Solvent Effects on Protonation Constants of Imatinib in Different Aqueous Solutions of Methanol at T = 298.15 K

Imatinib (Gleevec) is a drug that is applied to treat cancer. It inhibits the Bcr-Abl tyrosine-kinase and therefore, it can slow growth or result in programmed cell death of certain types of cancer cells. In 2001, the United States approved this drug. The protonation constants of imatinib were determined in mixed solvent of water and methanol containing 40, 50, 60, 70, and 80% (v/v) of methanol, using a combination of spectrophotometric and potentiometric methods at T = 298.15 K and constant ionic strength (0.1 mol dm–3 NaClO4). The obtained protonation constants were analyzed using Kamlet, Abboud, and Taft parameters. In this study, a good linear relationship was obtained between protonation constants (on the logarithmic scale) and dielectric constant (ɛ) of the water-methanol solvent. Dual-parameter correlation of log K versus π* (dipolarity/polarizability) and α (hydrogen-bond donor acidity), as well as versus π* and β (hydrogen-bond acceptor basicity) and multi-parameter π*, α, and β, gave good results for various mole fraction of methanol in methanol-water solvent. Finally, the results are discussed in terms of the solvent effect (increasing of mole fraction of methanol in methanol-water solvent) on the protonation constants.