A Search for the Protonation Model with Thermodynamic Dissociation Constants and (Extra)-Thermodynamics of Nilotinib Hydrochloride (TASIGNA)

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216275%3A25310%2F19%3A39914755" target="_blank" >RIV/00216275:25310/19:39914755 - isvavai.cz</a>

Result on the web

<a href="https://link.springer.com/article/10.1007%2Fs10953-019-00882-2" target="_blank" >https://link.springer.com/article/10.1007%2Fs10953-019-00882-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10953-019-00882-2" target="_blank" >10.1007/s10953-019-00882-2</a>

Result language

angličtina

Original language name

A Search for the Protonation Model with Thermodynamic Dissociation Constants and (Extra)-Thermodynamics of Nilotinib Hydrochloride (TASIGNA)

Original language description

Nilotinib 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10406 - Analytical chemistry

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Solution Chemistry

ISSN

0095-9782

e-ISSN

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Volume of the periodical

48

Issue of the periodical within the volume

5

Country of publishing house

DE - GERMANY

Number of pages

30

Pages from-to

702-731

UT code for WoS article

000469232600008

EID of the result in the Scopus database

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