Dissecting the thermodynamics of polyelectrolyte complexation and liquid-liquid phase separation using a dual-equilibrium reaction model

Dissecting the thermodynamics of polyelectrolyte complexation and liquid-liquid phase separation using a dual-equilibrium reaction model | 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 Dissecting the thermodynamics of polyelectrolyte complexation and liquid-liquid phase separation using a dual-equilibrium reaction model Yan Huang, Xiatong Ou, Yuandong Rao, Qing He This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6245306/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 thermodynamics of complexation between charged macromolecules determine their associative liquid-liquid phase separation (LLPS) behavior and condensed phase properties. However, a proper approach to accurately extract full thermodynamic parameters from polyelectrolyte complexation has been missing. In this study, we divide the polyelectrolyte complexation into two correlated equilibrium reactions - ion pairing and coacervation, and introduce a dual-equilibrium reaction model (DER) that successfully fits the binding isotherms obtained from isothermal titration calorimetry (ITC). The binding free energy and equilibrium constant of both ion-pairing and LLPS are obtained and validated against thermogravimetric analysis and coarse-grained molecular dynamics simulations. The equilibrium constant of coacervation exhibits a logarithmic Gaussian distribution along the polyelectrolyte molar ratio and well represents the polymer content distribution between the supernatant and condensed phases. The DER model captures the underlying physical nature and offers a reliable approach for extracting thermodynamic parameters of the complexation and LLPS between charged macromolecules. Physical sciences/Chemistry/Polymer chemistry Physical sciences/Physics/Chemical physics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files supplementarymaterials.pdf SupplementaryMovies.zip Coarse-Grained Molecular Dynamic Simulation Videos 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. 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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-6245306","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":434338852,"identity":"bda8d121-1b7f-4dd9-b559-1c8043e71476","order_by":0,"name":"Yan Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYJACZjDJ3vgARDE2EK+F57ABqVokkonUYnD87AHmwja7PPnIx8yfeRhsZDccYH72AK+WM3kJzDPbkosNbyczGPMwpBlvOMBmboBXy4EcA2beNubEjbPzDyTzMBxO3HCAh00Cr5bzb0Ba6hM3zjzMcJiH4T8RWm6AbTmcOF+CmbGZh+EAYS2SN94YHOY5dzxxA08yM+Mcg2TjmYfZzPBq4TufY/iYp6w6cX77YeYPbyrsZPuONz/Dq0XhAAPDAbALISQDLJpwA/kGdMYoGAWjYBSMAnQAAFi8R8r4/24KAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-6679-3355","institution":"Fuzhou University","correspondingAuthor":true,"prefix":"","firstName":"Yan","middleName":"","lastName":"Huang","suffix":""},{"id":434338853,"identity":"834b65f6-46c2-466a-afac-97060c2736ad","order_by":1,"name":"Xiatong Ou","email":"","orcid":"","institution":"Fuzhou University","correspondingAuthor":false,"prefix":"","firstName":"Xiatong","middleName":"","lastName":"Ou","suffix":""},{"id":434338854,"identity":"7c036f81-db69-417f-ae18-33e13f9bc57a","order_by":2,"name":"Yuandong Rao","email":"","orcid":"","institution":"Fuzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yuandong","middleName":"","lastName":"Rao","suffix":""},{"id":434338855,"identity":"34417cb9-3658-4ddf-937c-9894c4da9436","order_by":3,"name":"Qing He","email":"","orcid":"","institution":"Fuzhou University","correspondingAuthor":false,"prefix":"","firstName":"Qing","middleName":"","lastName":"He","suffix":""}],"badges":[],"createdAt":"2025-03-17 14:00:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6245306/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6245306/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79323577,"identity":"54a99c2c-536c-4c45-b555-8480a3a08633","added_by":"auto","created_at":"2025-03-27 04:58:49","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":1040032,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6245306/v1/643fa2d8c88bdd14627f4010.pdf"},{"id":79323579,"identity":"07e1d4c6-5cc4-4363-af29-3ba8e5a24802","added_by":"auto","created_at":"2025-03-27 04:58:51","extension":"zip","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":158597976,"visible":true,"origin":"","legend":"Coarse-Grained Molecular Dynamic Simulation Videos","description":"","filename":"SupplementaryMovies.zip","url":"https://assets-eu.researchsquare.com/files/rs-6245306/v1/1d32562dfe4dfed58a11921b.zip"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Dissecting the thermodynamics of polyelectrolyte complexation and liquid-liquid phase separation using a dual-equilibrium reaction model","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"","lastPublishedDoi":"10.21203/rs.3.rs-6245306/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6245306/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"The thermodynamics of complexation between charged macromolecules determine their associative liquid-liquid phase separation (LLPS) behavior and condensed phase properties. 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