{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T14:20:20Z","timestamp":1774362020378,"version":"3.50.1"},"reference-count":42,"publisher":"AIP Publishing","issue":"12","funder":[{"DOI":"10.13039\/100022627","name":"Fulbright U.S. Scholar Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022627","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3,28]]},"abstract":"<jats:p>Mixing polyelectrolytes and (oppositely charged) multivalent ions is a well-known technique used to produce nanoparticles (or nanogels) for various biomedical\/biotechnological applications, such as drug, protein, or nucleic acid delivery. Quantitative prediction of the complexation process\u2014in terms of polymer and ion properties and solution conditions\u2014remains a challenge. The entropy associated with counterion release and the energy associated with polyelectrolyte\u2013ion interactions are key mechanistic elements, and an important experimental development has been their isolation as distinct signatures within isothermal titration calorimetry (ITC) profiles. However, current models used to interpret ITC data generally neglect important electrostatic and polymer effects. We present here a theoretical model of the complexation process with an eye toward ITC, accounting for the long-range electrostatic energy plus translational entropy of the condensing\/binding ions (i.e., Manning theory) and short-range non-electrostatic ion\u2013polymer interactions (e.g., van der Waals, hydrogen bonding). We explore the influence of certain theoretical approximations and governing parameters on the predicted extent of ion condensation and test the model vs ITC experimental measurements of the biopolymer chitosan (and iron functionalized chitosan) complexing with the multivalent ionic nucleotides\/nucleotide analogs adenosine, gemcitabine, and cytidine tri-phosphate. Excellent agreement is observed, and the resulting parameters provide important insight into polyelectrolyte\u2013ion interactions. In particular, iron functionalization is seen not only to enhance the short-range ion\u2013chitosan enthalpic attraction, but also to increase the associated entropic penalty.<\/jats:p>","DOI":"10.1063\/5.0315874","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T13:32:24Z","timestamp":1774359144000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Polyelectrolyte complexation with biofunctionalized multivalent ions: Coarse-grained model and isothermal titration calorimetry experiment"],"prefix":"10.1063","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0628-7618","authenticated-orcid":false,"given":"Herv\u00e9","family":"Hillaireau","sequence":"first","affiliation":[{"name":"Institut Galien, Universit\u00e9 Paris-Saclay 1 , Orsay,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Costamagna","sequence":"additional","affiliation":[{"name":"Institut Galien, Universit\u00e9 Paris-Saclay 1 , Orsay,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrouchan","family":"Hotier","sequence":"additional","affiliation":[{"name":"Institut Galien, Universit\u00e9 Paris-Saclay 1 , Orsay,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5768-4945","authenticated-orcid":false,"given":"Pablo L.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Chemical and Environmental Engineering and Department of Biomedical Engineering, Yale University 2 , New Haven, Connecticut 06520-8286,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3194-961X","authenticated-orcid":false,"given":"Elias","family":"Fattal","sequence":"additional","affiliation":[{"name":"Institut Galien, Universit\u00e9 Paris-Saclay 1 , Orsay,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1952-9716","authenticated-orcid":false,"given":"Paul R.","family":"Van Tassel","sequence":"additional","affiliation":[{"name":"Department of Chemical and Environmental Engineering and Department of Biomedical Engineering, Yale University 2 , New Haven, Connecticut 06520-8286,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"317","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"issue":"9","key":"2026032409315182300_c1","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1002\/jps.2600820909","article-title":"Development of a new drug carrier made from alginate","volume":"82","year":"1993","journal-title":"J.\u00a0Pharm. 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