Synthesis, characterization, and biological activity using computational study of synthesized monocyclic β-lactam ligands

Synthesis, characterization, and biological activity using computational study of synthesized monocyclic β-lactam ligands | 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 Synthesis, characterization, and biological activity using computational study of synthesized monocyclic β-lactam ligands Shweta Shweta, Shabbir Muhammad, Mahesh Kumar Mishra, Aijaz Rasool Chaudhry, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4365126/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 The synthesis of monocyclic β-lactam ligands, their spectral as well as the X-ray crystallographic analysis, computational study, and biological activity are all covered in this article. The characterization of all these ligands is completed through FT-IR, 1 H NMR, 13 C NMR and X-ray crystallography study. We applied computational study to analyze the biological activity of all the designed monocyclic β-lactam ligands ( 4a , 4b , 4c and 4d ) against cancer. For this purpose, ligand-protein interactions are studied by molecular docking and quantum chemical computations. The frontier molecular orbitals (FMOs) results show a clear intramolecular charge transfer from central core (azetidine) towards thiadiazole ring more like donor and acceptor groups. Molecular electrostatic potentials (MEPs) are visualized to get insights to electrophilic and nucleophilic regions of studied compounds with the help of specific color codes. We calculated and compared bond lengths, bond and torsional angles for optimized geometry of 4a using M06-2X functional and 6-31G* basis sets. The matrix metalloproteases (MMP-9) protein which actively causes proliferation of cancer cells. Molecular docking results indicate that ligands 4a , 4b , 4c and 4d show the maximum binding energies (B.E) of -9.0, -9.4, -7.8 and 9.0 kcal.mol − 1 with MMP-9 protein. The studied 2-D and 3-D interactions show that compound 4b and 4d interact more vigorously with MMP-9 protein through three hydrogen bonds in each complex. For compound 4a , density of states (DOS) plot is calculated by dividing the molecule into three fragments. DOS results provide the major contributions of fragments containing thiadiazole ring towards HOMO and LUMO at ~ -13 eV to 5 eV, respectively. The current investigation highlights the importance of the entitle compounds as efficient bioactive candidates against cancer as investigated through experimental and quantum computational techniques. β-lactam FMOs MEPs DOS biological activity molecular docking Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryInformation.pdf 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-4365126","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":300312649,"identity":"c1f1a69c-4bc8-4d76-98d9-a6318e7b52b4","order_by":0,"name":"Shweta Shweta","email":"","orcid":"","institution":"National Institute of Technology Patna","correspondingAuthor":false,"prefix":"","firstName":"Shweta","middleName":"","lastName":"Shweta","suffix":""},{"id":300312652,"identity":"b35afbc4-d2b1-42b9-b542-51dff85a7424","order_by":1,"name":"Shabbir Muhammad","email":"","orcid":"","institution":"King Khalid 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docking","lastPublishedDoi":"10.21203/rs.3.rs-4365126/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4365126/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe synthesis of monocyclic β-lactam ligands, their spectral as well as the X-ray crystallographic analysis, computational study, and biological activity are all covered in this article. The characterization of all these ligands is completed through FT-IR, \u003csup\u003e1\u003c/sup\u003eH NMR, \u003csup\u003e13\u003c/sup\u003eC NMR and X-ray crystallography study. We applied computational study to analyze the biological activity of all the designed monocyclic β-lactam ligands (\u003cb\u003e4a\u003c/b\u003e, \u003cb\u003e4b\u003c/b\u003e, \u003cb\u003e4c\u003c/b\u003e and \u003cb\u003e4d\u003c/b\u003e) against cancer. For this purpose, ligand-protein interactions are studied by molecular docking and quantum chemical computations. The frontier molecular orbitals (FMOs) results show a clear intramolecular charge transfer from central core (azetidine) towards thiadiazole ring more like donor and acceptor groups. Molecular electrostatic potentials (MEPs) are visualized to get insights to electrophilic and nucleophilic regions of studied compounds with the help of specific color codes. We calculated and compared bond lengths, bond and torsional angles for optimized geometry of \u003cb\u003e4a\u003c/b\u003e using M06-2X functional and 6-31G* basis sets. The matrix metalloproteases (MMP-9) protein which actively causes proliferation of cancer cells. Molecular docking results indicate that ligands \u003cb\u003e4a\u003c/b\u003e, \u003cb\u003e4b\u003c/b\u003e, \u003cb\u003e4c\u003c/b\u003e and \u003cb\u003e4d\u003c/b\u003e show the maximum binding energies (B.E) of -9.0, -9.4, -7.8 and 9.0 kcal.mol\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e with MMP-9 protein. The studied 2-D and 3-D interactions show that compound \u003cb\u003e4b\u003c/b\u003e and \u003cb\u003e4d\u003c/b\u003e interact more vigorously with MMP-9 protein through three hydrogen bonds in each complex. For compound \u003cb\u003e4a\u003c/b\u003e, density of states (DOS) plot is calculated by dividing the molecule into three fragments. DOS results provide the major contributions of fragments containing thiadiazole ring towards HOMO and LUMO at ~ -13 eV to 5 eV, respectively. The current investigation highlights the importance of the entitle compounds as efficient bioactive candidates against cancer as investigated through experimental and quantum computational techniques.\u003c/p\u003e","manuscriptTitle":"Synthesis, characterization, and biological activity using computational study of synthesized monocyclic β-lactam ligands","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-09 06:35:31","doi":"10.21203/rs.3.rs-4365126/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":"2aef81d3-43af-4c10-92d9-6c934a526621","owner":[],"postedDate":"May 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-09T19:10:27+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-09 06:35:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4365126","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4365126","identity":"rs-4365126","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}