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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/22838
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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 Técnicas2025-09-03T09:48:27Zoai: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:34982025-09-03 09:48:27.675CONICET 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 |
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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/ |
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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 |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.13397 |