title: Study of the structural and electronic properties of valproic acid and new derivatives used as anticonvulsant agents.
abstract: The conformational and electronic characteristics of the polar O(9)═C(8)-X(10) moiety in the anticonvulsant valproic acid (Vpa) drug and some of their amides and ester derivatives are analyzed at the B3LYP level using the 6-31+G(d,p) and 6-311++G(d,p) 6d,10f basis sets. Exploring the delocalization of the electron density of the O(9)═C(8)-X(10) moiety by means of ELF, NBO, and AIM calculations, we found that the bending away from coplanarity of the atoms in O(9)═C(8)-X(10) is accompanied by a three-dimensional arrangement of donor and acceptor proton units closing nearly planar pseudorings of four, five, and six members arising from stabilizing interactions around the O(9)═C(8)-X(10) backbone. From the structure-property relationship analysis, we explain the origin of the change in the structural parameters and atomic charges in the polar moiety.
authors.affiliation: Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Facultad de Ciencias Exactas, Universidad Nacional de la Plata, La Plata, Argentina.
authors.forename: Nieves C
authors.initials: NC
authors.lastname: Comelli
authors.forename: Rosana M
authors.initials: RM
authors.lastname: Lobayan
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Castro
authors.forename: Alicia H
authors.initials: AH
authors.lastname: Jubert
mesh_terms: D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology; D004583:Electrons; D004597:Electroshock; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014635:Valproic Acid / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid