Acid Dissociation Constants, Enthalpy, Entropy and Gibbs Energy of Bedaquiline by UV-Metric Spectral and pH-Metric Analysis

• Published in: Journal of solution chemistry 2021-03, Vol.50 (3), p.315-339
• Main Authors: Meloun, Milan, Cyrmonová, Daniela, Javůrek, Milan, Pekárek, Tomáš
• Format: Article
• Language: English
• Subjects: Antibiotics; Chemistry; Chemistry and Materials Science; Condensed Matter Physics; Endothermic reactions; Enthalpy; Entropy; Geochemistry; Industrial Chemistry/Chemical Engineering; Inorganic Chemistry; Oceanography; Physical Chemistry; Spectra; Spectrophotometry; Spectrum analysis; Tuberculosis
• ISSN: 0095-9782; 1572-8927
• DOI: 10.1007/s10953-021-01055-w

Bedaquiline (trade name Sirturo) is an antibiotic used to treat pulmonary tuberculosis that is resistant to other antibiotics. The pH-spectrophotometric and pH-potentiometric titrations allowed the measurement of two near successive and one distant dissociation constants. The neutral bedaquiline LH molecule was able to protonate and dissociate in pure water to form soluble species L − , LH, LH 2 + , LH 3 2 + and LH 4 3 + . In the pH range 2–7, three dissociation constants can be reliably estimated. REACTLAB (UV-metric spectral analysis) values are: p K a 1 T  = 3.91(09), p K a 2 T  = 4.58(12) and p K a3 T  = 5.26(07) at 25 °C and p K a 1 T  = 3.61(30), p K a2 T  = 4.44(15) and p K a3 T  = 5.54(33) at 37 °C. ESAB (pH-metric analysis) values are: p K a 1 T  = 3.21(39), p K a2 T  = 3.68(31) and p K a3 T  = 5.21(42) at 25 °C and p K a 1 T  = 3.31(12), p K a2 T  = 3.67(15) and p K a3 T  = 5.73(08) at 37 °C. Molar enthalpy Δ H 0 , molar entropy Δ S 0 and Gibbs energy Δ G 0 were calculated from the spectra using the dependence of ln K on 1/ T . The potentiometric data showed positive enthalpy Δ H 0 (p K a1 ) = 85.49 kJ·mol −1 , Δ H 0 (p K a2 ) = 86.42 kJ·mol −1 , and Δ H 0 (p K a3 ) = 65.84 kJ·mol −1 values and the dissociation reactions were endothermic. The entropy Δ S 0 at 25 °C was positive for the three dissociation constants Δ S 0 (p K a1 ) = 217.47 J·K −1 ·mol −1 , Δ S 0 (p K a2 ) = 204.87 J·K −1 ·mol −1 , and Δ S 0 (p K a3 ) = 92.63 J·K −1 ·mol −1 at 25 °C and proved irreversible dissociation reactions. Graphic Abstract