Acid-base equilibrium of guttiferone-A in ethanol-water mixtures: Modeling and bootstrap-based evaluation of uncertainties

Acid dissociation constants are important parameters for indicating the extent of dissociation at different pH values, which is directly reflected in the absorption and elimination of drugs. In this present study, the acid-base equilibrium of guttiferone-A - an important natural benzophenone with innumerable biological activities - was investigated. The pK(a) values were determined, via the spectrophotometric method, in six different ethanol-water mixtures, and a significant linear correlation for pK(a2) as a function of the alcohol percentage was found. A proposition was made for the order of the dissociation sites of the guttiferone-A, based on the value of pK(a) for the 7-epiclusianone. The modeling and the study of sensitivity enabled the molar absorptivity spectra as well as the regions of highest sensitivity for inversion of the constants to be obtained. Complementing this study, the bootstrap of residuals technique was evaluated for assessment of the confidence intervals for the fitted constants - the results were equivalent to those encountered via the parametric method.