Fakulta elektrotechniky a informatiky / Faculty of Electrical Engineering and Informatics
Stálý URI pro tuto komunituhttps://hdl.handle.net/10195/3847
Práce obhájené před rokem 2008 jsou uloženy pouze v kolekci Vysokoškolské kvalifikační práce
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Článekpeer-reviewedpublished version Omezený přístup Acid Dissociation Constants, Enthalpy, Entropy and Gibbs Energy of Bedaquiline by UV-Metric Spectral and pH-metric Analysis(2021) Meloun, Milan; Cyrmonová, Daniela; Javůrek, Milan; Pekárek, TomášBedaquiline (trade name Sirturo) is an antibiotic used to treat pulmonary tuberculosis that is resistant to other antibiotics. The pH-spectrophotometric and pH-potentiometric titration allowed the measurement of two near successive and one distant dissociation constants. Bedaquiline neutral LH molecule was able to protonate and dissociate in pure water to form soluble particles L-, LH, LH2+, LH32+ and LH43+. In the pH range 2 to 7, three dissociation constants can be reliably estimated. REACTLAB (UV-metric spectral analysis): pKTa1 = 3.91(09), pKTa2 = 4.58(12) and pKTa3 = 5.26(07) at 25 °C and pKTa1 = 3.61(30), pKTa2 = 4.44(15) and pKTa3 = 5.54(33) at 37 °C. ESAB (pH-metric analysis): pKTa1 = 3.21(39), pKTa2 = 3.68(31) and pKTa3 = 5.21(42) at 25 °C and pKTa1 = 3.31(12), pKTa2 = 3.67(15) and pKTa3 = 5.73(08) at 37 °C. Molar enthalpy ΔH0, molar entropy ΔS0 and Gibbs free energy ΔG0 were calculated from the spectra using a dependence ln K to 1/T. The potentiometric data showed positive enthalpy ΔH0(pKa1) = 85.49 kJ·mol-1, ΔH0(pKa2) = 86.42 kJ·mol-1, ΔH0(pKa3) = 65.84 kJ·mol-1 and dissociation was endothermic. The entropy ΔS0 at 25 ° C was positive for 3 dissociation constants ΔS0(pKa1) = 217.47 J·mol-1, ΔS0(pKa2) = 204.87 J·mol-1, ΔS0(pKa3) = 92.63 J·mol-1 at 25 °C and proved irreversible dissociation.Článekpeer-reviewedpublished version Omezený přístup Determination of acid dissociation constants, enthalpy, entropy andGibbs free energy of the baricitinib by the UV-metric and pH-metricanalysis(2020) Meloun, Milan; Pfeiferová, Aneta; Javůrek, Milan; Pekárek, TomášBaricitinib is a drug used for the treatment of rheumatoid arthritis. It is a selective and reversible inhibitor of Janus kinases 1 and 2, which play an important role in signalling the pro-inflammatory pathway activated in autoimmune disorders such as rheumatoid arthritis. The pH-spectrophotometric and pH-potentiometric titrations allowed the measurement of three or four successive dissociation constants of Baricitinib. Baricitinib neutral LH2 molecule was able to protonate into two soluble cations LH42+, LH3+ and dissociate into two soluble anions LH− and L2- in pure water. The graph of molar absorption coefficients of differently protonated species versus wavelength indicated that the spectra εL, εLH, εLH2 were the nearly the same for these species and that the spectra εLH4 and εLH3 were also similar. In the pH range from 2–13, four pKa´s of spectra analysis were reliably estimated by REACTLAB at I =0.0020 mol. dm-3 values pKTa1 = 3.07, pKTa2 = 3.87, pKTa3 = 6.27, pKTa4 = 12.78 at 25 °C and pKTa1 = 3.00, pKTa2 = 3.79, pKTa3 = 6.12, pKTa4 = 12.75 at 37 °C. Potentiometric pH-titration analysis for a higher concentration of 1 × 10-3 mol. dm-3 estimated with ESAB at I =0.0001 mol. dm-3 values pKTa1 = 3.69, pKTa2 = 3.81, pKTa3 = 4.73 at 25 °C and pKTa1 = 3.62, pKTa2 = 3.73, pKTa3 = 4.43 at 37 °C. Molar enthalpy ΔH°, molar entropy ΔS° and Gibbs free energy ΔG° were calculated from the spectra using a dependence ln K to 1/T.Článekpeer-reviewedpublished version Omezený přístup A Search for the Protonation Model with Thermodynamic Dissociation Constants and (Extra)-Thermodynamics of Nilotinib Hydrochloride (TASIGNA)(Springer, 2019) Meloun, Milan; Pilařová, Lucie; Javůrek, Milan; Pekarek, TomášNilotinib hydrochloride (AMN107, TASIGNA, Novartis) is used to treat adults with chronic myeloid leukemia (CML), a type of leukemia. It is a novel, orally active BCR-ABL tyrosine kinase inhibitor derived from aminopyrimidine that is 30 times more effective against CML cells than is Imatinib. The nonlinear regression of the A versus pH spectra with REACTLAB and SQUAD84 and of the pH-titration curve with ESAB determined the four close and consecutive dissociation constants in the 11 steps of the newly proposed procedure. Prediction of pK(a) performed by MARVIN, PALLAS and ACD/Percepta determined the protonation sites. The sparingly soluble nilotinib hydrochloride denoted as L forms four water-soluble LH+, LH22+, LH33+, and LH44+ cations. Although the adjusted pH has less effect on the absorbance changes in the chromophore, four thermodynamic dissociation constants were reliably determined: pKa1T=3.600.04, pKa2T=4.42 +/- 0.07, pKa3T=4.71 +/- 0.04, and pKa4T=4.84 +/- 0.03 at 25 degrees C and pKa1T=3.61 +/- 0.11, pKa2T=4.29 +/- 0.18, pKa3T=4.49 +/- 0.02, and pKa4T=5.05 +/- 0.03 at 37 degrees C, and by regression analysis of potentiometric titration curves with ESAB, pKa1T=3.74 +/- 0.01, pKa2T=4.05 +/- 0.01, pKa3T=4.25 +/- 0.01, and pKa4T=4.91 +/- 0.20 at 25 degrees C and pKa1T=3.63 +/- 0.03, pKa2T=3.96 +/- 0.03, pKa3T=4.18 +/- 0.03, and pK41T=4.81 +/- 0.05 at 37 degrees C. Positive enthalpy values H degrees at 25 degrees C showed that the dissociation process is endothermic and is accompanied by heat absorption. Inasmuch as the entropy values of the dissociation process S degrees at 25 degrees C and 37 degrees C were negative, the dissociation process is reversible.Článekpeer-reviewedpostprint Otevřený přístup Multiwavelength UV-Metric and pH-Metric Determination of the Dissociation Constants of the Hypoxia-inducible Factor Prolylhydroxylase Inhibitor Roxadustat(2018) Meloun, Milan; Pilařová, Lucie; Javůrek, Milan; Pekárek, TomášUV-VIS spectra, molar absorption coefficients and protonation equilibriaRoxadustat is an orally bioavailable, hypoxiainducible factor prolyl hydroxylase inhibitor with potential anti-anemic activity. It is one of the Active Pharmacenutical Ingredients possessing acidic/basic functionalities their ionization state is controlled by solution pH and acid dissociation constants. Nonlinear regression of the pH-spectra with programs REACTLAB and SQUAD84 and of the pH-titration curve with ESAB determined four multiple consecutive dissociation constants with the protonation scheme. A sparingly soluble neutral molecule LH3 of Roxadustat was dissociated to the soluble anions LH2-, LH2- and L3- or protonated to the cation LH4+ in an aqueous medium. The graph of molar absorption coefficients of variously protonated species according to wavelength shows that the spectra of two anions LH2- and LH2-are nearly the same in colour. The Roxadustat spectrum exhibited five sharp isosbestic points related to the LH2-/L3- equilibrium. Four consecutive thermodynamic dissociation constants were estimated using UV-metric data pKTa1 = 3.60(04), pKTa2 = 5.62(14), pKTa3 = 7.66(16), pKTa4 = 9.08(02) at 25°C and pKTa1 = 3.60(04), pKTa2 = 5.73(10), pKTa3 = 7.52(10), pKTa4 = 8.99(02) at 37°C and using pH-metric data pKTa1 = 4.33(09), pKTa2 = 6.57(11), pKTa3 = 8.88(05), pKTa4 = 9.03(04) at 25°C and pKTa1 = 4.25(09), pKTa2 = 6.49(10), pKTa3 = 8.80(06), pKTa4 = 9.00(05) at 37°C The positive values of the enthalpy ΔH0 showed that the dissociation process is endothermic and the positive values of the Gibbs free energy ΔG0 at 25°C indicated that the dissociation process was not spontaneous, which also was confirmed by a negative value of the entropy ΔS0. Four macro-dissociation constants of Roxadustat and six protonation locations were predicted by MARVIN.