Novel Green Synthesis of Polyfunctionally Substituted Phthalazines Promoted by Visible Light, DFT Studies and Molecular Docking with Antimicrobial and Antibiofilm Potency

Novel Green Synthesis of Polyfunctionally Substituted Phthalazines Promoted by Visible Light, DFT Studies and Molecular Docking with Antimicrobial and Antibiofilm Potency | 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 Novel Green Synthesis of Polyfunctionally Substituted Phthalazines Promoted by Visible Light, DFT Studies and Molecular Docking with Antimicrobial and Antibiofilm Potency Ramadan Mekheimer, Basma Khalifa, Zeinab Hashem, Samar Allam, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7824731/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Visible-Light-Mediated synthesis is a green and efficient technique which garnered interest from organic chemists. A series of new polyfunctionally substituted phthalazine derivatives 3a-j have synthesized via the reaction of pyridazines 1a-d with arylidenes 2a-d in the presence of a catalytic amount of piperidine in abs. ethanol as a solvent and under white LED lamb irradiation in open air. All synthesized products 3a-j have screened as potential antimicrobial and antibiofilm agents. Both compounds 3g and 3j are the most promising derivatives. Compound 3g displayed outstanding activity against P. aeruginosa and K. pneumoniae with a MIC value of 3.12 and 12.5 µg/mL, respectively. Compound 3j gave a MIC value of 6.25 µg/mL for P. aeruginosa . As prospective antibiofilm agents against P. aeruginosa , compounds 3g and 3j exhibited inhibition with 81% and 75%, respectively. The geometrical structures were optimized using Density Functional Theory (DFT), frontier molecular orbitals (HOMO-LUMO), along with global reactivity descriptors, such as chemical potential, electronegativity and electrophilicity, were computed to assess the compounds' chemical reactivity and stability. Spectral characteristics were interpreted to support the theoretical findings, while Molecular Electrostatic Potential (MEP) mapping was employed to visualize charge distribution and potential reactive sites. Furthermore, topological analyses, including Electron Localization Function (ELF) and Reduced Density Gradient/Non-Covalent Interaction (RDG/NCI) analysis, offered insights into intra- and intermolecular interactions and the nature of non-covalent bonding. Molecular docking simulations were performed and revealed favorable binding affinities and key interactions within the active sites, indicating potential antimicrobial and enzyme-inhibitory properties, especially with 3j-3LD6 with binding energy of -9.5 kcal/mol. Physical sciences/Chemistry Biological sciences/Drug discovery Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryData8Oct2025.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 02 Dec, 2025 Reviews received at journal 30 Nov, 2025 Reviewers agreed at journal 21 Nov, 2025 Reviews received at journal 05 Nov, 2025 Reviews received at journal 30 Oct, 2025 Reviewers agreed at journal 27 Oct, 2025 Reviewers agreed at journal 27 Oct, 2025 Reviewers agreed at journal 27 Oct, 2025 Reviewers agreed at journal 27 Oct, 2025 Reviewers invited by journal 27 Oct, 2025 Editor assigned by journal 27 Oct, 2025 Editor invited by journal 27 Oct, 2025 Submission checks completed at journal 24 Oct, 2025 First submitted to journal 24 Oct, 2025 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-7824731","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":540523390,"identity":"c7e3c2f4-2bf8-4be8-af0a-34f6996db434","order_by":0,"name":"Ramadan 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A series of new polyfunctionally substituted phthalazine derivatives 3a-j have synthesized \u003cem\u003evia\u003c/em\u003e the reaction of pyridazines 1a-d with arylidenes 2a-d in the presence of a catalytic amount of piperidine in abs. ethanol as a solvent and under white LED lamb irradiation in open air. All synthesized products 3a-j have screened as potential antimicrobial and antibiofilm agents. Both compounds 3g and 3j are the most promising derivatives. Compound 3g displayed outstanding activity against \u003cem\u003eP. aeruginosa\u003c/em\u003e and \u003cem\u003eK. pneumoniae\u003c/em\u003e with a MIC value of 3.12 and 12.5 \u0026micro;g/mL, respectively. Compound 3j gave a MIC value of 6.25 \u0026micro;g/mL for \u003cem\u003eP. aeruginosa\u003c/em\u003e. As prospective antibiofilm agents against \u003cem\u003eP. aeruginosa\u003c/em\u003e, compounds 3g and 3j exhibited inhibition with 81% and 75%, respectively. The geometrical structures were optimized using Density Functional Theory (DFT), frontier molecular orbitals (HOMO-LUMO), along with global reactivity descriptors, such as chemical potential, electronegativity and electrophilicity, were computed to assess the compounds' chemical reactivity and stability. Spectral characteristics were interpreted to support the theoretical findings, while Molecular Electrostatic Potential (MEP) mapping was employed to visualize charge distribution and potential reactive sites. Furthermore, topological analyses, including Electron Localization Function (ELF) and Reduced Density Gradient/Non-Covalent Interaction (RDG/NCI) analysis, offered insights into intra- and intermolecular interactions and the nature of non-covalent bonding. 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