{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:45:29Z","timestamp":1792784729724,"version":"4.5.0"},"reference-count":42,"publisher":"American Chemical Society (ACS)","issue":"37","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004901","name":"Funda????o de Amparo ?? Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APD-00076-25"],"award-info":[{"award-number":["APD-00076-25"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda????o de Amparo ?? Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ-00144-24"],"award-info":[{"award-number":["APQ-00144-24"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda????o de Amparo ?? Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ-04537-22"],"award-info":[{"award-number":["APQ-04537-22"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda????o de Amparo ?? Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["RED-00045-23"],"award-info":[{"award-number":["RED-00045-23"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient??fico e Tecnol??gico","doi-asserted-by":"publisher","award":["303311\/2024-0"],"award-info":[{"award-number":["303311\/2024-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient??fico e Tecnol??gico","doi-asserted-by":"publisher","award":["310096\/2025-1"],"award-info":[{"award-number":["310096\/2025-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena????o de Aperfei??oamento de Pessoal de N??vel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Instituto Nacional de Ci??ncia e Tenologia - Nanobiofar","id":[{"id":"https:\/\/ror.org\/000p2dj48","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The supramolecular interactions between selegiline hydrochloride (SEL) and \u03b2-cyclodextrin (\u03b2CD) derivatives were investigated through isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR), and molecular dynamics (MD) simulations. Thermodynamic analyses revealed spontaneous complex formation in aqueous solution for both \u03b2CD and carboxymethyl-\u03b2-cyclodextrin (CM-\u03b2CD), with CM-\u03b2CD exhibiting higher equilibrium constants and more favorable thermodynamic parameters. The complexation process was predominantly entropy-driven, indicating significant contributions from hydrophobic interactions and solvent reorganization. Non-integer stoichiometric values (n \u2248 1.5) obtained by ITC suggested the formation of higher-order supramolecular assemblies. NMR experiments demonstrated strong spatial correlations between the aromatic hydrogens of SEL and the cavity hydrogens of CM-\u03b2CD, supporting deep inclusion within the CD cavity. MD simulations corroborated the experimental findings and demonstrated the feasibility of a 3:2 CM-\u03b2CD:SEL supramolecular organization. Overall, the combined thermodynamic, spectroscopic, and computational results provide compelling evidence for higher-order, multi-equilibrium cyclodextrin supramolecular assemblies in aqueous solution.<\/jats:p>","DOI":"10.1021\/acs.jpcb.6c03442","type":"journal-article","created":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T15:01:44Z","timestamp":1788706904000},"page":"9594-9604","source":"Crossref","is-referenced-by-count":1,"title":["Thermodynamic and\nStructural Evidence for Higher-Order\nSelegiline with Carboxymethyl-\u03b2-Cyclodextrin Supramolecular\nAssemblies in Aqueous Solution"],"prefix":"10.1021","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1911-9136","authenticated-orcid":true,"given":"Diego Caproni","family":"de Morais","sequence":"first","affiliation":[{"name":"Universidade Federal de Itajuba\u0301 (UNIFEI) , , , ,","place":["Itajuba\u0301, M G, Brazil, 37500-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6335-6406","authenticated-orcid":true,"given":"Roge\u0301rio R.","family":"Macedo","sequence":"additional","affiliation":[{"name":"Universidade Federal de Itajuba\u0301 (UNIFEI) , , ,","place":["Itajuba\u0301, Brazil, 37500-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca B. M.","family":"Vieira","sequence":"additional","affiliation":[{"name":"Universidade Federal de Itajuba\u0301 (UNIFEI) , , , ,","place":["Itajuba\u0301, M G, Brazil, 37500-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Lula","sequence":"additional","affiliation":[{"name":"Universidade Federal de Minas Gerais (UFMG) , , , ,","place":["Belo Horizonte, MG, Brazil, 31270-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5064-5478","authenticated-orcid":true,"given":"Juliana Fedoce","family":"Lopes","sequence":"additional","affiliation":[{"name":"Universidade Federal de Itajuba\u0301 (UNIFEI) , , ,","place":["Itajuba\u0301, Brazil, 37500-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7930-6867","authenticated-orcid":true,"given":"Frederico B.","family":"De Sousa","sequence":"additional","affiliation":[{"name":"Universidade Federal de Itajuba\u0301 (UNIFEI) , , , ,","place":["Itajuba\u0301, M G, Brazil, 37500-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"issue":"19","key":"2026091708473979400_cit1","doi-asserted-by":"publisher","first-page":"8888","DOI":"10.1039\/D4CS01037J","article-title":"Advances\nin applied supramolecular technologies 2021\u20132025","volume":"54","author":"Balderston","year":"2025","journal-title":"Chem. Soc. Rev."},{"issue":"15","key":"2026091708473979400_cit2","doi-asserted-by":"publisher","first-page":"7794","DOI":"10.1021\/cr500392w","article-title":"Biomedical Applications\nof Supramolecular Systems Based on Host\u2013Guest\nInteractions","volume":"115","author":"Ma","year":"2015","journal-title":"Chem. Rev."},{"key":"2026091708473979400_cit3","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.bioactmat.2026.01.040","article-title":"Programmable\nnext-generation supramolecular self-assembled\nmaterials as drug delivery systems","volume":"60","author":"Fu","year":"2026","journal-title":"Bioact.\nMater."},{"issue":"3","key":"2026091708473979400_cit4","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1021\/cr050576c","article-title":"Cyclodextrins as Supramolecular Hosts\nfor Organometallic Complexes","volume":"106","author":"Hapiot","year":"2006","journal-title":"Chem. Rev."},{"issue":"1","key":"2026091708473979400_cit5","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nchem.920","article-title":"Molecular\nrecognition scaled up","volume":"3","author":"Steed","year":"2011","journal-title":"Nat. Chem."},{"issue":"9","key":"2026091708473979400_cit6","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.ccr.2008.08.011","article-title":"Inclusion complexation,\nencapsulation interaction and inclusion number in cyclodextrin chemistry","volume":"253","author":"Song","year":"2009","journal-title":"Coord. Chem. Rev."},{"key":"2026091708473979400_cit7","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2022.859406","article-title":"Cyclodextrin-Based\nNanosponges: Overview and Opportunities","volume":"10","author":"Utzeri","year":"2022","journal-title":"Front.\nChem."},{"key":"2026091708473979400_cit8","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.jpba.2014.02.022","article-title":"Analytical\ntechniques for characterization of cyclodextrin complexes in aqueous\nsolution: A review","volume":"101","author":"Mura","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"2026091708473979400_cit9","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.jpba.2015.01.058","article-title":"Analytical\ntechniques for characterization of cyclodextrin complexes in the solid\nstate: A review","volume":"113","author":"Mura","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"5","key":"2026091708473979400_cit10","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1021\/cr970015o","article-title":"Complexation Thermodynamics\nof Cyclodextrins","volume":"98","author":"Rekharsky","year":"1998","journal-title":"Chem. Rev."},{"key":"2026091708473979400_cit11","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2022.121036","article-title":"Exploring 2:1 inclusion\ncomplexes of cyclodextrins and antispasmodics, Alverine citrate for\nenhancing bioavailability and sustained dischargement","volume":"370","author":"Rajbanshi","year":"2023","journal-title":"J. Mol. Liq."},{"issue":"12","key":"2026091708473979400_cit12","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1038\/nrd1576","article-title":"Cyclodextrin-based pharmaceutics:\npast, present and\nfuture","volume":"3","author":"Davis","year":"2004","journal-title":"Nat. Rev. Drug Discovery"},{"issue":"26","key":"2026091708473979400_cit13","doi-asserted-by":"publisher","first-page":"8426","DOI":"10.1021\/ja801080v","article-title":"Supramolecular\nSelf-Assembly of Cyclodextrin\nand Higher Water Soluble Guest: Thermodynamics and Topological Studies","volume":"130","author":"Sousa","year":"2008","journal-title":"J. Am. Chem. Soc."},{"issue":"1","key":"2026091708473979400_cit14","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ijpharm.2011.09.026","article-title":"Multi-equilibrium system based on\nsertraline and \u03b2-cyclodextrin supramolecular complex in aqueous\nsolution","volume":"421","author":"Passos","year":"2011","journal-title":"Int. J. Pharm."},{"issue":"6","key":"2026091708473979400_cit15","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1039\/c2cp22768a","article-title":"Superstructure\nbased on \u03b2-CD self-assembly induced by a small guest molecule","volume":"14","author":"De Sousa","year":"2012","journal-title":"Phys. Chem. Chem. Phys."},{"key":"2026091708473979400_cit16","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2023.122565","article-title":"Biperiden Hydrochloride\/\u03b2\n-Cyclodextrins supramolecular\nsystem and its cytotoxicity against lung adenocarcinoma cells","volume":"386","author":"Vieira","year":"2023","journal-title":"J. Mol. Liq."},{"issue":"16","key":"2026091708473979400_cit17","doi-asserted-by":"publisher","first-page":"4004","DOI":"10.1039\/D3TB02795C","article-title":"Unveiling the synergy:\na combined\nexperimental and theoretical study of \u03b2-cyclodextrin with melatonin","volume":"12","author":"Ferrero","year":"2024","journal-title":"J. Mater. Chem. B"},{"issue":"21","key":"2026091708473979400_cit18","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.drudis.2008.06.004","article-title":"New challenges\nfor pharmaceutical formulations and drug delivery systems characterization\nusing isothermal titration calorimetry","volume":"13","author":"Bouchemal","year":"2008","journal-title":"Drug\nDiscovery Today"},{"issue":"39","key":"2026091708473979400_cit19","doi-asserted-by":"publisher","first-page":"9604","DOI":"10.1021\/acs.jpcb.4c04516","article-title":"Exploring the Recognition Mechanism\nof Surfactant\u2013Cyclodextrin\nComplex Formation: Insights from SPR Studies on Temperature and Ionic\nLiquid Influence","volume":"128","author":"Marques","year":"2024","journal-title":"J. Phys. Chem. B"},{"key":"2026091708473979400_cit20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2021.102675","article-title":"Simultaneous determination of cyclodextrin\nstability constants as a function of pH and temperature \u2013 A\ntool for drug formulation and process design","volume":"65","author":"Samuelsen","year":"2021","journal-title":"J. Drug Delivery Sci. Technol."},{"issue":"1","key":"2026091708473979400_cit21","doi-asserted-by":"publisher","DOI":"10.1038\/s43586-023-00199-x","article-title":"Isothermal titration calorimetry","volume":"3","author":"Bastos","year":"2023","journal-title":"Nat. Rev. Methods Primers"},{"issue":"1","key":"2026091708473979400_cit22","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.molstruc.2003.07.011","article-title":"1H NMR titration and\nquantum calculation for the inclusion complexes of styrene and \u03b1-methyl\nstyrene with \u03b1, \u03b2 and \u03b3-cyclodextrins","volume":"660","author":"Cao","year":"2003","journal-title":"J. Mol. Struct."},{"key":"2026091708473979400_cit23","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2026.145692","article-title":"Structural\nand dynamic investigation\nof Wnt inhibitor complexes with sulfobutyl ether-\u03b2-cyclodextrin\nusing experimental and computational approaches","volume":"1361","author":"Ramos","year":"2026","journal-title":"J. Mol. Struct."},{"key":"2026091708473979400_cit24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2024.106111","article-title":"Development,\ncharacterization and pharmacokinetic evaluation\nof selegiline HCl loaded cubosomal thermoreversible mucoadhesive gel\nfor nose to brain delivery","volume":"100","author":"Kakulade","year":"2024","journal-title":"J. Drug Delivery\nSci. Technol."},{"issue":"4","key":"2026091708473979400_cit25","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.jpba.2007.11.039","article-title":"Optimization\nand validation of a dissolution test for selegiline hydrochloride\ntablets by a novel rapid HPLC assay using a monolithic stationary\nphase","volume":"46","author":"Tzanavaras","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"2","key":"2026091708473979400_cit26","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1208\/s12249-017-0868-0","article-title":"Appraisal\nof Transdermal Water-in-Oil Nanoemulgel of Selegiline HCl for the\nEffective Management of Parkinson\u2019s Disease: Pharmacodynamic,\nPharmacokinetic, and Biochemical Investigations","volume":"19","author":"Setya","year":"2018","journal-title":"AAPS PharmSciTech"},{"issue":"2","key":"2026091708473979400_cit27","doi-asserted-by":"publisher","first-page":"159","DOI":"10.4155\/tde-2020-0118","article-title":"Development\nand Characterization\nof Sublingual Films for Enhanced Bioavailability of Selegiline Hydrochloride","volume":"12","author":"Salatin","year":"2021","journal-title":"Ther. Delivery"},{"issue":"48","key":"2026091708473979400_cit28","doi-asserted-by":"publisher","first-page":"14859","DOI":"10.1021\/ja036166s","article-title":"On the Value of\nc: Can Low Affinity Systems Be Studied\nby Isothermal Titration Calorimetry?","volume":"125","author":"Turnbull","year":"2003","journal-title":"J. Am.\nChem. Soc."},{"key":"2026091708473979400_cit29","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2026.117372","article-title":"Composite nanoparticles based on\npolymeric deep eutectic solvents modified by carboxymethyl-\u03b2-cyclodextrin,\nas chiral selectors for enantioseparation in capillary electrophoresis","volume":"223","author":"Ji","year":"2026","journal-title":"Microchem. J."},{"key":"2026091708473979400_cit30","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance\nmolecular simulations through multi-level parallelism from laptops\nto supercomputers","volume":"1-2","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"issue":"45","key":"2026091708473979400_cit31","doi-asserted-by":"publisher","first-page":"11225","DOI":"10.1021\/ja9621760","article-title":"Development\nand Testing of the OPLS\nAll-Atom Force Field on Conformational Energetics and Properties of\nOrganic Liquids","volume":"118","author":"Jorgensen","year":"1996","journal-title":"J. Am. Chem. Soc."},{"issue":"24","key":"2026091708473979400_cit32","doi-asserted-by":"publisher","first-page":"6269","DOI":"10.1021\/j100308a038","article-title":"The missing term in effective pair\npotentials","volume":"91","author":"Berendsen","year":"1987","journal-title":"J. Phys. Chem. A"},{"issue":"1","key":"2026091708473979400_cit33","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.ijpharm.2018.04.036","article-title":"Thermodynamic\ncompatibility between cyclodextrin supramolecular complexes and surfactant","volume":"544","author":"Meira","year":"2018","journal-title":"Int. J. Pharm."},{"issue":"3","key":"2026091708473979400_cit34","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1007\/s10847-009-9723-6","article-title":"Structural\nand physical\u2013chemical evaluation of Bradykinin Potentiating\nPeptide and its high soluble supramolecular complex","volume":"67","author":"Sousa","year":"2010","journal-title":"J. Inclusion Phenom. Macrocyclic Chem."},{"key":"2026091708473979400_cit35","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2024.122962","article-title":"Guest inclusion by native cyclodextrins\nin solid state and solutions: A review","volume":"349","author":"Gatiatulin","year":"2025","journal-title":"Carbohydr.\nPolym."},{"key":"2026091708473979400_cit36","doi-asserted-by":"publisher","DOI":"10.1016\/j.cplett.2024.141500","article-title":"Thermodynamic investigation of biperiden hydrochloride\nand cyclodextrins supramolecular systems","volume":"851","author":"Morais","year":"2024","journal-title":"Chem.\nPhys. Lett."},{"issue":"4","key":"2026091708473979400_cit37","doi-asserted-by":"publisher","first-page":"3890","DOI":"10.1021\/acsomega.4c09559","article-title":"Chiral Recognition\nMechanism of Amlodipine by Capillary Electrophoresis Using Carboxymethyl-\u03b2-cyclodextrin:\nAn Experimental and Theoretical Study","volume":"10","author":"Silva","year":"2025","journal-title":"ACS Omega"},{"key":"2026091708473979400_cit38","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2021.132052","article-title":"Host-guest chemistry of the sulfasalazine-\u03b2-cyclodextrin\ninclusion complex","volume":"85","author":"Tahir","year":"2021","journal-title":"Tetrahedron"},{"issue":"3","key":"2026091708473979400_cit39","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1007\/s10973-020-10048-8","article-title":"Thermodynamics of antibiotics:\nnatural cyclodextrin inclusion complex formation and covering of nano-metric\ncalcite with these substances","volume":"146","author":"Szaruga","year":"2021","journal-title":"J. Therm. Anal.\nCalorim."},{"key":"2026091708473979400_cit40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119774","article-title":"Certain carboxylic\nacid buffers can\ndestabilize \u03b2-cyclodextrin complexes by competitive interaction","volume":"589","author":"Samuelsen","year":"2020","journal-title":"Int. J. Pharm."},{"key":"2026091708473979400_cit41","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.foodchem.2019.02.021","article-title":"The interaction mechanism of oligopeptides containing\naromatic rings with \u03b2-cyclodextrin and its derivatives","volume":"286","author":"Li","year":"2019","journal-title":"Food Chem."},{"issue":"8","key":"2026091708473979400_cit42","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1021\/acs.jafc.1c07018","article-title":"Computational\nMethods for the Interaction between Cyclodextrins and Natural Compounds:\nTechnology, Benefits, Limitations, and Trends","volume":"70","author":"Ding","year":"2022","journal-title":"J. Agric. Food Chem."}],"container-title":["The Journal of Physical\nChemistry B"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jpcb.6c03442","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/37\/9594\/68396350\/acs.jpcb.6c03442.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/37\/9594\/68396350\/acs.jpcb.6c03442.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:08:22Z","timestamp":1789654102000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article\/130\/37\/9594\/5421918\/Thermodynamic-and-Structural-Evidence-for-Higher"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,6]]},"references-count":42,"journal-issue":{"issue":"37","published-online":{"date-parts":[[2026,9,6]]},"published-print":{"date-parts":[[2026,9,17]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jpcb.6c03442","relation":{},"ISSN":["1520-6106","1520-5207"],"issn-type":[{"value":"1520-6106","type":"print"},{"value":"1520-5207","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,6]]}}}