Thermodynamic analysis of the binding of a hepatoprotectant drug, thioctic acid, by beta-cyclodextrin.
Spectroscopic and thermodynamic studies of the binding of a hepatoprotectant drug, thioctic acid, by beta-cyclodextrin (beta-CD) have been carried out using UV-vis and pH potentiometric measurements. The UV-vis spectra and the pH of the aqueous solutions of the drug were measured (i) as a function of total drug concentration in the absence of cyclodextrin, and (ii) as a function of cyclodextrin concentration at constant drug concentration. The spectroscopic study was done at pH = 7 and 25 degrees C, while the potentiometric study was performed at several temperatures ranging from 15 to 40 degrees C. From the spectroscopic data, the molar absorption coefficient, epsilon, for the pure drug in aqueous media and the stoichiometry of the inclusion complex with beta-CD were determined. The dissociation constant, Ka, of the pure drug (which is a weak acid), and the association constants of the complexes formed by beta-cyclodextrin and both the nonionized (HTIO) and ionized (TIO-) forms of the drug, have been simultaneously determined at several temperatures from the pH data, without the necessity of working with buffered solutions. The nonionic forms are complexed by the beta-CD with higher affinity than their ionic counterparts. From the dependency of the association constants on temperature (van't Hoff analysis), the inclusion complexes formed by HTIO or TIO- and the beta-CD were found to be enthalpy driven, with a favorable enthalpic term dominant over an unfavorable entropic term. Both contributions were found to show a possible dependence with temperature (DeltaCpo not equal 0). This pattern may reveal the contribution of van der Waals interactions, hydrophobic effect, and solvent reorganization as the main driving forces promoting the complexation.
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Departamento de Química Fisica I, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Aicart
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D003505:Cyclodextrins / Q000737:chemistry* / Q000378:metabolism; D005079:Excipients / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011199:Potentiometry; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D008063:Thioctic Acid / Q000737:chemistry* / Q000378:metabolism; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D005079:Excipients; D012996:Solutions; D047392:beta-Cyclodextrins; D014867:Water; D008063:Thioctic Acid; C031215:betadex