the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
| 27 May 2026
Heterogeneous Nitrosation Reactions of Amines Driven by Dinitrogen Tetroxide: A Missing Source of Particulate Nitrosamines
Abstract. Nitrosamines are highly carcinogenic and reactive nitrogen-containing pollutants that are widely detected in atmospheric particulate matter; however, their formation mechanisms remain poorly understood. Herein, we elucidate previously unrecognized yet kinetically viable heterogeneous mechanisms for nitrosamine formation via amine-mediated reactions with dinitrogen tetroxide (N2O4) at the air–water interface, using Born–Oppenheimer molecular dynamics simulations. The reactions proceed via two distinct pathways: (i) barrierless N-nitrosation of methylamine (MA) or dimethylamine (DMA) by N2O4, directly yielding nitrosamine cations and nitrate ions (NO3−); and (ii) MA/DMA-mediated hydrolysis of N2O4 produces interfacial HONO rapidly within ~2–16 ps, which can further react with amines to form nitrosamines, albeit with a relatively high reaction barrier of 7.65 kcal mol−1. Overall, the amine-mediated interfacial N-nitrosation reactions proceed rapidly and may represent an important source of particulate nitrosamines. Meanwhile, amine-mediated interfacial hydrolysis of N2O4 is a potential source of HONO, proceeding through the combined effects of interfacial water bridging and strong basicity of amines. Our findings reveal a previously overlooked role of heterogeneous interfacial chemistry in elevated particulate nitrosamine formation and coupled HONO production, with important implications for urban reactive nitrogen cycling and its representation in chemical transport models.
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Status: final response (author comments only)
- RC1: 'Comment on egusphere-2026-2401', Anonymous Referee #1, 10 Jun 2026
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RC2: 'Comment on egusphere-2026-2401', Anonymous Referee #2, 16 Jul 2026
General comments
The current study presents an interesting and potentially important contribution to the understanding of heterogeneous nitrosamine formation mediated by N2O4 at the air–water interface, that addresses a significant knowledge gap concerning observed concentrations of particulate nitrosamines. The Born–Oppenheimer molecular dynamics and metadynamics simulations are carefully designed and performed, demonstrating the mechanistic feasibility of spontaneous N2O4-mediated nitrosation. Nevertheless, the work establishes mechanistic plausibility more convincingly than quantitative kinetic significance, and several important issues require clarification before the atmospheric implications can be fully substantiated. For these reasons, I support publication after major revision, provided that the following points are satisfactorily addressed.Specific comments
The abstract should be written in a clearer way, with a more distinct presentation of the key findings. For example, a general overview of the competing reactions under different environments (as illustrated in Figure 5) could make the abstract more appealing and concise.
The introduction should be significantly improved, since key related preceding studies are missing. The “Theoretical Investigation of Nitration and Nitrosation of Dimethylamine by N2O4” (J. Phys. Chem. A 2008, 112, 7098–7105) as well as some of the references included in that study, should be presented and later compared/commented in the “Discussions” part. Also, a more in-depth search in the literature on experiments revolving around N-nitration of amines in the particle phase (e.g. Chemosphere 293 (2022) 133639) could help substantially in the discussion of the theoretical results.
The discussion would benefit from a more critical comparison with previous atmospheric kinetic models, particularly the SINTEF aqueous-phase chemistry mechanism (Karl et al., 2012) and the work of Choi et al. (2021, 2025a). Those studies employ effective rate coefficients for the reactions of DMA with HONO, N2O3, and N2O4 that are largely derived, estimated, or calibrated rather than directly measured or obtained from first-principles kinetics. The authors should therefore discuss how the proposed N2O4-mediated mechanism modifies or replaces these existing parameterizations and whether its inclusion would quantitatively alter current atmospheric models.
Furthermore, the conclusion that direct N2O4-mediated nitrosation represents the dominant heterogeneous pathway is based primarily on comparison with the HONO-mediated route, whereas another well-established atmospheric nitrosating agent, N2O3, is not considered. Since previous atmospheric models consistently identify both N2O4 and N2O4 as relevant nitrosating species, omission of the N2O3 pathway makes it difficult to assess whether the proposed mechanism is genuinely dominant or simply one of several competing routes. The authors are, therefore, encouraged to at least discuss the potential role of N2O3 and justify its exclusion from the present work.
While Interfacial N-nitrosation reactions and Interfacial Hydrolysis of t-ONONO2 were studied for both MA and DMA, interfacial reaction with HONO was studied only for DMA. Please provide justification for this selection.
Moreover, the TST-derived interfacial rate constant should be compared to the gas- and aqueous-phase rate constants derived directly from the authors' own calculated potential energy surfaces, rather than with values reported in technical reports (e.g., Karl et al., 2012).
In this context, the potential energy surface presented in Figure S12 raises several concerns. The pre-reactive complex (ER1) appears to adopt substantially different geometries in the gas and aqueous phases while exhibiting essentially identical relative energies, which deserves further explanation. In addition, the large change in the imaginary frequency of TS1 between the gas and aqueous phases, together with the presence of several low-frequency modes in the pre- and post-reactive complexes, raises concerns regarding the reliability of the B3LYP-D3/6-311++G(3df,2p) level of theory for describing such weakly bound systems.
Overall, I recommend either (i) re-evaluating this reaction using a higher-level electronic structure method (with a more robust characterization of the stationary points and TST analysis), or (ii) removing the quantitative kinetic discussion of the HONO pathway altogether.
Technical corrections
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. World Health Organization (WHO), 1978. The latest updated monograph should be cited.Citations missing from the Computational Methods section, e.g. Grimme’s D3 dispersion correction, CCSD(T) ab-initio method, should be added.
What do the yellow arrows of Scheme 1 represent?
In Section S4 of the Supporting Information, the degeneracy σ should be explicitly given, along with a reference for TST theory.
In Figure S4, does the green line actually represent the distance N1-N2 that is gradually increasing after 10 ps? Also, N1-O2 remains fixed at 2.0 Å? Please control.
Line 19: produce should be producing
Line 59: Add…mechanism can explain
Line 71: Delete “And” in the sentence “And the DZVP-MOLOPT-SR-GTH…”
Line 44: “Since HONO is also a key nitrosamine precursor, this pathway is explored in detail in a following section.
Line 240: ConclusionsCitation: https://doi.org/10.5194/egusphere-2026-2401-RC2
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- 1
Chi et al. present a well-designed theoretical study on the heterogeneous formation mechanisms of carcinogenic nitrosamines at the air–water interface. Using ab initio molecular dynamics simulations, the authors demonstrate that amines (MA/DMA) can rapidly react with dinitrogen tetroxide (N2O4) at aqueous aerosol surfaces, resulting in the direct formation of particulate nitrosamines and nitrate. This study provides in-depth mechanistic insights into the particulate nitrosamine production in urban atmospheres. Additionally, combination of BOMD and metadynamics simulations enables a precise monitoring of these ultrafast interfacial processes, and the accompanying wave function analyses enhance mechanistic interpretation. Overall, this manuscript is well-designed and contains substantial theoretical results. The obtained theoretical results are of significant importance to atmospheric multiphase chemistry and aerosol interfacial processes. The reviewer recommends publication of this manuscript in Atmos. Chem. Phys. after the following minor concerns are addressed:
1. Schemes 1 and 2 are very informative and greatly aid the understanding of the proposed reaction mechanisms. However, Scheme 2 (iii) should be explicitly referenced and discussed in Section 3.2 to better direct the readers to the mechanistic pathways presented. In addition, the authors should further clarify why the reaction pathway shown in Scheme 2 (iii) is not feasible. Notably, the preformed complex involved in Scheme 2 (iii) appears to be the same as that shown in Scheme 1 (ii). In Scheme 1 (ii), collision of this complex with the air–water interface directly leads to nitrosation at the interface. However, this does not adequately explain why hydrolysis cannot occur when the same complex interacts with the air–water interface. A more detailed mechanistic explanation distinguishing the feasibility of nitrosation versus hydrolysis pathways would strengthen the interpretation of the interfacial reaction mechanisms.
2. It is recommended to cite recent key studies in the “introduction” to offer a clear picture regarding the “reaction-accelerating effect of the air-water interface”.
3. The conclusion effectively summarizes the key findings. Please explicitly reiterate the “missing source” aspect in the final paragraph to tie it back to the Abstract and resonate with the readers.
4. The environmental implications of simultaneous HONO and nitrate formation deserve further emphasis. The manuscript primarily focuses on nitrosamine production, while the concurrent formation of HONO and nitrate is not strictly discussed. From an atmospheric chemistry perspective, this coupled production pathway could be highly important because it simultaneously influences oxidation capacity, aerosol nitrate burden, and reactive nitrogen cycling. The authors may consider expanding this discussion in the Conclusion section to better highlight the broader implications of the revealed chemistry beyond nitrosamine formation alone.
5. The discussion of HONO-mediated nitrosation could be strengthened to better contextualize its atmospheric significance. Although the HONO + DMA pathway is identified as secondary due to its higher free-energy barrier, the calculated interfacial rate constant is still reported to be 7-8 orders of magnitude faster than the corresponding aqueous-phase value. This represents a remarkably strong interfacial enhancement. The authors may therefore consider discussing under what atmospheric conditions this secondary pathway could nevertheless become important, such as in aged aerosols or HONO-rich nighttime environments.
6. Typos and non-scientific corrections:
a). Line 73: Add the missing article “the” before “plane-wave basis set”: “...while that for the plane-wave basis set was set to 280 Ry.”
b). Section 3.3: In the sentence “Although the calculated energy barrier... is 7.65 kcal mol−1... which is significantly lower...”, the relative clause is awkward. Please split this into two sentences or rephrase to “Although the calculated energy barrier is 7.65 kcal mol−1—a value significantly lower than...”
c). Table S1: Please specify “Vibrational frequencies” in the header instead of “Calculated frequencies”.