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

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 rho(bcp)(r) and the Laplacian of electron density del(2) rho(bcp)(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

Understanding the conformational flexibility and electrostatic properties of curcumin in the active site of rhAChE via molecular docking, molecular dynamics, and charge density analysis

<p>Acetylcholinesterase (AChE) is an important enzyme responsible for Alzheimer’s disease, as per report, keto-enol form of curcumin inhibits this enzyme. The present study aims to understand the binding mechanism of keto-enol curcumin with the recombinant human Acetylcholinesterase (rhAChE) from its conformational flexibility, intermolecular interactions, charge density distribution, and the electrostatic properties at the active site of rhAChE. To accomplish this, a molecular docking analysis of curcumin with the rhAChE was performed, which gives the structure and conformation of curcumin in the active site of rhAChE. Further, the charge density distribution and the electrostatic properties of curcumin molecule (lifted from the active site of rhAChE) were determined from the high level density functional theory (DFT) calculations coupled with the charge density analysis. On the other hand, the curcumin molecule was optimized (gas phase) using DFT method and further, the structure and charge density analysis were also carried out. On comparing the conformation, charge density distribution and the electrostatic potential of the active site form of curcumin with the corresponding gas phase form reveals that the above said properties are significantly altered when curcumin is present in the active site of rhAChE. The conformational stability and the interaction of curcumin in the active site are also studied using molecular dynamics simulation, which shows a large variation in the conformational geometry of curcumin as well as the intermolecular interactions.</p

Crystal structure and theoretical charge density studies of dilantin molecule

Dilantin molecule is an inhibitor of multiple protein targets such as prostate-specific antigen, lung cancer cells and it also reduces the tumor growth and invasion of the breast metastatic cancer cells. Understanding the precise geometry, charge density distribution and electrostatic properties of inhibitor pertain to predict the active site interaction between the inhibitor and receptor. Hence, the present study is aimed to determine these parameters through experimental and theoretical studies. Dilantin molecule crystallizes in orthorhombic system with Pna2(1) space group. The crystal and the molecular structure of dilantin molecule has been redetermined using X-ray crystal structure analysis. The two phenyl rings and imidazolidine ring in the molecule are not in coplanar and oriented in different directions, the dihedral angles are 66.6(3) and 65.3(3)degrees. The molecular packing of crystal is stabilized by strong N-H center dot center dot center dot O and weak C-H center dot center dot center dot O intermolecular hydrogen bonding interactions. A theoretical charge density analysis has been performed for the molecule lifted from the crystal, reveals the charge density distribution of dilantin molecule, this result has been compared with the corresponding gas phase studies. The electrostatic properties of the molecule also calculated. The calculated dipole moment of dilantin molecule in the crystal phase is (2.88 D), which is not very much different from its gas phase value (2.68 D). The electrostatic potential map displays strong electronegative regions near the O and N atoms, which are the possible reactive locations of the molecule. (C) 2018 Elsevier B.V. All rights reserved

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

Andrographolide (AGH) is a hepatitis C anti-viral agent which targets the host cell by covalently binding with the NF-kappa Breceptor. The experimental electron density distribution study of AGH has been carried out from high-resolution X-ray diffraction data collected at 110.2 (3) K. The unit-cell packing of AGH was stabilized by strong O-H center dot center dot center dot O and weak C-H center dot center dot center dot O types of intermolecular interactions. The dissociation energy of the strong hydrogen bond O2-H22 center dot center dot center dot O1 is very high, 32 kJ mol(-1). The percentage occupancy of H center dot center dot center dot H interactions is found to be maximum (68.5%) when it comparing with the other types of interactions occurring in the AGH crystalline phase. The atomic valance index (V-topo) of the C16 atom is low compared with other carbon atoms; this shows that C16 could be the possible reactive location of the AGH molecule. All atoms in the OH groups have very low V-topo values; this indicates their role in strong hydrogen bonding interactions. The electrostatic potential (ESP) surface of AGH shows the polarization of the C16=C17 bond and ESP contour map shows several maxima at the vicinity of the C16 atom; these results strongly demonstrate that the C16 atom is the reactive location of the AGH molecule. The molecular covalent docking analysis of AGH with the NF-kappa B receptor has been performed and confirmed this result. The highly electronegative region around gamma-butyrolactone can be helpful for initial alignment of the AGH molecule in NF-kappa B receptor active site. The atomic volumes of the hydrogen atoms which participate in the H center dot center dot center dot H interaction are found to be low

Topology of electron density and electrostatic potential of HIV reverse transcriptase inhibitor zidovudine from high resolution X-ray diffraction and charge density analysis

Azidothymidine (AZT) is a first anti-HIV drug namely Zidovudine used for HIV treatment, which binds to the viral DNA primer and inhibits the HIV reverse transcription. The side effects of this powerful drug are severe and the detailed understanding of its electronic structure helps to design new drugs from the AZT molecule. Present study aims to determine the structure of AZT at electronic level from the experimental charge density analysis as well as the solid state DFT calculations. AZT was crystallized and low temperature high resolution X-ray diffraction intensity data has been measured up to sin (theta/lambda)(max) = 1.1 angstrom(-1) at 100.0 (2) K. The crystal structure of AZT was determined, which reveals the information that the AZT compound crystallizes with two molecules in the asymmetric unit which are conformationally different and linked through strong hydrogen bonding interactions (dimer). The Hirshfeld surface of both molecules shows the locations of weak and strong interactions. Further, a multipole model refinement was carried out using Hansen-Coppens multipole formalism. The experimental topological properties of electron density of AZT molecules were determined and compared with the results of theoretical DFT calculations based on solid state and gas phase studies. The charge density distribution of the two molecules in the asymmetric unit is unequal and shows some difference. The topological properties of O-H center dot center dot center dot O, O-H center dot center dot center dot N, C-H center dot center dot center dot N, H center dot center dot center dot H and azide center dot center dot center dot azide group interactions are also determined. The electrostatic potential (ESP) surface of both AZT molecules in the crystal exhibits high electronegative regions around the O, N atoms and also around the azide group, however, ESP regions of molecules (I) and (II) are not similar. (C) 2018 Elsevier B.V. All rights reserved