Molecular simulation of the hydration Gibbs energy of barbiturates

Nuno M. Garrido, Miguel Jorge, António J. Queimada, Ioannis Economou, Eugénia A. Macedo

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

In the present work, molecular dynamics calculations of the Gibbs energy of hydration of 10 different substituted barbiturates in SPC/E water were performed using thermodynamic integration. Given that experimental determination of the Gibbs hydration energy for this class of compounds is currently unfeasible, computer simulations appear as the only alternative for the estimation of this important quantity. Several simulation parameters are discussed and optimized based on calculations for barbituric acid. It is concluded that accounting for electrostatic interactions with the Reaction-Field method can be up to two times faster than with Particle-Mesh-Ewald method, without loss of accuracy. Different number of solvent molecules and simulation lengths were also tested. Lennard-Jones and electrostatic contributions were scaled down to zero in an independent way. It is shown that the electrostatic contribution is dominant (representing approximately 90% of the total Gibbs energy of hydration) and that barbiturate intra-molecular interactions cannot be neglected. The importance of the electrostatic contribution is attributed to the formation of hydrogen bonds between the barbiturates and water, which play an important role in the solvation process. The influence of the different substituents and their contribution to the Gibbs energy of hydration was assessed. Finally, the Lennard-Jones contributions and the total hydration Gibbs energy can both be correlated against molecular weight or partition coefficient data for mono- and di-substituted barbiturates.

Original languageEnglish
Pages (from-to)148-155
Number of pages8
JournalFluid Phase Equilibria
Volume289
Issue number2
DOIs
Publication statusPublished - 15 Mar 2010
Externally publishedYes

Fingerprint

Barbiturates
Gibbs free energy
Hydration
hydration
electrostatics
Electrostatics
simulation
energy
Molecular interactions
Water
Solvation
molecular interactions
Coulomb interactions
water
solvation
Molecular dynamics
mesh
partitions
molecular weight
Hydrogen bonds

Keywords

  • Barbiturates
  • Free energy calculations
  • Hydration Gibbs energy
  • Molecular modeling
  • Thermodynamic integration

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Physical and Theoretical Chemistry
  • Physics and Astronomy(all)

Cite this

Molecular simulation of the hydration Gibbs energy of barbiturates. / Garrido, Nuno M.; Jorge, Miguel; Queimada, António J.; Economou, Ioannis; Macedo, Eugénia A.

In: Fluid Phase Equilibria, Vol. 289, No. 2, 15.03.2010, p. 148-155.

Research output: Contribution to journalArticle

Garrido, Nuno M. ; Jorge, Miguel ; Queimada, António J. ; Economou, Ioannis ; Macedo, Eugénia A. / Molecular simulation of the hydration Gibbs energy of barbiturates. In: Fluid Phase Equilibria. 2010 ; Vol. 289, No. 2. pp. 148-155.
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