Quantum Confinement of Proton Wavefunctions in Drug-Protein Cavities Governing Tunneling-Driven Catalysis and Controlled Drug Release

Quantum Confinement of Proton Wavefunctions in Drug-Protein Cavities Governing Tunneling-Driven Catalysis and Controlled Drug Release | 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 Quantum Confinement of Proton Wavefunctions in Drug-Protein Cavities Governing Tunneling-Driven Catalysis and Controlled Drug Release Moses Udoisoh, Lucky Endas, Patience Oinu Momoh, Salim Snai Haldu, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7095236/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 Context Proton transfer in drug–protein cavities is central to enzymatic catalysis and pH-responsive drug delivery, yet classical models often fail to capture the quantum mechanical behavior that governs these processes. The influence of nanoscale confinement on proton dynamics through quantum effects remains poorly understood, limiting our ability to design optimized therapeutic systems. We present a quantum theoretical framework that connects cavity geometry with measurable proton transfer properties, offering new insights for biocatalysis and nanomedicine. Method We developed an analytical model for proton confinement in biological cavities by solving the Schrödinger equation for two spherically symmetric potentials: finite square wells representing hydrophobic environments and Morse potentials for hydrogen-bonded systems. Our approach systematically calculates ground-state energies, wavefunctions, tunneling probabilities, and vibrational overtones. Results show confinement geometry exponentially modulates proton behavior, with tunneling probabilities spanning > 12 orders of magnitude under physiological conditions. Kinetic isotope effects (> 10¹¹) and catalytic enhancements (10³-fold) confirm quantum tunneling dominance. While finite wells promote classical localization, Morse potentials enable efficient proton transfer through delocalization. The model incorporates environmental decoherence and establishes design rules linking cavity parameters to spectroscopic and kinetic signatures, providing a bridge between quantum theory and structural biology. Quantum nanomedicine Drug-protein interactions Nanoscale catalysis pH-responsive nanomaterials 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. 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-7095236","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":490400597,"identity":"f6b8f0fa-f9da-4275-89c4-e8f74212355d","order_by":0,"name":"Moses 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nanomaterials","lastPublishedDoi":"10.21203/rs.3.rs-7095236/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7095236/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eContext\u003c/h2\u003e\u003cp\u003eProton transfer in drug\u0026ndash;protein cavities is central to enzymatic catalysis and pH-responsive drug delivery, yet classical models often fail to capture the quantum mechanical behavior that governs these processes. The influence of nanoscale confinement on proton dynamics through quantum effects remains poorly understood, limiting our ability to design optimized therapeutic systems. We present a quantum theoretical framework that connects cavity geometry with measurable proton transfer properties, offering new insights for biocatalysis and nanomedicine.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e\u003cp\u003eWe developed an analytical model for proton confinement in biological cavities by solving the Schr\u0026ouml;dinger equation for two spherically symmetric potentials: finite square wells representing hydrophobic environments and Morse potentials for hydrogen-bonded systems. Our approach systematically calculates ground-state energies, wavefunctions, tunneling probabilities, and vibrational overtones. Results show confinement geometry exponentially modulates proton behavior, with tunneling probabilities spanning\u0026thinsp;\u0026gt;\u0026thinsp;12 orders of magnitude under physiological conditions. Kinetic isotope effects (\u0026gt;\u0026thinsp;10\u0026sup1;\u0026sup1;) and catalytic enhancements (10\u0026sup3;-fold) confirm quantum tunneling dominance. While finite wells promote classical localization, Morse potentials enable efficient proton transfer through delocalization. The model incorporates environmental decoherence and establishes design rules linking cavity parameters to spectroscopic and kinetic signatures, providing a bridge between quantum theory and structural biology.\u003c/p\u003e","manuscriptTitle":"Quantum Confinement of Proton Wavefunctions in Drug-Protein Cavities Governing Tunneling-Driven Catalysis and Controlled Drug Release","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-25 03:28:01","doi":"10.21203/rs.3.rs-7095236/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":"d9561c92-734c-4e5d-af0d-ea1b9bac8d1d","owner":[],"postedDate":"July 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-30T16:23:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-25 03:28:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7095236","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7095236","identity":"rs-7095236","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}