Likelihood of atom-atom contacts in crystal structures of halogenated organic compounds IUCr Journals CHEMISTRYjCRYSTENG Likelihood of atom-atom contacts in crystal structures of halogenated organic compounds

International audienceThe likelihood of occurrence of intermolecular contacts in crystals of halogenated organic compounds has been analysed statistically using tools based on the Hirshfeld surface. Several families of small halogenated molecules (containing organic F, Cl, Br or I atoms) were analysed, based on chemical composition and aromatic or aliphatic character. The behaviour of crystal contacts was also probed for molecules containing O or N. So-called halogen bonding (a halogen making short interactions with O or N, or a interaction with C) is generally disfavoured, except when H is scarce on the molecular surface. Similarly, halogenÁ Á Áhalogen contacts are more rare than expected, except for molecules that are poor in H. In general, the H atom is found to be the preferred partner of organic halogen atoms in crystal structures. On the other hand, CÁ Á ÁC interactions in parallel-stacking have a high propensity to occur in halogenated aromatic molecules. The behaviour of the four different halogen species (F, Cl, Br, I) is compared in several chemical composition contexts. The analysis tool can be refined by distinguishing several types for a given chemical species, such as H atoms bound to O or C. Such distinction shows, for instance, that C-HÁ Á ÁCl and O-HÁ Á ÁO are the preferred interactions in compounds containing both O and Cl

π-Hole bonding in a new co-crystal hydrate of gallic acid and pyrazine: static and dynamic charge density analysis

A new cocrystal hydrate of gallic acid with pyrazine (4GA, Py, 4H2O; GA4PyW4) was obtained and characterized by single crystal X-ray diffraction. In addition to structure determination, experimental charge density analysis was carried out in terms of Multipole Modelling (MP), X-ray wavefunction refinement (XWR) and maximum entropy method (MEM). As a part of XWR, the structural refinement via Hirshfeld atom refinement was carried out and resulted in O-H bond lengths close to values from neutron diffraction. A systematic comparison of molecular conformations and aromatic interactions in this new cocrystal hydrate was performed with other existing polymorphs of gallic acid. In GA4PyW4, the two symmetry-independent gallic acid molecules have a syn COOH orientation and form the common (COOH)2 dimeric synthon. The carboxyl C atom displays the characteristics of π-holes with electropositive regions above and below the molecular plane and engages in acceptor-donor interactions with oxygen atoms of acidic O-H groups and phenol groups of neighbouring gallic acid molecules. The signature of the π-hole was identified from experimental charge density analysis, both in static density maps in MP and XWR as well as dynamic density in MEM, but it cannot be pinned down to a specific atom-atom interaction. This study presents the first comparison between an XWR and a MEM experimental electron-density determination

Aggregation in isomeric imides: analysis of the weak interactions in six N-(benzoyl)-N-(2-pyridyl)benzamides

International audienceCrystal structures of 4-chloro-N-(4-chlorobenzoyl)-N-(2-pyridyl)benzamide (I) Clpod, 3-chloro-N-(3-chlorobenzoyl)-N-(2-pyridyl)benzamide (II) Clmod and 2-chloro-N-(2-chlorobenzoyl)-N-(2-pyridyl)benzamide (III) Clood together with three methylated analogues, Mpod, Mmod and Mood, are presented herein. The Clxod acyclic imides are produced from reacting the 4-/3-/2-chlorobenzoyl chlorides (Clx) with 2-aminopyridine (o), respectively, together with their benzamide analogues Clxo; the Mxod/Mxo triad are produced similarly and in good yield. The five Clxod, Mpod and Mmod structures adopt the open transoid conformations as expected, but Mood crystallises with cisoid oriented benzoyl groups, and this conformation was unexpected, though not unknown. Halogen bonding contacts and weak hydrogen bonding C-H···N/O/π contacts are noted in the structures lacking strong hydrogen bonding donor atoms/groups but possessing a variety of strong and weaker acceptor atoms/groups. For Clxod, contact studies show that both hydrogen and carbon account for a high percentage of elements (70–75%) on the molecular surface and being the most abundant have C···H forming 26–30% of the contacts. Contact enrichment ratios are an indicator of the likelihood of chemical species to form intermolecular interactions with themselves and other species. The C-H···N and C-H···O are the most enriched (with EHN > 2.15), indicating that these weak hydrogen bonds are the driving force in the Clxod crystal packing formation. For Mxod, the C···H contact type at 40–52% is the most abundant contact type and C-H···O and C-H···N weak hydrogen bonds dominate with enrichment values in the 1.48–1.78 range. In Mxod, N/O···N/O contacts are effectively absent, except for Mpod (0.2%, N···N contacts) and both H···H and C···C non-polar contacts are moderately impoverished while the C···H interactions are slightly enriched (E = 1.1–1.21)

Experimental and theoretical charge-density analysis of 1,4-bis(5-hexyl-2-thienyl)butane-1,4-dione: applications of a virtual-atom model

International audienceThe experimental and theoretical charge densities of 1,4-bis(5-hexyl-2-thienyl)butane-1,4-dione, a precursor in the synthesis of thiophene-based semiconductors and organic solar cells, are presented. A dummy bond charges spherical atom model is applied besides the multipolar atom model. The results show that the dummy bond charges model is accurate enough to calculate electrostatic-derived properties which are comparable with those obtained by the multipolar atom model. The refinement statistics and the residual electron density values are found to be intermediate between the independent atom and the multipolar formalisms

Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations

The electron density and electrostatic potential in an aldose reductase holoenzyme complex have been studied by density functional theory (DFT) and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway by using NADPH as a cofactor. The ultra-high resolution of the diffraction data and the low thermal-displacement parameters of the structure allow accurate atomic positions and an experimental charge density analysis. Based on the x-ray structural data, order-N DFT calculations have been performed on subsets of up to 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with the program MOPRO by using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids. Electrostatic potentials calculated from the charge density database, the preliminary experimental electron density analysis, DFT computations, and atomic charges taken from the AMBER software dictionary are compared. The electrostatic complementarity between the cofactor NADP+ and the active site shows up clearly. The anchoring of the inhibitor is due mainly to hydrophobic forces and to only two polar interaction sites within the enzyme cavity. The potentials calculated by x-ray and DFT techniques agree reasonably well. At the present stage of the refinement, the potentials obtained directly from the database are in excellent agreement with the experimental ones. In addition, these results demonstrate the significant contribution of electron lone pairs and of atomic polarization effects to the host and guest mechanism.Instituto de Física de Líquidos y Sistemas BiológicosFacultad de Ciencias Exacta

Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations

The electron density and electrostatic potential in an aldose reductase holoenzyme complex have been studied by density functional theory (DFT) and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway by using NADPH as a cofactor. The ultra-high resolution of the diffraction data and the low thermal-displacement parameters of the structure allow accurate atomic positions and an experimental charge density analysis. Based on the x-ray structural data, order-N DFT calculations have been performed on subsets of up to 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with the program MOPRO by using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids. Electrostatic potentials calculated from the charge density database, the preliminary experimental electron density analysis, DFT computations, and atomic charges taken from the AMBER software dictionary are compared. The electrostatic complementarity between the cofactor NADP+ and the active site shows up clearly. The anchoring of the inhibitor is due mainly to hydrophobic forces and to only two polar interaction sites within the enzyme cavity. The potentials calculated by x-ray and DFT techniques agree reasonably well. At the present stage of the refinement, the potentials obtained directly from the database are in excellent agreement with the experimental ones. In addition, these results demonstrate the significant contribution of electron lone pairs and of atomic polarization effects to the host and guest mechanism.Instituto de Física de Líquidos y Sistemas BiológicosFacultad de Ciencias Exacta

Ultrahigh-resolution crystallography and related electron density and electrostatic properties in proteins

Ultrahigh-resolution protein diffraction data allow valence electron density modelling and calculations of experimental electrostatic properties. Protein–ligand interaction energy may therefore be estimated

Experimental Charge Density Analysis of the Anti-inflammatory Drug Meloxicam [sodium 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1$l^{6},2-benzothiazine-3-carboxamide Monohydrate]

The charge density analysis of meloxicam sodium monohydrate [sodium 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1$l^{6},2-benzothiazine-3-carboxamide monohydrate] was performed with high-resolution X-ray diffraction data measured at low temperature (90 K). The experimental results were compared with those derived from the corresponding periodic theoretical calculations at the B3LYP/6-31G** level of theory. The multipolar charge-density analysis highlights the regions of meloxicam which are the most electronegative. These regions correspond to those forming short electrostatic interactions with the Na+ cation. The molecular conformation in the crystal is maintained by a strong intramolecular N−H…O=C hydrogen bond. The Na+ cation interacts with as much as five neighboring oxygen atoms. The strong hydrogen bonds N/O−H…O/N, the Na…O short contacts and hydrophobic aromatic stacking between the two aromatic cycles constitute the most represented and enriched contact types and act as the driving force in the crystal packing formation. The crystal packing presents several meloxicam anion dimers but also one Na+…Na+ repulsive interactions which are largely compensated by the electrostatic favorable attractions between anions and cations. This work is licensed under a Creative Commons Attribution 4.0 International License

Aggregation in Three Benzamide or Pyridylcarboxamide Hydrates: Formation of 1D Chains Comprising Water Molecules in a Chloro(pyridyl)benzamide Dihydrate

Three benzamide hydrated derivatives as para-methyl-N-(3-pyridyl)benzamide monohydrate (I) or Mpm ∙ H2O; N-(3-fluorophenyl)-4-pyridylcarboxamide monohydrate (II) or NpmF ∙ H2O and para-chloro-N-(3-pyridyl)benzamide dihydrate (III) or Clpm ∙ 2H2O are obtained from a series of crystallization experiments using a range of solvents to obtain polymorphs and solvates (hydrates). Most of the crystallization experiment attempts did not provide hydrates and yielded the starting parent crystalline materials. However, from the experiments, two benzamides, Mpm as a monohydrate and Clpm as a dihydrate were isolated and together with a carboxamide monohydrate as NpmF ∙ H2O are reported herein. The water molecules play a key role in crystal structure formation using classical hydrogen bonding via amide N–H···OH2, O–H···Npyridine and O–H···O=C interactions. They compensate for the excess of strong hydrogen bonding acceptors over donors in the benzamide/pyridinecarboxamide molecules, by participating as O-H hydrogen bond donors twice and usually as an O acceptor once. In the Clpm dihydrate, both water molecules form hydrogen bonded chains along the a-axis direction. The lack of hydrate formation in the majority of related benzamides is presumably related to the relative hydrophobicity of these compounds. This work is licensed under a Creative Commons Attribution 4.0 International License

Bonding in Uranium(V) Hexafluoride Based on the Experimental Electron Density Distribution Measured at 20 K

International audienceThe electron density distribution of [PPh4][UF6] was obtained from high-resolution X-ray diffrac-tion data measured at 20 K. The electron density was mod-eled with an augmented Hansen-Coppens multipolar formalism. Topological analysis reveals that the U-F bond is of incipient covalent nature. Theoretical calculations add further support to the bonding description gleaned from the experimental model. The impact of the uranium anomalous dispersion terms on the refinement is also discussed