Revision and Extension of a Generally Applicable Group Additivity Method for the Calculation of the Refractivity and Polarizability of Organic Molecules at 298.15 K

Round 1

Reviewer 1 Report

The paper is part of a great series of papers that uses group additivity and QSAR to calculate molecular properties. The current paper extends previous framework for molecular refractivity and polarizability to include boron, silicon and ionic liquids. In general, I appreciate the work that Naef and Acree have been doing. I therefor recommend publication of their work after some minor revisions.

Before giving some minor suggestions to the manuscript, there is one major comment that I would like to bring up. The main downside of this work is the visibility and applicability. For the community to use the data or to apply the group additivity or QSAR, a lot of tedious data curation is required. It would be very valuable if the authors can provide their group additivity framework using the SMARTS language, and the molecular data using either SMILES or InChI molecular identifiers in a computer readable format (e.g. csv or excel). Their work would gain a lot more attention if the authors would be able to provide a web interface or software to apply their group additivity values.  

Minor comments:

-        Please provide the root-mean-square deviation on top of the absolute deviation for all comparisons in the manuscript

-        Line 76. It is not clear how the 5988 components are related to the 35952. I assume that the latter have been calculated but do not have the required experimental measurements for refractivity. Can the authors clarify this?

-        Did the authors look if some non-nearest-neighbor interactions are required? When the outliers were removed from the database (line 218), was this mainly due to experimental uncertainty or were there some consistent functional groups present in those outliers that might indicate the need for addition contributions? Can the authors discuss this in the manuscript?

-        Line 316 ‘boron-containing’

-        Line 309 ‘present’ is mentioned twice

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

This is an interesting article related to the development of the additive approach for the Refractivity and Polarizability сalculations. However, there are some questions and recommendations:

1.     There is no information in the article about the temperature of the Refractivity and Polarizability.

2.     In this work, an impressive compilation of experimental data for the Refractivity and Polarizability. There are corresponding references in the main text for experimental data on classes of compounds. However, in the SI, these data are already given without corresponding references, which makes it difficult to analyze.

3.     The authors use experimental data to develop a calculation procedure for Refractivity and the Polarizability. And then compare the calculated and experimental data with each other in tables 4-6. Usually, the verification of the proposed parameters is carried out on compounds that were not used to obtain the parameters.

4.      The units of "true" molecular volume should be added.

5.     The reason to find correlations between refractivity and volume is not clear. The authors know that there can be no good quality correlation between them. It is questionable to use them for prediction of the Refractivity or Polarizability.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The authors clearly answered my questions and made the appropriate changes to the manuscript

Reviewer 2 Report

Accept in present form