in C-product, and n(total) is the total number of moles of C atoms in the products from CO 2RR.
Similarly, the N−selectivity for NO 3 −-to-urea, NO 3 −-to-NO 2 − and NO 3 −-to-NH 3 conversion was calculated using the following equation:
N selectivity(N-product) = n(N-product) / n(total) × 100% (11)
where n(N-product) is the number of moles of nitrogen in as-produced urea, and n(total) is the total number of moles of N atoms in the products from NO 3RR.

DFT calculation details
First-principles calculations based on spin-polarized density functional theory (DFT) were performed using the Vienna Ab initio Simulation Package (VASP) 50, with the exchange-correlation interactions were described by the Perdew-Burke-Ernzerhof (PBE) functional within the generalized gradient approximation (GGA) 51. To model surface reactions, periodic slab models were constructed with a 15 Å vacuum layer along the non-periodic direction to eliminate spurious interactions between periodic layers. The plane-wave basis set was truncated at a cutoff energy of 450 eV, and Brillouin zone integration was sampled using a Monkhorst-Pack k-point grid of 2×2×1 for structural optimizations. Convergence thresholds were set to 10−5 eV for total energy and 0.01 eV Å−1 for atomic forces, ensuring high precision in geometry relaxations. The adsorption energy was calculated according to the Gibbs free energy difference between the product and reactant, and Gibbs free energy correction, including entropy and the zero-point energy correction, was taken into consideration at 298.15 K. For the intermediate species of H+, its Gibbs free energy was calculated as half of H 2. The averaged length of In-X (X=O, S, Se) and distortion index of polyhedron analyses were implemented to present the change of local structure. The distortion index (D) was calculated as the following equation:
D = 1/n Σ i=1 n |l i − l ave| / l ave (12)
where l i and l ave represent the distance from the central atom In to the ith coordinating atom (O, or S, or Se) and the average bond length of the polyhedron, respectively. Electron localization function 52 and Bader charge methods were employed to obtain the distribution and transfer of electron. The crystal orbital Hamilton population (COHP) 53 calculations were performed to reveal the chemical bonding and antibonding mechanism. For the dissociation of H 2O, the climbing-image nudged elastic band (CI-NEB) 54 method was used to obtain the dissociation barrier of H 2O.

Techno-economic evaluation
A comprehensive TEA was performed to assess the feasibility of urea electrosynthesis via the co-reduction of CO 2 and NO 3 − under industrially relevant conditions. The assessment included energy consumption estimation based on Faraday’s law, process-scale current and voltage inputs, and material balances for all relevant species (urea, NH 3, HCOOH, CO 2, H 2O, and O 2). Capital costs were calculated based on DOE H 2 guidelines, including stack and balance-of-plant components, with depreciation modeled over a 20-year plant lifetime. Operating costs accounted for electricity, water usage, membrane separation, and labor. Sensitivity analyses were conducted to evaluate the influence of current density, FE urea, cell voltage, and electricity price on financial net present value (FNPV) and urea production cost. Detailed parameters, assumptions, and numerical results are provided in the Supplementary Information.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "The electrocatalytic construction of C–N bonds for converting inorganic small molecules into high-value chemicals remains a significant research challenge. While this work designs a Se-InOx catalyst that achieves highly selective conversion of nitrate and CO2 to urea, the high selectivity is attributed to a \"hierarchical click-site\" mechanism, which is conceptually inappropriate as it bears no legitimate connection to click chemistry principles. Theoretical calculations indicate that CO2 and nitrate reduction occur at the same catalytic sites. However, the manuscript fails to resolve why a site inherently incapable of adsorbing CO2 becomes favorable for CO2 binding after *NO2 formation. Additionally, the catalyst's structure remains ambiguous, as all schematic diagrams fail to demonstrate a standard Se-InOx configuration convincingly. The cost analysis lacks practical significance due to the use of non-industrial current densities; CO2 reduction requires hundreds of mA cm⁻2 current densities to approach feasibility. Therefore, the manuscript does not meet Nature Communications' publication standards in its current form. Major Revision or Resubmission is required before further consideration. Specific concerns are as follows:\nRegarding concept and mechanism:\n1. The core of click chemistry involves efficient, modular reactions that stitch together small molecular units. This work describes sequential catalysis occurring at a single catalytic site, which does not align with the concept of click chemistry, making its appropriation unjustified.\n2. C–N coupling constitutes a more challenging step in the reaction pathway; however, experimental and theoretical calculations are lacking to explain how *NO2 subsequently couples with CO2 after its formation, whether the actual energy barrier for this step is genuinely lower than that of multisite catalysts, how CO2 becomes activated, and how the C–N covalent bond forms.\n3. Given that *NO2 should be preserved to enhance its coupling ability with CO2, theoretical calculations should supplement the energy barriers for *NO₂ dissociation or further hydrogenation and compare them with the barriers for C–N coupling.\n4. Theoretical calculations lack comparisons with other reaction pathways. A single reaction path does not explain why the catalyst favors urea formation.\nRegarding the catalyst structure:\nThe authors appear to have conducted extensive characterization but fail to clearly describe the surface structure of the catalyst. Based on the synthesis method, Se likely substitutes oxygen on the InOx surface, and the introduced Se alters the electronic structure of In, thereby influencing reactant binding affinity. Consequently, precise control over the amount of Se introduced is critical. What is the quantity of Se introduced? How many Se atoms are adjacent to an In atom? How would the activity change if the amount of introduced Se is altered? Furthermore, introducing Se via calcination can readily disrupt the original metal-oxygen bonds, potentially forming other structures like oxygen vacancies, which might be more favorable for reactant binding. Using EPR to claim the presence of vacancies is fundamentally inappropriate. Please supplement with more precise structural characterizations, such as XAFS, etc. All structural schematics in the manuscript do not represent the true structure of Se-InOx; not even an oxygen atom is depicted. XRD indicates that InOx should be In2O3, so why is it uniformly written as InOx?\nRegarding the cost and economic assessment:\nThe TEA assumes profitability at 50-100 mA cm⁻2 (Fig. 6c), but the actual operating current density is merely 10 mA cm⁻2 for the maximum Faradaic efficiency; therefore, the economic cost calculations based on this are meaningless. At the same time, the current density in TEA falls far below the industrial benchmark of hundreds of mA cm⁻2. Furthermore, the TEA ignored raw material costs. The reaction was conducted using highly concentrated CO2 and pure nitrate solutions; the purification of CO2 and synthesis of nitrates inherently involve energy-intensive processes. (Industrial KNO3 source cost, CO₂ capture energy, Waste nitrate purification…) Solely calculating the cost of the electrochemical step lacks practical significance.", "reviewer_2": "Inspired by click chemistry, the authors develop a hierarchical click-site catalyst (Se–InOx) that enables a sequential-chain coupling pathway. The catalyst achieves outstanding performance: 254.95 mmol h-1 g-1 urea yield, 78.61% FE, >85% N-selectivity, and 100% C-selectivity. Mechanistically, Se–InOx first selectively adsorbs/hydrogenates NO3- to *NO2, after which *NO2 acts as a secondary click-site to couple with CO2, forming the key *CO2NO2 intermediate. This work addresses the critical challenge of spatiotemporal intermediate mismatch in electrochemical C-N coupling for urea synthesis, minimizing side reactions. Overall, the manuscript is well-prepared, thus can be published after addressing the following issues:\n1. The coupling reaction of *NO2 with CO2 to form *CO2NO2 exhibits a DFT-calculated potential barrier of 0.55 eV. This barrier is notably high compared to typical DFT results. Crucially, it is significantly larger than the rate-determining barriers reported in the current literature for both the pure NO3- reduction pathway and the pure CO2 reduction pathway. Then, the thermodynamic feasibility should be further interpreted, or could this indicate a potential issue with the DFT calculation results for the coupling step? If feasible, incorporating the complete potential energy diagrams for the separate NO3- reduction and CO2 reduction pathways would provide a direct visual comparison of the relevant barriers.\n2. Se–InOx displayed the highest hydrogenation barrier toward *NOOH formation, why?\n3. The article mentions that when c(NO₃-) is lower than 0.15 M (0.05 and 0.10 M), HCOOH is detected as the main by-product. Does this mean that Se-InOx can adsorb CO₂ rather than selectively adsorb NO₃- and undergo subsequent reactions to produce HCOOH? However, the authors explain the mechanism is due to selenium doping causing In sites to selectively adsorb NO₃- rather than CO₂. Are these two explanations contradictory?\n4. Still for substrates adsorption, the fact is In-based catalysts exhibiting the weak CO2 affinity through C sites adsorption. How to simultaneously inhibit CO2 adsorption through O site, and facilitate O site adsorption for NO₃-.\n5. Additional intermediates, including *NH2 and *NH2OH, could play a crucial role in C–N coupling. The feasibility of their participation in such reactions can be assessed using DFT calculations.\n6. According to DFT results, the first C-N coupling step is non-spontaneous while the second step is spontaneous. What causes this difference - adsorption configuration, electronic state changes, or other factors?\n7. The flow rate of CO2 gas of 80 mL min-1 is very large compared with that in literature, do it the reason for high performance? The dependence of urea performance on CO2 flow rate like 10, 20, 40, and 60 mL min-1 under the identical NO₃- concentration e.g. 0.15 M should be investigated and talked about. Please indicate the flow rate of CO2 gas and NO₃- concentration when compared the urea formation performance with the reported electrocatalysts in the Supplementary Tab. 9.\n8. The in situ infrared spectra of the three samples exhibit some variations in their plots. For instance, the horizontal axis ranges differ between them. To facilitate better comparison, the plots should be standardized to ensure consistency across all samples.\n9. The in situ infrared spectra of Se-InOx reveals a prominent downward peak near 1100 cm-1 and a weaker but discernible signal around 1500 cm-1, both of which require consideration.\n10. After testing the 5×5 cm2 flow cell for 20 hours, the author obtained solid urea as the final product after purification. Please provide a detailed schematic diagram of the flow cell device in the supplementary information, describe the experimental steps for purifying solid urea, and indicate the final amount of solid urea obtained. How do the reaction potential, yield, and Faraday efficiency in a 25 cm2 flow cell compare to smaller-scale systems? Also, the catalytic performance like yield and Faraday efficiency should be calculated based on the obtained solid urea.\n11. The author only presented the FE values for liquid products of catalysts (Se–InOx, S–InOx and InOx), and the FE values are less than 100%. Are there other gas products, such as CO or H2? Please add the corresponding of gas products for Se–InOx, S–InOx and InOx.", "reviewer_3": "In this manuscript, the authors report the synthesis of a hierarchical click-site catalyst, Se–InOx, designed for the electrocatalytic and selective synthesis of urea via C–N coupling from CO2 and NO3‒. The synthesized Se–InOx catalyst exhibits a high urea yield of 254.95 mmol h‒1 g‒1 with a Faradaic efficiency of 78.61%. Furthermore, the study reveals that surface-anchored *NO2 functions as a second click-site, enabling coupling with CO2 to form the key *CO2NO2 intermediate, thereby enhancing C–N coupling selectivity toward urea production. The study presents interesting findings and offers valuable insights into the design of advanced electrocatalysts for selective urea synthesis. However, the following major concerns must be addressed before the manuscript can be considered for publication in “Nature Communications”.\n1. The introduction does not provide a detailed rationale for the specific selection of the Se–InOx catalyst. The authors should expand the discussion by explaining the individual roles and synergistic benefits of incorporating Se and InOx in enhancing C–N coupling selectivity for urea synthesis.\n2. The authors should perform X-ray Absorption Spectroscopy (XAS), including both XANES and EXAFS analyses, on InOx, Se–InOx, and S–InOx catalysts. This is essential to evaluate any changes in the oxidation state of In upon incorporation of Se and S into the InOx matrix.\n3. Although the Se–InOx catalyst shows enhanced selectivity for C–N coupling, the manuscript does not investigate the effect of varying Se content in the InOx catalyst. A systematic study of Se loading is necessary to understand its influence on urea synthesis performance.\n4. The manuscript reports that separate incorporation of Se and S improves urea synthesis selectivity. However, it remains unclear whether simultaneous co-incorporation of both Se and S into InOx could further enhance the yield and selectivity. The authors are encouraged to investigate this possibility experimentally.\n5. Supplementary Fig. 40 indicates that both Se–InOx and S–InOx catalysts exhibit the highest Faradaic efficiency for urea synthesis at –0.4 V vs. RHE. A more detailed discussion is required to explain why this specific potential is optimal and the underlying mechanism responsible for this observation.\n6. The authors should provide quantitative elemental analysis (e.g., via EDS or XPS) of In, Se, and O before and after long-term stability testing to determine if any leaching or dissolution of active components occurs during extended electrolysis.\n7. High-resolution TEM analysis of the Se–InOx catalyst after the stability test should be presented to assess any structural or morphological changes at the atomic/lattice level.\n8. Electrochemical in situ XAS studies should be conducted for InOx, Se–InOx, and S–InOx catalysts to probe real-time changes in oxidation states and the local chemical environment during the reaction. This would significantly strengthen the mechanistic insights.", "reviewer_4": "The proposed manuscript evaluates the performance of a novel Se-InOx catalyst system for urea electrosynthesis from wastewater streams. The techno-economic analysis (TEA) presented in this manuscript is well-executed and represents a significant contribution to the field of sustainable urea production.\nThe authors model an electrochemical urea synthesis process using Se–InOx catalysts and demonstrate economic feasibility under future low-cost electricity scenarios. Notably, the study estimates a urea production cost of $1.01/kg at $0.03/kWh electricity, which is in line with current market conditions, and a minimum cost of $0.16/kg when powered by electricity priced at $0.01/kWh and with valorization of by-products. These electricity prices are optimistic but realistic in a long-term renewable energy future.\nThe economic analysis is detailed and transparent, incorporating well-reasoned capital and operational cost assumptions grounded in U.S. DOE H2A data and established chemical engineering practice. The financial analysis includes payback periods and net present value projections, showing that profitability is achievable at current densities above 50 mA/cm², with a payback period as short as six years at 100 mA/cm². The univariate sensitivity analysis is also useful, identifying cell voltage, electricity price, Faradaic efficiency, and equipment and labor costs as primary cost drivers.\nHowever, the sensitivity plot in Figure 6 would benefit from formatting improvements—specifically, the inclusion of baseline parameter values alongside y-axis labels and the addition of units ($/kg Urea) to the output axis. The TEA methodology itself is sound, with appropriate treatment of depreciation, electricity and labor costs, and process-scale assumptions.\nWhile the economic assessment is compelling, the environmental claims would be substantially strengthened by the inclusion of a life cycle assessment (LCA), particularly to quantify net-negative carbon emissions and to benchmark against existing urea production pathways. Overall, the TEA is a strong and reproducible component of the work and supports the manuscript’s conclusions regarding the feasibility and scalability of electrochemical urea synthesis."}, "author_response": "Point-to-point responses to the comments of reviewers:\nWe would like to express our sincere appreciation of reviewers’ constructive comments concerning our manuscript. These comments are valuable and helpful for improving the quality of our manuscript. The reviewer comments are laid out below in italicized font and specific concerns have been numbered. Our response is given in normal font with blue text. The modifications provided in the revised Manuscript are shown with yellow highlight.\nReviewer #1 (Remarks to the author):\n[... Author response text for Round 1 ...]"}, {"round": 2, "reviewer_comments": {"reviewer_1": "The authors have adequately addressed the majority of the issues, and the revisions have significantly improved the clarity and scientific rigor of the manuscript. I would recommend the publication of this manuscript in Nature Communications.", "reviewer_2": "Can be publised as it is.", "reviewer_3": "The revised version improved well and it may be considered for publication.", "reviewer_4": "The manuscript has improved substantially. The TEA revisions are sound and the LCA is now generally consistent. However, one key issue remains regarding the fate of the CO2 used in the urea synthesis step. The LCA currently treats this CO2 as if it is permanently sequestered, but that is only valid if the carbon remains stored over a long timeframe. In conventional fertilizer use, urea hydrolyzes in the field and the CO2 is re-released to the atmosphere. Therefore, if the primary product is fertilizer urea, the CO2 must be counted as an emission at end use. This point is critical not only for accurate LCA accounting, but also for any claims related to carbon crediting: carbon markets require demonstration that captured CO2 is not subsequently re-emitted. If the CO2 is later released, the system cannot be credited as a net carbon removal pathway, and the LCA should reflect this by including the CO2 release during the product use phase.\nIf instead a portion of the urea carbon is embodied in non-fertilizer products (e.g., resins), the manuscript should report: (1) what fraction of production goes to such products, (2) the expected carbon storage lifetime, and (3) end-of-life fate. This would allow distinguishing between temporary storage and permanent sequestration. A simple carbon fate mass balance diagram (CO2 input → product → use → end-of-life) would clarify the assumptions. Without explicitly accounting for the ultimate CO2 release, the current LCA may overstate the system’s net climate benefit. If the authors choose to conduct a gate-to-grave analysis that includes CO2 credits, they should also consider N2O emissions.\nIn summary, the authors could maintain the LCA as a gate-to-gate analysis if they remove the CO2 credit claim and clarify the limitations of this approach. However, a gate-to-grave analysis will be closer to industry standards and require careful consideration of the product use."}, "author_response": "Point-to-point responses to the comments of reviewers:\nWe are grateful for the time and effort each reviewer has dedicated to evaluating our work. Your feedback has been invaluable in improving the clarity, scientific rigor, and overall quality of the manuscript. We are also encouraged by the reviewers' overall positive assessments and recommendations for publication. The reviewer comments are laid out below in italicized font and specific concerns have been numbered. Our response is given in normal font with blue text. The modifications provided in the revised Manuscript are shown with yellow highlight.\nReviewer #1 (Remarks to the author):\n[... Author response text for Round 2 ...]"}, {"round": 3, "reviewer_comments": {"reviewer_4": "The authors have addressed the review comments."}, "author_response": ""}]

Decision letter