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Multipole Refinement (multipole + refinement)

Distribution by Scientific Domains

Chemistry	100%

Selected Abstracts

Validation of experimental charge densities: refinement of the macrolide antibiotic roxithromycin

ACTA CRYSTALLOGRAPHICA SECTION B, Issue 5 2010
J. J. Holstein
Multipole refinements of larger organic molecules have so far been limited to a few exceptional cases. We report an investigation of the detailed experimental electron-density distribution (EDD) of roxithromycin, a macrolide antibiotic consisting of 134 atoms. Although the experimental multipole refinement on high-resolution synchrotron data converged smoothly, validation of the electron density by calculation of an `experiment minus invariom' difference density revealed conformational disorder of the H atoms. Hydrogen disorder is shown to affect the EDD, the electrostatic potential and atomic properties as defined by Bader's quantum theory of atoms in molecules. A procedure to obtain the electron density distribution in the presence of disorder is proposed. [source]

On the effect of neglecting anharmonic nuclear motion in charge density studies

ACTA CRYSTALLOGRAPHICA SECTION A, Issue 3 2010
Kathrin Meindl
The effect of neglecting anharmonic nuclear motion when it is definitely present is studied. To ensure the presence of anharmonic nuclear motion a model was used that was previously refined against experimental data including anharmonic nuclear motion, and these calculated structure factors were used as observed data for a multipole refinement. It was then studied how the neglect of anharmonic nuclear motion and noise in the data affects the usual crystallographic quality measure R, the density parameters and the residual density distribution. It is demonstrated that the neglect of anharmonic nuclear motion leads to a characteristic imprint onto the residual density distribution in terms of residual density peaks and holes, in terms of the whole residual density distribution and in terms of the number, location and strength of valence shell charge concentrations (VSCCs). These VSCCs differ from that of the input model in a way which heavily influences and misleads the chemical interpretation of the charge density. This imprint vanishes after taking anharmonic nuclear motion into account. Also the input model VSCCs are restored. The importance of modeling anharmonic nuclear motion is furthermore shown by the characteristic imprint on the residual density distribution, even in the case of a numerically almost unaffected R value. [source]

Experimental charge-density study of paracetamol , multipole refinement in the presence of a disordered methyl group

ACTA CRYSTALLOGRAPHICA SECTION A, Issue 6 2009
Joanna M. B
A high-resolution single-crystal X-ray study of paracetamol has been performed at 85,K. Different approaches to modeling the experimental electron density (ED) were tested for the dynamically disordered portions of the molecule in order to check to what extent it is possible to obtain a proper ED distribution in the ordered part. Models were examined in which the methyl-group ED was built from pseudoatoms taken from the University at Buffalo Pseudoatom Databank or the Invariom database, with multipole parameters for the remaining atoms being obtained from free refinement. The ,, restricted multipolar model (KRMM) and free ,, refinements were compared; restriction of the ,, parameters was essential in order to obtain values of the electrostatic interaction energy consistent with the results of theoretical single-point periodic calculations. After simultaneous use of KRMM refinement and the databases to model the methyl group, the bond critical point properties and interaction electrostatic energy values were found to be closer to those obtained from theory. Additionally, some discrepancies in the ED distribution and dipole moment among transferred aspherical atom model refinements utilizing both theoretical databases and parameters from theoretical periodic calculations are shown. Including the influence of the crystal field in the periodic calculations increases the ED in the hydroxyl and amide groups, thus leading to higher values of the electrostatic interaction energy, changes in the electrostatic potential values mapped on the isodensity surface and changes in the shape of the anisotropic displacement parameters with respect to results found for both database models. [source]

Validation of experimental charge densities: refinement of the macrolide antibiotic roxithromycin

Accurate charge density of the tripeptide Ala-Pro-Ala with the maximum entropy method (MEM): influence of data resolution

ACTA CRYSTALLOGRAPHICA SECTION B, Issue 4 2007
Andreas Hofmann
The accurate electron density of Ala-Pro-Ala is determined by the maximum entropy method (MEM), employing the same reflection data measured at 100,K which was used for a multipole refinement by Kalinowski et al. [(2007), Acta Cryst. Accepted for publication]. Properties of the electron density are compared with the corresponding properties of the static electron density from the multipole model and to the dynamic MEM electron density of trialanine at 20,K. It is thus shown that the increased thermal smearing at 100,K leads to lower electron densities in the bond critical points and atomic charges closer to zero for Ala-Pro-Ala than has been obtained for trialanine at 20,K. The influence of the resolution of the data is investigated by a series of MEM calculations. Atomic charges and atomic volumes are found not to depend on the resolution, but the charge density in the BCPs decreases with decreasing resolution of the dataset. The origin of this dependence is found to lie mostly in the more accurate estimate of the atomic displacement parameters (ADPs) for the higher-resolution datasets. If these effects are taken into account, meaningful information on chemical bonding can be obtained with data at a resolution better than dmin = 0.63,Å. Alternatively, low-resolution X-ray diffraction data can be used in accurate electron-density studies by the MEM, if another source of accurate values of the ADPs is available, e.g. from refinements with multipole parameters from a database of transferable multipole parameters. [source]

Extracting charge density distributions from diffraction data: a model study on urea

ACTA CRYSTALLOGRAPHICA SECTION B, Issue 1 2000
R. Y. De Vries
The quality of the extraction of electron density distributions by means of a multipole refinement method is investigated. Structure factors of the urea crystal have been obtained from an electron density distribution (EDD) resulting from a density function calculation with the CRYSTAL95 package. To account for the thermal motion of the atoms, the stockholder-partioned densities of the atoms have been convoluted with thermal smearing functions, which were obtained from a neutron diffraction experiment. A POP multipole refinement yielded a good fit, R = 0.6%. This disagreement factor is based on magnitudes only. Comparison with the original structure factors gave a disagreement of 0.8% owing to differences in magnitude and phase. The fitted EDD still showed all the characteristics of the interaction density. After random errors corresponding to the experimental situation were added to the structure factors, the refinement was repeated. The fit was R = 1.1%. This time the resulting interaction density was heavily deformed. Repetition with another set of random errors from the same distribution yielded a widely different interaction density distribution. The conclusion is that interaction densities cannot be obtained from X-ray diffraction data on non-centrosymmetric crystals. [source]

Charge-density study on cyclosporine A

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2009
S. K. J. Johnas
Two single-crystal X-ray diffraction data sets of cyclosporine A were measured to high resolution using synchrotron radiation at temperatures of 5 and 90,K. They allowed an accurate determination of its molecular and electronic structure. Three electron-density models based on pseudoatom scattering factors were compared in terms of derived bond topological properties and in terms of electron-density differences on a grid. In one model multipole parameters were freely refined, whereas in the other two models the density was built up from fixed database parameters from the invariom database and University at Buffalo Databank. The data quality not only allowed benchmarking of the quality of both databases with the refined density, but also judgement of the feasibility of a multipole refinement of a larger oligopeptide structure such as cyclosporine A. Both databases performed equally well and reproduced the experimentally determined charge density satisfactorily. [source]

Hydrophobin HFBII in detail: ultrahigh-resolution structure at 0.75,Å

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2006
Markus Linder
Hydrophobins are small proteins secreted by filamentous fungi that have a unique ability to spontaneously form amphiphilic layers. Hydrophobins have only recently been structurally characterized through the first crystal structure determination of a protein of this class, Trichoderma reesei hydrophobin HFBII [Hakanpää, Paananen et al. (2004), J.,Biol.,Chem.279, 534,539]. The resolution of the HFBII structure has now been extended to an ultrahigh resolution of 0.75,Å. The structure was refined conventionally and multipole refinement has been initiated. The ultrahigh-resolution structure is analyzed here in detail and comparison is made to the previous atomic resolution structure of the same protein as well as to other ultrahigh-resolution structures found in the Protein Data Bank. [source]

Progress in the Understanding of Drug,Receptor Interactions, Part,2: Experimental and Theoretical Electrostatic Moments and Interaction Energies of an Angiotensin II Receptor Antagonist (C30H30N6O3S)

CHEMISTRY - A EUROPEAN JOURNAL, Issue 24 2007
Raffaella Soave Dr.
Abstract A combined experimental and theoretical charge density study of an angiotensin II receptor antagonist (1) is presented focusing on electrostatic properties such as atomic charges, molecular electric moments up to the fourth rank and energies of the intermolecular interactions, to gain an insight into the physical nature of the drug,receptor interaction. Electrostatic properties were derived from both the experimental electron density (multipole refinement of X-ray data collected at T=17,K) and the ab initio wavefunction (single molecule and fully periodic calculations at the DFT level). The relevance of S,,,O and S,,,N intramolecular interactions on the activity of 1 is highlighted by using both the crystal and gas-phase geometries and their electrostatic nature is documented by means of QTAIM atomic charges. The derived electrostatic properties are consistent with a nearly spherical electron density distribution, characterised by an intermingling of electropositive and -negative zones rather than by a unique electrophilic region opposed to a nucleophilic area. This makes the first molecular moment scarcely significant and ill-determined, whereas the second moment is large, significant and highly reliable. A comparison between experimental and theoretical components of the third electric moment shows a few discrepancies, whereas the agreement for the fourth electric moment is excellent. The most favourable intermolecular bond is show to be an NH,,,N hydrogen bond with an energy of about 50,kJ,mol,1. Key pharmacophoric features responsible for attractive electrostatic interactions include CH,,,X hydrogen bonds. It is shown that methyl and methylene groups, known to be essential for the biological activity of the drug, provide a significant energetic contribution to the total binding energy. Dispersive interactions are important at the thiophene and at both the phenyl fragments. The experimental estimates of the electrostatic contribution to the intermolecular interaction energies of six molecular pairs, obtained by a new model proposed by Spackman, predict the correct relative electrostatic energies with no exceptions. [source]

A standard local coordinate system for multipole refinements of the estrogen core structure

JOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 6 2003
Kristin Kirschbaum
A comparative charge density study on a series of estrogen derivatives has been initiated. The study utilizes the Hansen,Coppens atom-centred multipole model to describe the valence electron density distribution. Direct comparison of the population parameters for each estrogen after the respective multipole refinements requires standardization of the atom-centred local coordinate systems. Such a standard coordinate system for the common estrogen core is reported, taking advantage of the shape of those multipoles which have the spatial characteristics of sp2 and sp3 hybrid orbitals. Additionally, populating these principal multipoles at the beginning stage of the refinements improves the stability of these large highly correlated calculations. [source]