Synthesis and Characterization of Zn-Salophen Complexes with Different D–A Distances: An Approach to Tuning the Intersystem-Crossing Process

Round 1

Reviewer 1 Report

This paper describes the syntheses, characterizations, and optical (absorption and emission) properties of [Zn(Salophen)] complexes with donor-acceptor structures. In addition, Influences of bridging group length between donor (triphenylamine) and acceptor ([Zn(Salophen)]) on producing reactive oxygen species (¹O₂ and O₂⁻) were examined in detail. This is a carefully done study and the findings are interesting. Thus, this paper is worth publishing in Inorganics with minor revisions. Some additional comments are listed below.

1) page 1, line 12: phenylenebis (salicylimine) --> phenylenebis(salicylimine)

2) page 3, line 83: lge --> loge

3) page 5, line149: reacts with with --> reacts with

4) Figure 8; page 8, line 227; page 9, line 257; page 10, line 302; page 11, line349: Abbreviation of N-salicylidene-1,2-phenylenediamine should be h-salophen, not h-Znsalophen.

Author Response

Dear Reviewer:

     Thank you very much for your valuable feedback and recognition of our manuscript. We have carefully read and understood your revision suggestions. We deeply appreciate every question you have raised and have made corresponding modifications based on your four points of feedback. We believe that this will greatly improve the quality of our paper.Detailed information please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Dear Authors,

The manuscript 2912375 by Ze-Hao Li and co-authors describes the synthesis and characterization of 4 Zn-salophen complexes and the studies of ROS production. In my opinion, the report is of general interest to Inorganics readers, in which concerns the design of metal complexes with potential medical applications based on zinc(II) and salophen derivatives ligands. The idea of tuning the energy between HOMO and LUMO by the gradual variation of the number of aromatic rings in the ligand is very interesting. However, at this stage, it is impossible to accept this manuscript for publication. The synthesis and characterisation section of the compounds is incomplete and very poorly described. In some aspects, it is difficult to read this manuscript because it lacks clarity on what is new and what is not, mainly because the comparison with literature is missing. There are more than 7 dozen articles that describe Zn-salophen-type complexes or their properties. Some may be useful for the discussions presented in this manuscript. In other words, a comparative discussion with the literature would be welcome both in the synthetic part and in describing the luminescent and ROS-generating properties.

Aiming to provide some help, we have some additional questions and suggestions listed below:

1.      Use Zn-salophen instead of Znsalophen.

2.      The title of this manuscript must be revised and in my replaced one that summarizes

3.      The Abstract must be rewritten to clarify what is new and what is not in this manuscript. The number of new compounds and the formulas should be included.   Moreover, it should be as much quantitative as possible. Which structure-spectroscopic correlation was found? Which compound gave the better ROS properties? The authors must make an effort to adapt this manuscript to Inorganics guidelines. All compounds should be mentioned by the correct chemical name, followed by any numerals used to refer to them in the paper. The use of the IUPAC nomenclature conventions is preferred.  

4.      Provide a less generalist introduction based on the update of the bibliographic review. Suitable references should be included, including the few ZnSalen/Salophen complexes that have been found to generate reactive oxygen species (ROS).  In the same way, the correlation between the photophysical properties and the nature of the substituents of the ligand in ZnSalen/Salophen complexes should be explored in deep and referenced.

5.      If these compounds are not new, the information must be clearly presented and the original synthesis properly referenced. Otherwise, if they are new, clearly full experimental details must be provided, or, in the case of many compounds prepared by a similar method, a representative typical procedure should be given. I could not reproduce these syntheses with the description provided. Are these syntheses carried out under under inert atmosphere? The quantities of reactants must also be given in quantity of matter (mols), and the volume of solvents must be included. Add the formulas of starting materials, source, and purity in the synthesis. Correct the significant numbers.

6.      Correct the units used for describing concentrations. Note: IUPAC convention recommends to avoid the unit Molar (M), being suggested mol L ^-1 or mol dm ^-3, with consistent use throughout your manuscript. You might use International System Units (SI), e.g., m, s, kg, Pa, mol L -1, etc, separated from quantities with a blank space. Example: 300 K, not 300K. See: https://iupac.org/what-we-do/books/color-books/. Describe the preparation of the solutions reporting concentrations. Are they freshly prepared prior to use?

7.      Elemental analyses (C, H, N) and metal content percentages are basic characterization techniques used to analyse the purity of new compounds. Please include this analysis after the description of the synthesis. Information about the solubility of samples will be also useful.

8.      Please, provide a suitable characterization of complexes.NMR, Infrared spectra and Mass spectrometry are not discussed in the main text. All the peaks in 13C NMR spectra must be assigned, and the main region of all spectra must be expanded as exerted in the spectra.  If the ligants are not new, please reference the original papers. Add a table of the main vibrational mode comparing the pre-ligand and the complexes synthesized in the supplementary material (SM) section.

9.      Trying to correlate the spectroscopic composition with the molecular structure of the complexes, even using a simple particle-in-a-box model, the spacing between the energy levels of the frontier orbitals is expected to decrease with increasing length of the conjugation chain. Thus, the spectra shown in Figure S38 should gradually shift towards the red when starting from compounds 1 to 4. However, there is no continuous trend of variation. What could be the explanation for the results shown when correlating structure-activity? As raised in the introduction, the variation of energy between HOMO and LUMO in complexes is relevant to the discussion of this system.

10.   What does the author want to say with the expression “under degas condition”? Wouldn't it be better to say what condition is used, such as vacuum or N2 atmosphere?

11.   The figures are of high quality. However, this manuscript needs some improvement, particularly in the accuracy and presentation of data that support the experimental description and characterization of the new complexes. The authors did not properly compare data with the literature and did not discuss or present an interpretation of the system under investigation, and some questions remain answered.

12.   Describe the statistical methods used to treat the data. Include error bars in Figures 6b and 6d and a statistical description in the manuscript. How many times were the ROS experiments reproduced?

13.   In the conclusion section: Authors should compare their findings with the literature data in the discussion. What is the real advantage of these findings over the previous ones?

Some minors typing mistakes may be found throughout the manuscript, however these can be fixed for the final version.

Author Response

Dear Reviewer:

     Thank you very much for your valuable feedback and recognition of our manuscript. We have carefully read and understood your revision suggestions. We deeply appreciate every question you have raised and have made corresponding modifications based on your four points of feedback. We believe that this will greatly improve the quality of our paper.Detailed information please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

The manuscript entitled “Synthesis and Characterization of ZnSalophen Complexes with the Ability to Producing Reactive Oxygen Species” is an interesting piece of work describing the synthesis and characterization of 4 Zn complexes with substituted Salophen ligands, studding different photophysical properties especially those related to the ROS production (superoxide and singlet oxygen). In my opinion it describes a sound, well performed and complete research.

Complexes are studied searching for theranostic compounds. To that end, solubility issues need to be discussed (are the complexes soluble in water or water/DMSO solutions? The ligands remain coordinated in that conditions?).

The synthesis of the complexes part should be revised to make it clearer. Perhaps it is not necessary to repeat similar schemes or procedures. In every technique used the solvent used should be clearly stated (it is present in some but not in all experiments). Some minor typo problems should be revised (for instance “number space unit”).

--

Author Response

Dear Reviewer:

     Thank you very much for your valuable feedback and recognition of our manuscript. We have carefully read and understood your revision suggestions. We deeply appreciate every question you have raised and have made corresponding modifications based on your four points of feedback. We believe that this will greatly improve the quality of our paper.Detailed information please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Dear authors,

 My suggestions have been answered. Congratulations on your work.

Reviewer 3 Report

Authors have improved the manuscript and it is adequate for publication.

--