Theoretical characterization of SOME amides and esters DERIVATIVES of valproic acid

• Published in: Journal of molecular modeling Vol. 16; no. 2; pp. 343 - 359
• Main Authors: Comelli, Nieves C., Fuentealba, Patricio, Castro, Eduardo A., Jubert, Alicia H.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.02.2010
• Subjects: Amides - chemistry; Anticonvulsants; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Enzyme Inhibitors; Esters - chemistry; Hydrogen Bonding; Models, Theoretical; Molecular Medicine; Original Paper; Theoretical and Computational Chemistry; Valproic Acid - chemistry; Electronic delocalization; DFT; Antiepileptic drugs; ELF; Non-conventional hydrogen bonds
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-009-0554-6

The equilibrium structures, the planarity of the C(=O)X linkage and the nature of the chemical bond in the Y−C(=O)−XR 1 R 2 [where: Y= −CH−(CH 2 −CH 2 −CH 3 ) 2 , X=N,O and R 1 , R 2 = 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[Ω i , Ω j ] reveals a dominating delocalization effect between the lone pair V(O 1 ), V(X) and the electron density of the H−C and H−X 1 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.