General Comments

The manuscript presents a multiscale computational investigation (DFT, MD, and QSAR) of the atmospheric fate of 2,4-dinitrophenol (2,4-DNP), concluding that oxidation is dominated by OH and O₃ pathways, that interfacial hydration modulates adsorption, and that ozonolysis products exhibit increased toxicity potential. While the computational work is detailed, the manuscript does not yet demonstrate sufficient novelty relative to existing phenolic oxidation literature and lacks adequate integration, atmospheric context, and validation of its conclusions. In particular, the study remains weakly connected to established multiphase phenolic chemistry, relies on simplified modeling assumptions (e.g., C60 surrogate), and overextends its interpretation to atmospheric and toxicological implications. Overall, the manuscript requires substantial revision to improve novelty definition, literature integration, quantitative atmospheric relevance, and consistency between the computational results and the conclusions. In its current form, the manuscript does not meet the standards for publication in ACP; however, the issues identified may be addressable through substantial revision.

Major Comments

1) The novelty of the work is not adequately established relative to prior phenolic oxidation studies. The manuscript should more clearly define its novelty relative to the extensive literature on phenolic oxidation in gas, aqueous, and interfacial environments. At present, the core conclusions (competitive O₃ and OH oxidation, multiphase reactivity, interfacial processes, and formation of secondary products) overlap substantially with established studies, and it is not clear what is fundamentally new for 2,4‑DNP beyond substituent effects. The work should explicitly compare their results with relevant experimental and mechanistic studies, including interfacial and heterogeneous catechol oxidation (Pillar et al., Environ. Sci. Technol., 2014, DOI: 10.1021/es504094x; Pillar et al., J. Phys. Chem. A, 2015, DOI: 10.1021/acs.jpca.5b07914; Pillar and Guzman, Environ. Sci. Technol., 2017, DOI: 10.1021/acs.est.7b00232), phenolic-aldehyde oxidation at air-water and air-solid interfaces (Rana and Guzman, J. Phys. Chem. A, 2020, DOI: 10.1021/acs.jpca.0c05944; Rana and Guzman, ACS Earth Space Chem., 2022, DOI: 10.1021/acsearthspacechem.2c00206; Rana and Guzman, J. Phys. Chem. A, 2022, DOI: 10.1021/acs.jpca.2c04963), and aqueous ozonolysis of phenolic aldehydes producing small organic acids (Witt et al., Sci. Total Environ., 2025, DOI: 10.1016/j.scitotenv.2025.180190). The manuscript should also address multiphase NO₂/O₃ chemistry in microdroplets (Rana et al., ACS ES&T Air, 2024, DOI: 10.1021/acsestair.3c00001), particularly in relation to the discussion of NO₂ reactivity. The manuscript should therefore add a clear novelty statement in the introduction, explicitly identifying what mechanistic features are unique to 2,4‑DNP, whether the hydration effects identified are new or an extension of known interfacial behavior, and how the predicted products differ from those observed in related phenolic systems.

2) The manuscript is missing aqueous SOA, brown-carbon, and multiphase aging context. The manuscript should better connect the computed chemistry to aqueous SOA formation, brown‑carbon production, and multiphase aging processes. At present, the discussion focuses on individual intermediates and QSAR toxicity predictions, without addressing the broader product distributions expected for phenolic systems. The work should incorporate relevant interfacial and multiphase literature, including oxidative oligomerization of catechol (Guzman et al., ACS Omega, 2022, DOI: 10.1021/acsomega.2c05290), which demonstrates formation of oligomeric products linked to aerosol aging and brown carbon. The manuscript should also acknowledge that particle composition and chemistry can significantly affect product formation, as shown for iron‑catalyzed aerosol reactions and aminophenol‑derived brown carbon (Al‑Abadleh et al., Environ. Sci. Technol., 2021, DOI: 10.1021/acs.est.0c05678; Al‑Abadleh et al., Commun. Chem., 2022, DOI: 10.1038/s42004-022-00732-1).

In addition, the broader framework of dynamic heterogeneous oxidation in the troposphere should be considered (Pillar‑Little and Guzman, Environments, 2018, DOI: 10.3390/environments5090104) to better place the results in an atmospheric context. The manuscript should therefore expand the introduction and discussion to relate 2,4‑DNP oxidation pathways to SOA formation, brown carbon, oligomerization, and experimentally observed multiphase aging mechanisms, or explicitly limit its interpretation to molecular-scale chemistry.

3) The atmospheric framework of the manuscript is fragmented and not quantitatively integrated. The manuscript should better integrate the DFT kinetics, MD adsorption results, and QSAR toxicity analysis into a coherent atmospheric framework. At present, these components remain disconnected and are not linked to realistic atmospheric conditions. The work should incorporate key elements required for integration, including phase partitioning or distribution estimates, a linkage between adsorption and reactivity, product-yield considerations, and exposure-relevant concentration context for toxicity. The manuscript should therefore introduce a clear conceptual or quantitative framework connecting gas-phase, aqueous-phase, and interfacial processes. At a minimum, a schematic mass‑fate diagram should be included to show how the different computational results collectively inform the atmospheric transformation and impact of 2,4-DNP.

4) The manuscript should better justify the use of C60 as an aerosol surrogate and explicitly acknowledge its limitations. While useful for probing simplified π-π and dispersion interactions, C60 does not represent the chemical complexity of atmospheric particles, which can include inorganic salts, oxidized organics, soot, metals, and variable phase states. The work should add a concise limitations paragraph noting that key processes (such as metal‑catalyzed reactions, acidity effects, and viscosity‑dependent chemistry) are not captured in the current model.

The manuscript should also acknowledge that iron‑catalyzed aerosol chemistry can strongly influence product distributions and brown‑carbon formation (Al‑Abadleh et al., Environ. Sci. Technol., 2021, DOI: 10.1021/acs.est.0c05678), and that aminophenol reactions can produce nitrogen‑containing brown carbon in metal‑containing systems (Al‑Abadleh et al., Commun. Chem., 2022, DOI: 10.1038/s42004-022-00732-1). In addition, the work should note that interfacial reactivity depends on surface composition, as demonstrated for catechol on TiO₂ surfaces (Hoque et al., J. Phys. Chem. C, 2024, DOI: 10.1021/acs.jpcc.4c05777). The manuscript should therefore clearly state that C60 is an idealized surrogate, moderate generalizations to atmospheric aerosols, and include a brief limitations section describing the missing aerosol properties and their implications for atmospheric interpretation.

5) MD simulations are insufficient to support atmospheric residence-time and transport conclusions. The manuscript should restrict the interpretation of the MD results to molecular-scale adsorption behavior in the idealized C60/water/2,4‑DNP system. The current conclusions regarding atmospheric residence time, long-range transport, and humidity-dependent persistence are not supported by the simulations alone.

The authors should therefore remove or substantially qualify these claims, unless they provide additional quantitative analysis (e.g., atmospheric lifetime estimates, gas–particle partitioning, uptake coefficients, or comparison with experimental/field data). The manuscript should also clarify that key aerosol properties controlling humidity effects (such as liquid water content, ionic strength, phase behavior, viscosity, and particle morphology) are not represented in the current MD model, and discuss how this limits the atmospheric interpretation of the results.

6) The kinetic analysis requires broader validation and atmospheric context. The manuscript should strengthen the validation and interpretation of the calculated rate constants. At present, comparisons are limited and do not adequately benchmark the results against established phenolic oxidation literature. The work should incorporate relevant interfacial and heterogeneous studies (e.g., Pillar et al., Environ. Sci. Technol., 2014, DOI: 10.1021/es504094x; Pillar et al., J. Phys. Chem. A, 2015, DOI: 10.1021/acs.jpca.5b07914; Pillar and Guzman, Environ. Sci. Technol., 2017, DOI: 10.1021/acs.est.7b00232; Rana and Guzman, J. Phys. Chem. A, 2020, DOI: 10.1021/acs.jpca.0c05944) to assess whether the predicted trends for OH and O₃ are consistent with known behavior. The work should also avoid interpreting bimolecular rate constants alone as indicators of atmospheric importance.

7) The treatment of NO₂ chemistry is oversimplified and should be refined. While the calculated rate constants suggest that direct NO₂ reaction with 2,4‑DNP is slow, the discussion should distinguish this from NO₂ involvement in secondary and multiphase processes. The authors should incorporate relevant multiphase studies (e.g., Rana et al., ACS ES&T Air, 2024, DOI: 10.1021/acsestair.3c00001) and clarify the difference between direct reaction of the parent compound and reactions involving oxidized intermediates. This distinction is already implied by the reported low‑barrier pathways for intermediate + NO₂ reactions, but is not consistently reflected in the conclusions. The manuscript should therefore clearly separate (i) direct NO₂ reaction with 2,4‑DNP, (ii) NO₂ reactions with oxidation intermediates, and (iii) multiphase NO₂/O₃ chemistry, and revise the discussion accordingly to avoid overly broad statements about negligible NO₂ reactivity.

8) Photochemistry and nitrate radical chemistry are insufficiently considered in the manuscript. Therefore, the revised manuscript should acknowledge and justify the exclusion of photolysis and nitrate radical chemistry. Given that 2,4‑DNP phototransformation in atmospheric water has been previously reported (Albinet et al., Chemosphere, 2010, DOI: 10.1016/j.chemosphere.2010.05.016), the work should explain why photolysis is not included in the reaction framework.

The manuscript should also incorporate relevant nitrate radical chemistry, including interfacial oxidation of catechols (Rana and Guzman, Environ. Sci. Technol., 2022, DOI: 10.1021/acs.est.2c05640) and its broader role in organic aerosol formation (Ng et al., Atmos. Chem. Phys., 2017, DOI: 10.5194/acp-17-2103-2017). The manuscript should therefore include a short limitations section addressing these excluded pathways and clarifying how their omission affects the atmospheric interpretation.

9) The toxicity amplification claim is overstated. The manuscript should moderate its interpretation of the toxicity results. The current claims of increased toxicity are based solely on QSAR predictions without experimental validation, product yield information, or exposure context. The revision should explicitly frame these results as screening-level predictions and revise the language accordingly. For example, “toxicity amplification” should be replaced with more cautious phrasing such as “predicted increase in selected toxicity indicators.” The discussion should also acknowledge uncertainties associated with QSAR classification thresholds and transformation‑product toxicity (e.g., Vom Eyser et al., Water Sci. Technol., 2013, DOI: 10.2166/wst.2013.452). The manuscript should either move detailed QSAR analysis to the supplement or clearly limit its role in the overall conclusions.

10) The atmospheric implications are overstated and should be revised. The manuscript should substantially revise or qualify its atmospheric implications. Current statements regarding long‑range transport, humidity‑dependent persistence, and underestimation in air‑quality models are not supported by quantitative analysis. The revision should limit conclusions to what is directly supported by the computational results or provide additional atmospheric context (e.g., partitioning, lifetime estimates, or exposure analysis). The discussion should also acknowledge that phenolic atmospheric chemistry is governed by multiple competing pathways, including metal‑catalyzed reactions, nitrate radical oxidation, and multiphase oligomerization (Al‑Abadleh et al., Environ. Sci. Technol., 2021, DOI: 10.1021/acs.est.0c05678; Rana and Guzman, Environ. Sci. Technol., 2022, DOI: 10.1021/acs.est.2c05640; Guzman et al., ACS Omega, 2022, DOI: 10.1021/acsomega.2c05290; Rana et al., ACS ES&T Air, 2024, DOI: 10.1021/acsestair.3c00001). The manuscript should therefore remove or clearly qualify claims about global or regulatory implications unless supported by additional analysis.

Minor Comments

1. The abstract should clearly distinguish gas-phase, aqueous-phase, and interfacial results.
2. Replace “governs” in the title (and elsewhere) with a weaker term such as “modulates” or “influences.”
3. Replace “toxicity amplification” in the title with more cautious language (e.g., “predicted increase in toxicity indicators”).
4. Clarify the definition and context of reported rate constants, and improve discussion of Table S2.
5. Add pseudo-first order loss estimates or limit interpretation to relative trends.
6. Clearly state that C60 is an idealized surrogate and not representative of real aerosols.
7. Justify the MD timescale or reduce the strength of related conclusions.
8. Explain why photolysis is not included in the reaction framework.
9. Acknowledge nitrate radical chemistry as a relevant but excluded pathway.
10. Correct the formatting error in Table S3 (next to the rate constant of nitrophenol).
11. Improve figure clarity and ensure all pathways, phases, and units are clearly labeled.
12. Move detailed mechanistic/geometric descriptions to the supplement where appropriate.
13. Expand discussion of QSAR uncertainty and threshold limitations (Table S4).
14. Revise the conclusions to clearly separate computational results from atmospheric implications and avoid unsupported claims.

This study constructs a coherent multiscale framework that systematically links the molecular reaction mechanisms, interfacial adsorption behavior, and toxicological evolution of 2,4-dinitrophenol. The integration of density functional theory, molecular dynamics, and QSAR approaches represents a clear strength of this work and reflects a modern, multidisciplinary research strategy. However, the important finding that ozonolysis does not detoxify but instead amplifies toxicity requires more robust support. The specific comments are as follows.

Major comments:

1. C60 is used as a proxy for carbonaceous aerosols, but it is not representative of real particles (mainly amorphous carbon with functional groups). The authors should justify this choice and discuss potential overestimation of π–π interactions and underestimation of polar interactions. Including a complementary simulation with a more realistic model (e.g., amorphous carbon) would strengthen the work.
2. The authors note the concentration gap between O₂ and NO₂ but do not perform the necessary competition calculation. Given that O₂ (~0.2 atm, ~5×10¹⁸ cm^-3) is about 10⁸ – 10⁹ times more abundant than NO₂ (~ppb, ~10¹⁰ cm^-3), the effective rate (k×[oxidant]) must be computed to identify the dominant pathway.
3. The 1 ns MD production run is too short for this complex interface. I recommend extending the simulation to at least 10–20 ns and showing convergence plots (e.g., RMSD and total energy vs. time). The choice of the AMBER99SB-ILDN + GAFF force field also needs justification, especially for polarisation in aromatic–fullerene interactions; benchmarking against a polarisable force field or ab initio MD would increase confidence.
4. Before concluding that ozonolysis amplifies toxicity, the authors should first establish whether it is indeed the dominant atmospheric transformation pathway for 2,4-DNP. Moreover, the toxicity assessment relies solely on the T.E.S.T. QSAR tool; cross‑validation with at least one independent model (e.g., ECOSAR, ADMETlab) is recommended, along with a clear discussion of applicability domains and prediction uncertainties. High‑risk products such as IM54 should be explicitly prioritised for experimental validation.
5. The introduction cites many references but does not clearly define the central knowledge gap. The conclusion mostly restates the findings without offering concrete recommendations for modelling, monitoring, or experimental validation. Please sharpen the research question in the Introduction and add specific action-oriented suggestions in the Conclusion.

Minor Comments:

1. Have the authors clearly described the methodology used to compute the aqueous-phase rate constants?
2. The statement “Green regions (Δfω > 0) … showing electrophilic features” is ambiguous. These regions indicate electron‐poor sites that are susceptible to nucleophilic attack; please revise to avoid confusion.
3. Figures 3 and 5: Energy units and axis labels are not clearly legible.
4. Although Tables S1–S4 are mentioned, no concise visual summary or comparative plot is included in the main text to help readers quickly grasp the key data. It would be helpful to present a summary (e.g., a bar chart of rate constants or a table of key energy barriers) in the main paper, with full details left to the Supplement.
5. In summary, while this manuscript is rich in content, its overall logic is not clearly presented. The authors should explicitly state the specific research questions and scope of this study in the final paragraph of the Introduction.

This study conceptualizes an integrated computational framework combining DFT, MD simulations, and QSAR models to systematically investigate the chemical degradation mechanisms, aerosol surface hydration behavior, and ecotoxicity evolution of 2,4-dinitrophenol in atmospheric multiphase environments. Although this closed-loop, interdisciplinary approach is somewhat novel at the theoretical level, however, due to the parallel comparison of multiphase rate constants being decoupled from atmospheric physical reality (failing to account for Henry's law partitioning and liquid water content), the selected black carbon aerosol surrogate model (pure fullerene C60​) being overly idealized, and the core toxicity conclusions relying entirely on boundary-unstable in silico software predictions lacking any experimental validation, the research findings exhibit a strong sense of being "castles in the air".

Specific Issues or Suggestions for Improvement:

The introduction exhibits obvious selective bias and logical leaps in its literature review. In fact, over the past five years, extensive literature has been published on the aqueous-phase ·OH oxidation and photochemical degradation of nitrophenolic compounds. The introduction fails to accurately delineate research progress across the three domains of "pure gas phase," "pure aqueous phase," and "gas-liquid/gas-solid interfaces," resulting in a rough and inaccurate summary of the existing research landscape.

The introduction completely fails to summarize existing literature on the surface adsorption of real atmospheric carbonaceous aerosols (such as black carbon, soot, and amorphous carbon). The introduction does not clarify "what bottlenecks existing studies have encountered in simulating carbonaceous particle surfaces," and instead abruptly introduces C₆₀ without accurately reflecting the actual research progress in the field of multiphase adsorption on atmospheric particles.

The introduction merely glosses over this with a single sentence—"traditional experiments are difficult to fully identify"—and fails to clearly summarize the latest progress in computational toxicology (QSAR) for evaluating atmospheric secondary products. This makes the subsequent discussion on toxicity appear abrupt and lacking a solid literature foundation.

The manuscript focuses exclusively on a single compound, 2,4-DNP, yet repeatedly draws overarching conclusions about the atmospheric fate and risk amplification of 'nitrophenolic compounds' or 'nitroaromatics' as a whole.

The authors convert the aqueous rate constants to cm3molecule−1s−1 and directly plot them alongside gas-phase constants in Figure 3. In the actual atmosphere, the overall contribution of a multi-phase pathway depends on the partitioning of the pollutant (Henry’s law) and the Liquid Water Content (LWC) of the aerosol. Merely comparing converted rate constants fails to establish whether the aqueous-phase reactions actually matter to the total atmospheric fate of 2,4-DNP.

The ecotoxicity profiling relies completely on the US EPA’s software. QSAR screening is excellent for high-throughput hazard prioritization, but drawing definitive conclusions about environmental risk amplification ("toxicity amplification") purely from in silico endpoints is speculative.

The authors claim that the direct transformation initiated by ∙NO2​ is completely negligible under ambient conditions because its barrier is much higher than OH pathways. This is an unbalance in atmospheric interpretation. During heavily polluted night events, ∙OH radical concentrations drop close, whereas ∙NO2​ accumulates significantly. Discarding a daytime-uncompetitive pathway without conducting a true diurnal chemical box-model or sensitivity analysis under varying pollution regimes is scientifically weak.