title: Protonation effects on the UV/Vis absorption spectra of imatinib: a theoretical and experimental study.
abstract: An experimental and theoretical investigation of protonation effects on the UV/Vis absorption spectra of imatinib showed systematic changes of absorption depending on the pH, and a new absorption band appeared below pH 2. These changes in the UV/Vis absorption spectra were interpreted using quantum chemical calculations. The geometry of various imatinib cations in the gas phase and in ethanol solution was optimized with the DFT/B3LYP method. The resultant geometries were compared to the experimentally determined crystal structures of imatinib salts. The semi-empirical ZINDO-CI method was employed to calculate the absorption lines and electronic transitions. Our study suggests that the formation of the extra near-UV absorption band resulted from an increase of imatinib trication concentration in the solution, while the rapid increase of the first absorption maximum could be attributed to both the formation of imatinib trication and tetracation.
authors.affiliation: University of Latvia, Faculty of Chemistry, Kr. Valdemara 48, Riga, LV 1013, Latvia. Electronic address: ilze.grante@lu.lv.
authors.forename: Ilze
authors.initials: I
authors.lastname: Grante
authors.affiliation: University of Latvia, Faculty of Chemistry, Kr. Valdemara 48, Riga, LV 1013, Latvia.
authors.forename: Andris
authors.initials: A
authors.lastname: Actins
authors.affiliation: University of Latvia, Faculty of Chemistry, Kr. Valdemara 48, Riga, LV 1013, Latvia.
authors.forename: Liana
authors.initials: L
authors.lastname: Orola
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D001549:Benzamides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D000068877:Imatinib Mesylate; D008958:Models, Molecular; D010879:Piperazines / Q000737:chemistry*; D011522:Protons; D011743:Pyrimidines / Q000737:chemistry*; D011789:Quantum Theory; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011522:Protons; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: Imatinib base; Polycationic API; Protonation; Quantum mechanical calculations; UV/Vis spectroscopy