Report on the Industrial Group Sessions of  the 2010 Spring Meeting of the BCA

Anne Kavanagh (AstraZeneca), Brett Cooper (Merck), Cheryl Doherty (Pfizer), Matt Johnson (GSK)

The 2010 Spring meeting of the BCA was held at Warwick University and brought together over 270 delegates from across academia and industry for three days of thought and talk on the subject ‘Data Matters’.  The conference was organized with three simultaneous programs covering Biological, Chemical, Physical and Industrial Crystallography.  A Young Crystallographers satellite meeting was held prior to the main meeting, and fourteen or so YC’s gave talks on their research projects across a wide range of disciplines.  The following summarizes the sessions organized by the Industrial Group.

The IG organized four lecture sessions on the subjects of:  Data—what goes in; Data – what comes out, Complementary and non-ambient techniques, and Unpublished Data and Almighty Blunders.  The IG also held an Alun Bowen memorial lecture given by Dave Taylor, and a teaching plenary lecture, given by Simon Billinge. The IG session organizers would like to thank all our organizers for their contributions.

David Taylor (ICDD and Pilkington (retired)) gave the Alun Bowen Lecture, titled ‘Phase Identification – How it’s Changed Over the Years’.  Dave firstly paid tribute to Alun Bowen who, as Chair of the Industrial Group encouraged Dave’s involvement in the BCA.  In this fascinating talk, Dave described his career in industrial crystallography with Pilkington’s Glass, and the application of new crystallographic techniques, such as hot-stage XRD and X-Ray reflectivity in the glass industry.  In keeping with the conference theme, most of Dave’s talk described how the collection and sharing of data have developed over the years, from Roentgen’s discovery of X-Rays and the first commercially-available Debye-Scherrer cameras (1918).   Dave described the developments of the ‘Hanawalt’ search based on the three most intense d-spacings, using data stored as a card index (initially hand-written!) through to today’s ICDD database which contains over 700,000 datasets, includes organic and calculated powder data, and is expected to increase at 30,000 entries per annum.  Following Dave’s lecture, the ICDD held a hands-on workshop in which participants were introduced to phase identification of single components and complex mixtures using PDF-4.

David’s contribution to industrial crystallography and commitment to the BCA (including serving as Treasurer of the BCA and Chairman of the Industrial Group) have been recognized by the award of Honorary Membership of the BCA, which was presented to Dave by Elspeth Garman, President of the BCA, at the Conference Dinner.  

Elspeth Garman, President of the BCA, awards Honorary membership to Dave Taylor.

Simon Billinge (Michigan State University) gave the teaching plenary, ‘Structure at the Nanoscale: Atomic Pair Distribution Function Analysis of Nanostructured Materials’.  The teaching plenary is always an excellent opportunity to learn about new techniques, and this year was no exception.  Simon explained how Bragg peaks are blind to order on the nanoscale but that diffuse scatter can be used to probe the nanoscale.  In a delightful look back to some of the first diffraction data ever collected, Simon showed a page from the Bragg’s notebook (available on the website of Leeds University: http://www.leeds.ac.uk/library/spcoll/bragg-notebook/pdf.htm).  Information on short range structural order of a variety of materials was extracted using the pair distribution function (PDF), providing enough information to fingerprint, and in some cases determine, the local structure.  PDF has been applied to crystalline materials but also promises to be an invaluable tool for understanding the local structure of ‘X-Ray amorphous’ structures.  Case studies included characterising stacking faults and stress within CdSe ‘quantum dots’, structure determination of buckyball (C60), and domain size and characterization of amorphous carbamazepine.  PDF is a technique that can be run on synchrotron or lab sources, and is steadily moving from its academic origins into industrial applications.

Matt Johnson (GSK) chaired the session ‘Data: What goes in’ in which three speakers shared their wealth of knowledge on the collection of high quality diffraction data.  Ross Harrington (Newcastle University) spoke on ‘Getting the Best Possible Data from Your Crystals’, giving a guide on what to look for in crystals before, during and after X-Ray analysis. The basic subjects, such as what a suitable crystal looks like, choice of radiation, and dealing with twinned data sets and other common problems were covered.  Ross gave many tips on single crystal analysis such as: leave your solution NMR samples at the back of the fume hood, and see if anything crystallises, keep single crystals in the growth medium until just before mounting, trust the data not the molecular structure supplied with the sample, sanity check the unit cell against known structures, and use your chemical knowledge, as well as crystallography.  And finally, a tip echoed by a later speaker: maintain your diffractometer well!

Sarah Barnett (Diamond Light Source) then gave a ‘Rough Guide to Synchrotron Diffraction’, explaining the advantages of using the I19 beamline, rather than a lab diffractometer for small molecule single crystal diffraction.  The synchrotron’s higher flux and tuneable energies make for high speed data collection even when the crystals are small or of poor quality.  The impact on the data is higher resolution combined with rapid data collection.  A further benefit of the synchrotron is the robots that can be used to mount and align crystals efficiently. Sarah advised future users of Diamond on how to make the best use of their beam time by preparation beforehand (possibly in consultation with Diamond staff) and monitoring the storage ring status during data collection.

The final speaker in this session was Alastair Florence (University of Strathclyde) who spoke about ‘XRPD Data in Physical Form Identification and Structure Determination’.  Alastair began by discussing the importance of physical forms to the pharmaceutical industry and the role XRPD plays in this.  He set out his thoughts on maximizing the chances of success when using XRPD for fingerprinting, phase identification and structure determination.  He recommended checking the calibration of the diffractometer using an in-house standard over a variety of angles, as well as the common industry standards, grinding the sample lightly before analysis (a drawback of high throughput screens being the lack of opportunity to grind the samples) and careful sample mounting and alignment in order to get the best possible data.  Alastair explained the data collection process for structure determination and presented examples of solving structures using the DASH software.  His results showed that although the crystal structure obtained was often close to the actual structure, it was not always as accurate as we would like.  He then demonstrated how software tools such as Mogul can improve the accuracy by using CSD data to generate probability distributions for bond angles, lengths and torsion angles and applying constraints based on these distributions.

Brett Cooper (MSD) and Cheryl Doherty (Pfizer) were co-chairs of the next session, Data: What Comes Out.  Trevor Rayment (Diamond) gave an overview of the capabilities of the Diamond synchrotron, ‘Food, Formulation, Foams and Fabrication – Modern Applications of Synchrotron Radiation for Industry’. Trevor introduced synchrotron radiation as an essential tool for scientific research in the 21^st century.  He gave as an example the massive increase in the number of biological structures deposited in the databases, thanks to the use of synchrotron radiation. Trevor is keen to enable industrial use of the synchrotron, and emphasized that the synchrotron is ready for use, that waiting times are short, data acquisition is rapid, and technical support and advice are available.  Trevor also described some recent developments at Diamond including real-time analysis of samples using the Pilatus detector, and the use of remote control operation.

The second talk of the session was presented by Robert Hammond (University of Leeds). His talk was entitled ‘A Molecular-Scale Perspective: New Insights into the Assembly of Crystalline Particles’.  Robert started by discussing the drive to understand materials properties, and that it is possible to apply molecular modelling techniques with inputs from crystallography to achieve this. He introduced the use of a molecular mechanics approach to model the critical clusters of the growth phase in nucleation. He then showed that it is possible to use these techniques to further explore the intermolecular interactions of pre-nucleation clusters with a variety of different solvents.

The third and forth talks of the session were the winner and the runner up of the Industrial Group Prize awarded to the best Industrial Relevant Presentations from the Young Crystallographers Meeting held prior to the main meeting. 

The winner of the prize was Mark Eddlestone (University of Cambridge), for his talk, ‘Analysing Pharmaceutical Materials by Transmission Electron Microscopy (TEM)’.  Mark introduced the technique of TEM and highlighted some of the issues including the difficulties involved in sample preparation and stability in the electron beam.  He went on to describe how the technique could be applied to the analysis of pharmaceuticals including obtaining information on morphology, phase ID as well as crystal structure and defects.  He described how individual crystals could be examined and phase determined with a possible application to patent infringement cases.

The runner up of the Industrial Group prize was Jonathan Foster (University of Durham) with his talk, ‘Supramolecular Gels; a New Medium for Crystal Growth’.  Jonathan described a new range of bis-urea gel forming agents that could be used as a medium to grow crystals in.  He described the advantages conferred by growing crystals in the gels: by slowing down crystal growth it may be possible to form  the thermodynamically stable form, in contrast to rapid growth in other media, in which a thermodynamically metastable form may predominate.  The gel structures can easily be broken up by the addition of a gel disrupting agent such as a simple anion.  Once disrupted the crystals could then easily be recovered by filtration and could be used for single crystal studies.  By varying the type of gel formers and the solvents it may be possible to grow a variety of crystalline phases. 

The session on ‘Complementary and non-Ambient Techniques’ was chaired by David Beveridge (Harman Ltd).