Studies on new dithiophosphonic acid derivatives: Synthesis, characterization, DFT and molecular docking calculations and in vitro cytotoxicity assessment

Studies on new dithiophosphonic acid derivatives: Synthesis, characterization, DFT and molecular docking calculations and in vitro cytotoxicity assessment | 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 Studies on new dithiophosphonic acid derivatives: Synthesis, characterization, DFT and molecular docking calculations and in vitro cytotoxicity assessment Elif Bulat, Ertuğrul Gazi Sağlam, Senem Akkoç, Celal Tuğrul Zeyrek, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3811619/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 2,4- bis (3,4-dimethoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide (SAV-A1) was treated with five different alcohols to obtain dithiophosphonic acids (HLn, HS 2 P((2,4-CH 3 O) 2 -C 6 H 3 )(ORn); n=1-5, R1=n-pentyl-; R2=2-pentyl-; R3=4- tert -but-benzyl-; R4=2-propyl-; R5=2-butyl-). HLn series were converted to their ammonium salts, ([NH 4 Ln]). [NH 4 Ln] were reacted with NiCl 2 .6H 2 O to obtain the corresponding Ni(II) coordination compounds ([Ni(Ln) 2 ]) in ethanol medium. The structures of all the compounds were elucidated by spectroscopic techniques. Single-crystal X-ray diffraction analysis of [Ni(L1) 2 ], [Ni(L2) 2 ], [Ni(L4) 2 ] and [Ni(L5) 2 ] were also carried out. The ligands and their nickel complexes were tested on human liver and colon cancer cell lines using (MTT) assay method. The salts [NH 4 L2] and [NH 4 L5] demonstrated more antiproliferative effects than others in colon cancer cell line with IC 50 values 82.73 and 74.87 µM, respectively. Density Functional Theory (DFT) calculations of [Ni(L1) 2 ], [Ni(L2) 2 ], [Ni(L4) 2 ] and [Ni(L5) 2 ] were done. The molecular docking studies of [Ni(L1) 2 ], [Ni(L2) 2 ], [Ni(L4) 2 ] and [Ni(L5) 2 ] with colon cancer antigen proteins, ID 2HQ6 and liver cancer protein, PDB ID: 3WZE were done to foresee the interactions of the complexes. 2 4-diorganyl-1 3 2 4-dithiadiphosphetane-2 4-disulfide Single Crystal X-Ray Analysis SAV-A1 Perthiophosphonic Acid Anhydrides Dithiophosphonates Phosphonodithioates Antiproliferative activity Cytotoxic activity DFT Molecular docking Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterialSM.docx 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. 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-3811619","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":263695457,"identity":"b44b3865-07bb-4e64-a007-e88d9b3a0888","order_by":0,"name":"Elif Bulat","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYBACAwbmBiBlwcM+//zDB0AWDx9hLYwNDAcYJHh4bvAwG4C0sBGrhQGohU0CJEJQi7lEYuPnDxUSMjzSvccqv+bYybAxMD98dAOPFssZic0SB84AHSZzLu227LZkoMPYjI1z8DnsRmKDxME2CR57hgSz25LbmIFaeNikCWhp/nHwH9AWoJZiyW31RGlpkzjYANQikWPG+HHbYcJaLHsetlmcOQbUwnMsWZpx23EeNmYCfjFnTz58o6LGxp6Hvfngx5/bqu352ZsfPsanBQUw84BJYpWDAOMPUlSPglEwCkbBiAEAVzlFXGkupcQAAAAASUVORK5CYII=","orcid":"","institution":"Marmara University","correspondingAuthor":true,"prefix":"","firstName":"Elif","middleName":"","lastName":"Bulat","suffix":""},{"id":263695458,"identity":"acc79908-f6c8-4bc9-9432-0f6c2f31b44e","order_by":1,"name":"Ertuğrul Gazi Sağlam","email":"","orcid":"","institution":"Marmara University","correspondingAuthor":false,"prefix":"","firstName":"Ertuğrul","middleName":"Gazi","lastName":"Sağlam","suffix":""},{"id":263695459,"identity":"ae9d5d02-8efc-45f0-bef6-a63509e22c6c","order_by":2,"name":"Senem Akkoç","email":"","orcid":"","institution":"Süleyman Demirel University","correspondingAuthor":false,"prefix":"","firstName":"Senem","middleName":"","lastName":"Akkoç","suffix":""},{"id":263695460,"identity":"60f9a235-69cb-49c6-bd3a-981a708cbf6d","order_by":3,"name":"Celal Tuğrul Zeyrek","email":"","orcid":"","institution":"Çankırı Karatekin University","correspondingAuthor":false,"prefix":"","firstName":"Celal","middleName":"Tuğrul","lastName":"Zeyrek","suffix":""},{"id":263695461,"identity":"d837eddd-8021-40d8-bce1-037df175936d","order_by":4,"name":"Yunus Zorlu","email":"","orcid":"","institution":"Gebze Technical University","correspondingAuthor":false,"prefix":"","firstName":"Yunus","middleName":"","lastName":"Zorlu","suffix":""},{"id":263695462,"identity":"92520a57-219f-406b-bed2-fa76fe79716a","order_by":5,"name":"Hakan Dal","email":"","orcid":"","institution":"Anadolu University","correspondingAuthor":false,"prefix":"","firstName":"Hakan","middleName":"","lastName":"Dal","suffix":""}],"badges":[],"createdAt":"2023-12-27 09:45:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3811619/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3811619/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49286950,"identity":"6abf831a-531a-4250-9d05-de43a5fd47eb","added_by":"auto","created_at":"2024-01-08 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assessment","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"2,4-diorganyl-1,3,2,4-dithiadiphosphetane-2,4-disulfide, Single Crystal X-Ray Analysis, SAV-A1, Perthiophosphonic Acid Anhydrides, Dithiophosphonates, Phosphonodithioates, Antiproliferative activity, Cytotoxic activity, DFT, Molecular docking","lastPublishedDoi":"10.21203/rs.3.rs-3811619/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3811619/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e2,4-\u003cem\u003ebis\u003c/em\u003e(3,4-dimethoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide (SAV-A1) was treated with five different alcohols to obtain dithiophosphonic acids (HLn, HS\u003csub\u003e2\u003c/sub\u003eP((2,4-CH\u003csub\u003e3\u003c/sub\u003eO)\u003csub\u003e2\u003c/sub\u003e-C\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e3\u003c/sub\u003e)(ORn); n=1-5, R1=n-pentyl-; R2=2-pentyl-; R3=4-\u003cem\u003etert\u003c/em\u003e-but-benzyl-; R4=2-propyl-; R5=2-butyl-). HLn series were converted to their ammonium salts, ([NH\u003csub\u003e4\u003c/sub\u003eLn]). [NH\u003csub\u003e4\u003c/sub\u003eLn] were reacted with NiCl\u003csub\u003e2\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO to obtain the corresponding Ni(II) coordination compounds ([Ni(Ln)\u003csub\u003e2\u003c/sub\u003e]) in ethanol medium. The structures of all the compounds were elucidated by spectroscopic techniques. Single-crystal X-ray diffraction analysis of [Ni(L1)\u003csub\u003e2\u003c/sub\u003e], [Ni(L2)\u003csub\u003e2\u003c/sub\u003e], [Ni(L4)\u003csub\u003e2\u003c/sub\u003e] and [Ni(L5)\u003csub\u003e2\u003c/sub\u003e] were also carried out. The ligands and their nickel complexes were tested on human liver and colon cancer cell lines using (MTT) assay method. The salts [NH\u003csub\u003e4\u003c/sub\u003eL2] and [NH\u003csub\u003e4\u003c/sub\u003eL5] demonstrated more antiproliferative effects than others in colon cancer cell line with IC\u003csub\u003e50\u003c/sub\u003e values 82.73 and 74.87 µM, respectively. Density Functional Theory (DFT) calculations of [Ni(L1)\u003csub\u003e2\u003c/sub\u003e], [Ni(L2)\u003csub\u003e2\u003c/sub\u003e], [Ni(L4)\u003csub\u003e2\u003c/sub\u003e] and [Ni(L5)\u003csub\u003e2\u003c/sub\u003e] were done. The molecular docking studies of [Ni(L1)\u003csub\u003e2\u003c/sub\u003e], [Ni(L2)\u003csub\u003e2\u003c/sub\u003e], [Ni(L4)\u003csub\u003e2\u003c/sub\u003e] and [Ni(L5)\u003csub\u003e2\u003c/sub\u003e] with colon cancer antigen proteins, ID 2HQ6 and liver cancer protein, PDB ID: 3WZE were done to foresee the interactions of the complexes.\u003c/p\u003e","manuscriptTitle":"Studies on new dithiophosphonic acid derivatives: Synthesis, characterization, DFT and molecular docking calculations and in vitro cytotoxicity assessment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 20:26:22","doi":"10.21203/rs.3.rs-3811619/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2fd42677-94b8-455a-ab68-6c26189442de","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-01-08T02:44:14+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-03 20:26:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3811619","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3811619","identity":"rs-3811619","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}