Comparisons between Crystallography Data and Theoretical Parameters and the Formation of Intramolecular Hydrogen Bonds: Benznidazole

Abstract

Abstract:The conformational preferences of benznidazole were examined through the application of DFT, PCM and QTAIM calculations, whose results were compared with crystallography data. The geometries were fully optimized with minimum potential energy surface by means of the Relaxed Potential Energy Surface Scan (RPESS) at AM1, followed by the B3LYP/6-311++G(d,p) theoretical level. As a result, the s-cis conformation (1C) was shown to be more stable (4.78 kcal¨mol´1) than s-trans (1T). The Quantum Theory Atoms in Molecules (QTAIM) was applied in order to characterize the (N-H¨¨¨O=N) and (C-H¨¨¨=N) intramolecular hydrogen bonds. The simulation of solvent effect performed by means of the implicit Polarized Continuum Model (PCM) revealed great results, such as, for instance, that the conformation 1W is more stable (23.17 kcal¨mol´1) in comparison to 1C. Our main goal was stressed in the topological description of intramolecular hydrogen bonds in light of the QTAIM approach, as well as in the solvent simulation to accurately obtain an important conformation of benznidazole.

Vibrational characterization of active drug to the treatment of chagas disease, benznidazole by using force fields and internal coordinates

“…The experimental benznidazole structure was determined by using X-ray diffraction by Soares-Sobrinho et al while their new polymorphs structures were elucidated by Honorato et al by using the same technique (Soares-Sobrinho, et al, 2008;Honorato, et al, 2014). Previously, the theoretical structures of benznidazole were studied by Tonin et al and, recently, two conformations were reported for this species by Oliveira et al in order to investigate the intra-molecular hydrogen bonds in their structures (Tonin, et al, 2009;Olivera, et al, 2016). These authors have optimized two structures of benznidazole in aqueous solution which are the s-cis and s-trans forms by using the B3LYP/6-311++G(d,p) method and the PCM model (Olivera, et al, 2016).…”

“…Previously, the theoretical structures of benznidazole were studied by Tonin et al and, recently, two conformations were reported for this species by Oliveira et al in order to investigate the intra-molecular hydrogen bonds in their structures (Tonin, et al, 2009;Olivera, et al, 2016). These authors have optimized two structures of benznidazole in aqueous solution which are the s-cis and s-trans forms by using the B3LYP/6-311++G(d,p) method and the PCM model (Olivera, et al, 2016). Those two conformations can be seen in Figure 1.…”

“…The N-benzyl-2-(2-nitroimidazol-1-yl)acetamide compound, named benznidazole, is one active drug used during the first phase to the treatment of Chagas disease (Caryn, 2015;Rassi, Rassi, & Marin-Neto, 2010;Bern, 2015;Figueroa, et al, 2018;Tonin, et al, 2009;Soares-Sobrinho, et al, 2008;Nogueira Silva, et al, 2008;Soares-Sobrinho, et al, 2010;Pires, Hideki Yoshizane, & Souza, 2010;Pires, et al, 2011;Soares-Sobrinho, et al, 2012;Arancibia, et al, 2013;Bezerra, et al, 2014;Honorato, et al, 2014;Arenas Velásquez, et al, 2014;Aguirre, et al, 2004;Trochine, et al, 2014;Olivera, et al, 2016;Streck, et al, 2016;Figueirêdo, et al, 2017;Morillo, et al, 2017). The cause of this illness in the humans is the parasite Trypanosoma Cruzi, as is largely known (Caryn, 2015;Rassi, Rassi, & Marin-Neto, 2010;Bern, 2015).…”