This is a well-written paper summarizing the area of multiphase chemistry and some important remaining challenges. It is difficult to appropriately reference all of the contributions to such a broad topic but overall, they have done a good job at this and the paper will be a valuable resource, especially to those not familiar with this area.

That said, a general comment is that there is some inconsistency in the referencing. In some cases, references are made to the original, foundational papers (e.g. line 77, Hoffmann and Edwards, 1975; Penkett et al., 1979; also references on lines 128, 130). In this reviewer’s opinion, this is excellent as there is an increasing tendency in the literature to only cite the last few years work that would not have happened without the seminal papers such as these. Since this paper will undoubtedly be read and highly cited, referencing the early work is important.

On the other hand, there are a number of instances where only recent papers are cited, and references to the earlier work would be helpful to a reader, e.g.,

Line 137: While Carpenter et al. (2013) have done very nice work on the ozone-iodide reaction, there are foundational papers on this that go back many decades before this that would be helpful to cite.

Line 167:  Pankow et al. published many papers on partitioning and volatility starting in the 1980’s, which laid the foundation for the Donahue et al. subsequent studies, and should be cited.

Line 206: Optical properties and photodegradation of brown carbon are discussed in detail in a 2015 Chem Rev article by Laskin et al and should be cited in addition to Hems et al.

Line 249: Gligorovski et al published a number of papers on indoor OH (e.g. Atmos. Env., 2014) and indoor chemistry, long before the Sloan Foundation funding pushed this area to the fore. Some of his work should be cited.

Line 267: Some of the original work on particles translocating to the brain, e.g. Oberdorster et al., should be cited.

Line 306: Zelenyuk et al field measurements on shielding of PAH inside particles should also be cited.

Other reference suggestions:

Line 161: Citing broader treatments of health effects of particles would be appropriate, e.g. some of the Landrigan et al articles summarizing the results from the commission on pollution and health.

Lines 351-353: Adding some references supporting the statements about absorption spectra and quantum yields being different from those in the gas phase would be helpful to the reader. Also mentioning the effects of viscosity and matrix on these (e.g. Nizkorodov et al)

Line 359: Zelenyuk and their SPLAT should be included here.

Other comments:

Line 180: The impact of temperature on SOA formation is mentioned. However, growth of particles is also affected and should be mentioned.

Lines 211, 212: A brief description of what is meant by the deposition and immersion modes would be helpful to non-experts in the field.

Lines 256-259: I think this statement regarding the impacts on health is grossly understated.  Particles have not been “implicated” as harmful, there is a ton of evidence showing they are. The statement that the toxicity mechanisms are not known is also somewhat misleading. For example, it has been known for decades that particles initiate an inflammatory response.

Line 291: The last sentence “It is not clear whether this effect is related to multiphase chemistry at biological surfaces” seems out of place. What is meant by this needs to be amplified or the sentence omitted.

Lines 309-311: The authors might want to mention that freezing also concentrates soluble species in the shrinking liquid layer, which can have significant impacts on the chemistry.

Section on chemical complexity: This is a nicely written section. In the complexity listed on lines 402-403, the authors might also want to mention the importance of the surface composition vs the bulk, e.g. Wingen et al, Chem Sci (2019).

This is a terrific, forward-looking review on multiphase chemistry written by two giants of the field.  I believe that it will be widely read and cited.  It is destined to be a wonderful resource for students and experts alike. My thanks to the authors for writing it.

Here are a few comments that I encourage the authors to consider before final publication:

70: The definition of the "boundary" appears to leave out its role as a thin region in which reactions as well as transport can occur.  This possibility is mentioned explicitly in the next paragraph.

I like figure 1, but the authors may wish to add a dashed line from Csurf pointing downward toward the bulk in the left hand panel (and all three panels): even if the reaction occurs in the interfacial region because A reacts quickly, the product C may be soluble and diffuse widely, or it may even be ionic and stay within solution.As a technical point, the reacto-diffusive length may not really apply to the left hand panel, at least as it is customarily defined by sqrt(D/k), where D and k are bulk-phase quantities.  D and k in the interfacial region might not be similar to their bulk-phase values.  It's not just that the bulk-phase reaction region is shallow, but that the energetics and solvation and motions could be quite different in the interfacial and bulk-phase regions.

91: I recommend adding "neutral" to "closed shell".  Reactions of charged species can be fast in the gas phase.

101: does "sorbed" mean at the surface and in the subsurface region?

102: Is there evidence that Cl+ forms as an independent solvated species? Perhaps it is more like an SN2 reaction with Cl- acting as a nucleophile attacking ClONO2. This idea follows from work by the J. T. Hynes group and others of this reaction on ice surfaces.

402:  Is "exasperated" the correct word?  Perhaps "exacerbated" or "amplified"?

426: I think that "the" in "the theory" should be deleted.

419 - 430.  I would like to recommend citations for two pioneers and their groups in the theoretical community for deducing multiphase reaction mechanisms. They are not mentioned here:  J. T. Hynes and R. B. Gerber. They could be cited through their 2006 and 2015 Accounts of Chemical Research articles.

lines 438-9 about AI and machine learning.

I think that this statement may be too sweeping.  AI could be used as a high-dimensional data fitting tool that makes predictions but does not necessarily reveal new insights. This may be what the authors have in mind.  But machine learning can also be used to build molecular models that lead to new and powerful mechanistic insights. Two examples of the latter are

Am. Chem. Soc. 2022, 144, 10524−10529

Acids at the Edge: Why Nitric and Formic Acid Dissociations at Air−Water Interfaces Depend on Depth and on Interface Specific Area

Science 371, 921–925 (2021)

Reactive uptake of N2O5 by atmospheric aerosol is dominated by interfacial processes

I hope that the authors can mention these new directions, as machine learning may become an essential tool to partner with laboratory experiments.

459 - 462.  Nicely stated.  How will the authors motivate the multiphase community to interact more closely with other atmospheric chemists?  As leaders of the field, the authors can benefit the community by making specific recommendations and leading us in these recommendations.