1,721,013 research outputs found
Comparative experimental electron density and electron localization function study of thymidine based on 20 K X-ray diffraction data
No full textFrom a high-resolution X-ray data set (sin theta/lambda = 1.1 A(-1)) measured at 20 K the electron-density distribution of the nucleoside thymidine was derived by a classical multipole refinement and by application of the invariom formalism. Owing to the presence of the heteroaromatic thymine ring system two invariom models were compared which considered the nearest and next-nearest neighbors for the invariom assignments. Differences between the two invariom models were small for the bond topological and atomic properties - about five times smaller than differences with the classical multipole refinement. Even the latter differences are in the uncertainty ranges which are commonly observed in experimental charge-density work and were found in molecular regions involved in intermolecular contacts. The application of the constrained wavefunction-fitting approach allowed the electron localization function (ELF) to be obtained from the experimental X-ray data, which was graphically represented and topologically analyzed. ELF basin populations were derived from experiment for the first time. The electron populations in the disynaptic valence basins were related quantitatively to bond orders
How to easily replace the independent atom model – the example of bergenin, a potential anti-HIV agent of traditional Asian medicine
No full textBergenin, 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. In a first step, positional parameters and ADPs were refined with fixed library multipoles (model E1). This model was suitable to be input into a second refinement of multipoles (model E2), which converged smoothly although based on Cu Kalpha room-temperature data. Quantitative results of a topological analysis of the electron density from both models were compared with Hartree-Fock and density-functional calculations. With respect to the independent atom model (IAM) more information can be extracted from invariom modelling, including the electrostatic potential and hydrogen-bond energies, which are highly useful, especially for biologically active compounds. The reliability of the applied invariom formalism was assessed by a comparison of bond-topological properties of sucrose, for which high-resolution multipole and invariom densities were available. Since a conventional X-ray diffraction experiment using basic equipment was combined with the easy-to-use invariom formalism, the procedure described here for bergenin illustrates how it can be routinely applied in pharmacological research
Electron density study of the anti-Alzheimer's disease drug donepezil from conventional x-ray data and invariom database application
No full textBackground: 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. The electrostatic potential mapped on the electron density isosurface shows how the positive charge of the donepezilium cation is distributed over a wide surface range. The presence of intermolecular contacts can be illustrated by the Hirshfeld surface. Comparable interactions are found in both the small-molecule structure and an acetylcholinesterase complex with donezepil from the literature. Conclusion: The electron density of donepezil in the small-molecule crystal structure mimics the intermolecular interactions within the receptor site. Complementing steric properties with electronic information can be a valuable procedure in the examination of molecular recognition of systems with biological activity.Deutsche Forschungsgemeinschaft [DI 921/3-1, Lu 222/29-2, 1178
Electron densities of bexarotene and disila-bexarotene from invariom application: a comparative study
No full textBy 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 angstrom) crystal structures. The density distributions allowed us to make a comparison of the electronic properties of these pharmacologically relevant compounds. Differences were found to be restricted to relatively small regions in the terminal six-membered rings of the tetrahydronaphthalene and tetrahydrodisilanaphthalene fragments. In total, the replacement of two carbon atoms in 1a by silicon atoms (-> 1b) does neither influence the electronic structures nor the pharmacological properties (RXR receptor activation) significantly. It should be noted that the almost completely software supported invariom formalism can yield electronic information for biologically interacting systems with moderate effort. This offers interesting possibilities for drug research, in that steric and electronic information can be combined for the analysis of intermolecular recognition and interaction on an atomic scale. This approach is also valuable for the design and development of silicon-containing drugs using the carbon/silicon switch strategy
Two modifications of L-alanyl-L-tyrosyl-L-alanine with the different solvent molecules in the crystal lattice
No full textThe low-temperature crystal and molecular structure analyses of two modi cations of L-alanyl-L-tyrosyl-l-alanine with water, C(15)H(21)N(3)O(5)(.)2.63H(2)O [(I), at 9 K], and ethanol, (C15H21N3O5C2H5O)-C-. [(II), at 20 K], solvent molecules in the crystal lattice show that the overall conformations of both modi cations of the title tripeptide are practically the same. Moreover, despite the presence of different solvent molecules in the crystal lattice, the specific intermolecular interactions characteristic for individual tripeptide molecules of (I) and (II) are conserved. The crystal packing of the two modi cations of Ala-Tyr-Ala differ from each other only in the solvent region. The tight arrangements of tripeptide molecules seem to be responsible for similar displacement parameters for all non-H atoms, despite the different distances from the molecular centre of mass. Comparison of the displacement parameters between the room- and low-temperature structures shows that an average U-eq value decrease of about 80% takes place at 9 K [for (I)] and 20 K [for (II)] with respect to room temperature
A Comparative Study on the Experimentally Derived Electron Densities of three Protease Inhibitor Model Compounds
No full textIn 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. A regioselective nucleophilic attack at carbon atom C1 could be predicted and even hints about the reaction's stereoselectivity could be obtained. Moreover, the comparison between two data sets of aziridine (conventional X-ray source vs. synchrotron radiation) gave an estimate concerning the reproducibility of the quantitative results
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Electron Densities of Three .Vitamins.
No full textThe 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 angstrom(-1) at 25 K. This modification contains only minor disorder at the solvent bulk. For methylcobalamin (MeCbl), only a severely disordered modification was found (sin theta/lambda = 1.00 angstrom(-1), 100 K, measured with synchrotron radiation). The already published data set of cyanocobalamin (CNCbl) (sin theta/lambda = 1.25 angstrom(-1), 100 K) was reintegrated to guarantee similar treatment of the three compounds and cut to sin theta/lambda = 1.11 angstrom(-1) to obtain a higher degree of completeness and redundancy. On the basis of these accurate experimental geometries of AdoCbl, MeCbl, and CNCbl, state-of-the-art density functional calculations, single-point calculations, and geometry optimizations were performed on model compounds at the BP86/TZVP level of theory to evaluate the electronic differences of the three compounds. AdoCbl and MeCbl are known to undergo different reaction paths in the body. Thus, the focus was directed toward the characterization of the dative Co-C-ax and Co-N-ax bonds, which were quantifed by topological parameters, including energy densities; the source function including local source; and the electron localizability indicator (ELI-D), respectively. The source function reveals the existence of delocalized interactions between the corrin macrocycle and the axial ligands. The ELI-D indicates unsaturated Co-C-ax bonding basins for the two biochemically active cofactors, but not for CNCbl, where a population of 2.2e is found. This may be related to significant pi-backbonding, which is supported by the delocalization index, delta, of 0.15 between the Co atom and the N atom of the cyano ligand. Considering all results, the inherent electronic differences between AdoCbl and MeCbl are found to be small thus, supporting earlier findings that the interaction with the protein site mainly controls the type of Co-C-ax bond cleavage.Deutsche Forschungsgemeinschaft (DFG) [222/29-2, SPP1178
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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