Ab Initio Calculations on some Antiepileptic Drugs such as Phenytoin, Phenbarbital, Ethosuximide and Carbamazepine

Abstract

This research deals with some antiepileptic agents that are used to treat antiepileptic seizures. Stable conformational structures corresponding to potential energy minima for each molecule are determined in the gas phase with both Hartree-Fock and density functional methods. Polarizable continuum models have been employed to assess solvent effects on the activity of global minimum structures, and each molecule has become stabilized with increasing solvent dielectric constant. To examine structure-activity relationships, electron propagator calculations of ionization energies, electron affinities, and corresponding energy gaps with the Outer Valence Green's Function (OVGF) and Partial Third Order (P3) approximations have also been performed to compare with Koopmans's Theorem results. The best correlation between logED(50) and electron affinity values, with a linear regression coefficient of 0.98 and a standard deviation of 0.19, is obtained for Koopmans's Theorem with the 6-311++g** basis set in chloroform.