title: Intermolecular interactions, charge-density distribution and the electrostatic properties of pyrazinamide anti-TB drug molecule: an experimental and theoretical charge-density study.
abstract: An experimental charge-density analysis of pyrazinamide (a first line antitubercular drug) was performed using high-resolution X-ray diffraction data [(sin θ/λ)max = 1.1 Å(-1)] measured at 100 (2) K. The structure was solved by direct methods using SHELXS97 and refined by SHELXL97. The total electron density of the pyrazinamide molecule was modeled using the Hansen-Coppens multipole formalism implemented in the XD software. The topological properties of electron density determined from the experiment were compared with the theoretical results obtained from CRYSTAL09 at the B3LYP/6-31G** level of theory. The crystal structure was stabilized by N-H...N and N-H...O hydrogen bonds, in which the N3-H3B...N1 and N3-H3A...O1 interactions form two types of dimers in the crystal. Hirshfeld surface analysis was carried out to analyze the intermolecular interactions. The fingerprint plot reveals that the N...H and O...H hydrogen-bonding interactions contribute 26.1 and 18.4%, respectively, of the total Hirshfeld surface. The lattice energy of the molecule was calculated using density functional theory (B3LYP) methods with the 6-31G** basis set. The molecular electrostatic potential of the pyrazinamide molecule exhibits extended electronegative regions around O1, N1 and N2. The existence of a negative electrostatic potential (ESP) region just above the upper and lower surfaces of the pyrazine ring confirm the π-electron cloud.
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*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D011718:Pyrazinamide / Q000737:chemistry*; D011789:Quantum Theory; D055672:Static Electricity
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide
keywords: Hirshfeld surface analysis; anti-tuberculosis drug; charge-density study; hydrogen bonds