Study of the structural and electronic properties Valproic Acid and new derivatives used as anticonvulsant agents

Abstract

The conformational and electronic characteristics of the polar O 9=C8-X10 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 O9=C 8-X10 moiety by means of ELF, NBO, and AIM calculations, we found that the bending away from coplanarity of the atoms in O 9=C8-X10 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 O9=C8-X10 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.