Dissociation Enthalpies and Thermodynamic Constants of Sildenafil Citrate by the Regression of Multiwavelength pH-spectrophotometric Titration Data

摘要

pH-spectrophotometric titration data were used to determine the mixed dissociation constants of sildenafil citrate at different ionic strengths I at temperatures of 288.15, 298.15 and 310.15 K, with the use of two different multiwavelength and multivariate treatments of spectral data, SPECFIT32 and SQUAD(84) nonlinear regression analyses, and INDICES factor analysis. The reliability of the dissociation constants of this drug was proven with goodness-of-fit tests of the pH-spectra. The thermodynamic dissociation constants $ {text{p}}K_{{{text{a}},i}}^{text{T}} $ were estimated by a nonlinear regression of (pK a , I) data using the Debye-Hückel equation: $ {text{p}}K_{{{text{a}}, 1}}^{text{T}} $ = 2.79 (1), 3.03 (3) and 3.53 (1); $ {text{p}}K_{{{text{a}}, 2}}^{text{T}} $ = 4.97 (2), 5.23 (2) and 5.34 (1); $ {text{p}}K_{{{text{a}}, 3}}^{text{T}} $ = 8.14 (2), 7.93 (1) and 7.47 (1); $ {text{p}}K_{{{text{a}}, 4}}^{text{T}} $ = 9.47 (2), 9.30 (1) and 9.13 (4); and $ {text{p}}K_{{{text{a}}, 5}}^{text{T}} $ = 10.73 (5), 10.75 (3) and 10.79 (5) at T = 288.15, 298.15 and 310.15 K, respectively, where the numbers in parentheses are the standard deviations in the last significant digits. Concurrently, the experimentally determined five thermodynamic dissociation constants are in a good agreement with their computational prediction of the SPARC program based on knowledge of the chemical structures. The factor analysis of spectra in the INDICES program predicts the correct number of light-absorbing components when the instrumental error is known and when the signal-to-error ratio SER is higher than 10. A rough estimation of the dissociation enthalpies ΔH 0 (kJ·mol−1) and entropies ΔS 0 (J·K−1·mol−1) has been obtained from the temperature variation of the thermodynamic dissociation constants by means of the van′t Hoff equation.