Conformation and equilibrium molecular structure of isoniazid in the gas phase

Abstract

Equilibrium structure of anti-tuberculosis drug isoniazid has been determined for the first time by joint application of gas electron diffraction (GED) and quantum-chemical (QC) calculations. Employment of QC calculations revealed the possibility of free isoniazid molecules to exist as a mixture of four conformers with different configuration of the hydrazide group. However, only one conformer was taken into account for fitting GED data, as the others were estimated to be present in insufficient quantities in vaporous phase by QC computations. The reasons of stability of the lowest energy form have been discussed in a view of NBO analysis. The GED values have been compared with those obtained from QC computations and X-ray diffraction studies.