Linear MgCp* vs Bent CaCp*: London Dispersion, Ligand-Induced Charge Localizations, and Pseudo-Pregostic C-H···Ca Interactions.

In the family of metallocenes, MgCp* (Cp* = pentamethylcyclopentadienyl) exhibits a regular linear sandwich structure, whereas CaCp* is bent in both the gas phase and solid state. Bending is typically observed for metal ions which possess a lone pair. Here, we investigate which electronic differences cause the bending in complexes lacking lone pairs at the metal atoms.

Validation of X-ray Wavefunction Refinement.

In this work, the quality of the electron density in crystals reconstructed by the multipolar model (MM) and by X-ray wavefunction refinement (XWR) is tested on a set of high-resolution X-ray diffraction data sets of four amino acids and six tripeptides. It results in the first thorough validation of XWR. Agreement statistics, figures of merit, residual- and deformation-density maps, as well as atomic displacement parameters are used to measure the quality of the reconstruction relative to the measured structure factors.

Accurate Bond Lengths to Hydrogen Atoms from Single-Crystal X-ray Diffraction by Including Estimated Hydrogen ADPs and Comparison to Neutron and QM/MM Benchmarks.

Amino acid structures are an ideal test set for method-development studies in crystallography. High-resolution X-ray diffraction data for eight previously studied genetically encoding amino acids are provided, complemented by a non-standard amino acid. Structures were re-investigated to study a widely applicable treatment that permits accurate X-H bond lengths to hydrogen atoms to be obtained: this treatment combines refinement of positional hydrogen-atom parameters with aspherical scattering factors with constrained "TLS+INV" estimated hydrogen anisotropic displacement parameters (H-ADPs).

Invariom based electron density studies on the C/Si analogues haloperidol/sila-haloperidol and venlafaxine/sila-venlafaxine.

The subjects of this study are the structures and electron densities of the carbon/silicon analogues haloperidol/sila-haloperidol (1a/1b) and venlafaxine/sila-venlafaxine (2a/2b). The parent carbon compounds 1a (an antipsychotic agent) and 2a (an antidepressant) are both in clinical use. For haloperidol/sila-haloperidol, three published structures were studied in more detail: the structures of haloperidol hydrochloride (1a·HCl), haloperidol hydropicrate (1a·HPic) and sila-haloperidol hydrochloride (1b·HCl).

Oxygen transfer from an intramolecularly coordinated diaryltellurium oxide to acetonitrile. Formation and combined AIM and ELI-D analysis of a novel diaryltellurium acetimidate.

The reaction of the intramolecularly coordinated diaryltellurium(IV) oxide (8-Me2NC10H6)2TeO with acetonitrile proceeds with oxygen transfer and gives rise to the formation of the novel zwitterionic diaryltelluronium(IV) acetimidate (8-Me2NC10H6)2TeNC(O)CH3 (1) in 57% yield. Hydrolysis of 1 with hydrochloric acid affords acetamide and the previously known diarylhydroxytelluronium(IV) chloride [(8-Me2NC10H6)2Te(OH)]Cl.

Electron densities of bexarotene and disila-bexarotene from invariom application: a comparative study.

By the application of the invariom formalism, which provides aspherical atomic scattering factors, the electron densities of the RXR-selective retinoid agonists bexarotene (1a) and disila-bexarotene (1b) were derived from their known low resolution (d = 0.76 Å) crystal structures. The density distributions allowed us to make a comparison of the electronic properties of these pharmacologically relevant compounds.

Electron density study of the anti-Alzheimer's disease drug donepezil from conventional x-ray data and invariom database application.

Background: The crystal structures of a very large number of compounds with biological relevance are known. Application of the invariom formalism provides the aspherical electron density distribution.

Results And Discussion: The electron density distribution of the anti-Alzheimer's disease drug donepezil was derived from its x-ray structure reported in the literature, using the invariom database.

Experimental electron density of sumanene, a bowl-shaped fullerene fragment; comparison with the related corannulene hydrocarbon.

The experimental electron density of sumanene, C(21)H(12), was extracted from a high resolution X-ray data set measured at 100 K and topologically analyzed. In addition to bond topological and atomic properties, information about the density distribution between adjacent molecules, which show close C···C approaches of ~3.4 Å within the columnar π-stacks in the crystal lattice, are discussed.

Experimental and theoretical electron-density study of three isoindole derivatives: topological and Hirshfeld surface analysis of weak intermolecular interactions.

A combined experimental and theoretical study of three isoindole derivatives was made on the basis of a topological analysis of their electron-density distributions. Experimental electron densities were determined from high-resolution X-ray diffraction data sets measured with synchrotron radiation at 100 K, whereas theoretical calculations were performed using DFT methods at the B3LYP\6-311++G(3df,3pd) level of approximation. Both experimental and theoretical models are in good agreement with each other.

Reactivity differences between α,β-unsaturated carbonyls and hydrazones investigated by experimental and theoretical electron density and electron localizability analyses.

It is still a challenge to predict a compound's reactivity from its ground-state electronic nature although Bader-type topological analyses of the electron density (ED) and electron localizability indicator (ELI) give detailed and useful information on electron concentration and electron-pair localization, respectively. Both ED and ELI can be obtained from theoretical calculations as well as high-resolution X-ray diffraction experiments. Besides ED and ELI descriptors, the delocalization index is used here; it is likewise derived from theoretical calculations as well as from experimental X-ray results, but in the latter case, demonstrated here for the first time.

Electron density of two bioactive oligocyclic indole and oxindole derivatives obtained from low-order X-ray data and invariom application.

For two indole and oxindole bioactive molecules, low-order room-temperature X-ray data were used to generate aspherical electron density (ED) distributions by application of the invariom formalism. An analysis of the ED using the quantum theory of atoms in molecules (QTAIM) was carried out, which allowed for quantitatively examining bond orders and charge separations in various parts of the molecules. The inspection of electrostatic potentials (ESPs) and Hirshfeld surfaces provided additional information on the intermolecular interactions.

Charge transfer via the dative N-B bond and dihydrogen contacts. Experimental and theoretical electron density studies of four deltahedral boranes.

In an approach combining high resolution X-ray diffraction at low temperatures with density functional calculations, two closo-borates, B12H12(2-) (1) and B10H10(2-) (2), and two arachno-boranes, B10H12L2 (L = amine (3) or acetonitrile (4)), are studied by means of Atoms In Molecules (AIM) theory and Electron Localizability Indicator (ELI-D). The charge transfer via the dative N-B bonds in the arachno-boranes and via dihydrogen contacts in the closo-borates is quantified. The dative N-B bond in 4 is significantly shorter and stronger than that in 3 and in small N-B Lewis acid base adducts from the literature.

Effect of electron-withdrawing substituents on the epoxide ring: an experimental and theoretical electron density analysis of a series of epoxide derivatives.

A series of acceptor-substituted epoxide derivatives is scrutinized by means of experimental and theoretical electron-density investigations. Due to the possibility of nucleophilic ring-opening, the epoxide ring is not only a very useful functional group in organic synthesis, but acceptor-substituted epoxides are valuable building blocks for the design of protease inhibitors. Therefore, the electron-density analysis in this work focuses on two main aspects that can contribute to rational drug design: (i) the quantification of the electron-withdrawing substituent effects on the epoxide ring and (ii) the intermolecular interactions involving the epoxide ring in combination with different substituents.

Real-space indicators for chemical bonding. Experimental and theoretical electron density studies of four deltahedral boranes.

In an approach combining high-resolution X-ray diffraction at low temperatures with density functional theory calculations, two closo-borates, B(12)H(12)(2-) (1) and B(10)H(10)(2-) (2), and two arachno-boranes, B(10)H(12)L(2) [L = amine (3) or acetonitrile (4)], were analyzed by means of the atoms-in-molecules (AIM) theory and electron localizability indicator (ELI-D). The two-electron three-center (2e3c) bonds of the borane cages are investigated with the focus on real-space indicators for chemical bonding and electron delocalization. In compound 2, only two of the three expected bond critical points (bcp's) are found.

Charge transfer via the dative N-B bond and dihydrogen contacts. Experimental and theoretical electron density studies of small Lewis acid-base adducts.

The electronic characteristics of the dative N−B bond in three Lewis acid−base adducts, hydrazine borane, hydrazine bisborane, and ammonia trifluoroborane, are analyzed by an approach combining experimental electron density determination with a broad variety of theoretical calculations. Special focus is directed to the weak dihydrogen contacts in hydrazine borane. The Atoms In Molecules partitioning scheme is complemented by additional methods like the Source Function, and the Electron Localizability Indicator.

A simple procedure for the derivation of electron density based surfaces of drug-receptor complexes from a combination of X-ray data and theoretical calculations.

To contribute to an understanding of biological recognition and interaction, an easy-to-use procedure was developed to generate and display molecular surfaces and selected electron density based surface properties. To overcome the present limitations to derive electron densities of macromolecules, the considered systems were reduced to appropriate substructures around the active centers. The combination of experimental X-ray structural information and aspherical atomic electron density data from theoretical calculations resulted in properties like the electrostatic potential and the Hirshfeld surface which allowed a study of electronic complementarity and the identification of sites and strengths of drug-receptor interactions.

How to easily replace the independent atom model - the example of bergenin, a potential anti-HIV agent of traditional Asian medicine.

Bergenin, which has been isolated from a variety of tropical plants, has several pharmacological applications in traditional Asian medicine. Its electron-density distribution was obtained from a room-temperature low-resolution X-ray data set measured with point detection making use of multipole populations from the invariom library. Two refinement models were considered.

Transferability and reproducibility in electron-density studies--bond-topological and atomic properties of tripeptides of the type L-alanyl-X-L-alanine.

In the last decade three different data bank approaches have been developed that are intended to make electron-density examinations of large biologically important molecules possible. They rely on Bader's concept of transferability of submolecular fragments with retention of their electronic properties. Therefore, elaborate studies on the quantification of transferability in experiment and theory are still very important.

Electron densities of three B12 vitamins.

The electron densities of the three natural B(12)-vitamins, two of them being essential cofactors for animal life, were determined in a procedure combining high-order X-ray data collection at low to very low temperatures with high-level density functional calculations. In a series of extensive experimental attempts, a high-order data set of adenosylcobalamin (AdoCbl) could be collected to a resolution of sin theta/lambda = 1.00 A(-1) at 25 K.

How to make the ionic Si-O bond more covalent and the Si-O-Si linkage a better acceptor for hydrogen bonding.

Variation of a bond angle can tune the reactivity of a chemical compound. To exemplify this concept, the nature of the siloxane linkage (Si-O-Si), the most abundant chemical bond in the earth's crust, was examined using theoretical calculations on the molecular model compounds H(3)SiOSiH(3), (H(3)Si)(2)OHOH, and (H(3)Si)(2)OHOSiH(3) and high-resolution synchrotron X-ray diffraction experiments on 5-dimethylhydroxysilyl-1,3-dihydro-1,1,3,3-tetramethyl-2,1,3-benzoxadisilole (1), a molecular compound that gives rise to the formation of very rare intermolecular hydrogen bonds between the silanol groups and the siloxane linkages. For theoretical calculations and experiment, electronic descriptors were derived from a topological analysis of the electron density (ED) distribution and the electron localization function (ELF).

N-Methyl-N-styrylcinnamamide (lansamide) from Clausena lansium in Vietnam.

The title compound, C(18)H(17)NO, was isolated from the seeds of Clausena lansium (wampee) (Rutaceae). The X-ray crystal structure analysis confirmed its chemical identity and revealed that it is solvent-free, in contrast to the previously reported monohydrate [Huang, Ou & Tang (2006 ▶). Acta Cryst.

A comparative study on the experimentally derived electron densities of three protease inhibitor model compounds.

In order to contribute to a rational design of optimised protease inhibitors which can covalently block the nucleophilic amino acids of the proteases' active sites, we have chosen three model compounds (aziridine , oxirane and acceptor-substituted olefin ) for the examination of their electron-density distribution. Therefore, high-resolution low temperature (9, 27 and 100 K) X-ray diffraction experiments on single-crystals were carried out with synchrotron and conventional X-radiation. It could be shown by the analysis of the electron density using mainly Bader's Theory of Atoms in Molecules, Volkov's EPMM method for interaction energies, electrostatic potentials and Gatti's Source Function that aziridine is most suitable for drug design in this field.