Theoretical study on the origins of sildenafil tautomers’ relative stability
Author:
Pajka Dariusz1, Lelek-Borkowska Urszula2, Zborowski Krzysztof K.1ORCID
Affiliation:
1. Faculty of Chemistry , Jagiellonian University , Gronostajowa 2 , 30-387 Kraków , Poland 2. Faculty of Foundry Engineering , AGH-University of Science and Technology , Reymonta 23 , 30-059 Kraków , Poland
Abstract
Abstract
Tautomers of sildenafil (5-{2-Ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one), a drug commonly used for treating the erectile dysfunction and pulmonary arterial hypertension were studied computationally at the DFT (B3LYP/6-311++G**) level. Four possible structures of sildenafil tautomers structures were considered. The geometries and chemical shifts of carbon and nitrogen nuclei were calculated and compared with available experimental data. The theoretical calculations proved to be consistent with experimental data and indicate the same lowest energy sildenafil structure. The energies of the all considered sildenafil tautomers were determined and ranked according to their energy values. This article presents calculations of several properties (aromaticity, atomic charges, atomic energies, intramolecular hydrogen bonding) and discusses their influence on the relative energies of sildenafil tautomers.
Publisher
Walter de Gruyter GmbH
Subject
Physical and Theoretical Chemistry
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