Computer-Assisted Conformational Analysis of Small Molecules Using VEGA ZZ, a Freely Available Software Program, as an Introduction to Molecular Modeling

Abstract

We report a molecular modeling study for undergraduate students aimed at carrying out an analysis of small molecules using a systematic conformational search with VEGA ZZ, a freely available software program. Conformational analyses were performed using a systematic search based on variations of torsion angles. First, the conformations of n-butane were characterized from its energetic diagram, showing the anti/gauche conformations as well as the unfavorable eclipsed conformations. A similar conformation analysis of buta-1,3-diene illustrated the mesomeric effect, leading to the preferential s-cis/s-trans conformations. Then, using the same approach, the conformational study of ethane-1,2-diol gave access to conformations with an intramolecular hydrogen bond. Another example of conformational analysis was the investigation of a cyclic acetal, in chair conformation, showing a preferential conformation with the equatorial substituent, rather than the axial substituent that results from unfavorable 1,3-diaxial interactions. Finally, a study of the amino acid derivative N-acetyl-N′-methyl-l-alanylamide revealed the planar amide functional group. For this example, the analysis, again using the systematic conformational search, was based on the variation of φ/ψ torsion angles, exemplifying these important angles in protein conformations.