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Theoretical characterization of SOME amides and esters DERIVATIVES of valproic acid

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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.

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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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Authors and Affiliations

  1. INIFTA, Theoretical Chemistry Division, Suc. 4, C.C. 16, La Plata 1900, Buenos Aires, Argentina

    Nieves C. Comelli & Eduardo A. Castro

  2. Departamento de Física, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Ñuñoa, 653, Santiago, Chile

    Patricio Fuentealba

  3. Departamento de Química, Facultad de Ciencias Exactas, UNLP, CEQUINOR, Centro de Química Inorgánica (CONICET, UNLP), C. C. 962, 1900 La Plata. Facultad de Ingeniería, UNLP, 1 y 47, 1900, La Plata, Argentina

    Alicia H. Jubert

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  1. Nieves C. Comelli
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  2. Patricio Fuentealba
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  4. Alicia H. Jubert
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Correspondence to Alicia H. Jubert.

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Comelli, N.C., Fuentealba, P., Castro, E.A. et al. Theoretical characterization of SOME amides and esters DERIVATIVES of valproic acid. J Mol Model 16, 343–359 (2010). https://doi.org/10.1007/s00894-009-0554-6

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  • DOI: https://doi.org/10.1007/s00894-009-0554-6

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