Journal of Molecular Modeling

, Volume 16, Issue 2, pp 343–359 | Cite as

Theoretical characterization of SOME amides and esters DERIVATIVES of valproic acid

  • Nieves C. Comelli
  • Patricio Fuentealba
  • Eduardo A. Castro
  • Alicia H. Jubert
Original Paper
First Online:
Received:
Accepted:

Abstract

The equilibrium structures, the planarity of the C(=O)X linkage and the nature of the chemical bond in the Y−C(=O)−XR1R2 [where: Y= −CH−(CH2−CH2−CH3)2, X=N,O and R1, R2= H; alkyl and aryl groups and lone pair electrons (lp)] molecular fragment of derivates of Valproic acid (Vpa) with antiepileptic activity were studied systematically by means of B3LYP calculations and topological analysis of the electron localization function (ELF). The covariance parameter cov[Ωi, Ωj] reveals a dominating delocalization effect between the lone pair V(O1), V(X) and the electron density of the H−C and H−X1 bonds resulting from the existence of not only non-conventional intramolecular hydrogen bonding patterns as C−H...O/N but also a weak closed-shell stabilizing interaction type arising from a dihydrogen bonding as C−H...H−N, where H...H contacts at a significantly shorter distance than twice the hydrogen atom van der Waals radius. The analyzed data derived from ELF domains were found to be in agreement with the known features and properties of the hydrogen bonding interactions discussed in this work.

Keywords

Antiepileptic drugs DFT ELF Electronic delocalization Non-conventional hydrogen bonds 
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Notes

Acknowledgments

N.C.C, acknowledges a fellowship from the Consejo Nacional de Investigaciones Científicas y Tecnologicas- (CONICET) and financial support from Dr Patricio Fuentealba to visit his lab. A.H.J., is a member of the Research Scientific Career (CIC-PBA), E.A.C is a member of the Research Scientific Career CONICET.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Nieves C. Comelli
    • 1
  • Patricio Fuentealba
    • 2
  • Eduardo A. Castro
    • 1
  • Alicia H. Jubert
    • 3
  1. 1.INIFTA, Theoretical Chemistry DivisionBuenos AiresArgentina
  2. 2.Departamento de Física, Facultad de CienciasUniversidad de ChileSantiagoChile
  3. 3.Departamento de Química, Facultad de Ciencias Exactas, UNLPCEQUINOR, Centro de Química Inorgánica (CONICET, UNLP)La PlataArgentina

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