Zuzana Ferenčíková

The thermodynamic dissociation constants of methotrexate by the nonlinear regression and factor analysis of multiwavelength spectrophotometric pH-titration data

AbstractThe mixed dissociation constants of methotrexate — chemically (2S)-2-[(4-{[(2,4-diamino-7,8-dihydropteridin-6-yl)methyl] (methyl)amino}phenyl)formamido]pentanedioic acid (the cas number 59-05-2) at various ionic strengths I of range 0.01–0.4, and at temperatures of 25°C and 37°C, were determined with the use of two different multiwavelength and multivariate treatments of spectral data, SPECFIT32 and SQUAD(84) nonlinear regression analyses and INDICES factor analysis according to a general rule of first, determining the number of components, and then calculating the spectral responses and concentrations of the components. Concurrently, the experimental determination of the thermodynamic dissociation constants was in agreement with its computational prediction of the PALLAS programme based on knowledge of the chemical structures of the drug. The factor analysis in the INDICES programme predicts the correct number of light-absorbing components when the data quality is high and the instrumental error is known. Three thermodynamic dissociation constants were estimated by nonlinear regression of {pKa, I} data: for methotrexate pKa1T= 2.895(13), pKa2T= 4.410(14), pKa3T= 5.726(15) at 25°C and pKa1T= 3.089(15), pKa2T= 4.392(12), pKa3T= 5.585(11) at 37°C, where the figure in brackets is the standard deviation in last significant digits. The reliability of the dissociation constants of the drug were proven by conducting goodness-of-fit tests of the multiwavelength spectrophotometric pH-titration data.

Thermodynamic dissociation constants of risedronate using spectrophotometric and potentiometric pH-titration

AbstractRisedronate inhibits bone resorption in diseases like osteoporosis, Paget’s disease, tumor bone diseases or the malfunction of phosphocalcium metabolism. The acid-base properties of risedronate in an aqueous solution have been studied in a pH range from 2 to 12 and can be described in terms of four dissociation steps: pKa,2, pKa,4, pKa,5 (related to the dissociation of POH groups) and pKa,3 related to the dissociation of protonated amino group NH3+. The mixed dissociation constants were determined at different ionic strengths I = 0.02 to 0.20 mol dm−3 KCl and of 25°C and 37°C using pH-spectrophotometric and pH-potentiometric titration methods. Determination of group parameters L0, HT might lead to false estimates of common parameterspKa;therefore, the computational strategy employed is important. A comparison between the two programs ESAB and HYPERQUAD demonstrated that the ESAB program provides a better fit of potentiometric titration curve. The thermodynamic dissociation constants pKaT were estimated by a nonlinear regression of (pKa, I) data and a Debye-Hückel equation at 25°C and 37°C, pKa,2T = 2.37(1) and 2.44(1), pKa,3T = 6.29(3) and 6.26(1), pKa,4T = 7.48(1) and 7.46(2) and pKa,5T = 9.31(7) and 8.70(3) at 25°C and 37°C using pH-spectroscopic data and pKa,2T = 2.48(3) and 2.43(1), pKa,3T= 6.12(2) and 6.10(2), pKa,4T = 7.25(2) and 7.23(1) and pKa,5T = 12.04(5) and 11.81(2) at 25°C and 37°C. The ascertained estimates of three dissociation constants pKa,3, pKa,4, pKa,5 are in agreement with the predicted values obtained using PALLAS

The thermodynamic dissociation constant of naphazoline by the regression analysis of potentiometric data

AbstractThe mixed dissociation constant of naphazoline is determined at various ionic strengths I [mol dm−3] in the range of 0.01 to 0.26 and at temperatures of 25°C and 37°C using ESAB and HYPERQUAD regression analysis of the potentiometric titration data. A strategy of efficient experimentation is proposed in a protonation constant determination, followed by a computational strategy for the chemical model with a protonation constant determination. Two group parameters, L0 and HT were ill-conditioned in the model and their determination is therefore uncertain. These group parameters, L0 and HT, can significantly influence a systematic error in the estimated common parameter pKa and they always should be refined together with pKa. The thermodynamic dissociation constant pKaT was estimated by nonlinear regression of {pKa, I} data at 25°C and 37°C: for naphazoline pKalT = 10.41(1) and 10.13(2). Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates to be found.

Thermodynamic protonation constants of vardenafil by the nonlinear regression of multiwavelength pH-spectrophotometric titration data

AbstractpH-spectrophotometric titration data were used to determine protonation constants of vardenafil at different ionic strengths I and temperatures of 25°C and 37°C. The use of two different multiwavelength and the multivariate treatment of spectral data, SPECFIT32 and SQUAD(84) nonlinear regression analyses and INDICES factor analysis is presented. The reliability of the protonation constants of the drug was proven with goodness-of-fit tests of the pH-spectra. The thermodynamic protonation constants log KTi were estimated by a nonlinear regression of (log K, I) data using the Debye-Hückel equation, yielding log K4T = 3.59(1) and 3.26(1), log K3T = 5.64(1) and 5.81(1), log K2T = 9.41(1) and 8.59(2), log K1T = 10.92(2) and 10.05(1) at 25°C and 37°C, where the figure in brackets is the standard deviation in last significant digit. Concurrently, the experimental determination of four thermodynamic protonation constants was combined with the computational prediction of the MARVIN program based on knowledge of the chemical structures of the drug and was in good agreement with its experimental value. The factor analysis of spectra in the INDICES program predicts the correct number of light-absorbing components when the instrument error is known and when the signal-to-error ratio SER is higher than 10.

Dynamic properties during wood humidification

Measurement of the moisture in solid materials is important almost at all industry areas. Removing of the volatile substances is very important step before packing or selling wood items. Inaccurate moisture measurement may affect product quality, lifespan and its price. Large proportion of production processes depend on measurement or control of moisture in some form. Within SIB64 Metefnet project, time stability and moisture penetration dynamics of timber samples by gravimetric method and electrical moisture meters are investigated. Strong focus was oriented on penetration hygrometers, which are mostly used. Device for wood humidification was constructed. It allows multiple samples moistening at defined humidity levels with wet air flowing through chambers. Device consists of 3 chambers, where samples can be placed. In each chamber can be achieved different level of humidity. Moisture inside of samples is continuously measured with humidity sensors working on resistance principle. Different kind of wooden samples can be inserted in chambers and data are stored onto a computer. One of the motivations for construction of this device was increasing the speed of the wooden samples humidification. Nowadays used method of moistening in desiccator needs significantly more time. Article will describe device design and measurement results.

Reliability of protonation constants of vildagliptin dimers by the regression analysis of pH-titration data

AbstractProtonation constants of protonated monomers and dimers of the vildagliptin are determined potentiometrically. For the low concentration cL = 3.3 mmol dm−3 the monomers L and LH dominate, while for a higher concentration cL = 6.3 mmol dm−3 the dimers L2H2, L2H3, L2H4 and L2H are mainly present. The algorithm used has little influence on the precision of the formation constants in comparison with the reproducibility of the titration. The mixed protonation constants of vildagliptin dimers LqHr at various temperatures are determined using FBSTAC4 and HYPERQUAD regression analysis of the potentiometric titration data. The accuracy of the protonation constants log10 βqr depends on the accuracy of the group parameters. As two group parameters L0, HT are ill conditioned in a model, their determination is therefore uncertain; both can significantly cause a systematic error in the estimated common parameters log10 βqr. Using various regression diagnostics the goodness-of-fit proves the reliability of all parameter estimates. A rough estimation of thermodynamic enthalpies ΔH0 (kJ mol−1) and entropies ΔS0 (J K−1 mol−1) is determined from the temperature variation of protonation constants. The enthalpy shows the protonation process is exothermic, and the entropy indicates that it is spontaneous.

Oligomers-model building in protonation equilibria of sitagliptin

AbstractMixed protonation constants of sitagliptin phosphate at various ionic strengths I (mol kg−1) in range 0.01 and 0.50 and at 298.15 K are determined using FBSTAC4 and HYPERQUAD nonlinear regression analyses of the potentiometric titration curve. At a low concentration cL = 1.1 mmol kg−1 the monomers L, LH, LH2, LH3 and LH4 dominate, while for a concentration range from cL = 13.7 to 24.7 mmol kg−1 dimers L2H2, L2H3, L2H4 and L2H are mainly present. The regression programme has almost no influence on the precision of the protonation constants. The accuracy of the protonation constants log βqr depends on the accuracy of the group parameters. As two group parameters cL,0, cH,T are ill-conditioned in a model, their determination is therefore uncertain: both can significantly cause a systematic error in the estimated common parameters log10βqr. Fitness tests using regression diagnostics have proven the reliability of the parameter estimates.