Experimental and theoretical charge density, intermolecular interactions and electrostatic properties of metronidazole

Abstract

Metronidazole is a radiosensitizer; it crystallizes in the monoclinic system with space group P21/c. The crystal structure of metronidazole has been determined from high‐resolution X‐ray diffraction measurements at 90 K with a resolution of (sin gθ/λ)max = 1.12 Å−1. To understand the charge‐density distribution and the electrostatic properties of metronidazole, a multipole model refinement was carried out using the Hansen–Coppens multipole formalism. The topological analysis of the electron density of metronidazole was performed using Bader's quantum theory of atoms in molecules to determine the electron density and the Laplacian of the electron density at the bond critical point of the molecule. The experimental results have been compared with the corresponding periodic theoretical calculation performed at the B3LYP/6‐31G** level using CRYSTAL09. The topological analysis reveals that the N—O and C—NO2 exhibit less electron density as well as negative Laplacian of electron density. The molecular packing of crystal is stabilized by weak and strong inter‐ and intramolecular hydrogen bonding and H…H interactions. The topological analysis of O—H…N, C—H…O and H…H intra‐ and intermolecular interactions was also carried out. The electrostatic potential of metronidazole, calculated from the experiment, predicts the possible electrophilic and nucleophilic sites of the molecule; notably, the hydroxyl and the nitro groups exhibit large electronegative regions. The results have been compared with the corresponding theoretical results.

Bonding features in Appel's salt from the orbital-free quantum crystallographic perspective

“…Recent studies (Gleiter & Haberhauer, 2017 considered the complicated cases of bonding between chalcogen atoms, including two-, three-and four-center bonds. The other studies covered aspects of bonding in biologically important molecules such as the drug metronidazole with a diazole heterocycle in its structure (Kalaiarasi et al, 2019), polymorphs of famotidine based on a thiazole ring (Overgaard & Hibbs, 2004) and (2-oxo-1,3benzoxazol-3(2H)-yl) acetic acid (Wang et al, 2016). The electron density point of view on halogen bonds has been thoroughly presented in the recent works dealing with the NÁ Á ÁI bond (Wang et al, 2018), interactions in tetrafluorodiiodobenzene (Wang et al, 2019) and short ClÁ Á ÁCl bonding (Wang et al, 2012(Wang et al, , 2017.…”

Metronidazole Cocrystal Polymorphs with Gallic and Gentisic Acid Accessed through Slurry, Atomization Techniques, and Thermal Methods

“…The crystal structures of MNZ and the GAL and GNT polymorphs have already been published − ,,− ,− and are discussed together with the cocrystal structures from the literature, and the structures are determined in this study.…”

“…To date, two different sets of lattice parameters have been reported for MNZ (CSD-Refcode family MNIMET). The first one, namely MNIMET and MNIMET02–06, is a P 2 1 / c cell, − whereas for MNIMET01, the P 11 2 1 / n space group has been assigned . Transforming the MNIMET01 cell to the standard setting indicates the presence of different lattice parameters.…”

Crystal engineering of a co-crystal of antipyrine and 2-chlorobenzoic acid: relative energetic contributions based on multipolar refinement

“…We then decided to discuss the stability of the cocrystal based on the I / σ > 2 levels as many authors currently do. 64–67…”

“…We then decided to discuss the stability of the cocrystal based on the I/σ > 2 levels as many authors currently do. [64][65][66][67] Fig. 2 Fourier residual electron density of the molecular complex (AN-CBA) after MM exp and MM theo refinement at contour level of 0.05 e Å −3 with sin θ/λ = 0.7 Å −1 .…”