A Combined Experimental and Modelling Study on Solubility of Calcium Oxalate Monohydrate at Physiologically Relevant pH and Temperatures

Round 1

Reviewer 1 Report

In this manuscript, Eral and coworkers study the solubility of calcium oxalate monohydrate by comparing the experimental results with a fundamental theoretical model based on Van’t Hoff equation to predict the variation of the solubility constant with the temperature and the Debye-Hückel theory to calculate the activity coefficients. The work is interesting for the mineralization community dealing with calcium oxalate and it is worthy of publication. However, I have several concerns that the authors address, explain or refute with solid arguments:

1. In the abstract the authors write: “ultrapure water, arguably the most basic solvent relevant for nephroliathiasis”. Why the “most basic”? Actually, pure water it is in principle neutral. In page 8, they write instead “the simplest solution”. With the term “most basic” do the authors mean “simplest”? In a chemical context, this terminology seems very confusing. The authors should explain this and avoid “basic” if they are not referring to pH.

2. Page 3, 3r paragraph and Table 1: the authors write “The solubility of calcium oxalate (CaOx)”. As the authors clearly know and explain correctly later, the solubility changes with the hydrate. They should avoid writing only “CaOx” if “COM” is meant. All values of Table 1 are referred to COM? If assume that this is the case, but this should be clearly indicated without confusion, since the values can fluctuate a lot if mixtures of different hydrates are present.

3. Materials and Methods: could the use of ion-selective electron have been an option? How does this technique would compare with the results of the authors? It is at least worthy to refer to it.

4. XRD/Figure 3: The figure is confusing. What are the COM, COD, and COT references? They do not seem to be the data form the Powder Diffraction File (PDF) database. The cards from the database used should be indicated. I would also recommend the authors to indicate with different symbols the possible mixtures (or at least the peaks not matching with COM) in the XRD diffraction patterns. Something that surprises me and does not seem quite correct is the unclear similarity between the pattern of the COD reference and the COM reference. I would expect COD to be clearly different from COM. The authors should check and clarify this point.

In this context, it seems problematic to me to make studies about the solubility of COM with samples that may have other hydrate phase present, since the solubility is clearly depending on the crystal phase. This point seems to be relevant enough to be clarified.

5. Minor language and style mistakes: the manuscript should be systematically checked, since there are several errors along the text and figures. I list below some examples (but not all):

a) Abuse of the use of nouns as adjectives (examples)

- Title: “Calcium Oxalate Monohydrate Solubility” should be replaced with “Solubility of Calcium Oxalate Monahydrate”

- “formation of kidney stones” instad of “Kidney stone formation”

- “solubility of COM” instead of “COM solubility”

b) p. 2: lines 66-67: “reported” twice in the same clause

c) Equations 1, 2, 3: only magnitudes and constants should be in Italics, but not chemical formulae

d) Revise the use of commas along the text.

e) Inset in Figure 2: fonts too small to be read

f) Figure 3 a) and b): “a.u.” (second period missing); “cm^(-1)” in the X-axis --> “1” should be in superindex

Author Response

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Reviewer 2 Report

The presented work is modern  accurate research of solubility of  сalcium Oxalate Monohydrate (whewellite), which is one of the most common phases of kidney stones. Neither the importance of the study, nor the reliability and originality of the results and proposed model is in doubt.

Minor notes:

1. Introduction. Lines 43-44. The main types of kidney stones are indicated not quite correctly. Of the phosphates, only brushite is represented. Refine, please.
2. The formula of Calcium Oxalate Monohydrate is given in the Part Materials and Methods (line 133) , and the well-known mineral name for this phase (whewellite) is not given at all. Please provide both the formula and the mineral name at the beginning of the article.
3. Figure 3. Designations (colors) are given twice (in the figure and in the caption under the figure). In addition, there are no references to published sources of reference spectra. Please correct.
4. What is the origin of the term "(pseudo) polymorphic transition" (this term is used throughout the article, starting with the abstract), how widely recognized is this term? Please add reference or remove this term. It is not difficult, since it is essentially about whewellite hydration.

Author Response

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Reviewer 3 Report

The paper prepared by F. Ibis and co-authors is devoted to the investigation of calcium oxalate monohydrate solubility at physiologically relevant pH and temperatures. Accurate calcium oxalate monohydrate solubility measurements are highly important for understanding physiochemical mechanisms behind kidney stone formation, as well as to search for methods of COM solubility increase for preventing stone formation.

I believe that the paper could be published after the minor revision. Please see my comments below.

1. At first, COM, COD and COT are NOT polymorphs. These are the phases with different structure and various H2O content.

2. Line 43. There are three main types of kidney stones that are usually described: oxalate, phosphate and urate stones.

3. Line 171. Is it possible that an increase in stirring time affects the concentration of ions in a solution for titration studies?

4. Formulae 6 and 7 are inserted as pictures, it would be better to include them into manuscript using the formula editor implemented in MS Word.

5. I think that the information given on pages 8-9 does not really apply to the results, and thus can be significantly reduced.

6.Why the ICP-MS method gave such a large deviation at 37 °С?

7. Figures 3 and 4 should be swapped as follows from the text.

Author Response

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