caa a22 4500 605512418 CHVBK 20210128100655.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00894-015-2639-8 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2639-8 Conformational landscape and low lying excited states of imatinib [Elektronische Daten] [Emil Vinţeler, Nicoleta-Florina Stan, Raluca Luchian, Călin Căinap, João Ramalho, Vasile Chiş] The conformational changes of imatinib (IMT) are crucial for understanding the ligand-receptor interaction and its mechanism of action [Agofonov et al. (2014) Nature Struct Mol Biol 21:848-853]. Therefore, here we investigated the free energy conformational landscape of the free IMT base, aiming to describe the three-dimensional structures and energetic stability of its conformers. Forty-five unique conformers, within an energy window of 4.8kcalmol−1 were identified by a conformational search in gas-phase, at the B3LYP/6-31G(d) theoretical level. Among these, the 20 most stable, as well as 4 conformers resulting from optimization of experimental structures found in the two known polymorphs of IMT and in the c-Abl complex were further refined using the 6-31+G(d,p) basis set and the polarizable continuum solvation model. The most stable conformers in gas-phase and water exhibit a V-shaped structure. The major difference between the most stable free conformers and the bioactive conformers consists in the relative orientation of the pyrimidine-pyridine groups responsible for hydrogen bonding interactions in the ATP-binding pocket. The ratio of mole fractions corresponding to the two known (α and β) polymorphic forms of IMT was estimated from the calculated thermochemical data, in quantitative agreement with the existing experimental data related to their solubility. The electronic absorption spectrum of this compound was investigated in water and explained based on the theoretical TD-DFT results, considering the Boltzmann population-averaged computed data at CAM-B3LYP/6-31+G(d,p) level of theory for the nine most stable conformers. Springer-Verlag Berlin Heidelberg, 2015 Imatinib nationallicence Conformational landscape nationallicence UV-vis nationallicence TD-DFT nationallicence Vinţeler Emil Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania aut Stan Nicoleta-Florina Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania aut Luchian Raluca Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania aut Căinap Călin The Oncology Institute "Prof. Dr. Ion Chiricuţă”, 400015, Cluj-Napoca, Romania aut Ramalho João Department of Chemistry, School of Science and Technology, University of Évora, Rua Romão Ramalho, 59, 7000-671, Évora, Portugal aut Chiş Vasile Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/4(2015-04-01), 1-13 1610-2940 21:4<1 2015 21 894 https://doi.org/10.1007/s00894-015-2639-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2639-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Vinţeler Emil Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania aut NATIONALLICENCE 700 1- Stan Nicoleta-Florina Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania aut NATIONALLICENCE 700 1- Luchian Raluca Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania aut NATIONALLICENCE 700 1- Căinap Călin The Oncology Institute "Prof. Dr. Ion Chiricuţă”, 400015, Cluj-Napoca, Romania aut NATIONALLICENCE 700 1- Ramalho João Department of Chemistry, School of Science and Technology, University of Évora, Rua Romão Ramalho, 59, 7000-671, Évora, Portugal aut NATIONALLICENCE 700 1- Chiş Vasile Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/4(2015-04-01), 1-13 1610-2940 21:4<1 2015 21 894