Electrochemical Oxidation of Amines Using a Nitroxyl Radical Catalyst and the Electroanalysis of Lidocaine

Round  1

Reviewer 1 Report

Sato et al. presented a demonstration of electrochemical oxidation of amines using the radical NNO. In addition, the demonstration for the detection of lidocaine is discussed. The contents and the topic fulfill with the requirements of the journal. However, in my opinion, a better discussion of the results could improve the manuscript. Here, I substantiate my opinion:

1)   Figure 1. From the discussion of the authors, the oxidation of the amine is performed by the radical NNO. However, in the Figure 1, the oxidized NNO form performed the oxidation of the amine.

2)   Could the authors quantify the concentration of radical NNO?

3)   The authors should discuss the reversibility of the reaction

4)   The following sentence is not understood: If NNO electrolytically oxidizes amines at a sufficiently fast reaction rate, the anodic current should increase and the cathodic current disappear, depending on the concentration of the amine, resulting in a voltammogram.

5)   Introduce the concentration of the NNO and amines used in the experimental part.

6)   The current obtained correspond to the concentration of amines. However, in the case of diethylamine a dependence is observed but, not in the case of ethylamine. Could the authors explain better that?

7)    Include a table with the potential for generation the radical and oxidation of amines.

Author Response

Catalysts - Manuscript number 385660

Reviewer: 1

1)      Figure 1. From the discussion of the authors, the oxidation of the amine is performed by the radical NNO. However, in the Figure 1, the oxidized NNO form performed the oxidation of the amine.

 I added it writing Line 59 -61.

 2) Could the authors quantify the concentration of radical NNO?

 The concentration of NNO in the experiment is 1 mM, and this part is oxidized in the vicinity of the electrode and is involved in the reaction.

 3) The authors should discuss the reversibility of the reaction

 You are right. However, in this report, we evaluated electrochemical sensors for amines using NNO. We are currently investigating TON and TOF, so I will report it in another paper.

 4) The following sentence is not understood: If NNO electrolytically oxidizes amines at a sufficiently fast reaction rate, the anodic current should increase and the cathodic current disappear, depending on the concentration of the amine, resulting in a voltammogram.

 I added it writing Line 75 – 78.

 5) Introduce the concentration of the NNO and amines used in the experimental part.

 I added it writing Line 163 - 164.

 6) The current obtained correspond to the concentration of amines. However, in the case of diethylamine a dependence is observed but, not in the case of ethylamine. Could the authors explain better that?

 It's being explained at the part Line 92 - 93 highlighted.

 7) Include a table with the potential for generation the radical and oxidation of amines.

 The peak potential for generation the radical and oxidation of amines was not observed at the reach from 0 V to + 0.7 V.  I added it writing Line 107 - 108.

Reviewer 2 Report

The MS describes new findings in the area of homogeneous catalysis, which can be important for both the area of catalysis and clinical studies. To reach a broader audience, I suggest the following:

Lines 71-3, Figure 2: It should be better explained - does the oxidation-reduction process that produces the voltammogram the oxidation of the amines? If so, how does the voltammogram look like with zero concentration of amines? Why should the anodic current increase and cathodic current decrease? Does the oxidation current follow a similar trend as the one in Fig. 7? If so, how do the authors explain the existence of the plateau, or the commencement of the current decrease past a certain concentration? The latter question also applies to Fig. 7.
Lines 124-6, Figure 7: The authors describe the use of cyclic voltammetry as the electrochemical sensor for the lidocaine drug concentration in a body, as opposed to more complex analytical techniques. If so, what is the "safe" concentration of the drug and which is the overdose limit, and where do those concentrations fall in the calibration curve of Fig. 7b? This is important as the electrochemical sensor seem to be useful to about ca. 4 mM.
Lines 133-4: Revise the sentence.

Author Response

Catalysts - Manuscript number 385660

Reviewer: 2

1)      Lines 71-3, Figure 2: It should be better explained - does the oxidation-reduction process that produces the voltammogram the oxidation of the amines? If so, how does the voltammogram look like with zero concentration of amines? Why should the anodic current increase and cathodic current decrease? Does the oxidation current follow a similar trend as the one in Fig. 7? If so, how do the authors explain the existence of the plateau, or the commencement of the current decrease past a certain concentration? The latter question also applies to Fig. 7.

I added it writing Line 75 – 78.

Fig. 7：　It is very interesting that the response range varies depending on the substrate. I am currently investigating, but I think that there is no problem with sensing.

2) Lines 124-6, Figure 7: The authors describe the use of cyclic voltammetry as the   electrochemical sensor for the lidocaine drug concentration in a body, as opposed to more complex analytical techniques. If so, what is the "safe" concentration of the drug and which is the overdose limit, and where do those concentrations fall in the calibration curve of Fig. 7b? This is important as the electrochemical sensor seem to be useful to about ca. 4 mM.

I added it writing Line 138 - 141 and Ref. 48..

3) Lines 133-4: Revise the sentence.

 I corrected it writing Line 144.

Round  2

Reviewer 1 Report

All question are well addressed . I recommend this article for publication.