|
|---|
| IG Home | Newsletters | Group Meetings | Administration | Industrial Applications | Hints & Tips | Group Information | Site Map |
|
|---|
Reports - Spring Meeting, Lancaster 4th to 6th April 2006
The Industrial Group award to Paul Fewster is reported elsewhere... Phase Identification Modular Workshop.
The modular structure and informal approach of the workshop allowed conference delegates to come to the sessions that best met their requirements. Between ~10 and ~30 people attended each session. There was plenty of opportunity to question the experts both during and after the presentations. David Rendle, a volunteer editor with ICDD with years of experience in the metropolitan police forensic science lab, led a session on the History and Structure of the ICDD Powder Diffraction File, from its inception very early in the history of XRD, to the present. The first set of hand-written cards was produced in 1941, with Set 3 in 1949 comprising ~2500 patterns. Today, nearly half a million patterns are available on electronic media, covering both experimental and calculated patterns. Information is gathered from all over the world and carefully reviewed before publication. The session on Phase Identification was led by David Taylor, currently ICDD volunteer treasurer and BCA IG web editor. Considerations for good measurements were discussed (such as scan parameters and instrument settings) and an understanding of the instrumental errors and effects different properties of the sample can have on the results, e.g. if it is textured or stressed. Sample preparation methods to minimise induced texture and stress were mentioned, and the usefulness of certified NIST Standard Reference Materials for characterising the instrument and providing an internal reference in a scan. Building on David's introduction of the main methods for identifying phases (alphabetic searches, Hanawalt, Fink and Long8) John Faber of ICDD gave more detail in his Advanced session, with explanation and discussion regarding quantification of phases within a specimen. The importance of applying all knowledge about a sample in order to obtain the most robust conclusions was brought out, e.g. any information from other measurement techniques, its physical properties (e.g. colour, density) and its history. The use of reference scans, concentration curves and internal standards are important for the most precise analyses, together with thorough understanding of instrumental and sample effects on the data, and at what level these need to be taken into account. Gather good evidence and argument in order to be sure of your conclusions. As ever, GIGO applies. The last workshop was a hands-on computer session with PDF4+, DDView+ and SIeve+ software from ICDD. Many thanks to the IT staff at Lancaster who prepared PCs in a suite so that each delegate could use the software. This was valuable experience, especially with expert guidance and the opportunity to ask questions throughout. We were working through standard examples which are usually used with a reduced PDF set. As such, some of the matches came out differently from the text-book answers - different card numbers for similar material. I was about to be concerned about this, but different cards for the same type of material can reflect for example the effects of different methods of sample preparation or the data quality, and do not necessarily mean that I've got the answer "wrong"! Tamzin Lafford 
Neutron & Synchrotron Opportunities for Industrial User.
Alan Hewat (ILL)* described the High Flux Neutron Diffractometers at ILL Grenoble. The ILL, a CCLRC laboratory, is open to all UK scientists provided that the work they do is published. The following instruments at the ILL are about to come on line again after an eight month period of refurbishment. A call is presently out for new research proposals before an August 2006 deadline. The following equipment is available on the high flux beam lines from the ILL reactor: SALSA (1), a neutron strain scanner capable of determining strains in industrial components weighing up to 0.5 tonne. Work on this is supported by the FaME38 industrial support laboratory (2). The super-D2B detector (3) which yields very high resolution neutron powder patterns in much less than an hour per temperature step.The D20 high flux powder diffractometer (4) which can collect complete diffraction patterns at 1-10 Hz thus enabling chemical kinetic studies to be carried out. Its rate of data acquisition is comparable with a synchrotron. The D20 can be used for example to examine ordering in metal oxides, and the detailed structure of fullerene based structures. Explosive reactions such as that between Ti, Si and C can also be studied at 300msec intervals. Its furnace can reach 2200 degrees Celsius, whilst 100kbar pressures can be applied during experiments. The new position sensitive detector on D19 (5) greatly accelerates data collection on organic fibres and protein single crystals. VIVALDI (6), a neutron image plate Laue camera can collect complete diffraction patterns from small single crystals in 30 minutes. DRACULA (7) is an order of magnitude faster than D20, and can be used similarly. CYCLOPS (8) (CYlindrical Ccd Laue Optics Photo-Scintillator will provide real time diffraction patterns covering 70% of 4pi in sub-second read-out time. All these instruments are designed to optimise the use of a continuous neutron source, and to complement new machines on pulsed neutron sources e.g. IBIS, which offer different advantages. * Diffraction Group, Institut Laue-Langevin, B.P. 156X Grenoble Cedax 9, FRANCE.
Andrew Jupe (Georgia Institute of Technology, USA) spoke on In situ synchrotron diffraction for studying oil well cement hydration at elevated temperatures and pressures in real time. He described the advantages of X-ray diffraction�using a synchrotron, and how he had applied them to the hydration of Portland cements�at both elevated temperatures and pressures. The experimental conditions used were based on the environments encountered in an oil well where Portland cement is used as a grout between the bore of the oil well and its steel liner. The cement mix is forced down the well using pressures of several kilobars�whilst the ambient (geothermal) temperature can reach 250 degrees Celsius. Five unambiguously identified Bragg reflections at high d-spacings were used to monitor the evolution of the five phases which occur in the final product cement. These phases�crystallise from the calcium hydroxide and amorphous calcium silicate hydrate�phases which are formed initially. It was shown that the presence of tartaric acid appears to influence the formation of aluminosilicate gels in the mixture; whilst pressure�had a strong influence on the beneficial formation of tobermorayite which is formed when silica flour and zeolite are added to the initial mix. Stephen Thompson (Diamond Light Source Ltd) gave an Update on powder diffraction on Diamond. This facility is planned to be operational in August 2008. The high flux available will enable high user throughput as�well as very high rates of data acquisition. Data will be collected�using X-rays with wavelengths between 0.4 and 2.5 Angstroms. The user hutch will be 9m by 4m in size, with user and preparation laboratories on hand. A double bounce X-ray mirror will be used, with Si, Rh and Pt strips to avoid the presence of harmonics in�the beam. The size of the X-ray beam will be 15 X 2 mm at 5kV�and 6 X 1 mm at 20kV. Particular design efforts have been made to provide a user friendly facility, which will avoid the need for the user to optimise the experimental conditions as well as minimising the time spend on user��training.���� Ian Ferguson
Crystallisation and Polymorphism of Pharmaceuticals
The Alun Bowen Lecture was given by Ulrich Griesser (University of Innsbruck), who discussed polymorphism in drug development (more than half the drugs in the European Pharmacopia) are listed as forming polymorphs or hydrates/solvates). His lecture illustrated how thermal microscopy can be used to understand this phenomenon and to determine the relationships between different forms. For instance, solid-solid transformations can be readily detected in the hot-stage microscope, but difficult to detect by DSC. In addition, crystallisations on the hot-stage microscope can be used to generate polymorphs which might be difficult or even impossible to achieve via crystallisation: this can be done by sublimation from a heated microscope slide onto the cover slip and by crystallisation from the melt followed by thermal cycling. The session on Crystallisation and Polymorphism of Pharmaceuticals opened with Roger Davey (University of Manchester), who considered nucleation from solution, and how it affects the outcome of crystallisation. There is a growing belief (based on computer simulation and some experimental evidence) that on nucleation an amorphous short-lived entity is formed. In another case (tetrolic acid) there is a direct relationship between self-assembly in solution and the H-bonding motifs in the resulting crystals. He considered mandelic acid, and the formation of the racemic compound versus the formation of a conglomerate. It was not possible to crystallise the conglomerate in preference to the compound from a racemic solution (even when seeded with the conglomerate). But if the solution contained an enantiomeric excess, and suitable additives were used, then it was possible to achieve enantiomeric enrichment in the crystals. Sally Price (UCL) talked about progress and problems in crystal structure prediction. She described success in the prediction of the crystal structure of planar molecules, such as 3-oxauracil. Difficulties arise when predicted energy landscapes have many polymorphs with very close energy minima, and also noted that kinetic factors might prevent nucleation or growth of some structures. A further difficulty arises from the fact that many compounds of practical interest, such as pharmaceuticals, are floppy and hence may adopt different conformations in different solid forms. Combining crystal structure prediction with experimental work was used in an automated polymorph screen of carbamazepine: the six known forms were found, along with three solvates. However, a polymorph with a chain motif, that was predicted, was not found experimentally. It was found that the polymorphic form was dependant on the crystallisation protocol rather than on the solvent. Terry Threlfall (University of Southampton) gave a personal overview of crystallisation and polymorphism studies. He advised that practical choices, such as container fabric, storage time, separation and drying regimes could all affect the polymorph obtained, as well as the more obvious variables. The chances of obtaining a novel form are maximised when crystallisation occurs in confined spaces, such as a capillary, hanging drop or emulsion, since the mother liquor is rapidly depleted once crystallisation occurs. His cautionary tales included how a previously unknown but thermodynamically stable form of the drug Ritanovir, appeared once the drug was on the market. The stable form was templated by the presence of an impurity, and its appearance required a total reformulation of the medicine to accommodate it. Terry left us with one last thought: that in isolation, the least useful piece of information you can have about a polymorph is its crystal structure. The last talk was given by Caroline Day, of GSK, on polymorph screening by automated techniques. Pharmaceutical companies need to make a suitable choice of solid form (i.e. the right salt and polymorph) fairly early in the development of a drug, so as to minimise the chances of nasty surprises and expensive changes later on. However, in early development the quantity of drug available is quite low, and as development progresses, the proportion of drug candidates that fail (for instance, due to toxicity) is very high. Caroline described how early development screens use automated crystallisation and analysis where possible; experimental variables include crystallisation method, solvent, temperature, supersaturation and slurries to identify the stable form. In addition, the design of the crystallising vessel, including the choice of material, is very important in firstly maximising the chances of obtaining a solid, and then being able to analyse that solid in-situ, by XRPD and/or Raman. Anne Kavanagh A bursary report on this session was published in Crystallography News No 97 June 2006. Crystal Structure and Growth at the Nano-Scale
How Crystals Are Born: Novel Insight from Small-Angle Scattering. In principle, the events that eventually lead to nucleation and growth of crystals from solutions or amorphous solids must involve density fluctuations at the nano-scale. This is the natural domain of small-angle scattering. The most general, direct observable is the specific inner surface, which is related to size and volume fraction of the fluctuations. The question is whether present X-ray techniques are sufficiently sensitive to detect the relevant pre-nucleation events. The lifetimes of these fluctuations are generally in the sub-microsecond range and their abundance at any instant, and the density differences between amorphous and nascent crystalline state, are extremely small. Technical innovations in small-and wide-angle scattering, mainly concerning the brilliance of X-ray sources (synchrotrons), refined X-ray optics with low background, and efficient detectors have opened this field for new experiments. Basically, three types of experiments can be distinguished: (a) observation of the equilibrium fluctuations at p, t, c - conditions below the thermodynamic transition boundary, (b) steady-state, real-time observation of fluctuations during slow-scan conditions, and (c) rapid jump-relaxation experiments. While (a) and (b) can be performed with advanced laboratory X-ray equipment, (c) essentially requires the brilliance of synchrotron facilities. Experiments were presented on crystallizing systems from solution, from amorphous solids, and from liquid-crystalline phase transitions. In his first example of mechanisms of crystallisation, Peter described glycine where concentration fluctuations lead to liquid-like clusters, which lead to the formation of nuclei and growth. This was measured using time resolved SAXS experiments at the synchrotron facility at Trieste. The use of the Guinier Radius and Porod exponent to calculate the fractal dimension was described. The fractal dimension changes with time, RG changes from 3.4 - 4.2 Å but there are doubts about its validity since the size scales are very small. In the laboratory, work on glycine using SWAX utilised experiments whereby solutions of glycine were pumped through a capillary and super-saturation was created by cooling. However, the results were disappointing as the interesting phenomena occurs at time spans shorter than 3 minutes. In his second experiment CdS and ZnS formation was monitored by SAXS but the size vs. time data did not fit the Oswald Ripening Equations (d3 vs. t). The third example discussed crystallisation from amorphous solids, specifically the transition from amorphous sucrose to crystalline sucrose - the SAXS intensity decreases due to the condensation of a porous solid to a dense solid, later WAXS intensity increases due to nucleation within the dense solid. Overall, the results demonstrated that SAXS/SWAXS is a powerful laboratory based analytical tool for the study of the mechanisms of crystallisation. However, depending on relaxation times, and hence the distance to equilibrium, these alternative approaches (SAXS/SWAXS vs. Synchrotron) could result in different data, i.e. the structural pathways to equilibrium can differ for the same initial and final states. Solution Phase Nucleation: Cluster Size and Shape and its
Correlation with Kinetics and Polymorph Selection. Kevin introduced the importance of surface crystallography in nano-crystals. This is not usually considered, as one is usually looking at large crystals where surfaces are not important. It is essential to be able to predict crystal morphology and to do this Kevin described a software suite - POLYPACK that can define a polyhedron and pack it with molecules. With such a model one can predict crystallinity, RDF, geometric scaling and calculate equivalent diameters surface area and volume. Kevin presented examples of aspirin, glutamic acid - a and � forms and d-mannitol and described the dependency of stability on size and nucleation rates vs. cluster sizes and asked the question; which polymorph do we want linked to nucleation? To decide this his team modelled small crystalline structures using XRD and the Polypack program. Cluster energy calculations yield lattice minimisation values for e.g. glutamic acid clusters 300-0 molecules. Crossover instability at ~50 molecules. Does this link to Oswald's Rule? Looking at spherical clusters - there is no crossover, the overall effect is due to shape and size, mannitol only crosses over when minimized and with benzophenone there is no cross over but convergence Does this mean that at small sizes all these clusters have essentially the same energies? Molecular confirmations become more restricted as clusters get larger. In conclusion; nano-cluster energies depend upon size. Polymorph stability is influenced by structure and shape. Small clusters have big spread of conformations. Overall trying to understand crystallography of nano-crystals at the post nucleation stage of crystallisation. Metal Nanocrystallites in Supercritical Fluids
The Solvation Process and Its Impact on the Nanostructure In investigating the effects of solvation and passivation on the equilibrium structure of metal nanoclusters dissolved in supercritical fluids, we have performed Molecular Dynamics simulations of bare and passivated 38-atom gold nanoparticle in ethane at several isotherms in the supercritical regime. The bare nanoparticle is found to be appreciably solvated with the solvation layer comprised of two regions: the inner region, located next to the cluster surface, making a dominant contribution to the degree of solvation, and the outer region making a relatively small contribution. The solvation gives rise to large distortion of the in-vacuum, minimum-energy, truncated octahedral structure of the particle, due essentially to the strong the solvent/metal atom interactions present in the solvated core.
The mode of solvation of the passivated particle is one of loose dispersion of the solvating molecules in the passivating layer. The access of the solvent molecules to the core surface is now greatly reduced due to steric hindrance presented by the sulphur atoms chemically bond to the core. Here also the core structure suffers a very large deviation from the minimum-energy nanocrystalline structure, which may be ascribed to the extraneous stresses imposed on the core by the S-Au bonds as well as by the interchain interactions in the passivating layer.
The main conclusion is that the truncated octahedral structure of the core is greatly distorted by the solvation and the passivation processes. Quantifying Solubility Enhancement due to Particle Size Reduction
and Crystal Habit Modification: Case Study of Acetyl Salicylic Acid.
The poor solubility potential drug molecules is one of the major problems facing pharmaceutical scientists. It is well known, however, that the solubility of crystalline materials is enhanced with the reduction of particle size to sub micron levels. One of the problems with this reduction in particle size is the availability of interfacial tension data. This can be expected to vary with both solvent and crystal surface orientation (hkl). This study presented a quantitative approach to interfacial tension considering such factors as molecular and surface chemistry. Surface molecular modelling was used to calculate the specific surface energies of different (hkl) faces of aspirin (acetyl salicylic acid) as a difference of the surface vacuum energy and surface solvent binding energy. The solvent binding energies were found using systematic search methods combined with solvent molecule docking on crystal surfaces. Using the modelled interfacial energies, the solubility enhancement as a function of the reduction of particle size was calculated as a function of growth morphologies for aspirin and solvent composition. Richard Morris Powder Diffraction in Industry Speakers - Left to Right: Martin Gill, David Beveridge, Judith Shackleton, Chris Staddon, Mary Vickers, Andrew Hodge, Paul Fewster. The citation for the Industrial Group award to Paul Fewster is reported with photographs elsewhere... The session started on time, after a short lunch. Judith Shackleton (chair) introduced Jeremy Cockroft who gave a brief introduction and awarded the Industrial Group prize to Professor Paul Fewster, in recognition for his sustained contribution to industrial crystallography including crystallographic and diffraction work in industry of all kinds. The award lecture was titled It's all in the detail. Paul initially talked about his previous jobs and the instruments they had to use thirty years ago, and how the technology has moved on since. A critical step had been interfacing of various pieces of apparatus to cheap PCs, "running in the face of management policy who preferred 'more standard' computer suppliers of the time". His work involved looking at superlattice structures, and the interfacial chemistry of Ga complexes. The accuracies of the structures were then analysed using the dynamical theory and reciprocal space mapping to see whether the materials would be suitable to make superconductor devices. These devices could be used as quantum dots (semiconductor nanocrystals) and then made into fibre optics for faster internet connections. Paul also included some work with a laboratory X-ray source on protein crystal perfection. He finished his talk with the analysis of polycrystalline thin film materials. The second speaker of the session was Dr. David Beveridge, and his talk was on The precipitation of pigment red 57:1 from homogenous solution for X-ray powder diffraction. David described the synthesis that was involved in producing the pillar box red pigment. The morphological properties of the pigment looked more crystalline than expected. So, with the help of powder diffraction, it was confirmed that the pigment was indeed crystalline. The red pigment is mainly used for colouring oil-soluble products such as Make-up, powders, lipsticks and foundation creams. Before the session break, Dr. Mary Vickers gave a lecture on X-ray diffraction at Materials Science, Cambridge. Mary talked about the typical samples that are analysed using powder diffraction such as metals, ceramics, and carbon nanotubes. She mentioned the Rietvield refinement and the quantitative phase analyses and cell parameters in steel. Mary has also carried out experiments using Small Angle X-ray Scattering (SAXS) on thin film materials like polyurethane, which is medically important in replacing discs in the human spinal cord. Staying on the topic, Mary highlighted the weakness of SAXS when it comes to identifying water molecules in cellulose fibres. The talk ended with a nice discussion on how students can be encouraged to learn more about X-ray diffraction. Helal Ahmed After the break: Chris Staddon - University of Nottingham Examples were given of how the Crystal quality of the semi-conductors could be measured and how the fractions of hexagonal and cubic phases can be determined. For ferromagnetic semiconductors where the Electron spin (magnetic properties) are important , Chris described how the Mn sustitutional concentration can be distinguished from the interstitials by measuring the Peak shift on annealing (lattice parameters changing due to diffusion of the interstitials) More sophisticated supperlatices were also described where a more complicated fringing pattern due to the multilayer interference was described. The layer thicknesses and concentration of the components can be determined by modelling the diffraction pattern with commercial EPITAXY software. Chris then finished by showing some recent results of Reciprocal space maps of InGaAs on GaAs where the layer is being used to strain the magnetic layer to produce a magnetic moment perpendicular to the plane for easier magnetic read write devices. Andrew Hodge - BP Andrew explained about the development of XRD at BP and its applications in catalyst development, refining and marketing (engine deposits), and mineral semiquantitative analysis for exploration. A potted background to BP was given as context to several moves of
equipment, and Andrew is now the sole person performing XRD in BP. Martin Gill, Imperial College Martin gave us a nice slide show of his travels in India and also talked about the perils of not getting analysis before you stick your million quid black & decker into the ground…… Loosing drill strings is very expensive
|
Industrial Group of the BCA
