On Conformation and Hydrogen Bonding in Vigabatrin Amino Acid Molecule

Structure and stability of 285 conformers of the vigabatrin molecule in the gas phase have been obtained by
using two combined approaches of conformer search. The first approach consisted of the successive recurrent
scanning of all the dihedral angles in the molecule, at the semiempirical AM1 and the ab initio HF/6-31G*
levels. The second approach involved the identification of conformers of vigabatrin through the use of a
Monte Carlo search coupled with molecular mechanics. The structures formed by using the two kinds of
searches were grouped into classes corresponding to defined carbon backbone arrangement and further
optimized at the HF/6-311++G** level. For each conformer, if a hydrogen donor−acceptor distance was
smaller than ca. 3 Å, the hydrogen bond analysis using the atoms in molecules (AIM) method was applied
by using the MP2/6-311++G** electron density. A new intramolecular NH···C hydrogen bonding was found.
The selected conformers, being those of the lowest energy in each class and representatives for all kinds of
hydrogen bonds, were further optimized at the MP2 level. Parameters of the hydrogen bonds were tabulated,
compared, and discussed.