Synthesis Characterization and X-ray Structure of 2-(2,6-Dichlorophenylamino)-2-imidazoline Tetraphenylborate: Computational Study
Round 1
Reviewer 1 Report
This work presents results a combined experimental and theoretical study of structure and reactivity of clonidine, 2-(2,6-dichlorophenylamino)-2-imidazoline tetraphenylborate. I will focus on the computational part. My general feeling is that this part of the paper is routinely done, and that more detailed analysis is needed. There are also many technical omissions that should be improved. Here are some of objections:
- The subsection entitled “The mean absolute errors (MAE)” should be rename into “geometry data” or so.
- Eq. 5-9 should be moved to section to 2.4.5.1. Global Reactivity Descriptors.
- an index, but not of a graph. This is not the case.
Author Response
Reviewer 1
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The subsection entitled “The mean absolute errors (MAE)” should be rename into “geometry data” or so. |
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Answer |
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The mean absolute error (MAE) has been changed to geometry data |
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Eq. 5-9 should be moved to section to 2.4.5.1. Global Reactivity Descriptors. |
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Eq.5-9 have been moved to section 2.4.5.1. |
Author Response File: 
Author Response.pdf
Reviewer 2 Report
In this manuscript, the authors detail the synthesis and characterization of a clonidine tetraphenylborate salt. DFT calculations were also used to describe additional properties of the complex. This clonidine salt has been prepared previously, as cited in the manuscript (Int. J. Electrochem. Sci, 2013, 8, 1999-
2008).
The utility of this research is unclear and not convincing as written. The computational investigation was focused on the ion pair interaction. What is the importance of understanding the ion-pairing interaction at the DFT level? Numerous methods were used to analyze the electronic structure without much interpretation of the results and how they might be useful. At some point, an interaction energy of 2385 kcal/mol was reported, which is clearly outrageously high for an ion-pairing interaction. The NCI analysis is lacking in interpretation. Steric interactions do not contribute to stability as suggested in the NCI section. It is unclear why reactivity descriptors are used to describe the ion pair. What kind of reactions do the authors expect from this ion pair? Is it worth investigating the reactivity descriptors of clonidine? The descriptors are also listed for the counterion. What is the purpose of investigating the reactivity descriptors of the tetraphenylborate counteranion? The electrostatic potential maps should contain the max and min potentials used. What are the differences between parts A-E? Why is there only red and blue for A-C? The concluding statement of "Generally speaking, the electronegativity of the anions in clonidine and tetraphenylborate determines the strength of electrostatic bonds between clonidine and tetraphenylborate" does not make physical sense. The overall conclusions do not appear to be strongly supported by these results.
The spelling, grammar, and style require substantial improvements. There were too many spelling errors to list here.
This work could be worth publishing, but the motivation for this research should be more explained. It is unclear what useful information the computational study provides, and the methods used to understand the interaction are questionable, particularly the reactivity descriptors. Perhaps those descriptors could be included in the SI.
Author Response
Reviewer 2
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The utility of this research is unclear and not convincing as written. |
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The utility of this work was synthesis of clonidine-TPB ion-pair complex, characterization, x-ray single crystal and theoretical study (has been clarified in the MS). |
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What is the importance of understanding the ion-pairing interaction at the DFT level? Numerous methods were used to analyze the electronic structure without much interpretation of the results and how they might be useful |
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Density functional theory (DFT) is an effective tool for predicting properties of molecular and solid-state systems a priori, and time-dependent DFT (TD-DFT) in particular has been demonstrated to be accurate in predicting excited-state features. In this contribution, we provide an overview of the properties that can be computed with DFT, such as geometries, energy, reaction processes, and spectroscopic properties. |
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At some point, an interaction energy of 2385 kcal/mol was reported, which is clearly outrageously high for an ion-pairing interaction. |
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We mean the electronic energy (εο), not an interaction energy |
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Numerous methods were used to analyze the electronic structure without much interpretation of the results and how they might be useful. |
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More details have been inserted. |
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The NCI analysis is lacking in interpretation. |
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To explore the features associated with small reduced gradients, we first examine 3D NCI plots in representative small molecules. |
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Steric interactions do not contribute to stability as suggested in the NCI section. |
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The arrangement of atoms in a molecule is determined by steric interactions (steric repulsion). These effects are caused by the fact that each atom in a molecule occupies a specific amount of space. Overlapping electron clouds (Pauli or Born repulsion) impose an energy cost when atoms are pressed too close together, which may alter the molecule's preferred shape (conformation) and reactivity. |
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It is unclear why reactivity descriptors are used to describe the ion pair. |
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We provided more details in the manuscript. |
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What kind of reactions do the authors expect from this ion pair? |
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We found the kinds of reactions according to QTAIM are the van der Waals interactions and weak electrostatic H-bonds. |
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Is it worth investigating the reactivity descriptors of clonidine? |
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We provided more details in the manuscript. |
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The descriptors are also listed for the counterion. What is the purpose of investigating the reactivity descriptors of the tetraphenylborate counter anion? |
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We provided more details in the manuscript. |
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The electrostatic potential maps should contain the max and min potentials used. What are the differences between parts A-E? Why is there only red and blue for A-C? |
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The electrostatic potential maps section and Figure 7 have been modified. |
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The concluding statement of "Generally speaking, the electronegativity of the anions in clonidine and tetraphenylborate determines the strength of electrostatic bonds between clonidine and tetraphenylborate" does not make physical sense. The overall conclusions do not appear to be strongly supported by these results. |
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The conclusion part has been modified |
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The spelling, grammar, and style require substantial improvements. There were too many spelling errors to list here. |
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The spelling, grammar and style have been improved. |
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The authors responded to all my objections. On the other hand, I found the objections of the second referee very important and constrictive. I really hope the authors will answer them satisfactorily.
Author Response
Reviewer 1
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The authors responded to all my objections. On the other hand, I found the objections of the second referee very important and constrictive. I really hope the authors will answer them satisfactorily. |
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Thank you very much for reviewer 1. The comments of the second reviewer have been resolved carefully. |
Author Response File: Author Response.pdf
Reviewer 2 Report
There are still some minor concerns regarding the utility of the results from some of the computational analysis of this ion pair including the reactivity descriptors, but perhaps it has some value to those interested. An additional proofread to improve grammar and spelling is necessary.
I don't understand the comment below. What are these energies being compared to? The lowest E as compared to what?
"Clonidine-tetraphenylborate complex has the lowest E and the largest absolute value of Eb, indicating that it is the most stable clonidine-tetraphenylborate complex
yet discovered.
Author Response
Reviewer 2
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There are still some minor concerns regarding the utility of the results from some of the computational analysis of this ion pair including the reactivity descriptors, but perhaps it has some value to those interested. An additional proofread to improve grammar and spelling is necessary. |
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We discussed the reactivity descriptors for both ions as well as the complex. Furthermore, we used the graph for more detail (Figure 8 and Table 9 have been inserted). |
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The grammar and spelling have been re-checked through the manuscript and have been improved. |
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I don't understand the comment below. What are these energies being compared to? The lowest E as compared to what? Clonidine-tetraphenylborate complex has the lowest E and the largest absolute value of DEb, indicating that it is the most stable clonidine-tetraphenylborate complex |
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We edited the paragraph before, but we missed adding it to the text. Now we have edited it in the text. |
Author Response File: Author Response.pdf
