Copper (II)-Catalyzed Oxidation of Ascorbic Acid: Ionic Strength Effect and Analytical Use in Aqueous Solution

Round 1

Reviewer 1 Report

This paper reports the development of the known analytical technique quantitative determination of the Cu(II) ions using autooxidation of the ascorbic acid as an indicator of the reaction. The effect of the ionic strength set by four different electrolytes on the rate of oxidation of the vitamin C was also studied. The influence for the chloride-containing salts was also studied. Overall, the performed study is sound, and the presented findings can be interesting for the readership of this journal. In my opinion, this paper certainly deserves to be published in this journal in the present form.

Author Response

Your kind words of support are much appreciated.

Reviewer 2 Report

The idea of the current work entitled “Copper(II)-Catalyzed Oxidation of Ascorbic Acid: Ionic Strength Effect and Analytical Use in Aqueous Solution” authored by Murekhina et. al. is a good one because of the involvement of ascorbic acid oxidation in many biological processes. In this work the authors have developed the known analytical technique where the linear dependence of the rate constant of ascorbic acid oxidation to copper(II) concentration has been employed. They also have investigated the effect of  concentration of the common background electrolyte and effect of other d and f block metal ions in the oxidation process. The overall work is nice however some modifications should be made before publication.

1. The abstract should reflect the total experimental results and the inference obtained in a summary form. I feel that the abstract can be modified, for example there is no indication of the effects of other metal ions which the authors have studied, it can be added even if there is no much effect.

2. Line 89 is not clear to understand, it could be modified.

3. In line 94 the authors are writing “where “Ascorbic acid” and “Dehydroascorbic acid” represent all the coexisting protonated species of the acids.” Question will arise here: how dehydroascorbic acid can be a protonated species if it is the deprotonated form of ascorbic acid. Can the authors clarify it?

4. In Figure 2d there is a mistake labeling the X-axis, it should be modified.

5. Reference 31 can be rechecked for the year of publication if there is any typo.

Author Response

We are grateful to the Reviewer for the time spent on our manuscript and valuable comments that help us to improve the contribution. Please, find the answer to the queries below:

1. Q.: "The abstract should reflect the total experimental results and the inference obtained in a summary form. I feel that the abstract can be modified, for example there is no indication of the effects of other metal ions which the authors have studied, it can be added even if there is no much effect."A.: We added to the abstract the following phrase to indicate the influence of other cations: "Cu²⁺ cations can be quantified in the presence of the 5-20 fold excess of Co²⁺, Ni²⁺, Zn²⁺ ions. The La³⁺, Ce³⁺, UO₂²⁺ ions also do not catalyze the ascorbic acid oxidation reaction.". Thanks for the recommendation.
2. Q.: "Line 89 is not clear to understand, it could be modified."                 A.: We agree that it is rather confusing. The revised phrase is now: "The dependence of the conditional rate constant of ascorbate oxidation on the copper(II) concentration is linear at any studied ionic strength value, which is set using the various indifferent electrolytes (Figures 1 and S1)." (the revision is indicated by italic)
3. Q.: "In line 94 the authors are writing “where “Ascorbic acid” and “Dehydroascorbic acid” represent all the coexisting protonated species of the acids.” Question will arise here: how dehydroascorbic acid can be a protonated species if it is the deprotonated form of ascorbic acid. Can the authors clarify it?" A.: We agree that it is confusing and additional explanation is required. Dehydroascorbic acid is the oxidized form of ascorbic acid, not the deprotonated (those are ascorbate monoanion and dianion). We mean the sum of equilibrium concentrations of both acids (ascorbic and the oxidized dehydroascorbic) protonated species. To clarify this, the line was revised as: "where “Ascorbic acid” and “Dehydroascorbic acid” represent all the coexisting protonated species of the reduced (ascorbate) and oxidized (dehydroascorbate) forms of the acid. In other words, C_total(AAH₂⁰) = [AAH₂⁰] + [AAH^-] + [AA^2-]; C_total (DHA) = [DHA⁰] + [DHA^-]." Why do we even bother with such sofisticated way of representing the ascorbic acid? Why we di not just indicate the total concentrations of both acids? It is for further discussion of the secondary salt effect, which can shift the equilibria between protonated species (those, in turn, have different reactivity in the oxidation process).
4. Q.: "In Figure 2d there is a mistake labeling the X-axis, it should be modified" A.: Thanks for pointing out our mistake. Of course, there should be "I(KNO₃), mol L^-1"
   
5. Q.: "Reference 31 can be rechecked for the year of publication if there is any typo." A.: We double-checked the mentioned reference and we are sure that there is no mistake: this paper is indeed placed into the January issue of the forthcoming year volume.

Once again, thanks for your comments. The revisions made in accordance with them are highlighted with green in the text of the revised manuscript.

Reviewer 3 Report

I consider the subject of the manuscript entitled “Copper(II)-Catalyzed Oxidation of Ascorbic Acid: Ionic Strength Effect and Analytical Use in Aqueous Solution” to be of high interest and appropriate for publication in the Inorganics journal.

Developing easily accessible analytical determination techniques of transition metal ions, especially in aqueous media is of high importance due to their presence in both biological media and in the environment.

The work presented in this manuscript is of high quality, the results are objectively analyzed, evaluated, and compared with other reported methods. The advantages and disadvantages of the proposed analytical method are clearly stated and pertinent conclusions are drawn based on the experimental results.

Considering all the facts mentioned, I recommend publication with a few minor revisions detailed below.

An initial question: How did the authors choose the electrolytes and their concentrations for the studies?

We consider that a few minor adjustments should be take into consideration:

Lines 89-91: This paragraph should be revised; the language is not clear. From Figure S1 one can actually deduce that in several situations, the dependence observed deviates significantly from linearity: (d), (h), (n)

Line 133: This subtitle should be revised. Maybe the authors meant to write: “Effect of the nature and concentration of electrolytes on the rate of ascorbic acid oxidation”?

Line 169: The authors probably refer to the primary salt effect

Line 218: Equation (18) should be explained

Author Response

We are grateful for the careful reading of our manuscript and the valuable comments risen, which are of great help in improving of the paper. Please, find the answers to the specific comments below:

1. Q.: "An initial question: How did the authors choose the electrolytes and their concentrations for the studies?"                                                                      A.: Very interesting question. First, we were afraid that such videly used background electrolytes as perchlorates or nitrates are capable of oxidizing ascorbic acid on its own. That is why the first choice of the electrolyte was NaCl, which was considered to be safe from the point of view of oxidation of ascorbate. Moreover, we used it in our previous study of ascorbic acid protonation porcess. We planned to perform the experiments in the range of the ionic strength values of 0.10-5.0 mol L^-1, which coincides with the interval of I we studied in the dissociation of ascorbic acid recently. However, the reality quickly took us to the ground: even at I = 0.50 mol L^-1 (NaCl) the rate of oxidation was very slow. Then we observed that the oxidation of ascorbic acid proceeds much faster at I = 0.05 mol L^-1 that at zero ionic strength! Having repeated five or six times the experimental series at I = 0.05 mol L^-1 to make sure that the reason does not lie in our crooked hands, we decided to study the dependence of the rate of ascorbate oxidation on the NaCl concentration very carefully with a large number of points. The anomalous influence was confirmed: small quantities of electrolyte really speeds up the reaction. The next natural question was: is it the unique feature of NaCl electrolyte as a whole entity? Or only Cl^- anion? Or only sodium cation? Therefore, three other electrolytes were chosen to reveal what has the anomalous effect: KCl, NaClO₄, and KNO₃, which contains no ions fallen under suspicion (we would take KClO₄ if it would have been soluble in water)_. As a result, we found that chloride ion is responsible for the extremal dependence of oxidation rate constant on the electrolyte concentration (at the same time we learned that ClO₄^- and NO₃^- are actually inert; they do not oxidize the ascorbate ion). That is how the experiment was designed.
2. Q.: "Lines 89-91: This paragraph should be revised; the language is not clear. From Figure S1 one can actually deduce that in several situations, the dependence observed deviates significantly from linearity: (d), (h), (n)"         A.: We agree that language was broken, and the phrase was re-written to make it clear. Regarging the linearity: since there is a measure of the closeness of the linear regression to the experimental data (we mean R_adj²), is can be used for discussion of the linearity. Therefore, the following sentence was added to the text: "R²_adj varies from 0.92 to 0.99; the worst value of R²_adj = 0.8624 is observed for the highest concentration of NaCl causing the significant slowing of the oxidation reaction."
3. Q.: "Line 133: This subtitle should be revised. Maybe the authors meant to write: “Effect of the nature and concentration of electrolytes on the rate of ascorbic acid oxidation”?                                                                                  A.: The subtitle was revised according to your suggestion. Indeed, we missed some words in it.
4. Q.: "Line 169: The authors probably refer to the primary salt effect"              A.: Primary salt effect in kinetics refers to the direct action of the electrolyte concentration on the rate constant of the reaction, while the secondary salt effects describes the influence of electrolyte on the current (equilibrium) concentration of the reactants (e.g. making some products with them of shifting the equilibria, e.g. acid-base ones). In the mentioned fragment we mean that the electrolyte affects the protolytic equilibria changing the concentrations of different protonated species which gave different reactivity. The phrase was revised to clarify it.
5. Q.: "Equation (18) should be explained"                                                          A.: Agree. The necessary explanations of the meaning of all symbols used is added after the mentioned equation.

Once again, thanks a lot for your attention given to our paper and the comments helping us to improve it. The revisions made in accordance with your queries are highlighted in the text with cyan.

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.