title: Topological analysis of electron density and the electrostatic properties of isoniazid: an experimental and theoretical study.
abstract: Isoniazid (isonicotinohydrazide) is an important first-line antitubercular drug that targets the InhA enzyme which synthesizes the critical component of the mycobacterial cell wall. An experimental charge-density analysis of isoniazid has been performed to understand its structural and electronic properties in the solid state. A high-resolution single-crystal X-ray intensity data has been collected at 90 K. An aspherical multipole refinement was carried out to explore the topological and electrostatic properties of the isoniazid molecule. The experimental results were compared with the theoretical charge-density calculations performed using CRYSTAL09 with the B3LYP/6-31G** method. A topological analysis of the electron density reveals that the Laplacian of electron density of the N-N bond is significantly less negative, which indicates that the charges at the b.c.p. (bond-critical point) of the bond are least accumulated, and so the bond is considered to be weak. As expected, a strong negative electrostatic potential region is present in the vicinity of the O1, N1 and N3 atoms, which are the reactive locations of the molecule. The C-H···N, C-H···O and N-H···N types of intermolecular hydrogen-bonding interactions stabilize the crystal structure. The topological analysis of the electron density on hydrogen bonding shows the strength of intermolecular interactions.
authors.affiliation: Laboratory of Biocrystallography and Computational Molecular Biology, Department of Physics, Periyar University, Salem 636 011, India.
authors.forename: Gnanasekaran
authors.initials: G
authors.lastname: Rajalakshmi
authors.affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Venkatesha R
authors.initials: VR
authors.lastname: Hathwar
authors.affiliation: Laboratory of Biocrystallography and Computational Molecular Biology, Department of Physics, Periyar University, Salem 636 011, India.
authors.forename: Poomani
authors.initials: P
authors.lastname: Kumaradhas
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D018360:Crystallography, X-Ray; D004583:Electrons; D006801:Humans; D006860:Hydrogen Bonding; D007538:Isoniazid / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D055672:Static Electricity
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium; D007538:Isoniazid
keywords: charge-density analysis; charge-density distribution; electrostatic properties; intermolecular interactions; isoniazid