Estudo do efeito da solvatação aquosa sobre os parâmetros geométricos da carbamazepina usando a dinâmica molecular de Car-parrinello

Abstract

The Car-Parrinello molecular dynamics using plane waves and non-conserved pseudopotential of Vanderbilt was applied to study the aqueous solvation effects on the geometric parameters of carbamazepine. In order to quantify the aqueous solvation effects, two simulation trajectories were carried out: one in isolated phase of carbamazepine and other in aqueous solvation phase. These trajectories were carried out on NVT ensemble, with temperature kept at 300K using the Nosé-Hoover thermostat. The results show that the geometric parameters of isolated carbamazepine and benzene and pyridine rings from solvated phase agree very well with the experimental results from x-ray. Did not observe geometric parameters difference in the benzene and pyridine rings between isolated and solvated phase, showing the hydrophobic character of this molecular region. The results show significant differences between the geometric parameters of carbamoyl group from isolated phase when compared to the solvated phase. The changes in these parameters are attributed to the formation of hydrogen bonds between the water molecules and the atoms comprised in the carbomoyl group. In addition, we determined the mean residence time and radial distribution functions of water molecules in the solvation spheres centered on oxygen, nitrogen and hydrogen atoms from carbamoyl group. The diffusion coefficient calculated with the Einstein equation using the trajectory of the Car-Parrinello dynamics shows a disagreement with the experimental value, due to simulation time, as well as the type of solvent used for the experimental procedure.