Electron Distribution in a Stable Carbene

For the first time neutron diffraction, X-ray diffraction and EXAFS data have been combined simultaneously using the RMC method to model the fast-ion conducting glass, (AgI)x(AgPO3)1−x. This material is of considerable technological and scientific interest due to its high ionic conductivity at ambient temperature. We present some details of the RMC technique and highlight some of the structural information obtained from our models. The origin of the “first sharp diffraction peak” in the neutron diffraction data is explained, about which there has been considerable speculation. Diffusion pathways for ionic conduction are observed. A simple analysis of available free volume shows that a percolation transition in the ionic conductivity occurs between x=0.2 and 0.3, in agreement with a prediction based on conductivity measurements. This study highlights the considerable power that these developments of the RMC method have for the structural modelling of complex amorphous materials.

Hydrogen atoms play key roles in enzyme mechanism, but as this study shows, even high-quality X-ray data to a resolution of 1 A cannot directly visualize them. Neutron diffraction, however, can locate deuterium atoms even at resolutions around 2 A. Both neutron and X-ray diffraction data have been used to investigate the transition state of the aspartic proteinase endothiapepsin. The different techniques reveal a different part of the story, revealing the clearest picture yet of the catalytic mechanism by which the enzyme operates. Room temperature neutron and X-ray diffraction data were used in a newly developed joint refinement software package to visualize deuterium atoms within the active site of the enzyme when a gem-diol transition state analogue inhibitor is bound at the active site. These data were also used to estimate their individual occupancy, while analysis of the differences between the bond lengths of the catalytic aspartates was performed using atomic resolution X-ray data. The two methods are in agreement on the protonation state of the active site with a transition state analogue inhibitor bound confirming the catalytic mechanism at which the enzyme operates.

We present a detailed and comprehensive structural study of molecular models of liquid methanol, ethanol, and 1-propanol that originate from a series of reverse Monte Carlo (RMC), molecular dynamics (MD), and united-atom Monte Carlo (UA:MC) simulations. We compare several modeling approaches: RMC simulations that employ experimental neutron and X-ray diffraction data as sole constraints, RMC with diffraction data complemented with partial radial distribution functions (PRDFs) from MD or UA:MC, and conventional MD and UA:MC simulations. The assessment is done in view of the structural parameters of the hydrogen bond and resulting morphological characteristics of molecular aggregates. To achieve these tasks, a computer program for structural analysis of molecular configurations together with the appropriate aggregate classification scheme has been developed. We have analyzed the morphology of clusters, their probability, and size distributions. Any cyclic structures that appeared in the configurations were extracted and characterized in the same manner. We found that MD and UA:MC simulations resulted in configurations with bulkier, more threadlike aggregates that were not entirely consistent with the experimental evidence from diffraction experiments. A combination of neutron and X-ray diffraction data with PRDFs from MD simulations, simultaneously applied as constraints in the RMC procedure, proved to be a modeling approach with the most conclusive results.

Difficulties encountered in modelling the scattering of fluorine in organic compounds have been investigated through refinements of accurate X-ray and neutron diffraction data measured on tetrafluoroterephthalonitrile, TFT, at 122.4 K. Multipole refinements led to a highly contracted octopole on fluorine. The subsequent analysis revealed that fluorine does not possess a valence octopole but exhibits anharmonic thermal motion that can be modelled by the octopole multipole parameters. The scattering contribution from the octopole shows the same cubic dependence in the scattering vector as the Gram-Charlier expansion of the nuclear displacements to third order. The analysis also showed that refinement of third-order Gram-Charlier coefficients on fluorine requires data to at least 0.93 A(-1) resolution in sinthetas/lambda. The X-ray data extending to 1.27 A(-1) were of sufficient resolution to include third-order Gram-Charlier coefficients for N, F and the cyano C atoms in the refinement, whereas the neutron data only enabled refinement of the third-order Gram-Charlier coefficients for nitrogen. The refinements of the neutron and X-ray diffraction data yielded identical atomic displacement parameters for all the atoms. Though inclusion of anharmonic motion for N and F atoms provides the best model, it does not affect the crystal electron density, and all intramolecular bond critical points have identical features. Application of the anharmonic model, however, leads to small differences in the intermolecular interactions, which is illustrated by the electrostatic potential adjacent to the N atom. The characteristics of the C-F bond were elucidated by the topological analysis of the crystal electron density, which also supported the proposed quinonoid structure of the benzene ring.

In this paper, the charge flipping method is proposed for ab initio structure determination using neutron diffraction data alone. For this purpose, a new variant of the dual-space iterative algorithm is introduced, which is called band flipping. Unlike the basic algorithm, it reverses the sign of scattering density only within a zero-centred band, develops large plateaus without forcing positivity, and often leads to Babinet solutions. Its phasing power was tested on two organic structures. These behave similarly when using X-ray diffraction data and the basic algorithm but, with neutron data and band flipping, their solution becomes orders-of-magnitude more difficult and strongly dependent on the hydrogen content. Surprisingly, when the constraint of positivity is added, convergence speeds up to the point where structure determination using neutron diffraction data is not more difficult than the X-ray case. However, by following the evolution of the R factor, such a solution can be easily missed, and band flipping must be used both as a probe of convergence and as a tool for developing negative densities. Apart from demonstrating the feasibility of charge flipping for ab initio neutron crystallography, the present study also leads to an important byproduct: the type of traps that occasionally block the iterative process are identified and a mathematical analysis of their origin is given.

A neutron-diffraction study of Fe 0.84Mn 7.16O 10Cl 3: Refinement of the nuclear structure and determination of the magnetic structure

The crystal structure of stoichiometric BaVS3 at room temperature, 100, 60 and 5K has been refined by the total profile analysis based on powder neutron diffraction data. The structural refinement at 100 K is consistent with the model that the driving mechanism for the 240 K transition is the freezing of the dynamical distortion and the static ordering of the V sublattice. The generalised R factor (Hamilton test) indicates that the space group for the phase stable between 240 and 80 K is Cmc21. The structural refinement of the 60 K data shows that the 80 K transition is not accompanied by an additional structural distortion. This means that the transition is not of Peierls type. The electron transfer model proposed by Massenet et al (1980) can explain all the physical properties of the phase stable between 80 and 31 K. The structural refinement of the 5 K data shows that the phase stable between 31 and 5 K has still the Cmc21 space symmetry. No reflections of magnetic origin have been observed at 5 K. This indicates that the magnetic ordering, observed for about half of the V sites at the 31 K transition by inelastic neutron scattering experiments, is not long range. The driving mechanism for the 31 K transition is not yet understood. The disproportionation of the V4+ cations into V3+ and V5+ would explain all the physical properties of the phase stable between 31 and 5 K; however, such a model is unlikely from the crystal chemical point of view. The NMR data of Nishihara and Takano (1981) indicating the presence at 1.3 K of two crystallographically independent V sites are reconciled with the neutron and X-ray diffraction data by assuming that either a fourth transition exists between 5 and 1.3 K or at the 31 K transition the space group changes from Cmc21 to Pmc21.

Cyclodextrins (CD's) have proved useful as model systems for the study of hydrogen bonding. They are torus-shaped molecules composed of six(alpha), seven(beta) or eight(gamma) (1----4) linked glucoses. Because of their particular geometry, they are able to act as a "host" to form inclusion complexes with "guest" molecules very much like enzymes. Cyclodextrins have been shown to exert catalytic activity on suitable included-substrate molecules; they catalyze the hydrolysis of phenylacetates, of organic pyrophosphates and of penicillin derivatives. They also accelerate aromatic chlorinations and diazo coupling by means of their primary and/or secondary hydroxyl groups, so that the rates of hydrolysis are enhanced by up to a factor of 400. In order to understand the hydrogen bonding in these enzyme models, neutron diffraction data were collected to unambiguously determine the hydrogen atom positions, which could not be done from the x-ray diffraction data. alpha-CD has been shown to have two different structures with well-defined hydrogen bonds, one "tense" and the other "relaxed". An "induced-fit"-like mechanism for alpha-CD complex formation has been proposed. Circular hydrogen bond networks have also been found for alpha-CD due to the energetically favored cooperative effect. beta-CD with a disordered water structure possesses an unusual flip-flop hydrogen bonding system of the type O-H...H-O representing an equilibrium between two states: O-H...O in equilibrium O...H-O. gamma-CD with a disordered water structure similar to beta-CD also possesses the flip-flop hydrogen bond. This study demonstrates that hydrogen bonds are operative in disordered systems and display dynamics even in the solid state.

Gaining an understanding of the protein-ligand complex structure along with the proper protonation and explicit solvent effects can be important in obtaining meaningful results in structure-guided drug discovery and structure-based drug discovery. Unfortunately, protonation and tautomerism are difficult to establish with conventional methods because of difficulties in the experimental detection of H atoms owing to the well known limitations of X-ray crystallography. In the present work, it is demonstrated that semiempirical, quantum-mechanics-based macromolecular crystallographic refinement is sensitive to the choice of a protonation-state/tautomer form of ligands and residues, and can therefore be used to explore potential states. A novel scoring method, called XModeScore, is described which enumerates the possible protomeric/tautomeric modes, refines each mode against X-ray diffraction data with the semiempirical quantum-mechanics (PM6) Hamiltonian and scores each mode using a combination of energetic strain (or ligand strain) and rigorous statistical analysis of the difference electron-density distribution. It is shown that using XModeScore it is possible to consistently distinguish the correct bound protomeric/tautomeric modes based on routine X-ray data, even at lower resolutions of around 3 Å. These X-ray results are compared with the results obtained from much more expensive and laborious neutron diffraction studies for three different examples: tautomerism in the acetazolamide ligand of human carbonic anhydrase II (PDB entries 3hs4 and 4k0s), tautomerism in the 8HX ligand of urate oxidase (PDB entries 4n9s and 4n9m) and the protonation states of the catalytic aspartic acid found within the active site of an aspartic protease (PDB entry 2jjj). In each case, XModeScore applied to the X-ray diffraction data is able to determine the correct protonation state as defined by the neutron diffraction data. The impact of QM-based refinement versus conventional refinement on XModeScore is also discussed.

Accurate structure of LiAlD4 studied by combined powder neutron and X-ray diffraction

The XCW method is a relatively new technique for analysing Xray diffraction experiments [1-5]. Rather than using the more common pseudo-atom expansion of the electron density [6], the X-ray diffraction data are introduced directly into the calculation of the quantum mechanical molecular wave function in such a way that the wave function is constrained to reproduce the X-ray data, at the expense of the smallest possible change in the quantum mechanical energy. The XCW method has been applied to a number of smallmolecule organic crystals [2-4] showing, for example, that the constrained wave functions could model the effects of higher level calculations, simply by including experimental data or that the effects of the crystal lattice could be incorporated [2]and that a number of derived properties, such as electrostatic potentials and multipole moments could be obtained [3-4]. In order to address the limitations of the XCW method as compared to other forms of analysis of the electron distribution in crystals, like the pseudo-atom model, and to extend the application of the XCW method to more complex systems for which ab-initio calculations cannot be expect to give very accurate results (e.g. for proteins), synchrotron and neutron diffraction data have been measured on the model dipeptide Glycyl-L-Alanine at multiple-temperatures in the range 10 to 295K. The multi-temperature data were used in a molecular Einstein model [5] to get a more complete description of the thermal motion in the crystal and to recover information on the atomic correlation of motion. These latter were then included in the XCW fitting procedure to see their influence on the predicted structure factors and on the derived electronic properties. The neutron data where essential to evaluate the contribution of the motion of the hydrogen atoms to the final XCWderived electron density.

RMC: modelling neutron diffraction, X-ray diffraction and EXAFS data simultaneously for amorphous materials

The polycrystalline spinel oxides NiX Co1-X Fe2O4 with composition x = 0.0, 0.2, 0.4, 0.6, 0.8 and 1.0 were prepared by conventional solid state ceramic sintering technique in air at 1300°C. X-ray diffraction experiments were carried out on all the samples at room temperature in order to characterize the materials. X-ray diffraction patterns showed sharp peaks indicating the formation of single phase cubic spinel structure. The neutron diffraction experiments were performed on all samples at room temperature, with an incident monochromatic neutron beam of wavelength λ = 1.5656 &Aring. The experimental neutron diffraction data were analyzed using the computer program FullProf in the Reitveld method. Reitveld refinement of the neutron diffraction data reveals that the samples possess cubic symmetry corresponding to the space group F d-3m. Cation distribution between the two sublattices of the spinel structure has been found from the analysis of the neutron diffraction data. Lattice parameters, oxygen position parameters, and overall temperature factors have also been determined from the analysis of neutron diffraction data. The lattice parameter decreases and oxygen position parameter increases with increasing Ni content in the system. Sublattices and net magnetic moments have been determined from the refinement of neutron diffraction data. The magnetic structure at room temperature was found to be ferrimagnetic for all the samples.

We have investigated the crystal structure of Ca(BD4)2 by combined synchrotron radiation X-ray powder diffraction, neutron powder diffraction, and ab initio calculations. Ca(BD4)2 shows a variety of structures depending on the synthesis and temperature of the samples. An unknown tetragonal crystal of Ca(BD4)2, the beta phase has been solved from diffraction data measured at 480 K on a sample synthesized by solid-gas mechanochemical reaction by using MgB2 as starting material. Above 400 K, this sample has the particularity to be almost completely into the beta phase of Ca(BD4)2. Seven tetragonal structure candidates gave similar fit of the experimental data. However, combined experimental and ab initio calculations have shown that the best description of the structure is with the space group P4(2)/m based on appropriate size/geometry of the (BD4)tetrahedra, the lowest calculated formation energy, and real positive vibrational energy, indicating a stable structure. At room temperature, this sample consists mainly of the previously reported alpha phase with space group Fddd. In the diffraction data, we have identified weak peaks of a hitherto unsolved structure of an orthorombic gamma phase of Ca(BD4)2. To properly fit the diffraction data used to solve and refine the structure of the beta phase, a preliminary structural model of the gamma phase was used. A second set of diffraction data on a sample synthesized by wet chemical method, where the gamma phase is present in significant amount, allowed us to index this phase and determine the preliminary model with space group Pbca. Ab initio calculations provide formation energies of the alpha phase and beta phase of the same order of magnitude (delta H < or = 0.15 eV). This indicates the possibility of coexistence of these phases at the same thermodynamical conditions.

Structure refinement of triclinic tungsten trioxide