Determination of acid dissociation constants, enthalpy, entropy and Gibbs free energy of the baricitinib by the UV-metric and pH-metric analysis.
Determination of acid dissociation constants, enthalpy, entropy and Gibbs free energy of the baricitinib by the UV-metric and pH-metric analysis.
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DOI：
10.1016/j.jpba.2020.113532
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发表时间：
2020-08
影响因子：
3.4
通讯作者：
M. Meloun;Aneta Pfeiferová;M. Javůrek;T. Pekárek
中科院分区：
文献类型：
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作者：
M. Meloun;Aneta Pfeiferová;M. Javůrek;T. Pekárek
巴利替尼是一种用于治疗类风湿性关节炎的药物。它是一种选择性和可逆的Janus激酶1和2的抑制剂，这两种酶在自身免疫性疾病(如类风湿性关节炎)中激活的促炎途径中发挥着重要作用。PH分光光度滴定和pH电位滴定可连续测定巴利替尼的三个或四个离解常数。巴利替尼中性分子在纯水中能质子化成两个可溶的阳离子LH42+、LH3+，并解离成两个可溶的阴离子：LH42+、LH3+、−和L2-。不同质子化物种的摩尔吸收系数随波长变化的曲线图表明，εL、εLh、εLH2的光谱基本相同，εLH4和εLH3的光谱也很相似。在pH为2-13的范围内，用REACTLAB在I=0.0020摩尔的条件下可靠地估计了光谱分析的4个pKa。PKTa1=3.07，pKTa2=3.87，pKTa3=6.27，pKTa4=12.78。37℃时，pKTa1=3.00，pKTa2=3.79，pKTa3=6.12，pKTa4=12.75。用ESAB法在I=0.0001摩尔时估算Dm-3。Dm-3在25℃时pKTa1=3.69，pKTa2=3.81，pKTa3=4.73，在37℃时pKTa1=3.62，pKTa2=3.73，pKTa3=4.43。根据光谱计算了摩尔热焓ΔH、摩尔熵ΔS和吉布斯自由能ΔG。
Baricitinib 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 pKas 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 ΔGwere calculated from the spectra using a dependence ln K to 1/T.