Dear Dr. Li,

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.

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We look forward to receiving your revised manuscript.

Kind regards,

Komal Rizwan, PhD

Academic Editor

PLOS ONE

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2) A list of the chemical shifts for all compounds characterised by NMR spectroscopy, specifying, where relevant: the chemical shift (δ), the multiplicity and the coupling constants (in Hz), for the appropriate nuclei used for assignment.

3)The full integrated NMR spectrum, clearly labelled with the compound name and chemical structure.

We also strongly encourage authors to provide primary NMR data files, in particular for new compounds which have not been characterised in the existing literature. Authors should provide the acquisition data, FID files and processing parameters for each experiment, clearly labelled with the compound name and identifier, as well as a structure file for each provided dataset. See our list of recommended repositories here: https://journals.plos.org/plosone/s/recommended-repositories .

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Additional Editor Comments (if provided):

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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?

Reviewer #1: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Review Report

• The manuscript details the design, synthesis, and assessment of 36 halogenated sulfite derivatives, drawing inspiration from the structures of propargite and flupentiofenox—an innovative and pertinent strategy in the development of acaricides and aphicides.

• The research illustrates distinct structure–activity relationships (SARs), indicating how particular substitutions (e.g., Cl, CF₃O, 2-fluoroethyl) augment bioactivity, supported by robust chemical rationale and justification.

• Compounds 5.16 and 5.32 are prominently identified as lead candidates. Compound 5.32 exhibits remarkable and uncommon dual acaricidal and aphicidal properties within this class of compounds.

• The analytical characterization is sufficient and substantiates the structural assertions.

• The biological screening is well-structured; however, additional information regarding assay conditions (replicates, controls, statistical analysis) would enhance reproducibility.

• The assessment of crop safety for cowpea seedlings is pertinent; however, it is advisable to include additional discussion on broader phytotoxicity and environmental safety.

• The conclusion is robust but would improve with a concise discussion of the mechanism of action, prospective research, and potential applications.

• The language is generally clear; however, a brief editing session is advisable to enhance the flow and expression in the abstract and conclusion.

Minor Revisions — The manuscript is scientifically robust and offers significant insights; several improvements in clarity, depth, and contextual framing will enhance the final version.

Reviewer #2: Comments:

In this work the authors were designed, synthesized thirty-six halogenated propargite analogues and characterized using 1H NMR, 13C NMR spectroscopy, and HRMS. Among these thirty-six compounds two compounds exhibiting good insecticidal activity. Therefore, through SAR design authors discovered two interesting lead compounds (compounds 5.16 and 5.32) for insecticides.I recommend to publish in the PLOS ONE after minor revision.

Other comments:

1. I have not seen chemical structure at Figure 1. Design of target compounds: introduction of halogens

2. Scheme 1. Try to mention on the arrow “a” “b” and “c”

3. You write one number after digit in the 13C data

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Review Report.docx

Design, synthesis, and biological activity of novel halogenated sulfite compounds

PONE-D-25-15070R1

Dear Author,

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,

Komal Rizwan, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: