Topological characterization of electron density, electrostatic potential and intermolecular interactions of 2-nitroimidazole: an experimental and theoretical study

Abstract

An experimental charge density distribution of 2-nitroimidazole was determined from high-resolution X-ray diffraction and the Hansen-Coppens multipole model. The 2-nitroimidazole compound was crystallized and a high-angle X-ray diffraction intensity data set has been collected at low temperature (110 K). The structure was solved and further, an aspherical multipole model refinement was performed up to octapole level; the results were used to determine the structure, bond topological and electrostatic properties of the molecule. In the crystal, the molecule exhibits a planar structure and forms weak and strong intermolecular hydrogen-bonding interactions with the neighbouring molecules. The Hirshfeld surface of the molecule was plotted, which explores different types of intermolecular interactions and their strength. The topological analysis of electron density at the bond critical points (b.c.p.) of the molecule was performed, from that the electron density ρ(r) and the Laplacian of electron density ∇ρ(r) at the b.c.p.s of the molecule have been determined; these parameters show the charge concentration/depletion of the nitroimidazole bonds in the crystal. The electrostatic parameters like atomic charges and the dipole moment of the molecule were calculated. The electrostatic potential surface of the molecule has been plotted, and it displays a large electronegative region around the nitro group. All the experimental results were compared with the corresponding theoretical calculations performed using CRYSTAL09.

Electrostatic potential of dynamic charge densities

“…It is found that at all temperatures the ESPs of all static and dynamic charge densities possess similar features on the 0.5 e Å À3 isosurfaces of the electron densities: the most negative values appear near O atoms and the most positive values appear near H atoms. These features are in agreement with the presence of intermolecular hydrogen bonds in the crystal, and they are in line with similar features observed for static ESPs of other molecules (Kalaiarasi et al, 2016;Niranjana Devi et al, 2017;Zhurova et al, 2016). Major differences between ESPs on these isosurfaces are found between MEM densities and model densities, with a 60% larger range of values ÁV S for the MEM densities.…”

“…Quantitative measures of the ESP have been obtained as integral properties over this surface according to Politzer et al (2001) (see Table 1 Table 1 Definitions of integral quantities of the ESP, integrated over isosurfaces of the electron density according to Politzer et al (2001 Sum of positive and negative variances of the ESP Degree of the electrostatic balance derived from the variances of the ESP atoms act as acceptors of intermolecular hydrogen bonds, and these three H atoms are part of a hydrogen bond too (Mondal et al, 2012). These features of the molecular ESP are in agreement with similar features of ESPs of other molecules (Kalaiarasi et al, 2016;Niranjana Devi et al, 2017;Zhurova et al, 2016). The ESP of the static electron density of AH (20) has also been computed for a cluster of 3 Â 3 Â 3 unit cells.…”

“…One method of analysis comprises the consideration of the ESP on a surface enveloping the molecule. In applications to small and large molecules up to proteins, the ESP has thus been used to identify electrophilic and nucleophilic sides, to characterize hydrogen bonds, and to analyse intermolecular interactions (Du et al, 2016;Kalaiarasi et al, 2016;Kirby et al, 2014;Malinska & Dauter, 2016;Niranjana Devi et al, 2017;Sirohiwal et al, 2017;Zarychta et al, 2015;Zhurova et al, 2016).…”

Charge density and electrostatic potential of hepatitis C anti-viral agent andrographolide: an experimental and theoretical study

“…Electrostatic potential. The electrostatic potential (ESP) of molecules provides rich information about the binding ability of molecules with the neighboring molecules in solids as well as the binding of ligands in the active site of enzymes (Arputharaj et al, 2012;Zhurova et al, 2016Zhurova et al, , 2009Zhurova, Matta et al, 2006;Yearley et al, 2007;Kalaiarasi et al, 2016;Kumar & Dominiak, 2016;Rajalakshmi, Hathwar et al, 2014b;Rajalakshmi, Pavan & Kumaradhas, 2014;Rajalakshmi, Hathwar et al, 2014a;Dominiak et al, 2007;Fournier et al, 2009). Furthermore, in drug-receptor interactions, the ESP of a drug molecule allows molecular recognition in the biological environment (active site of receptor) to be predicted and, specifically, the reactive locations of the molecule to be identified; this information shows how the drug molecules interact with the receptor.…”

“…Thus, the polarization effects on the molecule due to crystalline and the drug-receptor interaction environment are comparable. Experimental electron density studies of several drug and bio-molecules, such as estrone (Zhurova, Matta et al, 2006), 17-estradiolÁ0.5H 2 O (Zhurova et al, 2009), genistein (Yearley et al, 2007), paracetamol (Bouhmaida et al, 2009), aziridine, oxirane, olefin (Grabowsky et al, 2008), aspirin (Arputharaj et al, 2012), isoniazid (Rajalakshmi, Hathwar et al, 2014b), pyrazinamide (Rajalakshmi, Hathwar et al, 2014a), ethionamide (Rajalakshmi, Pavan & Kumaradhas, 2014), 2nitroimidazole (Kalaiarasi et al, 2016), 16,17-estriol (Zhurova et al, 2016), have been carried out and successfully established the importance of the electron density studies for understanding the nature of a molecule. The origin for the molecular recognition of a drug molecule is the structural and electrostatic complementarity with the receptor site aminoacid residues.…”