The Opinion article by Cox et al. is a valuable addition to the atmospheric chemistry scientific literature.  I fully support its acceptance to ACP.

In particular, the goal of the article is to (re)introduce our community to observations and experiments conducted roughly 50 years ago on the “Open Air Factor” of the atmosphere, which refers to the germicidal properties of ambient air.  The motivation for the publication of this Opinion is the ongoing pandemic.  However, the article illustrates more broadly the impacts that atmospheric composition has on the viability of biological life forms that are exposed to the air.  Although I have worked in the atmospheric chemistry field for roughly 35 years, I had never heard of the “Open Air Factor” and so I very much enjoyed reading the Opinion.

Specifically, this article describes research conducted on the viability of E. coli and Micrococcus albus bacteria when exposed either to ambient air or to controlled exposures of air containing ozone and alkenes.  It was known at the time of these experiments that alkene ozonolysis produces oxygenates such as Criegee intermediates, and a suggestion was made then that such species might be the molecular germicide. However, this chemistry has been explored in much more detail in the past few decades, and we now know that many oxygenates can form including peracids, multifunctional molecules containing -OH and –OOH groups, and organic peroxy radicals.  The Opinion contends that highly reactive species, such as the Criegees and OH, are unlikely to be the active agents and suggests instead that these other oxygenates are more important. One potential mechanism of action, for example, is the formation of radicals from the decomposition of multifunctional oxygenates.

I have very few suggestions and corrections to offer. The Opinion is clearly written and topical, and it will likely motivate important follow-up studies. During the pandemic we have learned how hard it has been to fund interdisciplinary research of this type, i.e. which bridges the physical and biological domains.  Papers like this will be valuable to encourage funding in this direction.

One suggestion: Secondary ozonides do not easily form in the gas phase, except perhaps from ozonolysis of endocylic alkenes (which apparently have strong germicidal properties).  Could secondary ozonides be playing a role?  Even if they are not produced in large amounts in the gas phase, they are known to form readily from multiphase ozonolysis of adsorbed alkenes.   

One correction: Line 48.  The author name for the 1934 reference on olive oil ozonolysis is missing.

General Comments

This manuscript describes a fascinating and impressive study that revisits questions about the germicidal properties of rural air, which has been called the Open-Air Factor (OAF). This term was proposed roughly 50 years ago based on a few studies showing that microbes could be efficiently killed by exposure to rural air, but then subsequently received little attention. It is highly relevant today for obvious reasons. Here, the authors consider possible chemical components that could be responsible for the effect, using a combination of modeling and literature data to interpret the results of the experiments of Dark and Nash (1970), which clearly demonstrated this phenomenon by exposing microbes to ozone and the products of reactions of ozone with various alkenes. The re-analysis is exceptionally thorough, and employs state-of-the-art mechanisms and the latest data on the ozonolysis reactions, as well as careful consideration of factors such as VOC vapor pressure and lipid solubility, which influence the interactions between reaction products and microbes. The authors are able to rule out a number of possible chemical components, and then focus primarily on peroxides, which are known to be formed in alkene ozonolysis and to act as disinfectants. Though the results do not provide a definitive answer as to the chemical identity of the OAF, they provide an excellent starting point for others to explore this important and mysterious phenomenon. I think the manuscript should certainly be published in ACP, after the following few comments are addressed.

Specific Comments

1. I did not see any mention of how much NO might have been present in the experiments of Druett and May (1968) and Dark and Nash (1970), and how this might have impacted the concentrations of peroxides formed through either bimolecular reactions or autoxidation. I can imagine that even in a rural area at this time NO might have been sufficient to quench the peroxide-forming reactions, though the authors probably have information on this.
2. The uptake of VOCs to the brass tube walls in the Dark and Nash (1970) experiments is likely to have been more complicated than the treatment used in the modeling. I suggest the authors read the paper by Deming et al., AMT, 2019, which shows that VOC adsorption to metal tubing walls is highly dependent on the composition and concentrations of VOCs in the mixture and the RH. Depending on the experimental conditions, this could possibly have resulted in complete removal of oxygenated VOCs of the type discussed here for periods on the order of an hour or more before surfaces became passivated.   

Technical Comments

1. None