Impact of Non-Covalent Interactions of Chiral Linked Systems in Solution on Photoinduced Electron Transfer Efficiency

Round 1

Reviewer 1 Report

Reviewer’s Comments:

The manuscript “Non-covalent interactions between chiral linked systems in solutions studied using photoinduced electron transfer” is a very interesting work. In this work, it is well known that non-covalent interactions play an essential role in the functioning of biomolecules in living organisms. The main attention of researchers is focused on the mechanisms of associates formation and the role of the chiral configuration of proteins, peptides, amino acids in the association. We have recently demonstrated the unique sensitivity of chemically induced dynamic nuclear polarization (CIDNP) in photoinduced electron transfer in chiral donor-acceptor dyads to non-covalent interactions of its diastereomers in solutions. The present study further develops the approach for quantitatively analyzing of the factors that determine the association by examples of the diastereomers dimerization of dyads with RS, SR and SS optical configurations. It has been shown that CIDNP under UV irradiation of dyads is formed in associates, which are homo (SS-SS), (SR-SR) and hetero (SS-SR) dimers of diastereomers. While I believe this topic is of great interest to our readers, I think it needs major revision before it is ready for publication. So, I recommend this manuscript for publication with major revisions.

1. In this manuscript, the authors did not explain the importance of photoinduced electron transfer in the introduction part. The authors should explain the importance of photoinduced electron transfer.

2) Title: The title of the manuscript is not impressive. It should be modified or rewritten it.

3) Correct the following statement “We show that the experimental dependences of the ratio of CIDNP enhancement coefficients of SS and RS, SR optical configuration of diastereomers on their concentration ratio can be described by varying the probability of electron transfer in homo, hetero dimers and monomers. We expect that the proposed approximation can be used to identify small size associates in peptides, which is still a problem”.

4) Keywords: The photoinduced electron transfer is missing in the keywords. So, modify the keywords.

5) Introduction part is not impressive. The references cited are very old. So, Improve it with some latest literature like 10.1016/j.molstruc.2021.131136, 10.3390/molecules27217368

6) The authors should explain the following statement with recent references, “An analysis of the time resolved CIDNP effects in photoinduced ET of the dyad II performed in this work has confirmed the implementation of ET through the BZ formation”.

7) Add space between magnitude and unit. For example, in synthesis “21.96g” should be 21.96 g. Make the corrections throughout the manuscript regarding values and units.

8) The author should provide reason about this statement “There is no increase, but a decrease in the K magnitudes with the ratio of diastereomers concentrations”.

9. Comparison of the present results with other similar findings in the literature should be discussed in more detail. This is necessary in order to place this work together with other work in the field and to give more credibility to the present results.

10) Conclusion part is very long. Make it brief and improve by adding the results of your studies.

11) There are many grammatic mistakes. Improve the English grammar of the manuscript.

Minor editing of English language required

Author Response

Dear editor, we send you response to the reviewers comments, which we took into account in full.

Response to reviewer 1

Comment1. In this manuscript, the authors did not explain the importance of photoinduced electron transfer in the introduction part. The authors should explain the importance of photoinduced electron transfer.

Answer 1. Added explanation: It should be noted that ET and its photoinduced variant (PET) are a universal processes used to model elementary stages in biological systems [11-14].

Comment 2. The title of the manuscript is not impressive. It should be modified or rewritten it.

Answer 2. The title changed: Impact of non-covalent interactions of chiral linked systems in solution on photoinduced electron transfer efficiency

Comment 3. Correct the following statement “We show that the experimental dependences of the ratio of CIDNP enhancement coefficients of SS and RS, SR optical configuration of diastereomers on their concentration ratio can be described by varying the probability of electron transfer in homo, hetero dimers and monomers. We expect that the proposed approximation can be used to identify small size associates in peptides, which is still a problem”.

Answer 3. Paragraph rewritten: In particular, the efficiency of PET in homo-, heterodimers, and monomers of dyads completely determines the forms of dependences of the CIDNP enhancement coefficients ratio of SS and RS, SR configurations on the ratio of diastereomers concentrations. We expect that the use of such a correlation can be useful in identifying small size associates in peptides, which is still a problem.

Comment 4. Keywords: The photoinduced electron transfer is missing in the keywords. So, modify the keywords.

Answer 4. Keywords already included this term, but for the convenience of readers, we moved PET higher.

Comment 5. Introduction part is not impressive. The references cited are very old. So, Improve it with some latest literature like 10.1016/j.molstruc.2021.131136, 10.3390/molecules27217368

Answer 5.The introduction has been rewritten (motivation and task statement have been strengthened), new references have been added. These are reference links 9, 14, and 22-24.

Comment 6. The authors should explain the following statement with recent references, “An analysis of the time resolved CIDNP effects in photoinduced ET of the dyad II performed in this work has confirmed the implementation of ET through the BZ formation”.

Answer 6. The following changes have been made: An analysis of the time resolved CIDNP effects in photoinduced ET of the dyad II performed in this work, according to existing rules, has confirmed the implementation of ET through the BZ formation [15] (Ivanov, K.; Yurkovskya, A.; Fishman, N.; Kiryutin, A.; and etc., Chemically Induced Spin Hyperpolarization: Coherence Formation in Reaction Products, Applied Magnetic Resonance, 2022, 53, 595–613).

Comment 7. Add space between magnitude and unit. For example, in synthesis “21.96g” should be 21.96 g. Make the corrections throughout the manuscript regarding values and units.

Answer 7. All corrections have been made.

Comment 8. The author should provide reason about this statement “There is no increase, but a decrease in the K magnitudes with the ratio of diastereomers concentrations”.

Answer 8. This is just a description of the shape of the experimental dependence,  extended explanations are given below. To avoid repeating them twice, this phrase has been removed.

Comment 9. Comparison of the present results with other similar findings in the literature should be discussed in more detail. This is necessary in order to place this work together with other work in the field and to give more credibility to the present results.

Answer 9. The available references are supplemented with references to similar works using molecular modeling, as well as studies of the influence of weak non-covalent interactions on the efficiency of ET and association processes of chiral systems ([9],[14],[22-24]).

Comment 10. Conclusion part is very long. Make it brief and improve by adding the results of your studies.

Answer 10. The conclusion has been rewritten and includes now 11 lines.

Author Response File: Author Response.docx

Reviewer 2 Report

Manuscript Number: ijms-2397602

entitled: Non-covalent interactions between chiral linked systems in solutions studied using photoinduced electron transfer

This is an interesting scientific study. Therefore, the manuscript is suitable for publication in the International Journal of Molecular Sciences after considering the below comments:

I'm afraid I have to disagree with the author's thesis: page 2 “Today, CIDNP is one of the most informative, albeit indirect, methods for studying radical processes [15].” Since the early works of Gomberg, a lot has been discovered, although there were no modern analytical methods such as EPR or NMR.

In the range 1968 – 2023 Scopus CIDNP, find 1211 documents only. (please see attached file). The documents are mainly from the USA, Russian Federation, and Germany.

In the Conclusion part, please indicate the advantages of the CIDNP technique over others for a broadly understood reader.

Author Response

Response to reviewer 2

Comment  1. I'm afraid I have to disagree with the author's thesis: page 2 “Today, CIDNP is one of the most informative, albeit indirect, methods for studying radical processes [15].” Since the early works of Gomberg, a lot has been discovered, although there were no modern analytical methods such as EPR or NMR.

In the range 1968 – 2023 Scopus CIDNP, find 1211 documents only. (please see attached file). The documents are mainly from the USA, Russian Federation, and Germany.

 Answer 1. Authors can only assume that when referring to Gomberg, the reviewer means the study of stable radicals. Here, undoubtedly, EPR and NMR (Rowan, Hahn, Mims, Webb, Tsvetkov, Sagdeev, Molin) made the main contribution. But for short-lived (nanosecond range) free radicals this is not the case at all. To eliminate discrepancies, the authors have changed the phrase that caused this comment: “To date, CIDNP is one of the most informative, albeit indirect, methods for identifying short-lived radical particles [15]”.  Note that the observation of polarized NMR signals of the products unambiguously indicates their radical origin, in contrast, for example, to the data of EPR spectroscopy.

Comment  2. In the Conclusion part, please indicate the advantages of the CIDNP technique over others for a broadly understood reader.

Answer 2. The conclusion has been rewritten, taking into account this recommendation: “The authors believe that the use of CIDNP methods provides additional opportunities for studying the elementary stages of the small linked systems association and identifying the influence of chiral centers on these processes.”

Author Response File: Author Response.docx

Reviewer 3 Report

The manuscript "Non-covalent interactions between chiral linked systems in solutions studied using photoinduced electron transfer" is a great contribution in the field of self-assembled chiral configuration of proteins photoinduced by the electron transfer. The novelty of the manuscript consists in highlighting the factors involved in the association process by means of dimerization of dyads with RS, SR and SS configurations.

The authors also highlighted the mechanism of formation of small associates through non-covalent interactions by determination of equilibrium constants and the probability of homo-/ heterodimers formation based on the contribution of the monomers. They also used time-resolved CIDNP to evaluate the effects of the chemical polarization in associates.

Overall, the paper stands out through theoretical and experimental approaches well performed and demonstrated, so that it can be accepted for publication in the present form.

Author Response

Comment

The manuscript "Non-covalent interactions between chiral linked systems in solutions studied using photoinduced electron transfer" is a great contribution in the field of self-assembled chiral configuration of proteins photoinduced by the electron transfer. The novelty of the manuscript consists in highlighting the factors involved in the association process by means of dimerization of dyads with RS, SR and SS configurations.

The authors also highlighted the mechanism of formation of small associates through non-covalent interactions by determination of equilibrium constants and the probability of homo-/ heterodimers formation based on the contribution of the monomers. They also used time-resolved CIDNP to evaluate the effects of the chemical polarization in associates.

Overall, the paper stands out through theoretical and experimental approaches well performed and demonstrated, so that it can be accepted for publication in the present form.

Answer Thank a lot for the comments

Author Response File: Author Response.docx