Conformational landscape and low lying excited states of imatinib
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| 024 | 7 | 0 | |a 10.1007/s00894-015-2639-8 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00894-015-2639-8 | ||
| 245 | 0 | 0 | |a Conformational landscape and low lying excited states of imatinib |h [Elektronische Daten] |c [Emil Vinţeler, Nicoleta-Florina Stan, Raluca Luchian, Călin Căinap, João Ramalho, Vasile Chiş] |
| 520 | 3 | |a 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. | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2015 | ||
| 690 | 7 | |a Imatinib |2 nationallicence | |
| 690 | 7 | |a Conformational landscape |2 nationallicence | |
| 690 | 7 | |a UV-vis |2 nationallicence | |
| 690 | 7 | |a TD-DFT |2 nationallicence | |
| 700 | 1 | |a Vinţeler |D Emil |u Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania |4 aut | |
| 700 | 1 | |a Stan |D Nicoleta-Florina |u Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania |4 aut | |
| 700 | 1 | |a Luchian |D Raluca |u Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania |4 aut | |
| 700 | 1 | |a Căinap |D Călin |u The Oncology Institute "Prof. Dr. Ion Chiricuţă”, 400015, Cluj-Napoca, Romania |4 aut | |
| 700 | 1 | |a Ramalho |D João |u Department of Chemistry, School of Science and Technology, University of Évora, Rua Romão Ramalho, 59, 7000-671, Évora, Portugal |4 aut | |
| 700 | 1 | |a Chiş |D Vasile |u Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania |4 aut | |
| 773 | 0 | |t Journal of Molecular Modeling |d Springer Berlin Heidelberg |g 21/4(2015-04-01), 1-13 |x 1610-2940 |q 21:4<1 |1 2015 |2 21 |o 894 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00894-015-2639-8 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00894-015-2639-8 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Vinţeler |D Emil |u Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Stan |D Nicoleta-Florina |u Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Luchian |D Raluca |u Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Căinap |D Călin |u The Oncology Institute "Prof. Dr. Ion Chiricuţă”, 400015, Cluj-Napoca, Romania |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Ramalho |D João |u Department of Chemistry, School of Science and Technology, University of Évora, Rua Romão Ramalho, 59, 7000-671, Évora, Portugal |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Chiş |D Vasile |u Faculty of Physics, Babeş-Bolyai University, 1 Kogălniceanu, 400084, Cluj-Napoca, Romania |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Molecular Modeling |d Springer Berlin Heidelberg |g 21/4(2015-04-01), 1-13 |x 1610-2940 |q 21:4<1 |1 2015 |2 21 |o 894 | ||