Assessment of Free Radical Scavenging Potency of Folates. A DFT Study

Assessment of Free Radical Scavenging Potency of Folates. A DFT Study | 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 Article Assessment of Free Radical Scavenging Potency of Folates. A DFT Study Zaruhi Manukyan, Sergey Arsentev, Samvel Stepanyan, Levon Tavadyan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6179333/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Folic acid (FA) is a widely known essential compound with various biochemical properties, including antioxidant. The antiradical/antioxidant properties of FA and its physiological reduced forms: 7,8-dihydrofolate (DHF), 5,6,7,8-tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF), and 5-formyltetrahydrofolate (5-FTHF) were studied using density functional theory (DFT) in gas phase and benzene, ethanol, aqueous medium. Three possible competing mechanisms for free radical inactivation are considered: hydrogen atom transfer (HAT), stepwise electron transfer-proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET). Thermodynamically preferred active sites of selected folate structures have been revealed, as well as a growing order of free radical scavenging activity: FA << 5-FTHF < 5-MTHF < THF < DHF . It has been accepted that folates act as antioxidants with many free radical scavenging sites, and the hydroxyl group of the reduced forms of folic acid is the most favorable site for free radical attack. Physical sciences/Chemistry/Physical chemistry Physical sciences/Chemistry/Theoretical chemistry Folic acid folate antioxidant activity DFT HAT SET-PT SPLET Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-6179333","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":447635491,"identity":"8c90d4d5-cd38-4898-857d-07f7cdb2f4aa","order_by":0,"name":"Zaruhi Manukyan","email":"","orcid":"","institution":"Institute of Chemical Physics NAS RA","correspondingAuthor":false,"prefix":"","firstName":"Zaruhi","middleName":"","lastName":"Manukyan","suffix":""},{"id":447635492,"identity":"719ff4a8-f3a3-4026-b286-68a5d8f81f84","order_by":1,"name":"Sergey Arsentev","email":"","orcid":"","institution":"Institute of Chemical Physics NAS RA","correspondingAuthor":false,"prefix":"","firstName":"Sergey","middleName":"","lastName":"Arsentev","suffix":""},{"id":447635493,"identity":"9ad6b639-1de8-43da-987f-f830ccc7210c","order_by":2,"name":"Samvel Stepanyan","email":"data:image/png;base64,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","orcid":"","institution":"Institute of Chemical Physics NAS RA","correspondingAuthor":true,"prefix":"","firstName":"Samvel","middleName":"","lastName":"Stepanyan","suffix":""},{"id":447635494,"identity":"1030d0cc-554c-4f38-893c-b32bf4b41b50","order_by":3,"name":"Levon Tavadyan","email":"","orcid":"","institution":"Institute of Chemical Physics NAS RA","correspondingAuthor":false,"prefix":"","firstName":"Levon","middleName":"","lastName":"Tavadyan","suffix":""},{"id":447635495,"identity":"c337192f-9b89-4feb-ab83-7d965b99f77f","order_by":4,"name":"Gaspar Kocharyan","email":"","orcid":"","institution":"Institute of Chemical Physics NAS RA","correspondingAuthor":false,"prefix":"","firstName":"Gaspar","middleName":"","lastName":"Kocharyan","suffix":""}],"badges":[],"createdAt":"2025-03-07 15:08:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6179333/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6179333/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90329237,"identity":"1e1ab14c-69ba-43bb-bcf4-805f94833d36","added_by":"auto","created_at":"2025-09-01 12:47:14","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1262184,"visible":true,"origin":"","legend":"","description":"","filename":"RevisedManuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6179333/v1_covered_8873f37b-f4a9-4922-a498-acad1834041b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessment of Free Radical Scavenging Potency of Folates. 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The antiradical/antioxidant properties of FA and its physiological reduced forms: 7,8-dihydrofolate (DHF), 5,6,7,8-tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF), and 5-formyltetrahydrofolate (5-FTHF) were studied using density functional theory (DFT) in gas phase and benzene, ethanol, aqueous medium. Three possible competing mechanisms for free radical inactivation are considered: hydrogen atom transfer (HAT), stepwise electron transfer-proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET). Thermodynamically preferred active sites of selected folate structures have been revealed, as well as a growing order of free radical scavenging activity: \u003cstrong\u003eFA \u0026lt;\u0026lt; 5-FTHF \u0026lt; 5-MTHF \u0026lt; THF \u0026lt; DHF\u003c/strong\u003e. It has been accepted that folates act as antioxidants with many free radical scavenging sites, and the hydroxyl group of the reduced forms of folic acid is the most favorable site for free radical attack.\u003c/p\u003e","manuscriptTitle":"Assessment of Free Radical Scavenging Potency of Folates. 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