PONE-D-23-41995Near infrared spectroscopic characterization of sesamin, a dietary lignan natural productPLOS ONE

Dear Dr. Baudry,

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PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have attempted to use IR to elucidate the different stereoisomers of sesamin. It should be noted that IR alone may not be sufficient to definitively identify stereoisomers. While IR spectroscopy provides valuable information about functional groups and molecular vibrations, it might not distinguish between stereoisomers that have the same atoms and functional groups but differ in their three-dimensional arrangement. NMR spectroscopy, specifically using chiral solvents or chiral shift reagents, can also provide information about the configuration of a chiral center by observing the splitting patterns or chemical shifts of surrounding atoms. Chromatographic techniques with chiral stationary phases and polarimetry are also used for chiral analysis, although they might not directly determine the configuration of a chiral carbon but can help identify enantiomers. Thus, it is better to do some NMR calculation in these molecules instead. The basis set also that they used is too small to distinguish such changes. As such, this paper is not suitable for publication in its present state.

There are some references that are excluded such as

https://doi.org/10.1080/10408398.2021.1881438

https://doi.org/10.1016/j.bpc.2004.10.001

Reviewer #2: This manuscript investigates sesamin, a lignan in sesame seed oil, by Fourier-transform infrared spectroscopy. The study compares the experimental spectrum with quantum chemical calculations of sesamin's stereoisomers, revealing potential hydrated and non-hydrated conformers. The findings pave the way for a comprehensive understanding of its structure and potential applications in pharmacology.

The work general employs correct methods and follows the right principles.

That being said, the employed methods are largely straightforward and part of the discussion presented in the manuscript should be approached with reserve. While credit may be given to the effort, the apparent in-depth discussion of the variations in the theoretical spectra of complexes with different number of water molecules are largely speculative (or, "academic"). In vacuo calculations for such systems are still only roughly representative to a solid/hydrated sample. This should be better reflected in the manuscript to prevent misleading readers not being experts in this area.

Nonetheless, the collected results and interpretations provide useful contribution to the field and I find this work publishable, provided a minor revision is considered by the authors.

1. The title and the abstract ("This work provides the first experimental near infrared spectrum of sesamin") both specifically mentions NIR region, yet NIR spectrum is not presented in this work at all. Instead, the reader is informed that NIR region is not interesting, i.e., "Wavenumbers below 500 cm-1 (and above 3500 cm-1) were not considered in the peak assignment since signal was low compared to noise.

2. B3LYP/6-31G* by contemporary standards should not be considered "appropriate for IR spectra calculations". But, judging from the figures shown in this work, it’s sufficient in the presented case.

3. What are the symmetries of each of the considered structures? If they differed by the number of symmetry elements, then the Eq. 1 should be refined with the use of symmetry cofactors (see, e.g. DOI: 10.3390/molecules24112189).

4. Molecular vibrations are 'antisymmetric' not 'asymmetric'.

5. Experimental FTIR spectra are of poor quality (noisy, distorted baseline with negative peaks, deformed bands), which is difficult to understand, as the measurements should be fairly straightforward.

6. Previous works modelling IR spectra on the basis of Boltzmann-weighted spectra of co-existing forms, done using anharmonic calculations and yielding highly accurate theoretical lineshape should be cited (e.g.:, 10.1021/acs.jpca.6b11734, 10.1038/s41598-019-53827-6, or 10.1016/j.molliq.2014.02.028).

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Reviewer #1: No

Reviewer #2: No

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PONE-D-23-41995R1Infrared spectroscopic characterization of sesamin, a dietary lignan natural productPLOS ONE

Dear Dr. Baudry,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jun 21 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Robert John O'Reilly, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

The modifications made to the manuscript have been accepted by the majority of the referees. There is one comment, which was provided by an additional referee who reviewed the revised version of the manuscript, that should be addressed (refer to the comment by Referee 4). Once this has been sufficiently addressed, the manuscript will be ready for acceptance.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

Reviewer #4: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: N/A

Reviewer #4: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have given their comments to the reviewers, unfortunately, I believe the topic that they present that using IR to determine the isomers is not enough. In addition, the authors have utilized sub-par calculation methods with the size of the molecules and the existing capacity now of the workstations they need to increase their theoretical methodology. Specifically,

1) The basis sets used is very small and they do not implement any scaling factor. In addition, anharmonic frequencies need to be included to get the overtones and combination bands that could arise from different isomeric forms.

2) How did they choose the location of the water molecules?

3) Never present energies in Hartrees, need to convert it into either kJ or kcal.

4) Based on the answer to comments

- "The 2021 paper by Majdalawieh, et al, is already cited by us (Ref #4) in the second sentence of our manuscript, where we introduce sesamin and the (limited) vibrational work available". This is a review paper and there is no mention about IR. Indeed, you can't hardly find papers regarding isomeric forms just merely using IR.

- Their goal is to "give a global “IR fingerprint” of sesamin, in several possible states and structures" again this fingerprint region is not conclusive given the theoretical methodology they utilized.

Reviewer #2: The authors' revisions were carried out exhaustively and addressed all points raised in the previous round of peer-review. The manuscript is recommended to be accepted in its present form.

Reviewer #3: I have reviewed Revision 1 of this manuscript.

The main claims of this study were that previously unassigned peaks from experimental FTIR of sesamin were able to be assigned with the support of EDF2/6-31G* computed FTIR spectra of sesamin's most prevalent stereoisomers. Further, to account for ambient hydration of sesamin samples, various states of hydration were modelled computationally. General agreement between the computational and experimental spectra were reported, within the bounds of previously reported error for organic molecules. The methodolgy used was appropriate and the authors have provided a clear presentation and discussion of results, and reached a measured conclusion that does not overstate the outcome.

The introduction of the manuscript oriented this study in the existing literature, highlighting its pharmocolgical significance.

The supporting information is thorough and complete and the methodolgy provides sufficient detail for the reproduction of the experiments. The manuscript is generally well written in easy to parse English, with minor typographical errors.

As acknowledged in the conclusion, updated FTIR characterisation of sesamin using an expanded basis set for this computational method (as mentioned in Ref [16]) and higher resolution experimental FTIR spectra would be an important next step towards a more complete characteristion of sesamin.

The author has addressed the concerns of Reviewer 2 well, particularly improving the clarity of the manuscript in the aim and in setting expectations of the audience, significantly curtailing this review.

The current manuscript is satisfactory in meeting the scientific, technical and ethical standards required for publication in this journal.

Reviewer #4:  (ii) In the abstract the author claims that this study provides 'the first experimental infrared spectrum of sesamin.' Although the work is comprehensive in structural assignments of previously unassigned frequencies, I take exception that it represents the "first" spectroscopic assignment of sesamin. I refer you to https://doi.org/10.1016/j.saa.2019.117777, published in 2019 in Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy where near-IR coupled with chemometric method was used in selective vibrational frequencies assignments of sesamin and sesamolin. I think the claim should be reevaluated but, regardless, it does contribute a wealth of data to important class of biological compounds.

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Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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Infrared spectroscopic characterization of sesamin, a dietary lignan natural product

PONE-D-23-41995R2

Dear Dr. Baudry,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Robert John O'Reilly, M.D., Ph.D.

Academic Editor

PLOS ONE

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