Understanding the NN bond cleavage and the electrostatic properties of isoniazid drug molecule via theoretical charge density study

Charge density distribution and the electrostatic properties of isoniazid drug molecule have been computed from HF and DFT methods with the basis set 6-311G∗∗ using Bader’s theory of atoms in molecules. The molecular geometric parameters predicted by DFT method are in agreement with the reported values. The predicted NN bond distance is 1.414 Å. The dihedral angle between the pyridine ring and the hydrazide group is 27.9°, indicates that these two groups are not coplanar in the molecule. The CN bond distances in the molecule are not equal. The electron density ρbcp(r) and the Laplacian of electron density ∇ 2 ρbcp(r) of NN bond are 2.131 eÅ–3 and −12.5 eÅ−5 respectively. The high degree of electronic charge density depletion at the bond critical point and the low bond dissociation energy of NN bond confirm that this bond is the weakest bond in the molecule, which cleaves during the catalase-peroxidase reaction. A large electronegative potential region is found at the vicinity of O(1) and N(1) atoms, which are the nucleophilic sites of the molecule. The dipole moment of the molecule is 2.04 Debye, implies, isoniazid is a polar molecule.