A Cheminformatics and DFT Exploration of a Brominated Sulfonamide with Nonlinear Optical and Bioactivity Promise

A Cheminformatics and DFT Exploration of a Brominated Sulfonamide with Nonlinear Optical and Bioactivity Promise | 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 A Cheminformatics and DFT Exploration of a Brominated Sulfonamide with Nonlinear Optical and Bioactivity Promise Bhijan Neupane, Khakendra Basnet, Jeevan Ghimire, Suresh Kumar Dhungel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9113160/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 12 You are reading this latest preprint version Abstract Sulfonamide derivatives are structurally versatile compounds that are relevant to molecular electronics, spectroscopy, and medicinal chemistry. In this study, cheminformatics-driven physicochemical analysis of 3-bromo- N -tert-butylbenzene-1-sulfonamide (BTBS) was performed by integrating density functional theory, electronic structure analysis, nonlinear optical descriptors, and bioactivity inference. Geometry optimization revealed a rigid sulfonyl framework with a planar aromatic core. The tert-butyl substituent enforced a non-coplanar sulfonamide orientation, which helped maintain its conjugation and modulated the charge distribution. Vibrational assignments from the infrared and Raman spectra reproduced the characteristic sulfonamide modes. This validates the bonding framework. BTBS exhibits a large frontier orbital energy gap. This means that it has high kinetic stability and low intrinsic reactivity, with solvent-dependent stabilization captured more effectively by the conductor-like continuum models. Electronic structure and density-of-states analyses revealed functional separation between the aromatic backbone, electron-withdrawing sulfonamide--bromine unit, and weakly donating tert-butyl group. This finding supports intramolecular charge transfer without a classical push--pull architecture. Time-dependent calculations predicted dominant \((\pi)\) -- \((\pi^\ast)\) transitions with solvent-induced red shifts and enhanced oscillator strengths. The calculated first-order hyperpolarizability exceeded that of urea. This confirms a significant second-order nonlinear optical response driven by electronic asymmetry. Local reactivity descriptors identified sulfonamide heteroatoms and brominated rings as the key reactive sites. Similarity-based read-across and molecular docking suggest favorable biological interactions. This supports the use of BTBS as a multifunctional scaffold linking electronic material chemistry and medicinal chemoinformatics. Density Functional Theory Read-across Spectroscopic analysis Electronic structure NLO Full Text Additional Declarations No competing interests reported. Supplementary Files document.pdf Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 17 May, 2026 Reviews received at journal 14 Apr, 2026 Reviews received at journal 14 Apr, 2026 Reviewers agreed at journal 09 Apr, 2026 Reviewers agreed at journal 05 Apr, 2026 Reviewers agreed at journal 05 Apr, 2026 Reviewers agreed at journal 05 Apr, 2026 Reviewers agreed at journal 04 Apr, 2026 Reviewers invited by journal 30 Mar, 2026 Editor assigned by journal 14 Mar, 2026 Submission checks completed at journal 14 Mar, 2026 First submitted to journal 13 Mar, 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. 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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-9113160","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":615511085,"identity":"647d40f7-b221-4d7e-a28f-c2cfd847751d","order_by":0,"name":"Bhijan 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In this study, cheminformatics-driven physicochemical analysis of 3-bromo-\u003cem\u003eN\u003c/em\u003e-tert-butylbenzene-1-sulfonamide (BTBS) was performed by integrating density functional theory, electronic structure analysis, nonlinear optical descriptors, and bioactivity inference. Geometry optimization revealed a rigid sulfonyl framework with a planar aromatic core. The tert-butyl substituent enforced a non-coplanar sulfonamide orientation, which helped maintain its conjugation and modulated the charge distribution. Vibrational assignments from the infrared and Raman spectra reproduced the characteristic sulfonamide modes. This validates the bonding framework. BTBS exhibits a large frontier orbital energy gap. This means that it has high kinetic stability and low intrinsic reactivity, with solvent-dependent stabilization captured more effectively by the conductor-like continuum models. Electronic structure and density-of-states analyses revealed functional separation between the aromatic backbone, electron-withdrawing sulfonamide--bromine unit, and weakly donating tert-butyl group. This finding supports intramolecular charge transfer without a classical push--pull architecture. Time-dependent calculations predicted dominant \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\((\\pi)\\)\u003c/span\u003e\u003c/span\u003e--\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\((\\pi^\\ast)\\)\u003c/span\u003e\u003c/span\u003e transitions with solvent-induced red shifts and enhanced oscillator strengths. The calculated first-order hyperpolarizability exceeded that of urea. This confirms a significant second-order nonlinear optical response driven by electronic asymmetry. Local reactivity descriptors identified sulfonamide heteroatoms and brominated rings as the key reactive sites. Similarity-based read-across and molecular docking suggest favorable biological interactions. 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