Heterointerface-engineered ZnO/CuO bimetallic sites enable pollutant-directed conversion with in situ catalyst regeneration

Domain: chemistry
Published: 2026-04-09
Editorial outcome: major_revision

Abstract
Polymerization-based wastewater treatment offers reduced oxidant demand and product recovery, yet practical application is hindered by catalyst fouling and unselective reactions due to single-site competition. Here, we report a readily synthesized and scalable ZnO/CuO catalyst featuring dual functional sites that decouple pollutant and oxidant activation. Zn sites preferentially adsorb/activate organics, whereas Cu sites predominantly activate the oxidant. This site differentiation programs two pathway regimes governed by pollutant electronic structure: electron-transfer-mediated polymerization for electron-rich substrates and radical-induced mineralization for electron-deficient substrates. Importantly, radicals generated during mineralization depolymerize the accumulated foulant layer in situ, effecting autonomous catalyst regeneration with a 2.5-fold performance recovery and reduced external regeneration demand. Process performance is validated in a 200 L self-circulating reactor, maintaining 98% removal efficiency for both pollutant classes over ten cycles. Toxicological profiling across multiple biological models, supported by metabolomics, confirmed effective detoxification of multi-pollutant wastewater, including restoration of normal metabolic function in zebrafish (e.g., lipid and glutathione metabolism). This study establishes a dual-site cooperative catalysis framework that leverages intrinsic wastewater chemistry for self-regeneration, showcasing a complete trajectory from atomic-scale design to reactor-scale implementation.

Introduction
Polymerization-based advanced oxidation processes (P-AOPs) offer a low-carbon route for concurrent pollutant abatement and resource recovery, owing to high reaction selectivity, reduced oxidant demand, and the prospect of value-added product reclamation 1, 2. However, translation to real wastewater remains constrained by several factors. First, large disparities in molecular size, charge, and hydrophobicity between pollutants and oxidants hinder their synergistic activation at a single catalytic site, limiting both efficiency and pathway control 3, 4. Second, electron-rich pollutants preferentially undergo polymerization, and the resulting polymeric deposits accumulate on the catalyst surfaces, blocking active sites and inducing deactivation 5, 6. High-temperature calcination affords only partial regeneration at substantial energy cost. Third, polymerization is intrinsically selective for electron-rich pollutants and exhibits poor removal of electron-deficient compounds prevalent in complex effluents 7. Thus, P-AOPs face three persistent challenges in wastewater treatment: inefficient dual-substrate activation, fouling-induced catalyst deactivation, and narrow pollutant applicability.

Traditional mineralization-base heterogeneous AOPs (M-AOPs) address the selectivity gap by employing catalyst-activated oxidants to generate highly reactive species, notably hydroxyl radicals (OH) and sulfate radicals (SO -), enabling non-selective degradation and mineralization of diverse organics 8. Yet, radical-dominated pathways are vulnerable to quenching by inorganic ions and dissolved organic matter 9. Moreover, these systems typically require high oxidant dosages and convert pollutants predominantly to CO , outcomes that run counter to carbon-neutrality objectives and preclude resource recovery. These complementary strengths and weaknesses motivate an integrated strategy that couples polymerization with mineralization, harnessing the advantages of each while mitigating their respective limitations.

Catalyst design is central to realizing such integration. Prevailing approaches emphasize single-substrate (oxidant) activation using single-site architectures, often neglecting pollutant activation and the construction of dedicated sites10, 11, 12. Inevitably, pollutants and oxidants competitively adsorb at the same sites, depressing turnover and confounding pathway selectivity (Fig. 1). Emerging evidence suggests that reaction routing is governed by a cooperative catalyst–pollutant system, not the catalyst alone 13, 14. Consequently, bifunctional, dual-site catalysts (one site tailored to pollutants and the other to oxidants) could spatially decouple activation events, enabling programmable switching between polymerization and mineralization according to pollutant electronic structure.

For practical deployment in wastewater treatment, dual-site catalysts should feature simple synthesis, scalable manufacture, operational stability, and ecological safety. Zinc oxide (ZnO) is attractive on these grounds 15; the relatively low electronegativity of Zn facilitates electronic interaction with organics, favoring adsorption/activation of pollutants. In contrast, copper sites in copper oxide (CuO) possess higher electronegativity and strong oxygen affinity, promoting selective adsorption and activation of oxidants 16, 17. Rational integration of ZnO and CuO thus provides complementary active sites for spatially separated activation of pollutants (Zn) and oxidants (Cu). Moreover, the Fermi-level mismatch across the ZnO/CuO heterointerface establishes a built-in electric field (BIEF) that drives directional electron transfer and modulates interfacial charge dynamics 18. Such an architecture furnishes a mechanistic basis to implement pollutant-directed polymerization and controlled radical mineralization within one catalyst, creating a pathway to address dual-substrate activation, fouling resistance via in situ depolymerization, and broad pollutant coverage.

Guided by the above analysis, ZnO and CuO were selected as the basis for a dual-site catalyst, and a facile hydrothermal–calcination route was developed to obtain bifunctional ZnO/CuO. In this unique design, Zn sites preferentially adsorbed and activated pollutants, whereas Cu sites selectively activated the oxidant. This site differentiation enabled dynamic pathway selection according to pollutant electronic structure: electron-rich substrates underwent electron-transfer-mediated polymerization, while electron-deficient substrates followed radical-induced mineralization. A key feature of the system was autonomous regeneration: radicals formed during mineralization depolymerized the accumulated foulant layer in situ, and the regenerated catalyst exhibited a 2.5-fold performance enhancement. Thus, the dual-site design simultaneously mitigated deactivation and provided continuous self-renewal under operating conditions. Theoretical calculations elucidated the site-specific adsorption energetics and clarified how pollutant electronics bias pathway selection, rationalizing the observed switching behavior. To assess practicality, a 200 L self-circulating reactor was constructed, demonstrating stable operation and effective treatment at scale. Comprehensive toxicological assessment using multiple biological models and metabolomics confirmed effective water purification and detoxification. Overall, this study defines a dual-site catalytic platform that couples pollutant-directed selectivity with in situ catalyst regeneration, offering actionable design principles for practical wastewater remediation.

Results
Rational Synthesis and Structural Characterization of the Bimetallic-Site Catalysts

A facile hydrothermal-calcination route yielded a bifunctional ZnO/CuO catalyst with gram-scale productivity (Fig. 2a) 19. X-ray diffraction (XRD) confirmed phase-pure ZnO and CuO, with reflections indexed to ZnO (PDF #36-1451) and CuO (PDF #45-0937), evidencing successful composite formation (Fig. 2b) 20, 21. Fourier-transform infrared (FTIR) spectroscopy probed interfacial bonding (Fig. 2c): bands at 465 cm-1 (Zn-O) and 536 cm-1 (Cu-O) shifted to 500 cm-1 upon hybridization, indicating the formation of Zn-O/Cu-O structures and the integration of the two oxides 22, 23. Transmission electron microscopy (TEM) showed spherical ZnO particles intimately interfaced with dense CuO nanoclusters (Fig. 2d, Supplementary Figs. 2-4). High-resolution TEM identified lattice spacings of 0.245 nm and 0.253 nm, corresponding to the (101) plane of ZnO and the (002) plane of CuO, respectively (Figs. 2e-f, Supplementary Figs. 5-6) 24, 25. These observations established an intimately coupled ZnO/CuO heterointerface with potential for synergistic catalysis.

To resolve oxidation states and coordination environments, we combined X-ray photoelectron spectroscopy (XPS) with X-ray absorption fine structure (XAFS) analyses (Supplementary Figs. 7-16). High-resolution XPS spectra showed Zn 2p core-level peaks at 1022.0 eV (2p ) and 1045.1 eV (2p ), consistent with Zn2+ (Fig. 2g) 26. Similarly, the Cu 2p region exhibited characteristic peaks at 933.7 eV (2p ) and 953.6 eV (2p ), confirming the presence of Cu2+ (Fig. 2h) 27. Importantly, positive shifts of Zn 2p and negative shifts of Cu 2p relative to the pristine oxides indicate electron transfer from ZnO to CuO, evidencing strong electronic coupling at the heterointerface 28. These charge-transfer signatures motivated a deeper analysis of local structure by X-ray Absorption Fine Structure (XAFS).

The valence states and local coordination of Zn and Cu atoms were further probed by X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS). The Zn K-edge XANES spectrum (Fig. 2i) of the ZnO/CuO composite closely matched the reference ZnO, indicating that Zn primarily existed in the +2 oxidation state 29. Similarly, the Cu K-edge spectrum exhibited an absorption profile nearly identical to that of CuO, confirming Cu2+ as the dominant state (Fig. 2j) 17. These findings were consistent with the XPS results. Fourier-transform EXAFS (FT-EXAFS, phase-uncorrected R-space) (Fig. 2k) for Zn showed two prominent peaks at ~1.46 Å and ~2.98 Å, attributable to Zn-O and Zn-Zn scattering paths of ZnO within the composite 30. Notably, both peaks exhibited slight shifts compared to pure ZnO, indicating a perturbed Zn coordination sphere due to CuO incorporation and supporting the presence of a strongly coupled ZnO/CuO heterointerface 31. Similarly, the Cu K-edge FT-EXAFS spectrum (Fig. 2l) displayed peaks at ~1.47 Å and ~2.49 Å, attributed to Cu-O and Cu-Cu paths of CuO in the composite 32. Their observable shifts compared with pure CuO further corroborate substantial interfacial interactions in the ZnO/CuO composite 33. Critically, no Zn-Zn (Zn foil) and Cu-Cu (Cu foil) contributions are detected, excluding metallic clustering and implying high dispersion of both cations within the heterostructure 34, 35. Wavelet transform (WT)-EXAFS (Figs. 2m-n) further resolved overlapping backscattering contributions and clearly discriminates Zn-O, Cu-O, Zn-Zn, and Cu-Cu signals. In sum, these results provided direct evidence of strong interfacial interactions at the ZnO/CuO heterointerface and confirmed enhanced electronic coupling between the two oxide phases.

Catalytic Activity and Matrix Robustness of the Fenton-Like Reaction System

To assess the efficacy of the dual-site ZnO/CuO catalyst for oxidant activation toward pollutants of contrasting electronic character, we employed bisphenol A (BPA; electron-rich) and atrazine (ATZ; electron-deficient) as model substrates, using peroxymonosulfate (PMS) as the oxidant. Optimal concentrations of ZnO/CuO, PMS, BPA, and ATZ were established a priori (Supplementary Figs. 17-22). Unless otherwise specified, all experiments were conducted under consistent conditions. Control tests showed negligible adsorption of BPA or ATZ on ZnO, CuO, or ZnO/CuO (Fig. 3a, Supplementary Fig. 23). Neither PMS alone nor homogeneous Cu2+-activated PMS effected appreciable removal (Supplementary Figs. 23-25). By contrast, the ZnO/CuO catalyst exhibited efficient PMS activation, achieving complete removal of BPA and ATZ within 5 min (Fig. 3a-d). Pseudo-first-order rate constants in the ZnO/CuO/PMS system were 13.0 and 5.8 times higher than those in the physically mixed ZnO+CuO/PMS control. (Fig. 3b, e, Supplementary Figs. 26-27), evidencing a synergistic heterostructure effect beyond simple mixture.

To compare oxidant utilization across substrate regimes, PMS consumption was quantified. Within 5 min, 74% of PMS was consumed for BPA versus 55% for ATZ (Supplementary Fig. 28), suggesting distinct activation pathways and degradation kinetics. Consistent with this trend, total organic carbon (TOC) analysis showed rapid BPA mineralization (87.7% at 6 min), far exceeding that of ATZ (35.4%) (Supplementary Fig. 29). Matrix-tolerance tests further differentiated the systems. The BPA regime maintained stable performance in the presence of common inorganic ions and across varied water matrices (Supplementary Figs. 30-32). The ATZ regime also showed robust anti-interference behavior, but high chloride ion (Cl-) partially inhibited removal, consistent with radical quenching in a radical-dominated pathway (Supplementary Figs. 33-35). Both systems showed high tolerance to dissolved organic matter (DOM), with minimal loss in the presence of humic acid or bovine hemoglobin, indicating suitability for complex waters (Fig. 3f, Supplementary Figs. 36-39). The ZnO/CuO/PMS system remained effective over pH 3.0-9.0 (Fig. 3g, Supplementary Figs. 40-41) and displayed a broad substrate scope, achieving near-complete removal within 5 min for phenol (PhOH), 4-chlorophenol (4-CP), ortho-chlorophenol (OCP), 2,4-dimethylphenol (2,4-DMP), sulfamethoxazole (SMX), sulfadiazine (SDZ), and sulfapyridine (SPY) (Fig. 3h). These results demonstrated the efficient water purification and strong practical potential of the ZnO/CuO/PMS system.

Despite comparable single-cycle performance, cycling tests revealed divergent stability (Supplementary Fig. 42). The BPA removal progressively declined with repeated runs, whereas ATZ removal remained stable. We attributed this contrast to pathway-dependent surface evolution: electron-rich BPA underwent electron-transfer-mediated polymerization, leading to polymeric deposit accumulation and active-site blockage (Figs. 3i-j). Electron-deficient ATZ followed a radical-dominated mineralization route that did not generate polymeric foulants, preserving activity. Based on these observations, we hypothesized that, in mixed-pollutant matrices, in situ-generated strong oxidizing radicals could depolymerize the accumulated foulant layer, enabling catalyst self-regeneration. The following experiments were designed to test this hypothesis.

Multi-Probe Recognition of Reactive Species and Catalytic Pathways

To resolve the dominant oxidizing pathways in the ZnO/CuO/PMS/BPA and ZnO/CuO/PMS/ATZ, we implemented a comprehensive quenching protocol. The scavengers used were: tert‑butanol (TBA) for hydroxyl radicals (OH), methanol (MeOH) for sulfate radicals (SO -), TEMPOL and p‑benzoquinone (p‑BQ) for superoxide radicals (O -), L‑histidine and β-carotene for singlet oxygen (1O ), dimethyl sulfoxide (DMSO) and methyl phenyl sulfoxide (PMSO) for high-valent metal species, and potassium dichromate (K Cr O ) for electrons. In the BPA system, various quenchers produced minor or negligible inhibition of pollutant decay (Fig. 4a). Even when radical scavenger concentrations were increased from 20 mM to 200 mM, both removal efficiency and apparent rate constant remained essentially unchanged (Fig. 4b, Supplementary Figs. 44-45), suggesting that neither radical species (e.g., OH, SO -, O -) nor non-radical species (e.g., 1O or high-valent copper) governed the reaction. By contrast, adding an electron scavenger led to a substantial suppression of BPA degradation (Supplementary Fig. 46), implicating a catalyst-mediated electron-transfer pathway (ETP) as the primary mechanism. In the ATZ system, MeOH markedly inhibited degradation: increasing MeOH from 0 to 100 mM reduced the removal from 99.2% to 27.3% and the rate constant from 0.92 to 0.07 min-1, indicating that SO - served as the primary role species (Fig. 4c, Supplementary Figs. 47-48). Probe experiments corroborated this finding (Supplementary Fig. 49), while quenching results showed limited contributions from 1O and high-valent metal species (Supplementary Fig. 50). Given the electron-deficient nature of ATZ, non-radical electrophilic routes are disfavored. The quenching data initially indicated ETP-dominant BPA oxidation and radical-dominated ATZ degradation. Electron spin resonance provided direct spectroscopic support. In the ZnO/CuO/PMS/BPA system, no detectable signals for OH, SO -, or 1O were detected, consistent with a non-radical, electron-transfer-driven process. (Fig. 4d). In contrast, the ZnO/CuO/PMS/ATZ system exhibited a strong SO - signal, confirming that SO - were the predominant active species (Fig. 4e).

To further elucidate the intrinsic catalytic activity and electron transfer pathways of ZnO/CuO, a series of electrochemical experiments was conducted. Open-circuit potential measurements showed an immediate increase upon PMS dosing at the ZnO/CuO electrode (Fig. 4f), indicating an activated surface complex (ZnO/CuO-PMS*) with enhanced oxidizing capacity 36. Subsequent addition of BPA induced a sharp potential drop, consistent with electron donation from BPA to ZnO/CuO-PMS* complex and thus catalyst-mediated ETP 37. Chronoamperometry (i-t, Fig. 4f) 38 further substantiated this assignment: sequential additions of PMS and then BPA produced stepwise current increases, evidencing electron flow from BPA (donor) to PMS (acceptor) facilitated by ZnO/CuO 39. Salt-bridge experiments yielded distinct current responses upon separate addition of PMS and BPA (Supplementary Fig. 51), reinforcing the through-catalyst electron-shuttle scenario. In contrast, ATZ additions caused negligible changes in OCP and current, excluding a significant ETP contribution and aligning with a radical-mediated mechanism. Electrochemical impedance spectroscopy (EIS) showed lower charge-transfer resistance for ZnO/CuO than for ZnO, CuO, or the physical mixture ZnO+CuO (Fig. 4g, Supplementary Fig. 53), confirming that heterojunction formation enhanced interfacial electron transport 40. Resistance decreased sharply upon PMS addition, consistent with ZnO/CuO-PMS* complex formation, and decreased further after BPA dosing, supporting accelerated electron transfer in the BPA regime (Supplementary Figs. 54-55) 41. No appreciable change was observed upon ATZ addition (Supplementary Fig. 56), again consistent with a radical-dominated ATZ pathway. Linear sweep voltammetry (LSV) corroborated these trends: ZnO/CuO showed substantially higher current density than ZnO, CuO, or their physical mixture (Fig. 4h), increased immediately after PMS dosing (active complex formation), and rose further upon BPA addition (pollutant-promoted electron transfer) 10 42. In the ATZ system, LSV showed no appreciable current increase after ATZ addition, in agreement with radical-driven oxidation without enhanced electron shuttling.

Dual-Function Catalysis at Zn-Cu Biphasic Sites via Interfacial Electron Coupling

To clarify how dual-site synergy governs the distinct degradation regimes, we deconvoluted the roles of Zn and Cu. In situ Raman of ZnO/CuO system upon PMS dosing displayed a distinct peak at 834 cm-1, attributed to the PMS* surface complex (Fig. 5a) 43. Control tests with ZnO and CuO showed that this PMS* feature appeared only on CuO (Figs. 5b-c), indicating that Cu sites preferentially adsorbed/activated PMS. PMS utilization corroborated this assignment: ZnO consumed 1.0% PMS, versus 39.7% for CuO and 73.6% for ZnO/CuO (Supplementary Fig. 57). Moreover, Cu-site masking nearly abolished degradation (Supplementary Fig. 58). Although ZnO alone scarcely activated PMS, its integration with CuO substantially boosted PMS utilization, consistent with a BIEF within the heterojunction that accelerated interfacial electron transfer and, in turn, PMS activation. After establishing the Cu role, we examined Zn. XPS after reaction revealed pronounced carbon accumulation on ZnO, whereas CuO showed negligible changes (Supplementary Fig. 59), indicating that Zn sites preferentially interacted with organics, while Cu sites activated PMS, constituting a dual-functional division of labor.

Density Functional Theory (DFT) further supported this interpretation (Atomic coordinates for the structural model are available in Supplementary Data 1). Calculations showed more exergonic PMS adsorption on Cu site than on Zn site (-1.92 eV vs.-0.91 eV) (Fig. 5d). Elongation of the O-O bond in PMS was also more pronounced on Cu sites (1.477 Å vs. 1.469 Å), consistent with stronger PMS activation at Cu, in agreement with in situ Raman, PMS utilization, and masking results. For pollutants, Zn sites in ZnO/CuO display enhanced adsorption of BPA and ATZ, with adsorption energies strengthened by 1.55 eV and 0.84 eV, respectively, relative to pristine ZnO (Fig. 5e), while Cu sites show weaker adsorption (Fig. 5f). Thus, Zn preferentially adsorbed/engaged pollutants, consistent with XPS. Furthermore, d-band center analysis further differentiated functions: the Zn site exhibited a downshift in the heterostructure relative to pristine ZnO (-4.70 eV vs. -5.13 eV), suggesting reduced PMS affinity (Fig. 5g). Whereas the d-band center of the Cu site remained essentially unchanged (-2.01 eV vs. -2.04 eV), supporting its primary role in PMS activation. The experimental-computational evidence established a well-defined division of functions: Zn sites adsorbed/activated organic substrates, and Cu sites activated PMS, with synergy mediated by interfacial electron coupling.

To elucidate the interfacial electron coupling mechanism between ZnO and CuO, work function analysis was performed. ZnO exhibited a lower work function (Φ = 5.70 eV) compared to CuO (Φ = 8.51 eV), indicating a greater tendency to act as an electron donor (Fig. 5h). Upon contact, electrons flowed from ZnO to CuO until Fermi-level equilibration, establishing a BIEF (ZnO→CuO). Bader charge analysis quantified this interfacial charge redistribution, revealing an electron transfer of 1.15 e- from ZnO to CuO (Fig. 5i). This field and charge redistribution, together with pollutant electronics, dictate pathway selection. For electron-rich substrates, pollutants acted as auxiliary electron donors, augmenting ZnO→CuO electron flux under the BIEF. The resulting electron-rich interface promoted PMS reduction to SO 2- and sustained electron-transfer pathways (ETP). For electron-deficient substrates, electron donation was disfavored; limited electron availability biases PMS toward O–O cleavage and formation of SO •-/ •OH, i.e., a radical-dominated route. This framework rationalized the ETP-dominant behavior of BPA versus the radical-dominant behavior of ATZ.

DFT with molecular orbital (MO) analysis of the ZnO/CuO–PMS complex and a set of ten representative pollutants (Fig. 5j) elucidated the electronic prerequisite for ETP 13. In the ZnO/CuO/PMS system, ETP required electron donation from the highest occupied molecular orbital (HOMO) of pollutants to the lowest unoccupied molecular orbital (LUMO) of the ZnO/CuO-PMS complex 37. Therefore, a smaller energy gap between the complex's LUMO and the pollutant's HOMO was thermodynamically favored by ETP. High-lying HOMO substrates (e.g., BPA and SMX) exhibited small ΔE and thus preferentially underwent ETP rather than radical oxidation. In contrast, electron-deficient pollutants (e.g., ATZ, BA) possessed lower HOMO energies, yielding larger ΔE and higher barriers for electron transfer; radical oxidation therefore prevailed. These results explained the divergent mechanisms in BPA vs ATZ systems and demonstrated that Fenton-like efficiency and pathway in ZnO/CuO/PMS were co-governed by catalyst electronic structure and pollutant frontier orbitals, validating the “zone-specific activation and cooperative reaction” design.

In Situ Depolymerization Enables Self-regenerating Catalysts with Practical Performance

To verify that radical-driven mineralization can remove polymeric foulants in situ, we examined mixed-substrate systems. When BPA and ATZ coexisted, polymerization preferentially consumed BPA prior to mineralization (Fig. 6a), consistent with literature indicating a lower activation barrier and thermodynamic favorability for polymerization over mineralization 44. This sequence established conditions under which radicals produced during mineralization could subsequently depolymerize the accumulated polymers. Thermogravimetric analysis (TGA) showed a larger weight loss for the catalyst after the BPA-only reaction than for the pristine material (Fig. 6b), evidencing polymer deposition. Following ATZ/PMS treatment, the weight-loss fraction decreased, indicating removal of surface-bound polymers (Fig. 6b). Elemental analysis corroborated this trend: C and O contents increased after BPA exposure and declined after ATZ/PMS treatment (Fig. 6c). Functionally, a catalyst subjected to ten cycles with high BPA concentration exhibited attenuated PMS activation and stagnant BPA removal, consistent with active-site blockage. By contrast, a catalyst subsequently treated with ATZ/PMS displayed a 2.5-fold performance recovery (Fig. 6d). TEM further confirmed substantial reduction or removal of surface polymers after mineralization treatment (Fig. 6f) 45. Together, these results demonstrate effective in situ depolymerization of polymeric foulants and catalyst regeneration via the mineralization pathway. In BPA-only cycling, removal efficiency declined over successive runs, whereas introducing ATZ maintained stable, high BPA removal (Fig. 6e). These observations indicate that radicals generated during ATZ activation mediate in situ decomposition of BPA-derived polymers, thereby sustaining long-term activity and stability of the catalytic system.

To evaluate the practical potential of this synergistic system, a pilot-scale study was conducted using a 200 L self-circulating reactor operating without external mixing (Fig. 6g). The reactor exploited hydraulic head differences and an internal slope to achieve spontaneous circulation (Fig. 6h, Supplementary Fig. 78). The catalyst was immobilized on polyurethane sponges (32 units in series) suspended in the wastewater, which enhanced contact among catalyst, oxidant, and pollutants, facilitated recovery/reuse, and minimized secondary contamination 46. In mixed-wastewater operation, the system sustained 98% (BPA) and 96% (ATZ) removal over ten consecutive cycles (Fig. 6i), demonstrating operational robustness at pilot scale.

To quantify environmental performance, we conducted a life cycle assessment (LCA) of the ZnO/CuO/PMS process against ZnO/PMS and CuO/PMS comparators (Supplementary Figs. 79-82), covering catalyst synthesis through pollutant degradation and evaluating 18 impact categories. The dual-site ZnO/CuO/PMS system exhibited lower impact scores across all categories relative to single-component benchmarks, indicating superior environmental compatibility (Supplementary Fig. 83) 47. Notably, the 200 L pilot displayed ~10 orders of magnitude lower aggregate impact scores than laboratory-scale setups (Supplementary Fig. 84), reflecting substantial gains in eco-efficiency. Overall, the ZnO/CuO/PMS platform, coupled with cost-effectiveness, environmental compatibility, and operational sustainability, supporting its scalability as a practical water purification technology.

Matrix-Robust Detoxification and Safety Profiling of Catalytic Processes

The ecological safety and practical relevance of the ZnO/CuO/PMS system were assessed across microbial, plant, and animal models to capture toxicity outcomes for both the polymerization and mineralization pathways. Two representative bacterial strains, Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), were selected as microbial toxicity models (Supplementary Fig. 85). Colony-forming assays showed that solutions containing untreated BPA or ATZ strongly inhibited growth of both strains, evidencing high baseline toxicity. In contrast, post-treatment solutions from the ZnO/CuO/PMS process restored bacterial growth to control levels, indicating effective detoxification under both pathways.

For plant-based toxicity assessment, Chlorella vulgaris and wheat seedlings served as model systems. Wheat exposed to treated solutions exhibited stem lengths comparable to controls (Supplementary Figs. 86-87), whereas untreated pollutant solutions significantly suppressed growth. Consistently, Chlorella cultures in treated solutions showed higher optical density (OD) and chlorophyll a content than in untreated matrices (Supplementary Fig. 88), confirming substantial reduction of phytotoxicity by either pathway.

Multi-parameter assays in zebrafish were further conducted to evaluate organism-level safety 48, 49. Zebrafish exposed to treated solutions showed no morphological abnormalities, cardiac dysfunction, or mortality during 96 h, matching control outcomes (Figs. 7a-b). This contrasted sharply with the developmental deformities, cardiac abnormalities, and mortality in the untreated groups. Body length in treated cohorts did not differ significantly from controls, indicating normal growth (Figs. 7c-f). Fluorescent imaging of intracellular reactive oxygen species (ROS) revealed weak signals in control and treated groups, whereas intense fluorescence in untreated BPA exposure indicated substantial ROS accumulation and oxidative stress (Figs. 7g-i) 50, 51.

To probe systemic effects of BPA and the extent of detoxification, untargeted metabolomics was performed in zebrafish 52, 53. Relative to controls, BPA exposure yielded 720 significantly altered metabolites (345 up-regulated, 325 down-regulated; Fig. 7j), predominantly in lipids and lipid-like molecules, organheterocycles, and nucleotides (Fig. 7k). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated perturbations in lipid metabolism, pyrimidine metabolism, purine metabolism, glutathione metabolism, alanine metabolism, and ABC transporters (Fig. 7l). These pathway disruptions align with oxidative stress, developmental dysregulation, and energy imbalance; notably, dysregulated nucleotide and lipid metabolism can directly impair embryonic development 54, 55, 56. Furthermore, disturbed glutathione metabolism weakened antioxidant defenses, thus promoting ROS accumulation and oxidative stress-induced damage in zebrafish 57, 58. These molecular signatures were concordant with the observed developmental defects and ROS stress in untreated BPA groups and demonstrated that the ZnO/CuO/PMS treatment restored metabolic homeostasis and suppressed oxidative injury.

Across bacteria, algae, plants, and zebrafish, the ZnO/CuO/PMS system mitigated toxicity to near-control levels and reversed pollutant-induced metabolic disturbances, particularly in pathways integral to development and antioxidant defense. These findings established the platform’s dual function, an efficient water purification technology coupled with robust protection of aquatic health, and supported its suitability for safe and practical deployment.

Methods
Chemicals and reagents. Detailed information is provided in the Supplementary Information.

Characterizations. The crystalline structures of the synthesized materials were characterized by X-ray diffraction (XRD; Rigaku Ultima IV, Japan) using Cu Kα radiation over a 2θ range of 10°-80°. Transmission electron microscopy was performed using a JEOL JEM-F200 instrument operated at an accelerating voltage of 200 kV and equipped with a JEOL EX-37270VUP energy-dispersive X-ray spectrometer for elemental analysis. Chemical states were analyzed using X-ray photoelectron spectroscopy (XPS; ESCALAB Xi+, Thermo Fisher Scientific, USA) with a monochromatic Al Kα source (12.5 kV). Fourier-transform infrared (FT-IR) spectra were acquired on a Thermo Scientific iN10 spectrometer with KBr as background reference. Electron spin resonance (ESR) measurements were conducted on a Bruker ER200-SRC spectrometer using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and 2,2,6,6-tetramethyl-4-piperidone (TEMP) as spin-trapping agents. Electrochemical properties were evaluated with a CHI660E electrochemical workstation (Chenhua, China) configured with a standard three-electrode system comprising a catalyst-modified glassy carbon working electrode, platinum wire counter electrode, and Ag/AgCl (saturated KCl) reference electrode. Total organic carbon (TOC) content was quantified using a CD800s analyzer (Hangzhou Qikun Technology Co., China). XANES spectra at the Zn and Cu K-edges were collected in transmission mode on a laboratory-scale XAFS instrument (easyXAFS300, easyXAFS LLC). The spectrometer used Rowland circle geometry with spherically bent crystal analyzers and an Ag X-ray tube source, and detection was performed with a silicon drift detector (AXAS-M1, KETEK GmbH).

Catalytic performance evaluation. Degradation experiments were performed in 50 mL aqueous suspensions containing the synthesized catalyst (0.1 g L-1) and either PMS 0.3 mM + BPA 10 mg L-1 or PMS 0.5 mM + ATZ 10 mg L-1. Prior to oxidant dosing, the catalyst was pre-equilibrated with the respective pollutant by stirring for 5 min to establish adsorption–desorption equilibrium. After PMS addition, 1 mL aliquots were withdrawn at 1-min intervals and immediately quenched with 0.1 mL of 100 mM sodium thiosulfate to terminate the reaction. Samples were then centrifuged at 18630 g for 20 min to remove suspended particles, and the resulting supernatants were analyzed for BPA or ATZ by high-performance liquid chromatography (HPLC; Agilent 1260 Infinity, Agilent Inc., USA).

Density functional theory (DFT) calculations. All DFT calculations were performed within the generalized gradient approximation (GGA) using the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional. The Brillouin zone was sampled with a 1*1*1 k-points mesh for geometry optimization. A plane-wave basis set with a kinetic energy cutoff of 400 eV was employed to describe valence electrons, and a Gaussian smearing width of 0.05 eV was applied for partial orbital occupation. Electronic and geometric convergence criteria were set to 10−5 eV and 0.02 eV Å−1, respectively. A vacuum layer of 20 Å was introduced along the non-periodic direction to suppress spurious interactions between periodic images. Van der Waals interactions were accounted for using the Grimme DFT+D3 empirical correction scheme.

Catalyst preparation. (a) Preparation of ZnO/CuO: First, 2 mmol Zn(NO ) •5H O, 2 mmol Cu(NO ) •3H O, and 4 mmol citric acid were dissolved in 45 mL of ethanol and stirred for 30 min. Subsequently, the solution underwent solvothermal reaction at 120 °C for 20 h. After washing with ethanol and drying, the intermediate product was calcined at 350°C for 2 h with a heating rate of 2°C min-1, yielding the final ZnO/CuO material.

(b) Preparation of ZnO: ZnO was synthesized using a procedure identical to that of ZnO/CuO, except for the omission of Cu(NO ) •3H O.

(c) Preparation of CuO: CuO was synthesized using a procedure identical to that of ZnO/CuO, except for the omission of Zn(NO ) •5H O.

Determination of pollutant concentrations and their degradation intermediates. The concentration of target pollutants was determined using a high-performance liquid chromatograph (1260 Infinity, Agilent Technologies, USA) equipped with a ZORBAX SBC-18 column (5 μm, 4.6 × 250 mm), maintained at a column temperature of 35 ± 1°C, and fitted with a UV detector. For BPA detection, the mobile phase consisted of acetonitrile and 0.2% acetic acid aqueous solution (60:40 v/v), with a flow rate of 1.0 mL min-1 and an injection volume of 20 μL. The detection wavelength was set at 273 nm, and the analysis time was 6 min. For SMX detection, the mobile phase consisted of acetonitrile and 0.1% formic acid aqueous solution (40:60 v/v), with a flow rate of 1.0 mL min⁻¹ and an injection volume of 20 μL. The detection wavelength was set at 269 nm, and the analysis time was 6 min. For ATZ detection, the mobile phase consisted of acetonitrile and 0.2% acetic acid aqueous solution (60: 40 v/v), with a flow rate of 1.0 mL min-1, injection volume of 20 μL. The detection wavelength was set to 272 nm, and the analysis time was 6 min. Testing conditions for other pollutants are detailed in Supplementary Table 17.

BPA degradation products were characterized by liquid chromatography-mass spectrometry (LC-MS) using an Agilent 6460 HPLC system coupled to an API 3000 mass analyzer, with separation performed on a Kromasil C18 column (4.6 × 250 mm). All other analytical conditions matched those employed for BPA concentration quantification.

Pilot-scale experiments for treating 200 L of BPA wastewater and mixed wastewater. Thirty-two polyurethane sponge blocks (5 cm × 5 cm × 5 cm) were employed as catalyst supports due to their porous structure and ease of recovery. To prepare the catalyst-loaded sponges, 10 g of catalyst was dispersed in a mixture of 100 mL of ethanol and 2 mL of Nafion, followed by ultrasonication to achieve homogeneous catalyst distribution. The resulting suspension was uniformly coated onto the 32 sponge units, establishing the foundation for subsequent wastewater treatment experiments. For BPA wastewater degradation experiments, the initial BPA concentration was set at 2.5 mg L-1 with 0.1 mM PMS. Each treatment cycle lasted 2 hours. Upon cycle completion, the BPA concentration was restored to 2.5 mg L-1, and additional PMS was introduced, with ten consecutive cycles performed to evaluate catalyst efficiency and durability. In mixed wastewater treatment, the system contained 2.5 mg L-1 BPA and 2.5 mg L-1 ATZ initially, with the PMS concentration increased to 0.2 mM while maintaining other experimental conditions identical to those described above.

Assessment of toxicity by E. coli and S. aureus culture experiments. Activated bacterial strains were prepared by inoculating 50 μL of frozen E. coli and S. aureus stock into LB medium. The culture was incubated at 37°C with shaking at 180 rpm for 10 h in a rotary incubator (Honour, HNY-200B). Subsequently, fresh LB medium was supplemented with solutions collected from various reaction systems. The activated E. coli and S. aureus culture was transferred to this conditioned medium and incubated under identical conditions for an additional 10 hours. Following incubation, the bacterial suspension was adjusted to an optical density of 0.1 at 600 nm (OD = 0.1) using sterile deionized water. Serial ten-fold dilutions were performed to achieve a final dilution factor of 106, and 100 μL aliquots of the diluted suspensions were spread onto agar plates. After 18 h of incubation at 37°C, bacterial growth was assessed by colony counting. All procedures were conducted in a laminar flow cabinet (AIRTECH, SW-CJ-1FD), with consumables sterilized by autoclaving at 121°C for 15 min (IMJ-85A, STIK Co., USA) or by exposure to 254 nm ultraviolet radiation for 20 min.

No statistical method was used to predetermine the sample size. No data were excluded from the analyses. The experiments were not randomized. The Investigators were not blinded to allocation during experiments and outcome assessment.

Toxicity assessment by wheat seed culture experiments. The influence of various post-treatment solutions on wheat growth was systematically investigated using a hydroponic cultivation system. Uniformly plump wheat seeds were selected and surface-sterilized by immersion in 3% hydrogen peroxide (H O ) for 20 min, followed by thorough rinsing with deionized water. Twenty seeds were evenly arranged on filter paper in petri dishes and supplied with 8 mL of solution from different treatment systems. The dishes were maintained at 25°C under a 12-hour light/12-hour dark photoperiod with a light intensity of 3000 lux. Wheat growth was monitored at 24-hour intervals, and solutions were periodically replenished to maintain consistent moisture levels. Upon stabilization of germination rates, indicating completion of the primary sprouting phase, stem lengths were measured to assess seedling growth. Continuous observation throughout the experimental period enabled comprehensive evaluation of treatment effects on plant development and potential phytotoxicity.

No statistical method was used to predetermine the sample size. No data were excluded from the analyses. The experiments were not randomized. The Investigators were not blinded to allocation during experiments and outcome assessment.

Toxicity assessment by Chlorella vulgaris culture. Chlorella vulgaris was cultivated in BG-11 medium within conical flasks placed in an illuminated incubator under controlled conditions (25 ± 1 °C, 4000 lux illumination, 12 h/12 h light/dark cycle) for 10 days. Cells harvested during the logarithmic growth phase (OD ≈ 0.5) were then transferred to fresh BG-11 medium prepared using water from different experimental groups, including blank controls, untreated BPA or ATZ solutions, and treated BPA or ATZ samples. All media and solutions were sterilized by autoclaving (121 °C, 20 min) prior to use. Biomass accumulation (OD ) and chlorophyll a content were monitored at daily intervals across all experimental conditions.

No statistical method was used to predetermine the sample size. No data were excluded from the analyses. The experiments were not randomized. The Investigators were not blinded to allocation during experiments and outcome assessment.

Determination of chlorophyll a. Chlorophyll a concentration was determined spectrophotometrically after acetone extraction according to established protocols. Specifically, 10 mL aliquots of algal culture were centrifuged at 10000 rpm for 10 min. The resulting pellets were resuspended in 10 mL of 90% (v/v) acetone and maintained in complete darkness at 4 ℃ for 24 h to ensure thorough pigment extraction. Absorbance readings were obtained at 750, 663, 645, and 630 nm using a UV-vis spectrophotometer with 90% acetone serving as the blank reference. The concentration of chlorophyll a was calculated using the following equation:
Chlorophyll a (mg L-1) = 11.64 ×(OD -OD ) – 2.16 ×(OD -OD ) + 0.1 ×(OD -OD ) (S1)

Toxicity assessment by zebrafish culture experiments. To obtain a sufficient number of viable embryos, three healthy zebrafish (one female and two males) were housed together in nutrient-enriched water for 12 h. The collected embryos were thoroughly rinsed with water from the aquaculture system to remove potential surface contaminants. Under microscopic examination, embryos at the eight-cell developmental stage were specifically selected and separated for subsequent experimental procedures. Exposure solutions were prepared for different experimental groups: the treatment group received solutions collected from various reaction systems; the blank control group was maintained in nutrient solution alone; and the pollutant control group was exposed to untreated BPA or ATZ solutions. The embryos were distributed into 24-well plates, with each well containing 1 mL of nutrient solution and 1 mL of the designated exposure solution, and one embryo per well (n=10 per group). From the initiation of exposure until zebrafish hatching, embryonic development was monitored every 24 h using microscopy. These observations aimed to assess the teratogenic effects of the exposure solutions on both embryonic and larval stages, ensuring accurate and reliable evaluation of potential developmental toxicity. Intracellular reactive oxygen species (ROS) in zebrafish larvae were detected using the fluorescent probe DCFH-DA. After 120 hours of exposure, larvae were incubated with 10 μM DCFH-DA in darkness at 28 °C for one hour. ROS levels were subsequently visualized and analyzed using an AE31E inverted fluorescence microscope.

All zebrafish experiments were conducted in accordance with the guidelines of the China Laboratory Animal Administration and approved by the Laboratory Animal Welfare and Ethics Committee of the Third Military Medical University, under license No. SCXK (Yu) 20170002. No statistical method was used to predetermine the sample size. No data were excluded from the analyses. The experiments were not randomized. The Investigators were not blinded to allocation during experiments and outcome assessment.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "Zhang et al. report a heterogeneous catalyst featuring spatially separated dual active sites that independently activate pollutants (Zn sites) and oxidants (Cu sites). This architecture steers two distinct reaction pathways: electron-transfer-induced polymerization for electron-rich organics, and radical-mediated mineralization for electron-deficient species. Importantly, radicals generated during mineralization can in situ depolymerize accumulated polymeric deposits, thereby enabling autonomous catalyst regeneration. The scalability of the strategy is demonstrated in a 200 L self-circulating reactor, and multispecies toxicological assessments confirm effective detoxification of complex wastewater. Collectively, the study presents a coherent progression from atomic-level catalyst design to practical reactor implementation. Overall, this work integrates conceptual innovation with comprehensive mechanistic and application-oriented analyses, and the presentation is strengthened by schematics of notable clarity and depth. I recommend publication in Nature Communications after minor revisions. Specific suggestions are provided below.\n(1) The manuscript states that electron-rich pollutants undergo polymerization; beyond BPA, additional validation using other electron-rich substrates is recommended to further substantiate this pathway.\n(2) The authors propose preferential polymerization of electron-rich pollutants, in contrast to electron-deficient species. To strengthen the proposed selectivity mechanism, further tests using additional mixed-pollutant systems are recommended.\n(3) The presence of ATZ is reported to promote depolymerization of BPA-derived polymers; whether a similar effect occurs for other electron-rich pollutant systems merits further verification.\n(4) Several figures are not sufficiently clear; further optimization of image resolution, contrast, and labeling is recommended.\n(5) Reaction conditions and the dosages of quenching agents should be explicitly specified in the figure legends.\n(6) The experimental procedures for zebrafish metabolomics analysis should be described in greater detail to ensure reproducibility.\n(7) The naming of comparison groups should be standardized throughout the manuscript (e.g., “ATZ system” and “treated ATZ system”).\n(8) Legend formatting is not fully standardized in some places (e.g., inconsistent use of singular/plural forms). A careful editorial pass is recommended to harmonize these elements.", "reviewer_2": "This study reports a catalyst with dual functional sites enabling the compartmentalized activation of pollutants and oxidants. Reaction pathway selectivity is achieved based on the electronic structure of pollutants, while real-time catalyst regeneration is realized through in situ depolymerization. Overall, this research demonstrates innovation and rigor, featuring substantial content and considerable effort, with forward-looking significance. It is recommended for publication in Nature Communications after minor revisions. Specific suggestions are as follows:\n1. The activation process of PMS inevitably releases homogeneous Cu2+ ions. This comparative experiment should be supplemented to rule out the contribution of homogeneous Cu2+ to the degradation reaction.\n2. Ferulic acid (FA) can reduce phenoxy radicals to their original phenolic molecules. It is recommended to conduct additional experiments under FA conditions to confirm whether phenoxy radicals serve as the primary intermediates in the polymerization reaction.\n3. The manuscript attributes PMS activation primarily to the Cu sites. It is recommended to supplement the experiment with Cu site masking to fully validate the crucial role of Cu site activation in PMS.\n4. In addition to laboratory ultrapure water, other water sources should also be tested to validate the system's practical application potential.\n5. The synthesis steps for different catalysts in the manuscript should be described in detail.\n6. The specific experimental procedures for toxicity testing should be described, such as the wheat test and the chlorella cultivation experiment.\n7. Photographs of the actual 200L self-circulating reactor mentioned in the manuscript should be provided.\n8. The embedded images in the diagram are somewhat unclear. Please optimize and adjust them further.\n9. Regarding catalyst stability, how does metal leaching occur during the degradation process?\n10. The authors need to thoroughly investigate the functional relationship between results: For pure ZnO or CuO, can doping with Cu or Zn achieve equivalent performance?", "reviewer_3": "In this study, Zhang et al. develop a dual-site catalyst where zinc centers activate pollutants while copper sites activate oxidants. The authors demonstrate scalability using a large reactor and environmental safety via thorough toxicological analysis. This work provides a cooperative catalytic strategy that overcomes single-site limitations and offers practical principles for wastewater treatment. The research is innovative and comprehensive, with findings that are clearly illustrated through effective and well-designed schematics. I recommend publication in Nature Communications after minor revisions.\n1. Both the BPA system and the ATZ system demonstrate effective degradation of pollutants. The TOC removal performance of each system should be supported by data.\n2. The manuscript mentions that Zn sites adsorb and activate pollutants, while Cu sites adsorb and activate oxidants. When encountering different types of pollutants, does the electron transfer pattern between Zn and Cu change? Please clarify the influence of pollutants with different electron types on the reaction mechanism.\n3. How does the zinc-to-copper ratio impact on the wastewater degradation efficiency?\n4. How is the heartbeat of zebrafish monitored? How many parallel data points are there in each group?\n5. The manuscript employs a variety of biological models to assess toxicity. Please provide specific experimental details for each model study.\n6. The symbols “RS, Ox, Cat, P” in Figure 1 should be annotated with explanatory notes within the figure.\n7. Some fonts in the image are too small to read clearly. Please optimize them further.\n8. Metabolomics analysis was employed in the manuscript. The numbers and codes in Figure 7 should be provided with specific corresponding explanations."}, "author_response": "Response to Reviewer 1’s Comments\nZhang et al. report a heterogeneous catalyst featuring spatially separated dual active sites that\nindependently activate pollutants (Zn sites) and oxidants (Cu sites). This architecture steers two distinct\nreaction pathways: electron-transfer-induced polymerization for electron-rich organics, and radical-\nmediated mineralization for electron-deficient species. Importantly, radicals generated during\nmineralization can in situ depolymerize accumulated polymeric deposits, thereby enabling\nautonomous catalyst regeneration. The scalability of the strategy is demonstrated in a 200 L self-\ncirculating reactor, and multispecies toxicological assessments confirm effective detoxification of\ncomplex wastewater. Collectively, the study presents a coherent progression from atomic-level catalyst\ndesign to practical reactor implementation. Overall, this work integrates conceptual innovation with\ncomprehensive mechanistic and application-oriented analyses, and the presentation is strengthened by\nschematics of notable clarity and depth. I recommend publication in Nature Communications after\nminor revisions. Specific suggestions are provided below.\nResponse: We sincerely thank the reviewers for recognizing the innovative contributions of our work\nand for their professional and detailed feedback, which is invaluable for improving the manuscript.\n1. The manuscript states that electron-rich pollutants undergo polymerization; beyond BPA, additional\nvalidation using other electron-rich substrates is recommended to further substantiate this pathway.\nResponse: We are grateful for the valuable feedback from the reviewers. We have conducted\ninvestigations using another electron-rich contaminant, sulfamethoxazole (SMX). A series of\nquenching experiments with various concentrations of quenchers revealed that no reactive species\nwere present in the ZnO/CuO/PMS/SMX system, confirming that the electron transfer pathway\npredominates in this system (Figures R1-2). Furthermore, the addition of ferulic acid (FA), which\nreduces phenoxyl radicals back to their parent phenolic forms, completely suppressed SMX\ndegradation (Figure R3). This observation confirms that phenoxyl radicals serve as key intermediates\nin the polymerization process. These findings are consistent with those obtained in the\nZnO/CuO/PMS/BPA system. Additionally, cycling tests with SMX demonstrated a decline in\nperformance after five cycles, indicating that catalyst deactivation was caused by the accumulation of\npolymeric products, a phenomenon also observed in the ZnO/CuO/PMS/BPA system (Figure R4).\nThese results collectively confirm that in the ZnO/CuO/PMS system, electron-rich contaminants\nreadily trigger an electron transfer pathway, thereby inducing polymerization. Detailed information\ncan be found below (In the revised Supplementary information, Supplementary Figures 75-76,\nSupplementary Figure 63, Supplementary Figure 43):\nFigure R1 (Supplementary Figure 75) | Degradation of SMX by the ZnO/CuO/PMS system under\ndifferent quencher conditions and (b) corresponding removal efficiencies. (c) Degradation of SMX by\nthe ZnO/CuO/PMS system in the presence of electron quencher and (d) corresponding removal\nefficiency. Error bars indicate standard deviations based on duplicate experiments.\nFigure R2 (Supplementary Figures 76-77) | (a) Degradation of SMX by ZnO/CuO/PMS system\nunder different concentrations of TBA and the corresponding (b) reaction rate constants and (c)\nremoval efficiencies. Error bars indicate standard deviations based on duplicate experiments. (d)\nDegradation of SMX by ZnO/CuO/PMS system under different concentrations of MeOH and the\ncorresponding (e) reaction rate constants and (f) removal efficiencies. Error bars indicate standard\ndeviations based on duplicate experiments.\nFigure R3 (Supplementary Figure 63) | The effect of FA on (a) BPA and (b) SMX degradation. Error\nbars indicate standard deviations based on duplicate experiments.\nFigure R4 (Supplementary Figure 43) | Efficiency comparison of continuous cycling removal of\nSMX and ATZ in the ZnO/CuO/PMS system.\n2. The authors propose preferential polymerization of electron-rich pollutants, in contrast to electron-\ndeficient species. To strengthen the proposed selectivity mechanism, further tests using additional\nmixed-pollutant systems are recommended.\nResponse: We are grateful for the valuable feedback from the reviewers. To further investigate the\ndegradation preference between pollutants with distinct electronic characteristics, we have studied a\nmixed system comprising the electron rich contaminant sulfamethoxazole (SMX) and the electron\ndeficient pollutant atrazine (ATZ). The results demonstrate that SMX underwent rapid and preferential\ndegradation, with complete removal achieved within one minute, while ATZ degradation only\ncommenced during the extended reaction period (Figure R5). This sequential degradation behavior,\nconsistent with observations in the BPA/ATZ system, provides clear evidence that the ZnO/CuO/PMS\nsystem selectively targets electron rich pollutants over electron deficient ones when both coexist,\naligning with findings reported in the existing literature. Detailed information can be found below (In\nthe revised Supplementary information, Supplementary Figure 61):\nFigure R5 (Supplementary Figure 61) | (a) Mixed removal performance of the ZnO/CuO/PMS\nsystem for SMX and ATZ, (b) Kinetic constants, (c) Removal efficiency. Error bars indicate standard\ndeviations based on duplicate experiments. (Conditions: [Catal.] = 0.4 g L-1, [PMS] = 0.7 mM,\n0 0\n[SMX] = 10 mg L-1, [ATZ] = 10 mg L-1).\n0 0\n3. The presence of ATZ is reported to promote depolymerization of BPA-derived polymers; whether a\nsimilar effect occurs for other electron-rich pollutant systems merits further verification.\nResponse: We appreciate the thoughtful suggestions provided by the reviewer. To verify whether the\npresence of ATZ can enhance the cyclic degradation capability for other electron-rich pollutants, we\nhave selected sulfamethoxazole (SMX) as a representative electron-rich pollutant for investigation.\nExperimental results show that the degradation performance of the ZnO/CuO/PMS/SMX system\ngradually declines with increasing cycles, which may be attributed to the accumulation of polymeric\nproducts (Figure R6). In sharp contrast, when ATZ is present, the cyclic degradation capability of the\nZnO/CuO/PMS/SMX system remains largely unchanged. This likely results from the targeted removal\nof polymeric products by radicals generated in the presence of ATZ, thereby enabling continuous\nregeneration of the catalyst. These experimental findings confirm that the mechanism of catalyst in\nsitu regeneration via radicals induced by electron-deficient pollutants remains valid in systems\ncontaining other electron-rich pollutants. Detailed information can be found below (In the revised\nSupplementary information, Supplementary Figure 43):\nFigure R6 (Supplementary Figure 43) | SMX recycling performance with and without ATZ ([SMX]\n0\n= 10 mg L-1, [ATZ] = 2 mg L-1).\n0\n4. Several figures are not sufficiently clear; further optimization of image resolution, contrast, and\nlabeling is recommended.\nResponse: We appreciate the reviewer’s feedback. We have carefully reviewed and optimized the\nimages in the manuscript to ensure they are clear and accurate in content. Detailed information can be\nfound below (In the revised manuscript, Figure 3):\nFigure R7 (Figure 3) | Removal performance and environmental robustness of the constructed Fenton-\nlike system. a, BPA degradation in different reaction systems (Conditions: [Catal.] = 0.2 g L-1, [PMS]\n0 0\n= 0.3 mM, [pH] = 6.96, [BPA] = 10 mg L-1, [Temp.]= 20±2 °C). b, Comparison of BPA removal\n0 0\nefficiencies and apparent rate constants across systems. c, Reported apparent rate constants (k) for BPA\nand ATZ removal versus this work. d, ATZ degradation in different reaction systems (Conditions: [Catal.] = 0.2 g L-1, [PMS] = 0.5 mM, [pH] = 7.03, [ATZ] = 10 mg L-1, [Temp.]= 20±2 °C). e,\n0 0 0 0\nComparison of ATZ degradation efficiencies and apparent rate constants. f, Effect of dissolved organic\nmatter surrogates (humic acid, HA; bovine serum albumin, BSA) on BPA and ATZ degradation. g,\nBPA and ATZ degradation by ZnO/CuO/PMS system at different initial pH values. h, Substrate scope:\ndegradation of representative pollutants by ZnO/CuO/PMS system. Error bars indicate standard\ndeviations from duplicate experiments. i, Conceptual scheme showing how mineralization resolves\npolymerization-induced issues.\n5. Reaction conditions and the dosages of quenching agents should be explicitly specified in the figure\nlegends.\nResponse: We are grateful for the valuable feedback from the reviewers. We have provided detailed\nspecifications for the reaction conditions and the dosage of the quenching agent, with clear annotations\nin the legend. Detailed information can be found below (In the revised manuscript, Figure captions\n3-4):\n“Fig. 3. | Removal performance and environmental robustness of the constructed Fenton-like system.\na, BPA degradation in different reaction systems (Conditions: [Catal.] = 0.2 g L-1, [PMS] = 0.3 mM,\n0 0\n[pH] = 6.96, [BPA] = 10 mg L-1, [Temp.]= 20±2 °C). b, Comparison of BPA removal efficiencies and\n0 0\napparent rate constants across systems. c, Reported apparent rate constants (k) for BPA and ATZ\nremoval versus this work. d, ATZ degradation in different reaction systems (Conditions: [Catal.] =\n0\n0.2 g L-1, [PMS] = 0.5 mM, [pH] = 7.03, [ATZ] = 10 mg L-1, [Temp.]= 20±2 °C). e, Comparison of\n0 0 0\nATZ degradation efficiencies and apparent rate constants. f, Effect of dissolved organic matter\nsurrogates (humic acid, HA; bovine serum albumin, BSA) on BPA and ATZ degradation. g, BPA and\nATZ degradation by ZnO/CuO/PMS system at different initial pH values. h, Substrate scope:\ndegradation of representative pollutants by ZnO/CuO/PMS system. Error bars indicate standard\ndeviations from duplicate experiments. i, Conceptual scheme showing how mineralization resolves\npolymerization-induced issues.”\n“Fig. 4. | Active-species identification and electrochemical diagnostics. a, BPA degradation in the\nZnO/CuO/PMS system with quenchers ([TBA] = [MeOH] = 50 mM, [TEMPOL] = [p-BQ]= 1 mM,\n[L‑histidine] = [β-carotene] =1 mM, [PMSO] = 1 mM, [DMSO] = 20 mM). b, BPA degradation by\nthe ZnO/CuO/PMS reaction system in the presence of different TBA and MeOH concentrations. c, ATZ\ndegradation by the ZnO/CuO/PMS reaction system in the presence of different TBA and MeOH\nconcentrations. Error bars indicate standard deviations based on duplicate experiments. d, DMPO\nspin-trapping ESR spectra for DMPO-SO - and TEMP-based ESR spectra for 1O in the\n4 2\nZnO/CuO/PMS/BPA system. e, DMPO spin-trapping ESR spectra for DMPO-SO - in the\nPMS and contaminants (inset: i-t (current-time) curves). g, Electrochemical impedance spectra (EIS)\nof catalysts (inset: EIS for ZnO/CuO under different conditions). h, Linear sweep voltammetry (LSV)\nof catalyst electrodes (inset: LSV curves of ZnO/CuO electrodes under different conditions).”\n6. The experimental procedures for zebrafish metabolomics analysis should be described in greater\ndetail to ensure reproducibility.\nResponse: Thanks to the reviewer for this reminder. We have provided a detailed description of the\nexperimental workflow for zebrafish metabolomics analysis mentioned in the manuscript to ensure the\nreproducibility of the experimental results. Detailed information can be found below (In the revised\nSupplementary information, Supplementary method 11):\n“1.11 Non-targeted metabolomics analysis\nFor metabolomic analysis, approximately 50 mg of zebrafish tissue was collected per\nexperimental group (including BPA and BPA-treated systems) as biological replicates (n=3 per group).\nMetabolite extraction was performed according to the following procedure: 200 μL of ice-cold water\nand two steel beads were added to each sample, followed by homogenization using a high-throughput\ntissue grinder at 55 Hz for 60 s (repeated twice). Subsequently, 800 μL of methanol: acetonitrile (1:1,\nv/v) was added, and the mixture was subjected to ultrasonic extraction for 30 min. After incubation at\n-20°C for 45 min, samples were centrifuged at 12,000 rpm for 20 min at 4°C. An 800 μL aliquot of the\nsupernatant was collected and concentrated to complete dryness under vacuum. The residue was\nreconstituted in 150 μL of 50% methanol containing 5 ppm 2-chlorophenylalanine, vortexed for 30 s,\nand centrifuged at 12,000 rpm for 10 min at 4°C. The resulting supernatant was filtered through a 0.22\nμm membrane, followed by an additional centrifugation step under identical conditions. The final\nfiltrate was transferred to autosampler vials for subsequent analysis.\nChromatographic separation was performed using an ACQUITY UPLC HSS T3 column (100Å,\n1.8 μm, 2.1 mm × 100 mm) maintained at 40°C. The mobile phase flow rate and injection volume were\nset to 0.4 mL min-1 and 2 μL, respectively. For both positive and negative ionization modes, mobile\nphase A consisted of 0.1% formic acid in water, while mobile phase B was acetonitrile containing 0.1%\nformic acid.\nMass spectrometric analysis was conducted on a Thermo Q Exactive HF-X instrument controlled\nby Xcalibur software (v4.7) operating in data-dependent acquisition (DDA) mode for both positive\nand negative ionization. The HESI source parameters were configured as follows: spray voltage 3.5\nkV, sheath gas 40 arb, auxiliary gas 10 arb, capillary temperature 320°C, and auxiliary gas heater\ntemperature 300°C. Full MS scans were acquired at a resolution of 60,000 across the m/z range 70-\n1000 with an AGC target of \"standard\" and maximum injection time of 100 ms. The top 10 most intense\nions were selected for fragmentation with a dynamic exclusion duration of 4 s. MS/MS spectra were\ncollected at a resolution of 15,000 using 30% HCD collision energy with automatic maximum injection\ntime.\nRaw data files were processed using MS-DIAL software (v4.9.221218) for peak picking,\nalignment, filtering, and metabolite annotation. Metabolite identification was performed against the\nPSNGM database, which integrates multiple reference libraries including in-house standards,\nmzCloud (https://www.mzcloud.org/), LIPIDMAPS (https://www.lipidmaps.org/), HMDB\n(https://hmdb.ca/), MoNA (https://mona.fiehnlab.ucdavis.edu/), NIST_2020_MSMS, and AI-predicted\nMS/MS spectra. Database search parameters were set as follows: MS1 tolerance for identification\n0.01, MS2 tolerance for identification 0.05, Smoothing level 3, Minimum peak height 10000, Minimum\npeak width 5, Mass slice width 0.05, Identification score cutoff 70.”\n7. The naming of comparison groups should be standardized throughout the manuscript (e.g., “ATZ\nsystem” and “treated ATZ system”).\nResponse: We appreciate the reviewer’s suggestions. We have carefully reviewed the manuscript and\nstandardized the naming conventions for each group to ensure consistent terminology. Detailed\ninformation can be found below (In the revised Supplementary information, Supplementary\nFigures 79-82; in the revised manuscript, Figure 7):\nFigure R8 (Supplementary Figure 79) | Photographs of E. coli and S. aureus colonies incubated\nwith solutions treated with different systems.\nFigure R9 (Supplementary Figure 80) | Photographs of wheat seeds after cultivation in solutions\nfrom different treatment systems.\nFigure R10 (Supplementary Figure 81) | Violin plots of wheat shoot length distribution in various\nsystems.\nOD\n0.5 680\n0.40\nChlorophyll a\n) 1\n0.4 -\nL\n0.35\ng\nm\n(\n0 0.3\n8 a\ny\nO\nh\n0.2 p\no\nr\no\n0.25 l\nh\nC\n0.1\n0.20\n0.0\nContro B l PA T s r y e s a te te m d BPA A sy T s Z te T s m y re s a te te m d ATZ system\nFigure R11 (Supplementary Figure 82) | Comparison of growth indicators for Chlorella cultured in\nsolutions processed by different systems.\nFigure R12 (Figure 7) | Comprehensive toxicity assessment under realistic conditions. a, Zebrafish\nsurvival and deformity ratios across treatment systems. b, Heartbeat counts of zebrafish at 48-96 h\npost-fertilization. c, Zebrafish body length comparisons. d, Representative image of zebrafish in blank\nsolution. e, Zebrafish in ZnO/CuO/PMS/BPA-treated solution. f, Zebrafish in ZnO/CuO/PMS/ATZ-\ntreated solution (scale bar, 1 mm). Representative images of intracellular ROS production detected by\nfluorescent staining in zebrafish at 120 h post-fertilization (hpf): (i) blank group, (j) BPA-treated group,\nand (k) BPA-untreated group. l, Volcano plot of differentially expressed genes between the BPA-treated\ngroup and the untreated group. m, Marker metabolites differing between the two groups. n, Top 20\nenriched KEGG pathways for BPA-treated vs. untreated groups.\n8. Legend formatting is not fully standardized in some places (e.g., inconsistent use of singular/plural\nforms). A careful editorial pass is recommended to harmonize these elements.\nResponse: We are grateful to the reviewers for their constructive and insightful comments. We have\ncarefully reviewed and proofread all captions throughout the manuscript to ensure the accuracy and\nstandardization of both formatting and content presentation. Detailed information can be found below\n(In the revised manuscript, Figure caption 2):\n“Fig. 2. | Validation of ZnO/CuO heterostructures with dual Zn and Cu sites. a, Schematic of ZnO/CuO\nsynthesis. b, XRD patterns of ZnO, CuO, and ZnO/CuO. c, FTIR spectra of ZnO, CuO, and ZnO/CuO.\nd, TEM images of ZnO/CuO. e-f, HRTEM images of ZnO/CuO. g, Zn 2p XPS spectra of ZnO and\nZnO/CuO. h, Cu 2p XPS spectra of CuO and ZnO/CuO. i, Normalized Zn K-edge XANES spectra of\nZnO/CuO sample with Zn foil and ZnO standards (inset: magnified region). g, Normalized Cu K-edge\nXANES spectra of ZnO/CuO sample with Cu foil, Cu O, and CuO standards (inset: magnified region).\n2\nk, k -weighted FT-EXAFS spectra of ZnO/CuO with Zn foil and ZnO references. l, k -weighted FT -\n3 3\nEXAFS spectra of ZnO/CuO with Cu foil, Cu O, and CuO references. m, WT-EXAFS (Zn K-edge) of\nResponse to Reviewer 2’s Comments\nThis study reports a catalyst with dual functional sites enabling the compartmentalized activation of\npollutants and oxidants. Reaction pathway selectivity is achieved based on the electronic structure of\npollutants, while real-time catalyst regeneration is realized through in situ depolymerization. Overall,\nthis research demonstrates innovation and rigor, featuring substantial content and considerable effort,\nwith forward-looking significance. It is recommended for publication in Nature Communications after\nminor revisions. Specific suggestions are as follows:\nResponse: We greatly appreciate the reviewers' acknowledgment of the innovative aspects of our\nwork and are thankful for their professional and detailed feedback, which is essential for enhancing\nthe quality of our manuscript.\n1. The activation process of PMS inevitably releases homogeneous Cu2+ ions. This comparative\nexperiment should be supplemented to rule out the contribution of homogeneous Cu2+ to the\ndegradation reaction.\nResponse: We appreciate the reviewer’s feedback. To rule out the contribution of homogeneous Cu2+\nin catalyzing PMS for pollutant degradation, comparative experiments have been conducted. The\nresults show that in BPA, SMX, and ATZ systems, Cu2+ contributed minimally to pollutant degradation,\nwith efficiencies of only 2.2%, 4.8%, and 2.8%, respectively (Figures R13-R15). These findings rule\nout a significant role of homogeneous Cu2+ catalysis and further confirm the high efficiency of the\nZnO/CuO/PMS system developed in this study. Detailed information can be found below (In the\nrevised Supplementary information, Supplementary Figures 24-25, Supplementary Figures 65):\nFigure R13 (Supplementary Figure 24) | (a) The effect of Cu2+ activation on PMS degradation of\nBPA and the corresponding (b) reaction rate constant and (c) removal efficiency (Cu2+=1 mg L-1). Error\nbars indicate standard deviations based on duplicate experiments.\nFigure R14 (Supplementary Figure 65) | (a) The effect of Cu2+ activation on PMS degradation of\nSMX and the corresponding (b) reaction rate constant and (c) removal efficiency (Cu2+=1 mg L-1).\nError bars indicate standard deviations based on duplicate experiments.\nFigure R15 (Supplementary Figure 25) | (a) The effect of Cu2+ activation on PMS degradation of\nATZ and the corresponding (b) reaction rate constant and (c) removal efficiency (Cu2+=1 mg L-1).\nError bars indicate standard deviations based on duplicate experiments.\n2. Ferulic acid (FA) can reduce phenoxy radicals to their original phenolic molecules. It is\nrecommended to conduct additional experiments under FA conditions to confirm whether phenoxy\nradicals serve as the primary intermediates in the polymerization reaction.\nResponse: We sincerely thank the reviewers for their valuable feedback. Comparative experiments\nhave been conducted in both BPA and SMX systems by introducing varying concentrations of ferulic\nacid (FA). The results showed that the addition of 1 mM FA significantly inhibited the degradation\nperformance in both systems (Figure R16). These findings suggest that phenoxy radicals act as key\nintermediates in the polymerization process, and that FA can reduce these radicals back to their original\nphenolic forms, thereby impeding polymerization. The results further confirm that the reaction\nmechanism of the ZnO/CuO/PMS system for electron-rich pollutants proceeds via a polymerization\npathway. Detailed information can be found below (In the revised Supplementary information,\nSupplementary Figures 63):\nFigure R16 (Supplementary Figure 63) | The effect of FA on (a) BPA and (b) SMX degradation.\nError bars indicate standard deviations based on duplicate experiments.\n3. The manuscript attributes PMS activation primarily to the Cu sites. It is recommended to supplement\nthe experiment with Cu site masking to fully validate the crucial role of Cu site activation in PMS.\nResponse: We sincerely thank the reviewers for their valuable feedback. To verify the role of Cu sites,\nwe have performed masking experiments using three different Cu-site masking agents. The results\nshowed that the degradation efficiency was almost completely suppressed in the presence of these\nmasking agents (Figure R17). These findings clearly demonstrate that Cu sites are responsible for\nactivating PMS and play a crucial role in the reaction process. Detailed information can be found below\n(In the revised Supplementary information, Supplementary Figures 58):\nFigure R17 (Supplementary Figure 58) | (a) Degradation efficiency of BPA by the ZnO/CuO/PMS\nsystem under different masking agent conditions and corresponding (b) reaction rate constants and (c)\nremoval efficiencies (The masking agent concentration was 10 mM). Error bars indicate standard\ndeviations based on duplicate experiments.\n4. In addition to laboratory ultrapure water, other water sources should also be tested to validate the\nsystem's practical application potential.\nResponse: We appreciate the reviewer’s feedback. To evaluate the practical application potential of\nthis system, experiments have been conducted using three additional water sources: tap water, river\nwater, and reverse osmosis water. Results show that in both electron-rich and electron-deficient\npollutant systems, the degradation performance was not significantly inhibited, achieving nearly 100%\npollutant removal within a short time (Figures R18-20). These findings fully demonstrate the practical\napplication potential of the ZnO/CuO/PMS system. Detailed information can be found below (In the\nrevised Supplementary information, Supplementary Figures 32, 71, 35):\nFigure R18 (Supplementary Figure 32) | (a) Degradation of BPA by ZnO/CuO/PMS system under\ndifferent water sources and the corresponding (b) reaction rate constants and (c) removal efficiencies\n([PMS] =0.5 mM). Error bars indicate standard deviations based on duplicate experiments.\ndifferent water sources and the corresponding (b) reaction rate constants and (c) removal efficiencies\n([PMS] =0.5 mM). Error bars indicate standard deviations based on duplicate experiments\ndifferent water sources and the corresponding (b) reaction rate constants and (c) removal efficiencies\n([PMS] =1 mM). Error bars indicate standard deviations based on duplicate experiments.\n0\n5. The synthesis steps for different catalysts in the manuscript should be described in detail.\nResponse: We sincerely thank the reviewers for their valuable feedback. A detailed description of the\ncatalyst synthesis procedure has been provided, including specific parameters such as precursor\nquantities, reaction temperature, and heating rates. Detailed information can be found below (In the\nrevised Supplementary information, Supplementary method 3):\n“1.3 Catalyst preparation\nPreparation of ZnO/CuO: First, 2 mmol Zn(NO ) •5H O, 2 mmol Cu(NO ) •3H O, and 4 mmol citric\n3 2 2 3 2 2\nacid were dissolved in 45 mL of ethanol and stirred for 30 min. Subsequently, the solution underwent\nsolvothermal reaction at 120 °C for 20 h. After washing with ethanol and drying, the intermediate\nproduct was calcined at 350°C for 2 h with a heating rate of 2°C min-1, yielding the final ZnO/CuO\nmaterial.\nPreparation of ZnO: ZnO was synthesized using a procedure identical to that of ZnO/CuO, except for\nthe omission of Cu(NO ) •3H O.\n3 2 2\nPreparation of CuO: CuO was synthesized using a procedure identical to that of ZnO/CuO, except for\nthe omission of Zn(NO ) •5H O.”\n3 2 2\n6. The specific experimental procedures for toxicity testing should be described, such as the wheat test\nand the chlorella cultivation experiment.\nResponse: We appreciate the reviewer’s feedback. The bioassay protocols have been described in\ndetail, encompassing both wheat seed cultivation and Chlorella culture experiments. Additionally, the\nmethodology for quantifying chlorophyll a has been fully elaborated. Detailed information can be\nfound below (In the revised Supplementary information, Supplementary methods 7-9):\n“1.7 Toxicity assessment by wheat seed culture experiments\nThe influence of various post-treatment solutions on wheat growth was systematically investigated\nusing a hydroponic cultivation system. Uniformly plump wheat seeds were selected and surface-\nsterilized by immersion in 3% hydrogen peroxide (H O ) for 20 min, followed by thorough rinsing with\n2 2\ndeionized water. Twenty seeds were evenly arranged on filter paper in petri dishes and supplied with\n8 mL of solution from different treatment systems. The dishes were maintained at 25°C under a 12-\nhour light/12-hour dark photoperiod with a light intensity of 3000 lux. Wheat growth was monitored\nat 24-hour intervals, and solutions were periodically replenished to maintain consistent moisture\nlevels. Upon stabilization of germination rates, indicating completion of the primary sprouting phase,\nstem lengths were measured to assess seedling growth. Continuous observation throughout the\nexperimental period enabled comprehensive evaluation of treatment effects on plant development and\npotential phytotoxicity.\n1.8 Toxicity assessment by Chlorella vulgaris culture\nChlorella vulgaris was cultivated in BG-11 medium within conical flasks placed in an illuminated\nincubator under controlled conditions (25 ± 1 °C, 4000 lux illumination, 12 h/12 h light/dark cycle)\nfor 10 days. Cells harvested during the logarithmic growth phase (OD ≈ 0.5) were then transferred\n680\nto fresh BG-11 medium prepared using water from different experimental groups, including blank\ncontrols, untreated BPA or ATZ solutions, and treated BPA or ATZ samples. All media and solutions\nwere sterilized by autoclaving (121 °C, 20 min) prior to use. Biomass accumulation (OD ) and\n680\nchlorophyll a content were monitored at daily intervals across all experimental conditions.\n1.9 Determination of chlorophyll a\nChlorophyll a concentration was determined spectrophotometrically after acetone extraction\naccording to established protocols. Specifically, 10 mL aliquots of algal culture were centrifuged at\n10000 rpm for 10 min. The resulting pellets were resuspended in 10 mL of 90% (v/v) acetone and\nmaintained in complete darkness at 4 ℃ for 24 h to ensure thorough pigment extraction. Absorbance\nreadings were obtained at 750, 663, 645, and 630 nm using a UV-vis spectrophotometer with 90%\nacetone serving as the blank reference. The concentration of chlorophyll a was calculated using the\nfollowing equation:\nChlorophyll a (mg L-1) = 11.64 ×(OD -OD ) – 2.16 ×(OD -OD ) + 0.1 ×(OD -OD )(S1)”\n663 750 645 750 630 750\n7. Photographs of the actual 200L self-circulating reactor mentioned in the manuscript should be\nprovided.\nResponse: We are grateful to the reviewers for their constructive and insightful comments.\nPhotographs of the practical reactor, including front and top views, have been provided to adequately\nillustrate its design and construction (Figure R21). Detailed information can be found below (In the\nrevised Supplementary information, Supplementary Figure 78):\nFigure R21 (Supplementary Figure 78) | (a) Front view and (b) top view of a self-circulating water\ntreatment reactor driven by water flow without external agitation.\n8. The embedded images in the diagram are somewhat unclear. Please optimize and adjust them further.\nResponse: We appreciate the reviewer’s feedback. The images have been optimized to ensure\nsufficient clarity, specifically Figure 4 and Figure 6. Detailed information can be found below (In the\nrevised manuscript, Figures 4, 6):\nFigure R22 (Figure 4) | Active-species identification and electrochemical diagnostics. a, BPA\ndegradation in the ZnO/CuO/PMS system with quenchers ([TBA] = [MeOH] = 50 mM, [TEMPOL] =\n[p-BQ]= 1 mM, [L‑histidine] = [β-carotene] =1 mM, [PMSO] = 1 mM, [DMSO] = 20 mM). b, BPA\ndegradation by the ZnO/CuO/PMS reaction system in the presence of different TBA and MeOH\nconcentrations. c, ATZ degradation by the ZnO/CuO/PMS reaction system in the presence of different\nTBA and MeOH concentrations. Error bars indicate standard deviations based on duplicate\nexperiments. d, DMPO spin-trapping ESR spectra for DMPO-SO - and TEMP-based ESR spectra for\n4\n1O in the ZnO/CuO/PMS/BPA system. e, DMPO spin-trapping ESR spectra for DMPO-SO - in the\n2 4\nZnO/CuO/PMS/ATZ system. f, Open-circuit potentials (OCP) changes upon sequential addition of\nPMS and contaminants (inset: i-t (current-time) curves). g, Electrochemical impedance spectra (EIS)\nof catalysts (inset: EIS for ZnO/CuO under different conditions). h, Linear sweep voltammetry (LSV)\nof catalyst electrodes (inset: LSV curves of ZnO/CuO electrodes under different conditions).\nFigure R23 (Figure 6) | In-Situ depolymerization and pilot-scale validation. a, Simultaneous removal\nof BPA and ATZ by ZnO/CuO/PMS. b, TGA curves of ZnO/CuO before and after reaction with BPA\n(inset: after BPA/PMS and after ATZ/PMS depolymerization). c, Surface C and O atomic contents for\npristine ZnO/CuO, after BPA/PMS, and after ATZ/PMS depolymerization. d, BPA removal by\npolymer-fouled ZnO/CuO versus the same catalyst after ATZ/PMS depolymerization. e, BPA\nrecycling performance with and without ATZ ([BPA] = 10 mg L-1, [ATZ] = 2 mg L-1). f, TEM images\n0 0\nof ZnO/CuO after polymerization and after depolymerization. g, Schematic diagram of a water-driven\nself-circulating reactor. h, Photograph of sponge-supported catalyst in the reactor. i, Ten-cycle\ntreatment of 200 L mixed wastewater (BPA + ATZ) by ZnO/CuO/PMS. j, Relative environmental\nimpacts for treating 1 kg of BPA by ZnO/PMS, CuO/PMS, ZnO/CuO/PMS systems, and (k) Relative\nenvironmental impacts for the large-scale ZnO/CuO/PMS system.\n9. Regarding catalyst stability, how does metal leaching occur during the degradation process?\nResponse: We appreciate the reviewer’s feedback. To evaluate catalyst stability, metal leaching has\nbeen monitored under different reaction conditions. The results indicate that a measurable amount of\nZn leaches, while Cu leaching consistently remains at a low level (Figure R24). This is attributed to\nthe ZnO component sacrificing itself to maintain a neutral microenvironment, which enhances the\nstability of Cu sites and thereby facilitates the sustained activation of PMS for pollutant removal.\nDetailed information can be found below (In the revised Supplementary information, Figure R24):\nFigure R24 | a-b, Comparison of metal ion leaching in the ZnO/CuO/PMS/BPA system under different\nPMS dosages.\n10. The authors need to thoroughly investigate the functional relationship between results: For pure\nZnO or CuO, can doping with Cu or Zn achieve equivalent performance?\nResponse: We thank the reviewers for their careful evaluation and helpful recommendations. Based\non the experimental findings of this study, it has been reasonably inferred that pure ZnO, CuO, or their\ndoped counterparts are unlikely to achieve comparable catalytic performance. The key rationale lies\nin the built-in electric field (BIEF) generated by Fermi-level mismatch at the ZnO/CuO heterojunction\ninterface, which plays an essential role in driving directional electron transfer and regulating interfacial\ncharge dynamics. This mechanism governs the distinct reaction pathways observed with different\npollutant types.Theoretical calculations have revealed distinct work functions for ZnO (Φ = 5.70 eV)\nand CuO (Φ = 8.51 eV), indicating that ZnO preferentially acts as an electron donor (Figure R25).\nUpon contact, electrons flow from ZnO to CuO until Fermi-level alignment is achieved, establishing\na ZnO→CuO BIEF. Bader charge analysis has quantified this interfacial charge redistribution,\nconfirming a net transfer of 1.15 electrons from ZnO to CuO. The BIEF, in conjunction with the\nintrinsic electronic properties of the pollutants, determines the reaction pathway selection. For\nelectron-rich pollutants, which serve as auxiliary electron donors, the BIEF enhances electron flux\nfrom ZnO to CuO, resulting in an electron-rich interface that promotes PMS reduction to SO 2- via an\n4\nelectron-transfer pathway (ETP). In contrast, for electron-deficient pollutants, limited electron supply\nsuppresses donor-mediated pathways, favoring O-O bond cleavage of PMS to generate SO •-/ •OH\n4\nthrough a radical-dominated mechanism. Thus, the interfacial electronic coupling between ZnO and\nCuO has been demonstrated as crucial for enabling pollutant-adaptive reaction mechanisms.\nConsequently, neither pure oxides nor their doped analogs are expected to replicate this adaptive\ncatalytic behavior. Detailed information can be found below (In the revised manuscript, Figure 5):\nFigure R25 (Figure 5) | Dual-site functions and reaction pathway analysis. a, In-situ Raman spectra\nin different ZnO/CuO systems. b, In-situ Raman spectra in different CuO systems. c, In-situ Raman\nspectra in different ZnO systems. d, Comparison of adsorption energies for PMS on Zn and Cu Sites\nin ZnO/CuO catalysts. e, Comparison of adsorption energies for BPA and ATZ on ZnO and ZnO/CuO\ncatalysts. f, Comparison of adsorption energies for BPA and ATZ on CuO and ZnO/CuO catalysts. g,\npDOS of ZnO, CuO, and ZnO/CuO. h, Calculated work functions of ZnO and CuO. i, Schematic of\nbuilt-in electric field and interfacial charge transfer in ZnO/CuO. j, Energy gap difference between the\nLUMO of the ZnO/PMS complex and the HOMO of each pollutant.\nResponse to Reviewer 3’s Comments\nIn this study, Zhang et al. develop a dual-site catalyst where zinc centers activate pollutants while\ncopper sites activate oxidants. The authors demonstrate scalability using a large reactor and\nenvironmental safety via thorough toxicological analysis. This work provides a cooperative catalytic\nstrategy that overcomes single-site limitations and offers practical principles for wastewater treatment.\nThe research is innovative and comprehensive, with findings that are clearly illustrated through\neffective and well-designed schematics. I recommend publication in Nature Communications after\nminor revisions.\nResponse: We sincerely thank the reviewers for their supportive feedback and insightful suggestions,\nwhich have greatly enhanced the quality of the manuscript.\n1. Both the BPA system and the ATZ system demonstrate effective degradation of pollutants. The TOC\nremoval performance of each system should be supported by data.\nResponse: We greatly appreciate the reviewers' detailed feedback. The total organic carbon (TOC)\nremoval in both the BPA and ATZ systems has been monitored, with removal efficiencies of 87.7%\nand 35.4%, respectively (Figure R26). The TOC removal efficiency in polymerization-based aqueous\nsystems generally exceeds that in radical-driven systems, consistent with current literature reports.\nDetailed information can be found below (In the revised Supplementary information,\nSupplementary Figure 29):\n100\n87.7\n)\n%\n( 80\ny\nc\nn\ne\nci 60\nfi\nf\ne\nal\nv 40\no 35.4\nm\ne\nr\nC 20\nO\nT\nFigure R26 (Supplementary Figure 29) | Comparison of TOC removal efficiency for BPA and ATZ\nin the ZnO/CuO/PMS System.\n2. The manuscript mentions that Zn sites adsorb and activate pollutants, while Cu sites adsorb and\nactivate oxidants. When encountering different types of pollutants, does the electron transfer pattern\nbetween Zn and Cu change? Please clarify the influence of pollutants with different electron types on\nthe reaction mechanism.\nResponse: We appreciate the constructive feedback from the reviewers. In this reaction system, the\nelectron interaction pattern between zinc and copper has been shown to adapt depending on the type\nof pollutant encountered. Specifically, theoretical calculations have revealed distinct work functions\nfor ZnO (Φ = 5.70 eV) and CuO (Φ = 8.51 eV), with ZnO exhibiting a lower work function, indicating\nits preferential role as an electron donor (Figure R27). Upon contact, electrons flow from ZnO to CuO\nuntil Fermi-level alignment is achieved, resulting in the formation of a built-in electric field (BIEF)\noriented from ZnO to CuO. Bader charge analysis has quantified this interfacial charge redistribution,\nconfirming a net transfer of 1.15 electrons from ZnO to CuO. The BIEF, combined with charge\nredistribution and the intrinsic electronic properties of the pollutants, collectively governs the selection\nof the reaction pathway. For electron-rich pollutants, which act as auxiliary electron donors, the BIEF\nenhances the electron flux from ZnO to CuO. This creates an electron-rich interface that promotes the\nreduction of PMS to SO 2- and sustains an electron transfer pathway (ETP). In contrast, for electron-\n4\ndeficient pollutants, the electron donor function is suppressed. The limited electron supply favors\ncleavage of the O-O bond in PMS, generating SO •-/ •OH through a radical-dominated mechanism.\nwhich confirm an electron transfer mechanism in electron-rich pollutant systems and a radical-based\nmechanism in electron-deficient pollutant systems. Detailed information can be found below (In the\nrevised manuscript, Figure 5):\nFigure R27 (Figure 5) | Dual-site functions and reaction pathway analysis. a, In-situ Raman spectra\nin different ZnO/CuO systems. b, In-situ Raman spectra in different CuO systems. c, In-situ Raman\nspectra in different ZnO systems. d, Comparison of adsorption energies for PMS on Zn and Cu Sites\nin ZnO/CuO catalysts. e, Comparison of adsorption energies for BPA and ATZ on ZnO and ZnO/CuO\ncatalysts. f, Comparison of adsorption energies for BPA and ATZ on CuO and ZnO/CuO catalysts. g,\npDOS of ZnO, CuO, and ZnO/CuO. h, Calculated work functions of ZnO and CuO. i, Schematic of\nbuilt-in electric field and interfacial charge transfer in ZnO/CuO. j, Energy gap difference between the\nLUMO of the ZnO/PMS complex and the HOMO of each pollutant.\n3. How is the heartbeat of zebrafish monitored? How many parallel data points are there in each group?\nResponse: We sincerely thank the reviewers for their thoughtful and constructive suggestions.\nZebrafish heartbeat was observed using a stereomicroscope and quantified by counting beats over a\n20-second interval. Ten biological replicates were included for each experimental group.\n4. The manuscript employs a variety of biological models to assess toxicity. Please provide specific\nexperimental details for each model study.\nResponse: We greatly appreciate the reviewers' detailed feedback. The detailed experimental\nprocedures for the biological models referenced in the manuscript have been provided. Detailed\ninformation can be found below (In the revised Supplementary information, Supplementary\nmethods 6-11):\n“1.6 Assessment of toxicity by E. coli and S. aureus culture experiments\nActivated bacterial strains were prepared by inoculating 50 μL of frozen E. coli and S. aureus\nstock into LB medium. The culture was incubated at 37°C with shaking at 180 rpm for 10 h in a rotary\nincubator (Honour, HNY-200B). Subsequently, fresh LB medium was supplemented with solutions\ncollected from various reaction systems. The activated E. coli and S. aureus culture was transferred to\nthis conditioned medium and incubated under identical conditions for an additional 10 hours.\nFollowing incubation, the bacterial suspension was adjusted to an optical density of 0.1 at 600 nm\n(OD = 0.1) using sterile deionized water. Serial ten-fold dilutions were performed to achieve a final\n600\ndilution factor of 106, and 100 μL aliquots of the diluted suspensions were spread onto agar plates.\nAfter 18 h of incubation at 37°C, bacterial growth was assessed by colony counting. All procedures\nwere conducted in a laminar flow cabinet (AIRTECH, SW-CJ-1FD), with consumables sterilized by\nautoclaving at 121°C for 15 min (IMJ-85A, STIK Co., USA) or by exposure to 254 nm ultraviolet\nradiation for 20 minutes.\n1.7 Toxicity assessment by wheat seed culture experiments\nThe influence of various post-treatment solutions on wheat growth was systematically\ninvestigated using a hydroponic cultivation system. Uniformly plump wheat seeds were selected and\nsurface-sterilized by immersion in 3% hydrogen peroxide (H O ) for 20 min, followed by thorough\n2 2\nrinsing with deionized water. Twenty seeds were evenly arranged on filter paper in petri dishes and\nsupplied with 8 mL of solution from different treatment systems. The dishes were maintained at 25°C\nunder a 12-hour light/12-hour dark photoperiod with a light intensity of 3000 lux. Wheat growth was\nmonitored at 24-hour intervals, and solutions were periodically replenished to maintain consistent\nmoisture levels. Upon stabilization of germination rates, indicating completion of the primary\nsprouting phase, stem lengths were measured to assess seedling growth. Continuous observation\nthroughout the experimental period enabled comprehensive evaluation of treatment effects on plant\ndevelopment and potential phytotoxicity.\n1.8 Toxicity assessment by Chlorella vulgaris culture\nChlorella vulgaris was cultivated in BG-11 medium within conical flasks placed in an illuminated\nincubator under controlled conditions (25 ± 1 °C, 4000 lux illumination, 12 h/12 h light/dark cycle)\nfor 10 days. Cells harvested during the logarithmic growth phase (OD ≈ 0.5) were then transferred\n680\nto fresh BG-11 medium prepared using water from different experimental groups, including blank\ncontrols, untreated BPA or ATZ solutions, and treated BPA or ATZ samples. All media and solutions\nwere sterilized by autoclaving (121 °C, 20 min) prior to use. Biomass accumulation (OD ) and\n680\nchlorophyll a content were monitored at daily intervals across all experimental conditions.\n1.9 Determination of chlorophyll a\nChlorophyll a concentration was determined spectrophotometrically after acetone extraction\naccording to established protocols. Specifically, 10 mL aliquots of algal culture were centrifuged at\n10000 rpm for 10 min. The resulting pellets were resuspended in 10 mL of 90% (v/v) acetone and\nmaintained in complete darkness at 4 ℃ for 24 h to ensure thorough pigment extraction. Absorbance\nreadings were obtained at 750, 663, 645, and 630 nm using a UV-vis spectrophotometer with 90%\nacetone serving as the blank reference. The concentration of chlorophyll a was calculated using the\nfollowing equation:\nChlorophyll a (mg L-1) = 11.64 ×(OD -OD ) – 2.16 ×(OD -OD ) + 0.1 ×(OD -OD ) (S1)\n663 750 645 750 630 750\n1.10 Toxicity assessment by zebrafish culture experiments\nTo obtain a sufficient number of viable embryos, three healthy zebrafish (one female and two\nmales) were housed together in nutrient-enriched water for 12 h. The collected embryos were\nthoroughly rinsed with water from the aquaculture system to remove potential surface contaminants.\nUnder microscopic examination, embryos at the eight-cell developmental stage were specifically\nselected and separated for subsequent experimental procedures. Exposure solutions were prepared for\ndifferent experimental groups: the treatment group received solutions collected from various reaction\nsystems; the blank control group was maintained in nutrient solution alone; and the pollutant control\ngroup was exposed to untreated BPA or ATZ solutions. The embryos were distributed into 24-well\nplates, with each well containing 1 mL of nutrient solution and 1 mL of the designated exposure\nsolution, and one embryo per well (n=10 per group). From the initiation of exposure until zebrafish\nhatching, embryonic development was monitored every 24 h using microscopy. These observations\naimed to assess the teratogenic effects of the exposure solutions on both embryonic and larval stages,\nensuring accurate and reliable evaluation of potential developmental toxicity. Intracellular reactive\noxygen species (ROS) in zebrafish larvae were detected using the fluorescent probe DCFH-DA. After\n120 hours of exposure, larvae were incubated with 10 μM DCFH-DA in darkness at 28 °C for one hour.\nROS levels were subsequently visualized and analyzed using an AE31E inverted fluorescence\nmicroscope.\n1.11 Non-targeted metabolomics analysis\nFor metabolomic analysis, approximately 50 mg of zebrafish tissue was collected per\nexperimental group (including BPA and BPA-treated systems) as biological replicates (n=3 per group).\nMetabolite extraction was performed according to the following procedure: 200 μL of ice-cold water\nand two steel beads were added to each sample, followed by homogenization using a high-throughput\ntissue grinder at 55 Hz for 60 s (repeated twice). Subsequently, 800 μL of methanol: acetonitrile (1:1,\nv/v) was added, and the mixture was subjected to ultrasonic extraction for 30 min. After incubation at\n-20°C for 45 min, samples were centrifuged at 12,000 rpm for 20 min at 4°C. An 800 μL aliquot of the\nsupernatant was collected and concentrated to complete dryness under vacuum. The residue was\nreconstituted in 150 μL of 50% methanol containing 5 ppm 2-chlorophenylalanine, vortexed for 30 s,\nand centrifuged at 12,000 rpm for 10 min at 4°C. The resulting supernatant was filtered through a 0.22\nμm membrane, followed by an additional centrifugation step under identical conditions. The final\nfiltrate was transferred to autosampler vials for subsequent analysis.\nChromatographic separation was performed using an ACQUITY UPLC HSS T3 column (100Å,\n1.8 μm, 2.1 mm × 100 mm) maintained at 40°C. The mobile phase flow rate and injection volume were\nset to 0.4 mL min-1 and 2 μL, respectively. For both positive and negative ionization modes, mobile\nphase A consisted of 0.1% formic acid in water, while mobile phase B was acetonitrile containing 0.1%\nformic acid.\nMass spectrometric analysis was conducted on a Thermo Q Exactive HF-X instrument controlled\nby Xcalibur software (v4.7) operating in data-dependent acquisition (DDA) mode for both positive\nand negative ionization. The HESI source parameters were configured as follows: spray voltage 3.5\nkV, sheath gas 40 arb, auxiliary gas 10 arb, capillary temperature 320°C, and auxiliary gas heater\ntemperature 300°C. Full MS scans were acquired at a resolution of 60,000 across the m/z range 70-\n1000 with an AGC target of \"standard\" and maximum injection time of 100 ms. The top 10 most intense\nions were selected for fragmentation with a dynamic exclusion duration of 4 s. MS/MS spectra were\ncollected at a resolution of 15,000 using 30% HCD collision energy with automatic maximum injection\ntime.\nRaw data files were processed using MS-DIAL software (v4.9.221218) for peak picking,\nalignment, filtering, and metabolite annotation. Metabolite identification was performed against the\nPSNGM database, which integrates multiple reference libraries including in-house standards,\nmzCloud (https://www.mzcloud.org/), LIPIDMAPS (https://www.lipidmaps.org/), HMDB\n(https://hmdb.ca/), MoNA (https://mona.fiehnlab.ucdavis.edu/), NIST_2020_MSMS, and AI-predicted\nMS/MS spectra. Database search parameters were set as follows: MS1 tolerance for identification\n0.01, MS2 tolerance for identification 0.05, Smoothing level 3, Minimum peak height 10000, Minimum\npeak width 5, Mass slice width 0.05, Identification score cutoff 70.”\n5. The symbols “RS, Ox, Cat, P” in Figure 1 should be annotated with explanatory notes within the\nfigure.\nResponse: We thank the reviewers for their careful evaluation and helpful recommendations. The\nabbreviations used in the figures have been clearly defined to ensure standardization and accuracy.\nDetailed information can be found below (In the revised manuscript, Figure 1):\nFigure R28 (Figure 1) | Design principles and research approach for dual-substrate systems activated\nby dual-function site catalysts.\n6. Some fonts in the image are too small to read clearly. Please optimize them further.\nResponse: We greatly appreciate the reviewers' detailed feedback. The text labels in the figures have\nbeen optimized to ensure clarity and accuracy. Detailed information can be found below (In the\nrevised manuscript, Figure 4):\nFigure R29 (Figure 4) | Active-species identification and electrochemical diagnostics. a, BPA\ndegradation in the ZnO/CuO/PMS system with quenchers ([TBA] = [MeOH] = 50 mM, [TEMPOL] =\n[p-BQ]= 1 mM, [L‑histidine] = [β-carotene] =1 mM, [PMSO] = 1 mM, [DMSO] = 20 mM). b, BPA\ndegradation by the ZnO/CuO/PMS reaction system in the presence of different TBA and MeOH\nconcentrations. c, ATZ degradation by the ZnO/CuO/PMS reaction system in the presence of different\nTBA and MeOH concentrations. Error bars indicate standard deviations based on duplicate\nexperiments. d, DMPO spin-trapping ESR spectra for DMPO-SO - and TEMP-based ESR spectra for\n4\n1O in the ZnO/CuO/PMS/BPA system. e, DMPO spin-trapping ESR spectra for DMPO-SO - in the\n2 4\nZnO/CuO/PMS/ATZ system. f, Open-circuit potentials (OCP) changes upon sequential addition of\nPMS and contaminants (inset: i-t (current-time) curves). g, Electrochemical impedance spectra (EIS)\nof catalysts (inset: EIS for ZnO/CuO under different conditions). h, Linear sweep voltammetry (LSV)\nof catalyst electrodes (inset: LSV curves of ZnO/CuO electrodes under different conditions).\n7. Metabolomics analysis was employed in the manuscript. The numbers and codes in Figure 7 should\nbe provided with specific corresponding explanations.\nResponse: We sincerely thank the reviewers for their valuable feedback. The numerical labels and\ncoding used in the figures have been fully explained and defined. (In the revised Supplementary\ninformation, Supplementary tables 15-16):\nSupplementary Table 15 | Table of absolute abundance of metabolites ranked by importance (Top\n20, Default).\nMetabolite ID Super-Class\nMP21278 Lipids and lipid-like molecules\nMP11285 Lipids and lipid-like molecules\nMP13705 /\nMP14770 Lipids and lipid-like molecules\nMP10181 Lipids and lipid-like molecules\nMP7694 Organoheterocyclic compounds\nMP14716 Nucleosides, nucleotides, and analogues\nMP10411 /\nMP15223 /\nMP4999 /\nMP18742 Lipids and lipid-like molecules\nMP16686 Organoheterocyclic compounds\nMP18498 Lipids and lipid-like molecules\nMP8401 Organic acids and derivatives\nMP9793 Lipids and lipid-like molecules\nMP22128 Organic acids and derivatives\nMP16811 Organoheterocyclic compounds\nMP4513 Organoheterocyclic compounds\nMP9898 Organic acids and derivatives\nMP13591 Organic acids and derivatives\nSupplementary Table 16 | Pathway name corresponding to the ID in the KEGG pathway diagram.\nPathway ID Pathway name\n1 beta-Alanine metabolism\n3 3.9±0.6 Purine metabolism\n15 mTOR signaling pathway\nGlycosaminoglycan biosynthesis - chondroitin sulfate /\n16\ndermatan sulfate"}, {"round": 2, "reviewer_comments": {"reviewer_2": "The authors have comprehensively and adequately addressed all reviewers' comments. The additional data provided for the experimental section effectively support the conclusions. The language and logic of the manuscript have been significantly improved through revision. Therefore, it is recommended that this manuscript be accepted.", "reviewer_3": "Zhang et al. develop a dual-site catalyst where zinc centers activate pollutants while copper sites activate oxidants. This work provides a cooperative catalytic strategy that overcomes single-site limitations and offers practical principles for wastewater treatment. The authors have addressed the reviewers questions point by point. The research is innovative and comprehensive, with findings that are clearly illustrated through effective and well-designed schematics. I recommend to accept for the publication in Nature Communications."}, "author_response": "Response to Reviewer 2’s Comments\nThe authors have comprehensively and adequately addressed all reviewers' comments. The\nadditional data provided for the experimental section effectively support the conclusions. The language\nand logic of the manuscript have been significantly improved through revision. Therefore, it is\nrecommended that this manuscript be accepted.\nResponse: Thank you for your positive response and recognition of our revisions.\nR1\nResponse to Reviewer 3’s Comments\nZhang et al. develop a dual-site catalyst where zinc centers activate pollutants while copper sites\nactivate oxidants. This work provides a cooperative catalytic strategy that overcomes single-site\nlimitations and offers practical principles for wastewater treatment. The authors have addressed the\nreviewers questions point by point. The research is innovative and comprehensive, with findings that\nare clearly illustrated through effective and well-designed schematics. I recommend to accept for the\npublication in Nature Communications..\nResponse: We appreciate your recognition of our work and your efforts in the revision process.\nR2"}]

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