Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods

Autores
Onnainty, Renée; Schenfeld, Esteban Martin; Quevedo, Mario Alfredo; Fernández, Mariana Adela; Longhi, Marcela Raquel; Granero, Gladys Ester
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hydrochlorothiazide (HCT) is one of the most commonly prescribed antihypertensive drugs. In an attempt to gain an insight into the physicochemical and molecular aspects controlling the complex architecture of native β-cyclodextrin (β-CD) with HCT, we performed multiple-temperature−pH isothermal titration calorimetric measurements of the HCT: β-CD system, together with proton nuclear magnetic resonance spectroscopy (1 H NMR), phase solubility analysis, and molecular modeling methods. The AL-type diagrams, obtained at different pH values and temperatures, suggested the formation of soluble 1:1 inclusion complexes of β-CD with HCT. The corresponding stability constants (K1:1) were determined by phase solubility studies and compared with those obtained by ITC, with good agreement between these two techniques being found. The three-dimensional array of the complex was studied by 1 H NMR and molecular modeling methods. Both techniques confirmed the formation of the inclusion complex, with good agreement between the experimental and theoretical techniques regarding the HCT binding mode to β-CD. Also, the forces involved in the association process were determined, both from the thermodynamic parameters obtained by ITC (association enthalpy, binding constant, Gibbs free energy, and entropy) and from energetic decomposition analyses derived from computational methods. We concluded that the formation of the HCT:β-CD complex was enthalpy driven, with the inclusion mode of HCT being highly dependent on its ionization state. In all cases, sustained hydrogen bond interactions with hydroxyl groups of β-CD were identified, with the solvation energy limiting the affinity. Regarding the pH and temperature dependence, lower affinity constants were found at higher HCT ionization states and temperatures.
Fil: Onnainty, Renée. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Schenfeld, Esteban Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Quevedo, Mario Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Fernández, Mariana Adela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
Fil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Granero, Gladys Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Materia
Hydrochlortiazida
Cyclodextrin
Complexes
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/22838
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/22838
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical MethodsOnnainty, RenéeSchenfeld, Esteban MartinQuevedo, Mario AlfredoFernández, Mariana AdelaLonghi, Marcela RaquelGranero, Gladys EsterHydrochlortiazidaCyclodextrinComplexeshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Hydrochlorothiazide (HCT) is one of the most commonly prescribed antihypertensive drugs. In an attempt to gain an insight into the physicochemical and molecular aspects controlling the complex architecture of native β-cyclodextrin (β-CD) with HCT, we performed multiple-temperature−pH isothermal titration calorimetric measurements of the HCT: β-CD system, together with proton nuclear magnetic resonance spectroscopy (1 H NMR), phase solubility analysis, and molecular modeling methods. The AL-type diagrams, obtained at different pH values and temperatures, suggested the formation of soluble 1:1 inclusion complexes of β-CD with HCT. The corresponding stability constants (K1:1) were determined by phase solubility studies and compared with those obtained by ITC, with good agreement between these two techniques being found. The three-dimensional array of the complex was studied by 1 H NMR and molecular modeling methods. Both techniques confirmed the formation of the inclusion complex, with good agreement between the experimental and theoretical techniques regarding the HCT binding mode to β-CD. Also, the forces involved in the association process were determined, both from the thermodynamic parameters obtained by ITC (association enthalpy, binding constant, Gibbs free energy, and entropy) and from energetic decomposition analyses derived from computational methods. We concluded that the formation of the HCT:β-CD complex was enthalpy driven, with the inclusion mode of HCT being highly dependent on its ionization state. In all cases, sustained hydrogen bond interactions with hydroxyl groups of β-CD were identified, with the solvation energy limiting the affinity. Regarding the pH and temperature dependence, lower affinity constants were found at higher HCT ionization states and temperatures.Fil: Onnainty, Renée. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Schenfeld, Esteban Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Quevedo, Mario Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Fernández, Mariana Adela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Granero, Gladys Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaAmerican Chemical Society2012-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/22838Onnainty, Renée; Schenfeld, Esteban Martin; Quevedo, Mario Alfredo; Fernández, Mariana Adela; Longhi, Marcela Raquel; et al.; Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods; American Chemical Society; Journal of Physical Chemistry B; 117; 1; 12-2012; 206-2171520-6106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/jp311274cinfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/jp311274cinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:41:41Zoai:ri.conicet.gov.ar:11336/22838instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:41:42.25CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods
title Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods
spellingShingle Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods
Onnainty, Renée
Hydrochlortiazida
Cyclodextrin
Complexes
title_short Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods
title_full Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods
title_fullStr Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods
title_full_unstemmed Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods
title_sort Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods
dc.creator.none.fl_str_mv Onnainty, Renée
Schenfeld, Esteban Martin
Quevedo, Mario Alfredo
Fernández, Mariana Adela
Longhi, Marcela Raquel
Granero, Gladys Ester
author Onnainty, Renée
author_facet Onnainty, Renée
Schenfeld, Esteban Martin
Quevedo, Mario Alfredo
Fernández, Mariana Adela
Longhi, Marcela Raquel
Granero, Gladys Ester
author_role author
author2 Schenfeld, Esteban Martin
Quevedo, Mario Alfredo
Fernández, Mariana Adela
Longhi, Marcela Raquel
Granero, Gladys Ester
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Hydrochlortiazida
Cyclodextrin
Complexes
topic Hydrochlortiazida
Cyclodextrin
Complexes
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Hydrochlorothiazide (HCT) is one of the most commonly prescribed antihypertensive drugs. In an attempt to gain an insight into the physicochemical and molecular aspects controlling the complex architecture of native β-cyclodextrin (β-CD) with HCT, we performed multiple-temperature−pH isothermal titration calorimetric measurements of the HCT: β-CD system, together with proton nuclear magnetic resonance spectroscopy (1 H NMR), phase solubility analysis, and molecular modeling methods. The AL-type diagrams, obtained at different pH values and temperatures, suggested the formation of soluble 1:1 inclusion complexes of β-CD with HCT. The corresponding stability constants (K1:1) were determined by phase solubility studies and compared with those obtained by ITC, with good agreement between these two techniques being found. The three-dimensional array of the complex was studied by 1 H NMR and molecular modeling methods. Both techniques confirmed the formation of the inclusion complex, with good agreement between the experimental and theoretical techniques regarding the HCT binding mode to β-CD. Also, the forces involved in the association process were determined, both from the thermodynamic parameters obtained by ITC (association enthalpy, binding constant, Gibbs free energy, and entropy) and from energetic decomposition analyses derived from computational methods. We concluded that the formation of the HCT:β-CD complex was enthalpy driven, with the inclusion mode of HCT being highly dependent on its ionization state. In all cases, sustained hydrogen bond interactions with hydroxyl groups of β-CD were identified, with the solvation energy limiting the affinity. Regarding the pH and temperature dependence, lower affinity constants were found at higher HCT ionization states and temperatures.
Fil: Onnainty, Renée. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Schenfeld, Esteban Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Quevedo, Mario Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Fernández, Mariana Adela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
Fil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Granero, Gladys Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
description Hydrochlorothiazide (HCT) is one of the most commonly prescribed antihypertensive drugs. In an attempt to gain an insight into the physicochemical and molecular aspects controlling the complex architecture of native β-cyclodextrin (β-CD) with HCT, we performed multiple-temperature−pH isothermal titration calorimetric measurements of the HCT: β-CD system, together with proton nuclear magnetic resonance spectroscopy (1 H NMR), phase solubility analysis, and molecular modeling methods. The AL-type diagrams, obtained at different pH values and temperatures, suggested the formation of soluble 1:1 inclusion complexes of β-CD with HCT. The corresponding stability constants (K1:1) were determined by phase solubility studies and compared with those obtained by ITC, with good agreement between these two techniques being found. The three-dimensional array of the complex was studied by 1 H NMR and molecular modeling methods. Both techniques confirmed the formation of the inclusion complex, with good agreement between the experimental and theoretical techniques regarding the HCT binding mode to β-CD. Also, the forces involved in the association process were determined, both from the thermodynamic parameters obtained by ITC (association enthalpy, binding constant, Gibbs free energy, and entropy) and from energetic decomposition analyses derived from computational methods. We concluded that the formation of the HCT:β-CD complex was enthalpy driven, with the inclusion mode of HCT being highly dependent on its ionization state. In all cases, sustained hydrogen bond interactions with hydroxyl groups of β-CD were identified, with the solvation energy limiting the affinity. Regarding the pH and temperature dependence, lower affinity constants were found at higher HCT ionization states and temperatures.
publishDate 2012
dc.date.none.fl_str_mv 2012-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/22838
Onnainty, Renée; Schenfeld, Esteban Martin; Quevedo, Mario Alfredo; Fernández, Mariana Adela; Longhi, Marcela Raquel; et al.; Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods; American Chemical Society; Journal of Physical Chemistry B; 117; 1; 12-2012; 206-217
1520-6106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/22838
identifier_str_mv Onnainty, Renée; Schenfeld, Esteban Martin; Quevedo, Mario Alfredo; Fernández, Mariana Adela; Longhi, Marcela Raquel; et al.; Characterization of the Hydrochlorothiazide: β-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods; American Chemical Society; Journal of Physical Chemistry B; 117; 1; 12-2012; 206-217
1520-6106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/jp311274c
info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/jp311274c
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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