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Characterization of the Hydrochlorothiazide: ß-Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods.
MedLine Citation:
PMID:  23237196     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hydrochlorthiazide (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 ß-cyclodextrin (ßCD) with HCT, we performed multiple-temperature-pH isothermal titration calorimetric measurements of the HCT:ßCD system, together with proton nuclear magnetic resonance spectroscopy (1H 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 ßCD 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 1H 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 ßCD. 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), as well as from energetic decomposition analyses derived from computational methods. We concluded that the formation of the HCT:ßCD 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 ßCD 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.
Authors:
Renée Onnainty; Esteban Martin Schenfeld; Mario Alfredo Quevedo; Mariana Adela Fernandez; Marcela Raquel Longhi; Gladys Ester Granero
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-13
Journal Detail:
Title:  The journal of physical chemistry. B     Volume:  -     ISSN:  1520-5207     ISO Abbreviation:  J Phys Chem B     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101157530     Medline TA:  J Phys Chem B     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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