Central-to-Helical-to-Axial Chirality Transfer in Chiroptical Sensing with Ferrocene Chromophore

Round 1

Reviewer 1 Report

Inorganics_2023_2415331 The manuscript entitled “Central-to-Helical-to-Axial Chirality Transfer in Chiroptical Sensing with Ferrocene” by Marko Nuskol, Petar Šutalo, Monika Kovačević, Ivan Kodrin, and Mojca Čakić Semenčić.

This group of Croatian scientists is successfully investigating the conformational and chiropractic properties of dipeptides with an attached ferrocene chromophore.

The manuscript represents the research article and is devoted to ferrocene-modified amino acids with achiral linker, 1-aminocyclohexanecarboxylic acid, as a potential chiroptical sensor based on a ferrocene chromophore.

The authors logically substantiated the choice of 1-aminocyclohexanecarboxylic acid as a linker that regulates the chiroptic properties of the target compounds.

The authors carried out a very serious and thorough research, which seems important for the development of optical sensors for investigation of chiroptical properties of chiral molecules.

Along with the synthesis of new molecular frameworks, infrared studies, NMR, circular dichroism, and computational studies were also widely presented. Moreover, the results of the experimental and theoretical approaches correlate perfectly. The material is presented in a logical and interesting way.

These materials could be useful to specialists in the field of analytic medicinal chemistry and pharmacology. They will also be of interest to biochemists and chemists working with bioactive compounds, especially in the field of ferrocene chemistry.

In general, the manuscript is excellently prepared and carefully verified.

The manuscript does not raise any objections, and can be published in Inorganics in present form.

I was able to notice only one inaccuracy in the manuscript.

1.    Abstract. Line 10. ’…acyclic 1-aminocyclohexanecarboxylic acid’. Should be corrected: cyclic.

Comments for author File: Comments.pdf

Author Response

Thank you for your positive observations. Typo in line 10 is corrected.

Reviewer 2 Report

1.     I cannot find the figure from the IR part, pls also explain and discuss it in detail.

2.     Please also provide the UV spectra data.

3.     I suggest the author highlight your introduction, it is poor now.

4.     The work on some DFT methods using the energy calculation could be cited, including, Monatsh Chem, 2017, 48, 1259–1267; Chemical Physics Letters, 2015, 633, 265–272; ACS Omega, 2018, 3, 17986−17990; Theor. Chem. Acc. 2022, 141, 68; Molecules 2023, 28, 3282.

5.     The Figure 2 is not well, it should reflect your design, I suggest the author give more information on this figure.

Author Response

Thank you for providing your constructive and detailed review comments on our manuscript. We agree with all your suggestions, and we corrected point by point the manuscript accordingly.

1. IR data is provided in Figure 3 and in the Materials and methods section.

2. UV/Vis spectra of compounds 2-5 are added in the Supplementary material.

3. Since most of the introduction is devoted to our research, which this study directly follows, we feel that additional data would only burden the paper.

4. Thank you for the suggestion. We have carefully read these papers and although they use DFT methods, we cannot find any direct connection with ferrocene compounds, amino acids, and CD spectra analysis. With all due respect, citing these references will not significantly contribute to the quality of our paper. However, if the Editor thinks these citations are mandatory, we can reconsider our decision.

5. Figure 2 has been updated with an additional explanation included in the description.