In-Silico Evaluation of Novel Quercetin Derivatives as Antimalarial Agents Targeting Plasmodium falciparum Dihydrofolate Reductase: Molecular Docking, Molecular Dynamics Simulations, and Pharmacokinetic and Toxicity Predictions

In-Silico Evaluation of Novel Quercetin Derivatives as Antimalarial Agents Targeting Plasmodium falciparum Dihydrofolate Reductase: Molecular Docking, Molecular Dynamics Simulations, and Pharmacokinetic and Toxicity Predictions | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article In-Silico Evaluation of Novel Quercetin Derivatives as Antimalarial Agents Targeting Plasmodium falciparum Dihydrofolate Reductase: Molecular Docking, Molecular Dynamics Simulations, and Pharmacokinetic and Toxicity Predictions Mansita Saha, Krishna Jyoti Deka, Sabnam Nargis, Dhrubajyoti Gogoi, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8425313/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 15 You are reading this latest preprint version Abstract The global rise in malaria mortality is largely driven by the increasing resistance of Plasmodium falciparum to widely used and affordable antimalarial drugs, emphasizing the urgent need for novel therapeutic agents. In this study, thirty-five ligands were computationally evaluated as potential inhibitors of the bifunctional enzyme dihydrofolate reductase–thymidylate synthase (DHFR-TS; PDB ID: 1J3K), a validated antimalarial drug target. Virtual screening and molecular docking were performed using AutoDock implemented in PyRx v0.8, followed by molecular dynamics simulations using GROMACS v2024.4. Pharmacokinetic and toxicity profiles were assessed using SwissADME and Protox 3.0. ADME analysis revealed favorable pharmacokinetic properties for most compounds, while toxicity predictions classified the majority into Classes IV and V, indicating low acute toxicity, with all promising ligands predicted to be non-hepatotoxic, non-cardiotoxic, and non-carcinogenic. Among the evaluated compounds, six ligands (b.II, b.III, b.VIII, I.b, II.b, and VII.b) exhibited higher binding affinities toward DHFR-TS than the reference drugs cycloguanil and pyrimethamine. These ligands formed strong hydrogen bonding and van der Waals interactions with key active-site residues, including SER A:167, LEU A:40, ILE A:14, LEU A:164, ASN A:33, THR A:36, GLU A:25, and CYS A:27, contributing to enhanced binding stability. Notably, ligand b.II demonstrated the strongest binding affinity and sustained stability, identifying it as a promising lead candidate for further experimental validation against multidrug-resistant Plasmodium falciparum. Malaria molecular docking Pharmacokinetics 1j3k proteins Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 28 Jan, 2026 Reviews received at journal 23 Jan, 2026 Reviews received at journal 20 Jan, 2026 Reviews received at journal 20 Jan, 2026 Reviews received at journal 15 Jan, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviewers invited by journal 13 Jan, 2026 Editor invited by journal 13 Jan, 2026 Editor assigned by journal 07 Jan, 2026 Submission checks completed at journal 01 Jan, 2026 First submitted to journal 01 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8425313","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":574266403,"identity":"0b5b2d5b-4467-470b-aa50-0cfceb77e047","order_by":0,"name":"Mansita Saha","email":"","orcid":"","institution":"Institute of Pharmacy, Assam Don Bosco University, Tapesia, Sonapur, Assam-782402, India","correspondingAuthor":false,"prefix":"","firstName":"Mansita","middleName":"","lastName":"Saha","suffix":""},{"id":574266404,"identity":"db192a93-6cf3-47bd-b673-dcbb95c4e796","order_by":1,"name":"Krishna Jyoti Deka","email":"","orcid":"","institution":"Regional College of Pharmaceutical Sciences, Srimanta Sankaradeva University of Health Sciences, Guwahati-781032, Assam, India","correspondingAuthor":false,"prefix":"","firstName":"Krishna","middleName":"Jyoti","lastName":"Deka","suffix":""},{"id":574266406,"identity":"4b7def5b-a522-4b8c-8819-9c3173638876","order_by":2,"name":"Sabnam Nargis","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIiWNgGAWjYFACHhiDsYEhwcAGxGg8QLyWBwVpYAaxWoBqH3w4DGbg1SLffvbYg585d+TN+xc3f0gwOG+3tv0w0JYam2hcWgzO5KUb9m57ZjjnxsM2iQSD28nbziQCtRxLy23ApYUhx0yCd9thxhkSB9sYQFrMDgC1MDYcxqlFvv+NmeTfbYftgVpADjuXbHb+IX4tDDdyzKSBtiTO4G9sADrsgJ3ZDQK2GNx4lyYtu+1w8gwJRpBfkhPMbgBtScDjF/n+3GOSb7cdtp3Bf/zxxx9/7OzNzqc/fPChxga3w+BAIgFMJYJVJhBUDgL8B8CUPVGKR8EoGAWjYEQBAAfKauogQ2D0AAAAAElFTkSuQmCC","orcid":"","institution":"Royal School of Pharmacy, The Assam Royal Global University, Guwahati-781035, Assam, India","correspondingAuthor":true,"prefix":"","firstName":"Sabnam","middleName":"","lastName":"Nargis","suffix":""},{"id":574266407,"identity":"3c52ff5b-08e8-40d7-b7be-0f0dace6d1b0","order_by":3,"name":"Dhrubajyoti Gogoi","email":"","orcid":"","institution":"Programme of Biotechnology, Faculty of science, Assam down town University, Guwahati, Assam","correspondingAuthor":false,"prefix":"","firstName":"Dhrubajyoti","middleName":"","lastName":"Gogoi","suffix":""},{"id":574266408,"identity":"f44bd96d-3cef-464f-a0ba-dd0fc78256e2","order_by":4,"name":"Pallab kumar Nath","email":"","orcid":"","institution":"Royal School of Pharmacy, The Assam Royal Global University, Guwahati-781035, Assam, India","correspondingAuthor":false,"prefix":"","firstName":"Pallab","middleName":"kumar","lastName":"Nath","suffix":""},{"id":574266409,"identity":"e11bb09b-fb15-457b-8abe-c6ad89d27b67","order_by":5,"name":"Debarupa Dutta Chakraborty","email":"","orcid":"","institution":"Royal School of Pharmacy, The Assam Royal Global University, Guwahati-781035, Assam, India","correspondingAuthor":false,"prefix":"","firstName":"Debarupa","middleName":"Dutta","lastName":"Chakraborty","suffix":""},{"id":574266410,"identity":"a9a01bd9-b02f-4a8f-80a1-943a58522186","order_by":6,"name":"Prithviraj Chakraborty","email":"","orcid":"","institution":"Royal School of Pharmacy, The Assam Royal Global University, Guwahati-781035, Assam, India","correspondingAuthor":false,"prefix":"","firstName":"Prithviraj","middleName":"","lastName":"Chakraborty","suffix":""}],"badges":[],"createdAt":"2025-12-22 14:05:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8425313/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8425313/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100547465,"identity":"28bb80f2-d79b-4006-b1d4-3648236c60ec","added_by":"auto","created_at":"2026-01-19 08:15:39","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2388481,"visible":true,"origin":"","legend":"","description":"","filename":"InSilicoEvaluationofNovelQuercetinDerivativesasAntimalarialAgentsTargetingPlasmodiumfalciparumDihydrofolateReductase4.docx","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/5af2fb241c2776fded00878a.docx"},{"id":100440451,"identity":"d9714150-8c0d-42de-8797-56ead019a432","added_by":"auto","created_at":"2026-01-16 16:29:28","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8547,"visible":true,"origin":"","legend":"","description":"","filename":"579fe1797b744b3f979bf7d10ec68bc9.json","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/103e27433bc12d7720a59e4e.json"},{"id":100547180,"identity":"bc9c9bb0-bfb2-494a-bed4-72193c621730","added_by":"auto","created_at":"2026-01-19 08:14:44","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":188835,"visible":true,"origin":"","legend":"","description":"","filename":"579fe1797b744b3f979bf7d10ec68bc91enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/f0e806293b3d736d55d46c8d.xml"},{"id":100547034,"identity":"dd75c16a-4e85-4228-865c-b3e6767bcde8","added_by":"auto","created_at":"2026-01-19 08:14:05","extension":"emf","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":18364,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.emf","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/2bcb9946f6b8ba1dc29d7767.emf"},{"id":100547154,"identity":"ec6ad396-0b5b-4739-a146-67f1d29b3522","added_by":"auto","created_at":"2026-01-19 08:14:41","extension":"emf","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":19968,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.emf","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/ce68a7170edc967129ae60aa.emf"},{"id":100440455,"identity":"34fa81c8-8dc5-41c2-b393-da91aaf4b857","added_by":"auto","created_at":"2026-01-16 16:29:28","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":746350,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/b99cf0dcd2da271a5a25a9b7.jpeg"},{"id":100546603,"identity":"ab095e57-df0f-4d8a-9588-5134aaec13a6","added_by":"auto","created_at":"2026-01-19 08:11:11","extension":"jpeg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1241507,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/adc4e5c653e4e0e25d41a21a.jpeg"},{"id":100546703,"identity":"375a2934-c8bb-4832-b4b0-ff561dcc4f66","added_by":"auto","created_at":"2026-01-19 08:12:00","extension":"jpeg","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1216186,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/3cb31bf7ce9cc6d8ff03c6c2.jpeg"},{"id":100546987,"identity":"d2e3f35e-8cb9-4e30-a09f-c3e00fd95ee9","added_by":"auto","created_at":"2026-01-19 08:13:49","extension":"jpeg","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":951865,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/6aad41ab516d9f9df3ba9f2b.jpeg"},{"id":100546921,"identity":"4ba14cb9-ba97-4216-967f-27edbf8d07e5","added_by":"auto","created_at":"2026-01-19 08:13:09","extension":"jpeg","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":65443,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/d734fcc4680a59e4a544bc72.jpeg"},{"id":100546673,"identity":"eedc419d-f1c0-4465-b5d8-ffabcca4c1b7","added_by":"auto","created_at":"2026-01-19 08:11:44","extension":"jpeg","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":75308,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage8.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/8aaec1f2573554c9966f88f0.jpeg"},{"id":100547287,"identity":"1c5871d9-e1f1-4469-97ce-79fb2c5c1ad0","added_by":"auto","created_at":"2026-01-19 08:15:09","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1310,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/559fc0c109ccc230567ff30c.png"},{"id":100547279,"identity":"239b7025-7c0b-4d7f-a0fa-706ff22a44a2","added_by":"auto","created_at":"2026-01-19 08:15:07","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1421,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/af87670cff75d4bcf6626fdb.png"},{"id":100440467,"identity":"0d4b4fc8-2ebc-4dc8-8f80-37c42adfed14","added_by":"auto","created_at":"2026-01-16 16:29:28","extension":"png","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":174640,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/7dba1b376ab354d34730820c.png"},{"id":100547582,"identity":"78bee94f-57ac-4352-83c8-66c553133882","added_by":"auto","created_at":"2026-01-19 08:16:03","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":287408,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/02c833808bc0fe0ed2f94d4a.png"},{"id":100547176,"identity":"546cc116-a5f3-4c36-a498-bd67552b613a","added_by":"auto","created_at":"2026-01-19 08:14:44","extension":"png","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":274230,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/8db355c38ca68f1265c2c533.png"},{"id":100547697,"identity":"a33dc5a7-f0b9-4f54-a2a1-d4e9fc800409","added_by":"auto","created_at":"2026-01-19 08:16:22","extension":"png","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":198235,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/cb31658b43f8da6684eb74eb.png"},{"id":100440462,"identity":"73570cdb-a67c-4489-87ba-c1bdb665c80c","added_by":"auto","created_at":"2026-01-16 16:29:28","extension":"png","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":24331,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/1ea8d14f50343f9077d07b56.png"},{"id":100440469,"identity":"fcb2da69-fcae-4013-a9e1-81f7b06cfb4a","added_by":"auto","created_at":"2026-01-16 16:29:28","extension":"png","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":43523,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/3847899ac07ff37b90447894.png"},{"id":100440471,"identity":"795b14d7-9019-42c1-81d4-ab6d1ecaeed6","added_by":"auto","created_at":"2026-01-16 16:29:28","extension":"xml","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":184871,"visible":true,"origin":"","legend":"","description":"","filename":"579fe1797b744b3f979bf7d10ec68bc91structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/99c36347688a816b97fb1c6a.xml"},{"id":100547417,"identity":"02b6eca5-8b62-4268-8e2f-950b7ffb13a7","added_by":"auto","created_at":"2026-01-19 08:15:28","extension":"html","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":201056,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1/8f5d74f009aaec1b9ea371d2.html"},{"id":100595042,"identity":"33737b76-ab1c-4e83-9f03-fefbd86de0e7","added_by":"auto","created_at":"2026-01-19 13:47:12","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1236914,"visible":true,"origin":"","legend":"","description":"","filename":"InSilicoEvaluationofNovelQuercetinDerivativesasAntimalarialAgentsTargetingPlasmodiumfalciparumDihydrofolateReductase4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8425313/v1_covered_c2a2d3f9-5ee1-42fa-bccf-d353af534731.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"In-Silico Evaluation of Novel Quercetin Derivatives as Antimalarial Agents Targeting Plasmodium falciparum Dihydrofolate Reductase: Molecular Docking, Molecular Dynamics Simulations, and Pharmacokinetic and Toxicity Predictions","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-chemistry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Chemistry](https://link.springer.com/journal/44371)","snPcode":"44371","submissionUrl":"https://submission.nature.com/new-submission/44371/3","title":"Discover Chemistry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Malaria, molecular docking, Pharmacokinetics, 1j3k proteins","lastPublishedDoi":"10.21203/rs.3.rs-8425313/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8425313/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe global rise in malaria mortality is largely driven by the increasing resistance of \u003cem\u003ePlasmodium falciparum\u003c/em\u003e to widely used and affordable antimalarial drugs, emphasizing the urgent need for novel therapeutic agents. In this study, thirty-five ligands were computationally evaluated as potential inhibitors of the bifunctional enzyme dihydrofolate reductase\u0026ndash;thymidylate synthase (DHFR-TS; PDB ID: 1J3K), a validated antimalarial drug target. Virtual screening and molecular docking were performed using AutoDock implemented in PyRx v0.8, followed by molecular dynamics simulations using GROMACS v2024.4. Pharmacokinetic and toxicity profiles were assessed using SwissADME and Protox 3.0. ADME analysis revealed favorable pharmacokinetic properties for most compounds, while toxicity predictions classified the majority into Classes IV and V, indicating low acute toxicity, with all promising ligands predicted to be non-hepatotoxic, non-cardiotoxic, and non-carcinogenic. Among the evaluated compounds, six ligands (b.II, b.III, b.VIII, I.b, II.b, and VII.b) exhibited higher binding affinities toward DHFR-TS than the reference drugs cycloguanil and pyrimethamine. These ligands formed strong hydrogen bonding and van der Waals interactions with key active-site residues, including SER A:167, LEU A:40, ILE A:14, LEU A:164, ASN A:33, THR A:36, GLU A:25, and CYS A:27, contributing to enhanced binding stability. Notably, ligand b.II demonstrated the strongest binding affinity and sustained stability, identifying it as a promising lead candidate for further experimental validation against multidrug-resistant Plasmodium falciparum.\u003c/p\u003e","manuscriptTitle":"In-Silico Evaluation of Novel Quercetin Derivatives as Antimalarial Agents Targeting Plasmodium falciparum Dihydrofolate Reductase: Molecular Docking, Molecular Dynamics Simulations, and Pharmacokinetic and Toxicity Predictions","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 16:29:20","doi":"10.21203/rs.3.rs-8425313/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-28T10:16:05+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-24T04:16:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-20T08:30:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-20T05:03:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-16T00:08:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"253501025038765178856575449311039837775","date":"2026-01-14T04:17:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"15403920189367670149021804577102334101","date":"2026-01-13T16:44:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"271740984088495481051866668486161466472","date":"2026-01-13T16:40:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"243343811191137776390714241199323686081","date":"2026-01-13T16:30:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"10998809177525728577661213747116966387","date":"2026-01-13T16:25:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-13T16:22:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-13T08:01:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-07T09:21:15+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-01T05:24:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Chemistry","date":"2026-01-01T05:19:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-chemistry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Chemistry](https://link.springer.com/journal/44371)","snPcode":"44371","submissionUrl":"https://submission.nature.com/new-submission/44371/3","title":"Discover Chemistry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"725eb81f-d5c0-472d-b1c7-22b175b8a371","owner":[],"postedDate":"January 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T16:38:34+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-16 16:29:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8425313","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8425313","identity":"rs-8425313","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}