A Data Resource for Prediction of Gas-Phase Thermodynamic Properties of Small Molecules
Round 1
Reviewer 1 Report
This is the resubmitted manuscript and it was my pleasure to revise the previous version. I am very glad that the Authors have significantly revised their work, most importantly they have used the PM7 semiempirical QM method instead of PM3 which was used in the previous version. I am aware that it costs the Authors a lot of work and time, but looking at the final results I think that it was worth it. I surely recommend the publication of this revised version, however, after deep review I have found a few more issues that need to be addressed. The list can be found below.
Lines 16 and 44, should be added here that it applies to isobaric-isothermal conditions. Otherwise, i.e. under isochoric and isothermal conditions, enthalpy should be substituted by internal energy (U).
Line 33, instead of “constants” I would suggest using “parameters” or “values”. As the thermodynamic constants are universal such as R, k, NA, etc.
Line 80, actually not so small number… (i.e. look at NIST database)
Line 119, what about ΔHo?
Line 291, I think that the basis set is stated incorrectly, there is no such basis set as 611-G.
Besides, the Authors should describe the limitations of the accuracy of calculations of entropy by QM methods. I.e., in the standard calculations only the vibrational contributions to the entropy are included, while the translational and conformational contributions are neglected.
Author Response
Please see the attachment
Author Response File: 
Author Response.docx
Reviewer 2 Report
The authors have addressed my earlier comments. I recommend that the manuscript be accepted for publication.
Author Response
We thank this reviewer for their help and support.
Round 2
Reviewer 1 Report
The Authors have corrected their manuscript and this version can be accepted for publication.
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
Manuscript describes a dataset of enthalpies of formation and standard entropies, which was compiled from published literature references, for prediction of thermodynamic properties for compounds and its application to a set of 16,411 small molecules. The compiled data source will be immense value to those individuals working in the chemical industry, as well as to thermodyanmicists and computational chemistry. The datasets provide in a single compilation experimental values that otherwise would take individuals many hours to assemble. I know that there are other large data sets of thermodynamic properties that have been compiled, in fact R. Naef published in Molecules a group contribution method for estimating enthalpies of combustion and enthalpies of formation. As part of publication, Naef placed in the supplementary material a comparison of the predicted and experimental values for many relatively small organic molecules. The data set used in the current submission will not contain newly published values as the literature references from which the values were compiled from the publications prior to 2003. Even so, the compilation will still be extremely useful.
The major shortcoming that I find in the present submission is the lack of comparison of how well the authors’ predictive compares to other predictive methods that have been published. There have been many predictive methods and models developed over the years for estimating enthalpies of formation and standard entropies. There have been both quantum mechanic methods, as well as group contribution methods and fragment atom methods. Each of the published methods does have their advantages and limitations. Some methods offer speed and simplicity, at the expense of accuracy. Other methods are more time consuming and require more knowledge on the part of the user. Group contribution methods are limited in application to those compounds for which group values are available. Perhaps the authors could expand on their discussion and provide readers with an indication of how their approach compares to some of the other available estimation methods.
Reviewer 2 Report
The idea behind this manuscript is very good and it is needed by a lot of researches. Creation of such a database and equations was surely a demanding job. I really enjoyed reading it and I have done this very carefully. I think that this work is worth publishing, however I have some really major concerns about some of the methods used in this work. My detailed comments are presented below.
I am very worried about one thing. Most of the molecules in the ASM are gases, which is perfectly fine as the calculations have been done in the gas phase. However, there are also a lot of solid molecules, i.e. urea derivatives. In such case the calculations of enthalpy or entropy using the methods described in this study would be VERY inaccurate as you do not include the intermolecular interactions that significantly contribute to the enthalpy and entropy values.
The Authors have used VERY OLD semiempirical methods. It has been shown in a vast number of studies that PM7 or even PM6 methods are far more accurate that very old and inaccurate PM3, i.e. please look here: doi: 10.1007/s00894-012-1667-x . You should not do the calculations using PM3 anymore. And I think you should use the PM7 in the current study as well.
Line 13, word „properties” is repeated twice in the same line, please rewrite
Lines 39-48, this is true only in the case of constant pT conditions. It must be mentioned in the text. It should also be mentioned that in the case of constant VT the Helmholtz free energy (ΔF) is the key thermodynamic parameter, that decides if the reaction proceeds spontaneously.
Line 67, I can’t agree with this statement. The information about the experimentally measured ΔH and S values can be easily found for a lot of small molecules, i.e. in the NIST database.
Line 67-80, it should be mentioned that it is possible to calculate enthalpy and entropy using molecular mechanics methods, though they are usually significantly less accurate.
Table 3, DH gradient, do you assume that the enthalpy changes with the temperature in a linear trend?
Line 145, why those 6 calculations have failed? Some details should be provided. Maybe the number of optimization steps was too small?
Line 177, I know it is not your fault but this is horrifying! Shouldn’t this compound be removed from the models then?
Figure 2, a similar figure should be created for the entropy.
The cited website ( http://www.allmols.org/ASM5_0.html ) is not working anymore.
Next to all of the figures there should be R2 in order to confirm the linearity.
