Studies on charge transfer of enalapril maleate: from solid-state to molecular dynamics.
J Mol Model
; 29(6): 197, 2023 Jun 03.
Article
em En
| MEDLINE
| ID: mdl-37268806
INTRODUCTION: Enalapril maleate is an antihypertensive ethyl ester pro-drug with two crystalline forms. A network of hydrogen bonds in both polymorphs plays an important role on solid-state stability, charge transfer process and degradation reactions (when exposed to high humidity, temperature and/or pH changes). COMPUTATIONAL PROCEDURES: Supramolecular arrangement was proposed by Hirshfeld surface using the CrystalExplorer17 software and quantum theory of atoms in molecules. The electronic structure properties were calculated using the functional hybrid M06-2X with 6-311++G** base function employing diffuse and polarization functions to improve the description of hydrogen atoms on intermolecular interactions. Also, the H+ charge transfer between enalapril and maleate molecules was performed using Car-Parrinello molecular dynamics with the Verlet algorithm. In both simulations, the temperature of the ionic system was maintained around 300 K using the Nosé-Hoover thermostat and the electronic system evolved without the use of the thermostat. RESULTS: This work evaluates the effect of maleate on the structural stability of enalapril maleate solid state. The electronic structural analysis points out a partially covalent character for N1-HâââO7 interaction; and the molecular dynamic showed a decentralized hydrogen on maleate driving a decomposition by charge transfer process while a centered hydrogen driving the stabilization. The charge transfer process and the mobility of the proton (H+) between enalapril and maleate molecules was demonstrated using supramolecular modeling analyses and molecular dynamics calculations.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Enzima Conversora de Angiotensina
/
Enalapril
Idioma:
En
Revista:
J Mol Model
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Alemanha