Synthesis, Characterization and Structural Analysis of Two New Biguanide Complexes

Round 1

Reviewer 1 Report

This work reports on the synthesis and characterization of two compounds based on Co and Cu metals. The compounds were characterized by FTIR, thermal analysis and single crystal X-ray diffraction. I recommend the publication of the manuscript after minor revision according to following comments:

1)      The authors state in the abstract that the compounds were also characterized by UV-Vis spectroscopy, but they don’t present the results. Please present the UV-vis.

2)      Characterization of the complexes should be fulfilled by mass spectrometry.

3)      In the experimental section please list all the FTIR and UV-vis bands for each compound to characterize the complexes.

 

4)      I could not confirm some of the information because I did not have access to the supporting information. Also, all the spectra should be provided in supporting information.

   

Author Response

Ploy Assavajamroon

Editor

Crystals

Dear Editor

On behalf of my co-authors, I am respectfully sending a point-by-point response to the submitted manuscript "Crystals-2498845".

Considering the strong suggestion of the referees, we put major efforts into improving the manuscript to be accepted in Crystals.

In this sense, we carefully examined all the comments and subsequently, all raised points were amended and explained as presented below. We would like to thank you and the referees for your time and valuable comments, which have helped us enhance our manuscript's quality.

Sincerely

Prof. Dr. Richard D’Vries

Universidad Santiago de Cali

 

Comments and Suggestions for Authors

Referee: 1

This work reports on the synthesis and characterization of two compounds based on Co and Cu metals. The compounds were characterized by FTIR, thermal analysis and single crystal X-ray diffraction. I recommend the publication of the manuscript after minor revision according to following comments:

• The authors state in the abstract that the compounds were also characterized by UV-Vis spectroscopy, but they don’t present the results. Please present the UV-vis.

Response: Dear reviewer, thank you for your valuable comments. In the document, the UV-Vis analysis was mentioned by mistake; since the Met-Co-2 compound was obtained in small quantities, it was not possible to perform this analysis for this compound. For this reason, we decided to omit this result from the manuscript, and the information was removed from the abstract.

• Characterization of the complexes should be fulfilled by mass spectrometry.

Response: We agree with the reviewer, but considering that the characterization was performed by single crystal X-ray diffraction, we can conclude that the structural data are sufficient to report the new complexes. Also, it is important to note that we currently do not have the equipment to perform this analysis. 

• In the experimental section please list all the FTIR and UV-vis bands for each compound to characterize the complexes.

Response: FTIR bands were added to experimental section.

4)      I could not confirm some of the information because I did not have access to the supporting information. Also, all the spectra should be provided in supporting information.

Response: Thank you very much for the comment. Due to an error, the supplementary material where the FT-IR spectra and the thermal analyses are found was not uploaded. This information will be uploaded as an annexe to the corrections.

 

Reviewer 2 Report

This is a fairly standard study of the cobalt and copper complexes with metformin biguanide as ligand. The structure of two complexes has been stablished by X-ray diffraction studies. Supramolecular interactions have been studied and compared with previously described examples, with the aim of deepening the knowledge of their use as potential drugs.

Although the work is focused on structural aspects, I believe that the difference in the synthesis processes between the current research and that reported in reference 6, by the same authors, should be commented on: changes in the ratio of reagents, relative amount of base, effect of air in the oxidation to cobalt(III)... The yields obtained in each synthesis should be included.

The structure of the copper dimer in figure 5, left, is confusing because it looks like two trigonal bipyramids sharing an edge. The perspective of figure 6 is more accurate.

Finally, once the structure of the compounds is known, FTIR analysis add little if it does not include a comparison between the spectrum of the ligand and those of the complexes. 

I recommend publication in Crystals, but major revision is necessary.

I suggest a thorough revision of the wording to improve the English at several points in the text.

Author Response

Ploy Assavajamroon

Editor

Crystals

Dear Editor

On behalf of my co-authors, I am respectfully sending a point-by-point response to the submitted manuscript "Crystals-2498845".

Considering the strong suggestion of the referees, we put major efforts into improving the manuscript to be accepted in Crystals.

In this sense, we carefully examined all the comments and subsequently, all raised points were amended and explained as presented below. We would like to thank you and the referees for your time and valuable comments, which have helped us enhance our manuscript's quality.

Sincerely

Prof. Dr. Richard D’Vries

Universidad Santiago de Cali

Referee: 2

 

This is a fairly standard study of the cobalt and copper complexes with metformin biguanide as ligand. The structure of two complexes has been stablished by X-ray diffraction studies. Supramolecular interactions have been studied and compared with previously described examples, with the aim of deepening the knowledge of their use as potential drugs.

• Although the work is focused on structural aspects, I believe that the difference in the synthesis processes between the current research and that reported in reference 6, by the same authors, should be commented on: changes in the ratio of reagents, relative amount of base, effect of air in the oxidation to cobalt(III)... The yields obtained in each synthesis should be included.

Response: Thank you very much for the comment. The yields of the reactions were added in the experimental part. It should be clarified that the Met-Co-2 complex was obtained in tiny amounts. The obtained crystals were used for FTIR, thermal and diffraction analysis.

The suggestion to mention the differences between the previously reported work and the current one were added in the conclusions section. “The synthesis methodology used to obtain the reported compounds was based on the work previously carried out in our group. A metal-ligand ratio of 1:3 and an excess of base (NaOH) were used to obtain the Met-Co-2 complex. In this case, the excess base and the presence of moisture favoured the partial oxidation of Co(II) to Co(III) and the formation of the Met-Co-2 compound. Something similar was observed in the synthe-sis of the Met-Cu-2 complex, where the use of methanol as solvent and an excess of base favoured the formation of the dimer. These results show that small modifications in the reaction conditions can lead to the formation of different crystalline phases.”

• The structure of the copper dimer in figure 5, left, is confusing because it looks like two trigonal bipyramids sharing an edge. The perspective of figure 6 is more accurate.

Response: Figure 5 was modified for clarity.

• Finally, once the structure of the compounds is known, FTIR analysis add little if it does not include a comparison between the spectrum of the ligand and those of the complexes.

Response: The FTIR spectrum for metformin hydrochloride was added in the supporting information S1.

I recommend publication in Crystals, but major revision is necessary.

Reviewer 3 Report

This paper reported by the authors is completely devoid of any data and description of the purities of the synthesized samples (IR and TG-DTA generally cannot prove the purities of samples). Supplementary files mentioned in the manuscript are also missing. Therefore, I request that this paper should be rejected.

 

1.     In the synthesis section, the yields of Co and Cu complexes should be added.

2.     The results of mass spectroscopies, elemental analyses, and magnetic measurements should be added to prove the purities of Co and Cu complexes. 

3.     In Figure 1, the percentage of thermal ellipsoids (%) should be added.

4.     Figure S1 and S2 could not confirmed from submitted files. The only files verified by the reviewer were the CIF files and the check CIF reports.
5.     The DSC is generally “Differential Scanning Calorimetry”. So, in this case, TGA-DSC is probably wrong and TG-DTA is maybe correct.  

Author Response

Ploy Assavajamroon

Editor

Crystals

Dear Editor

On behalf of my co-authors, I am respectfully sending a point-by-point response to the submitted manuscript "Crystals-2498845".

Considering the strong suggestion of the referees, we put major efforts into improving the manuscript to be accepted in Crystals.

In this sense, we carefully examined all the comments and subsequently, all raised points were amended and explained as presented below. We would like to thank you and the referees for your time and valuable comments, which have helped us enhance our manuscript's quality.

 

Sincerely

Prof. Dr. Richard D’Vries

Referee: 3

This paper reported by the authors is completely devoid of any data and description of the purities of the synthesized samples (IR and TG-DTA generally cannot prove the purities of samples). Supplementary files mentioned in the manuscript are also missing. Therefore, I request that this paper should be rejected.

Response: Dear reviewer, I would like to apologize for the error made at the time of uploading the files, as the supplementary material was missing. At this stage of corrections, I am adding the missing material.

1. In the synthesis section, the yields of Co and Cu complexes should be added.

Response: The information about reaction yield was added to the experimental section.

2. The results of mass spectroscopies, elemental analyses, and magnetic measurements should be added to prove the purities of Co and Cu complexes.
3. In Figure 1, the percentage of thermal ellipsoids (%) should be added.

Response: the suggestion was rewritten and added in the text of figure 1.

4. Figure S1 and S2 could not confirmed from submitted files. The only files verified by the reviewer were the CIF files and the check CIF reports.

Response: As previously mentioned, the supplementary material was not uploaded due to an error in the uploading of the documents. On this occasion, supplementary material is added to the submission.

5. The DSC is generally “Differential Scanning Calorimetry”. So, in this case, TGA-DSC is probably wrong and TG-DTA is maybe correct.

Response: In this case the analyses performed were thermogravimetric analysis and differential scanning calorimetry. No DTA data are presented in the document.  

 

Universidad Santiago de Cali

 

Reviewer 4 Report

Suggestions

 

·         In scheme 1, some of the bonds look thicker than others. Check it out.

·         Include in section 2.2 and 2.3, the yield, melting point, description of the main stretch bands assigned to the functional groups or bonds observed in the FTIR, as well as the wavelengths and molar extinction coefficients observed in UV-Vis.

·         In experimental section, the stoichiometric metal-ligand ratio in the cobalt complex is 1 to 4.3, while in the copper complex it is 1 to 2. Explain how this decision was made.

·         In the crystal structure, the stoichiometric metal-ligand ratio in the cobalt complex is 1 to 3, while in the copper complex it is 1 to 1. How do you explain these differences with respect to the experimental section?

·         How common is it to find a mixed valence coordination complex (Co(III)/Co(II)) when starting from a cobalt(II) salt? Discuss it in the manuscript with supporting references.

·         Put the meaning of the acronyms the first time they are mentioned in the text, example, What is RMSD?

·         At the foot of figure 3, highlight which of the superimposed molecules comes from reference 6 and which is the one obtained from this work.

·         At the foot of figure 4, highlight which of the graphs comes from literature compounds (give citation [6]) and which of the molecules obtained from this work.

·         I was not able to access in the ZIP file the supplementary information for FTIR and TGA, to which the authors refer. Only the CIF and CHECKCIF files were found.

·         However, I suggest that the authors place a figure that overlaps the three IR spectra (ligand and its two complexes) in order to follow the discussion in section 3.2.

·         In the same sense, a figure where the thermograms of both compounds are placed would facilitate the reading and understanding of the stability of the complexes. 

 

Check line by line that there are no spelling errors in the manuscript.

Author Response

Santiago de Cali, July 19, 2023

 

Ploy Assavajamroon

Editor

Crystals

 

Dear Editor

 

On behalf of my co-authors, I am respectfully sending a point-by-point second round response to the submitted manuscript "Crystals-2498845".

Considering the strong suggestion of the referees, we put major efforts into improving the manuscript to be accepted in Crystals.

In this sense, we carefully examined all the comments and subsequently, all raised points were amended and explained as presented below. We would like to thank you and the referees for your time and valuable comments, which have helped us enhance our manuscript's quality.

 

 

Sincerely

 

 

Prof. Dr. Richard D’Vries

Universidad Santiago de Cali

Comments and Suggestions for Authors

Referee: 4

1. In scheme 1, some of the bonds look thicker than others. Check it out.

Response: All the bonds have the same thickness; I have copied the metformin template in each case so that they all look the same.

2. Include in section 2.2 and 2.3, the yield, melting point, description of the main stretch bands assigned to the functional groups or bonds observed in the FTIR, as well as the wavelengths and molar extinction coefficients observed in UV-Vis.

Response: The requested information was added to the manuscript.

3. In experimental section, the stoichiometric metal-ligand ratio in the cobalt complex is 1 to 4.3, while in the copper complex it is 1 to 2. Explain how this decision was made.

Response: I thank the reviewer for this correction, as we have a typo in the document. The synthesis of this compound was planned with a 1:3 ratio, taking into account that we were looking for an octahedral complex. For this reason, the amount of metformin used was 208.3 mg 1.26 mmol. The values were corrected in the text.

4. In the crystal structure, the stoichiometric metal-ligand ratio in the cobalt complex is 1 to 3, while in the copper complex it is 1 to 1. How do you explain these differences with respect to the experimental section?

Response: As mentioned in the previous answer, we had a typing error, so the ratio was 1:3 for the cobalt complex, looking for an octahedral complex. In the case of the copper complex, we were initially looking for the formation of a square planar complex, which is why we used a 1:2 ratio. The results were not what we expected in both cases, but we obtained pure complexes.

5. How common is it to find a mixed valence coordination complex (Co(III)/Co(II)) when starting from a cobalt(II) salt? Discuss it in the manuscript with supporting references.

Response: The discussion and references were added in the text.

6. Put the meaning of the acronyms the first time they are mentioned in the text, example, What is RMSD?

Response: RMSD means “Root-mean-square deviation”. This information was added in the text.

7. At the foot of figure 3, highlight which of the superimposed molecules comes from reference 6 and which is the one obtained from this work.

Response: This information was added in the text.

8. At the foot of figure 4, highlight which of the graphs comes from literature compounds (give citation [6]) and which of the molecules obtained from this work.

Response: Figure 4 refers only to the Met-Co-2 complex obtained in this work. The foot of Figure 8 is modified.

9. I was not able to access in the ZIP file the supplementary information for FTIR and TGA, to which the authors refer. Only the CIF and CHECKCIF files were found. However, I suggest that the authors place a figure that overlaps the three IR spectra (ligand and its two complexes) in order to follow the discussion in section 3.2.

 In the same sense, a figure where the thermograms of both compounds are placed would facilitate the reading and understanding of the stability of the complexes. 

Response: Infrared and TGA-DSC analyses were added to the supplementary material.

 

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The review was in line with my comments; therefore, I recommend the manuscript for publication in its current form.

Author Response

Santiago de Cali, July 19, 2023

 

Ploy Assavajamroon

Editor

Crystals

 

Dear Editor

 

On behalf of my co-authors, I am respectfully sending a point-by-point second round response to the submitted manuscript "Crystals-2498845".

Considering the strong suggestion of the referees, we put major efforts into improving the manuscript to be accepted in Crystals.

In this sense, we carefully examined all the comments and subsequently, all raised points were amended and explained as presented below. We would like to thank you and the referees for your time and valuable comments, which have helped us enhance our manuscript's quality.

 

 

Sincerely

 

 

Prof. Dr. Richard D’Vries

Universidad Santiago de Cali

 

 

 

 

 

 

 

 

 

 

 

Comments and Suggestions for Authors

Referee: 1

The review was in line with my comments; therefore, I recommend the manuscript for publication in its current form.

Response: I would like to thank the reviewer for his contributions and time dedicated to this work.

Reviewer 3 Report

I commented that the evidence regarding the purities of the developed complexes are should be added to the revised manuscript. However, no additional experiments are found in the revised manuscript. There is no evidence in this manuscript that the product ca be isolated. Authors should add the data of elemental analyses, ESI-MS, or X-ray powder diffraction to prove the purities of developed complexes.

Author Response

Santiago de Cali, July 19, 2023

 

Ploy Assavajamroon

Editor

Crystals

 

Dear Editor

 

On behalf of my co-authors, I am respectfully sending a point-by-point second round response to the submitted manuscript "Crystals-2498845".

Considering the strong suggestion of the referees, we put major efforts into improving the manuscript to be accepted in Crystals.

In this sense, we carefully examined all the comments and subsequently, all raised points were amended and explained as presented below. We would like to thank you and the referees for your time and valuable comments, which have helped us enhance our manuscript's quality.

 

 

Sincerely

 

 

Prof. Dr. Richard D’Vries

Universidad Santiago de Cali

 

 

 

 

 

 

 

 

 

 

 

Comments and Suggestions for Authors

Referee: 1

The review was in line with my comments; therefore, I recommend the manuscript for publication in its current form.

Response: I would like to thank the reviewer for his contributions and time dedicated to this work.

Referee: 3

I commented that the evidence regarding the purities of the developed complexes are should be added to the revised manuscript. However, no additional experiments are found in the revised manuscript. There is no evidence in this manuscript that the product ca be isolated. Authors should add the data of elemental analyses, ESI-MS, or X-ray powder diffraction to prove the purities of developed complexes.

Response: I would like to thank the reviewer for his comments and contribution to this work. There is no doubt that the compounds were isolated and characterized. Powder X-ray diffraction and elemental analysis were performed for both compounds. We had problems with the analysis for the Met-Co-2 compound because it was obtained in a very low yield, so we could only report the elemental analysis in manuscript. Also, it can be observed in the pictures (supporting information S3) that the compound presents a small contamination because the metformin also crystallizes upon recrystallisation, and the crystal selection was hand performed.

 

 

Author Response File: Author Response.pdf