Thermodynamic analysis of the binding of a hepatoprotectant drug, thioctic acid, by β-cyclodextrin

Abstract

Spectroscopic and thermodynamic studies of the binding of a hepatoprotectant drug, thioctic acid, by β-cyclodextrin (β-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 °C, while the potentiometric study was performed at several temperatures ranging from 15 to 40 °C. From the spectroscopic data, the molar absorption coefficient, ε, for the pure drug in aqueous media and the stoichiometry of the inclusion complex with β-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 β-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 β-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 β-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 (ΔCp0 ≠ 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.