www.ccdc.cam.ac.uk

The newsletter of The Cambridge Crystallographic Data Centre

CrystallineMay 2012

New CCDC Website Launchedinstallation and configuration issues thedatabase also features advice from ourapplications scientists on the most effectiveusage of our tools. As this database grows it willprovide an increasingly valuable resource forresolving specific issues as well as helping usersgain maximum benefit from their software.

In addition to this service and productinformation, a new blog provides insights intothe activities and personalities of the researchscientists, software developers and editorial staffwho comprise the CCDC. In fact, this blog is justpart of our recent efforts to better inform andinteract with our depositors and users. Forexample, you can now also follow us on twitter(@ccdc_cambridge) or Facebook(www.facebook.com/ccdc.cambridge), where wereport the very latest views, news anddevelopments.

The new CCDC website has been built using theMicrosoft SharePoint 2010 content managementsystem with a SQL Server database back-end. Aspecialist SharePoint developer was brought in-house to implement the website based on thewireframe designs produced by our graphicdesigners. A number of bespoke customisationswere applied in order for us to deliver the

features and user-experience our visitor’s desire.This technology is a huge departure from thatused by the previous generation website, whichwas built using the more traditional Apache/PHP platform.

One of the attractions of SharePoint was itsability to integrate efficiently with otherMicrosoft server technologies currently beingimplemented at the CCDC, including DynamicsCRM, which has been selected as the platformfor our new internal user relations managementsystem. Our ultimate goal is to provide aservice portal on our public website which willallow visitors to interact directly with theiraccounts and to manage their depositedstructures, subscriptions and software licenses.We believe SharePoint will provide thefoundations for developing these exciting newservices.

The views and opinions of our users are crucialas we continue to develop the website. Please letus know what you think by filling in ourfeedback form which is accessible from a link atthe top of every page.

Gary Battle, Marketing and CommunicationsManager

CCDC are excited to announce the beta launchof our new website, which went live on 25th

April, and is now available from the web addressbeta-www.ccdc.cam.ac.uk.

The new website is just part of our commitmentto provide our user communities with the mostaccurate and up-to-date service and productinformation. We also hope it will help strengthenresearch partner relations and allow us to sharemore effectively our knowledge and expertise inthe fields of structural chemistry andcrystallography.

Our solutions section contains detailedinformation about the products and services weoffer, whilst an interactive solutions matrixenables visitors to easily locate solutions basedon their area of science or specific applicationneed. The website also features new types of richcontent in the form of articles, case studies,videos, interviews, presentations and teachingresources. This material is hosted in a dedicatedresources section and can be queried based onscientific application, product, and resource type.

During the development of the site particularattention was given to the implementation of anew fully searchable support database. Inaddition to addressing a range of technical

1 The website offers a new layout and refreshed content to allow users to efficiently find the information they require. 2 Information on CCDCsoftware is integrated with links to case studies, documentation and support pages. 3 The new website covers the whole range of CCDC activities,from research initiatives to the latest news on upcoming software releases and conference visits. 4 The new support database enables users to quicklyfind assistance to their queries regarding CCDC software and services.

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Our stand at the recent Spring ACS in San Diego The terrace at the San Diego convention centre

Since the beginning of human history, we haveused plants and plant materials as a source offoodstuffs, dyes, cosmetics, medicines andmany other things. Scientists have found plantsto be a fertile source of many useful chemicalsand have sought to understand and developtheir actions to maximise the benefits. This hasled to a large number of naturally occurringcompounds being studied by X-raycrystallography and, therefore, being included inthe CSD.

www.ccdc.cam.ac.uk

CCDC has been workingwith Cambridge UniversityBotanic Garden to develop atrail to highlight some of thesecompounds and their sourceplants.

Each plant on the trail has aninformation board, containing details of the compound of interest and itsuses. The CSD entry can beaccessed directly (in WebCSD)via a Smartphone, using a QRcode. The trail can also befollowed virtually at www.bit.ly/CCDCTrail

In addition to textual information, thevirtual trail shows a 2D diagram and 3Drepresentation of the structure and linksto the entry in WebCSD.

Currently, the trail consists of 22 plantsincluding Feverfew (Tanacetum parthenium)which is a source of melatonin (CSD refcodeMELATN) which can be used to treat jetlag andcircadian rhythm sleep disorders and is involvedin the mechanism by which some reptiles andamphibians change colour. A more sinisterexample is scopolamine (CSD refcode JAYZEO,as the hydrobromide), from Henbane

(Hyoscyamus niger). This is a bitter tastingalkaloid with hallucinogenic properties. Itspresence in the plant deters grazers and it hasreputedly been used as a truth drug.

The trail is designed to appeal to all ages andto the non-scientist as well as scientists. Morecompounds will be added as the virtual trailcontinues to evolve.

Gwenda Kyd, Principal Scientific Editor

Date Conference, meeting or event Venue Activity

24-26 May 2012 Annual meeting of Pharmaceutical Kobe, Japan Exhibition and Talk

Science and Technology

10-15 June 2012 Gordon Research Conference on Crystal Engineering Waterville Valley, NH, USA Attendance and Talk

15-18 July 2012 SLA Annual Conference & INFO-EXPO Chicago, IL, USA Exhibition

28 July-1 August 2012 American Crystallographic Association 2012 Boston, MA, USA Exhibition and Talk

7-11 August 2012 European Crystallographic Meetings Bergen, Norway Exhibition

19-23 August 2012 American Chemical Society Philadelphia, PA, USA Attendance

20-23 August 2012 Chinese Crystallographic Association Meeting Beijing, China Workshop

Events Over the coming months you can come and meet us at various meetings and events around the world.

Educating a budding young crystallographer!

Up the Garden Path: A Chemical TrailThrough the Cambridge University Botanic Garden

www.ccdc.cam.ac.uk

a Consortium we will focus on providing toolsto help achieve this. The team here at CCDC isdelighted to be joined by Dr Neil Feeder,formerly of the Materials Science group atPfizer Global R&D who will bring highlyvaluable insight from the pharma industry tothe CCDC. We are looking forward to the nextphase of the Consortium and the puzzles andchallenges it will bring.

Elna Pidcock, Senior Research and ApplicationsScientist

few years ago the developmentsector of the agrochemical andpharmaceutical industries wasidentified as an area where an

expanded use of the CSD would be beneficial.The development sectors are fundamentalcogs in the “molecule to market” machineand they take the active molecule and turn itinto the saleable product – a tablet or asprayable herbicide for example.

Broadly speaking, this means taking the activeingredient and finding the “right form”; themost stable polymorph, the best salt, the mostappropriate coformer which turns that initialmaterial into a solid that has the right stability,the right bioavailability or efficacy, and theright processability. The chosen solid form thenhas to be formulated for delivery. Forpharmaceuticals that may involve ensuring thatthe active ingredient can be compressed fortableting without compromising any of therequired properties. For the agrochemicalindustries formulations are designed which caneasily transform a settled solid into a sprayablesuspension. These are complex problems andthe science and ingenuity employed by thechemists and engineers is impressive.

Very simplistically, many of the problems facedwhen turning the active ingredient into aproduct come down to how that moleculeinteracts with other molecules in the crystallineenvironment. Polymorphism for example is anexpression of the different ways a molecule caninteract with itself in a 3D lattice. Screeningsuccessfully for a new cocrystal can be targetedthrough consideration of how the activeingredient might interact with the coformers.

APreventing crystals fromgrowing into hard-to-process needles can beachieved by poisoning afast growing face with a“blocker” molecule. Wehave a database of smallmolecule crystal structures coveringmillions and millions of intermolecularinteractions, a resource that could beput to good use by those scientistsdeveloping active ingredients. We feltit was a good time to start to talk.

Through our involvement in the PfizerInstitute of Pharmaceutical MaterialsScience we have benefittedfrom the focus on real problemsthat Pfizer Global R&D brought toour software development. To expand onthis collaborative approach we established aCrystal Form Consortium in 2008 with 11industrial partners from around the world inthe agrochemical and pharmaceutical sectors.We held our first meeting in early 2009 andestablished our first software developmentgoal: to provide a tool to help with riskassessment for polymorphism. Three years laterwe have come to the end of the first phase ofthe Consortium and it has been enjoyable aswell as successful. We have built strong,trusting relationships with our Consortiummembers, we have delivered useful softwareand have received even more valuablefeedback. The second phase of the Consortium,will start later this year. There is a move awayfrom achieving quality through testing andtowards designing quality into the products. As

Although historically considered to be aspecialised research tool, the CambridgeStructural Database (CSD) System isfundamentally a library of accurate 3Dmolecular structures. As such, this uniquedatabase is finding increasing application as ageneral purpose chemical informationresource.

Currently, one of our biggest goals at theCCDC is to broaden the use of the CSD and

to make structures accessible andcomprehensible to all of our users, particularlyto students and teachers. We also have a roleto play in promoting scientific literacy and abroader understanding of structuralchemistry. In order to achieve these goals, wehave focussed our efforts on encouraging sitewide licensing and distribution of the CSD viauniversity libraries. Our intention is to enableteachers and students at all levels to fullyutilise this unique source of 3D structures.

Approximately 1200 academic institutionssupport the CSD through a licence, andincreasing numbers of these institutions arenow switching over to unlimited site-widelicensing (a 21.5% increase in the last yearalone).

WebCSD, the online search interface to thedatabase received over 25000 unique visitorsfrom the 1st April 2011 to the 31st March2012, an increase of 13% on the same perioda year earlier. Figure 1. Shows the

demographic breakdown of visitors at sitesbased in Illinois, to show how extensivelyWebCSD is being used. From the 1st April2011 to the 31st March 2012, we received1666 visits from 49 cities in this state.

The value of the CSD as a chemicalinformation resource has recently beenrecognised by the Chemistry Division of theSpecial Libraries Association and ACS Divisionof Chemical Information in their publication“Information Competencies for ChemistryUndergraduates: the elements of informationliteracy. 2nd ed. Sept 2011.”http://units.sla.org/division/dche/il/cheminfolit.pdf

The key information competencies outlined inthis publication encompass the skills andknowledge that undergraduates should haveby completion of a bachelor's degree inchemistry.

Gary Battle, Marketing and CommunicationsManager

The Developing Role of the CSD in Academia

Solid Form Informatics in the Front Line

the CCDC’s YouTube ChannelSpotlight

www.ccdc.cam.ac.uk

The CCDC team frequently publish results oftheir research, which is often the work ofcollaboration with industrial or academicscientists. You can find the full list of our publications atwww.ccdc.cam.ac.uk/publications.Here are our most recent titles, published sinceSince November 2011.Successful Prediction of a Model Pharmaceutical inthe Fifth Blind Test of Crystal Structure Prediction A. V. Kazantsev, P. G. Karamertzanis, C. S. Adjiman, C.C. Pantelides, S. L. Price, P. T. A. Galek, G. M. Day, andA. J. Cruz-Cabeza, Int. J. Pharm. (2011) 418, 168-178. 10.1016/j.ijpharm.2011.03.058

Teaching chemistry in 3D using crystal structuredata S. Henderson, G. M. Battle, F. H. Allen, Education inChemistry (2011) 48, 175-178.

Towards crystal structure prediction of complexorganic compounds – a report on the fifth blind test D. A. Bardwell, C. S. Adjiman, Y. A. Arnautova, E.Bartashevich, S. X. M. Boerrigter, D. E. Braun, A. J.Cruz-Cabeza, G. M. Day, R. G. Della Valle, G. R.Desiraju, B. P. van Eijck, J. C. Facelli, M. B. Ferraro, D.Grillo, M. Habgood, D. W. M. Hofmann, F. Hofmann,K. V. J. Jose, P. G. Karamertzanis, A. V. Kazantsev, J.Kendrick, L. N. Kuleshova, F. J. J. Leusen, A. V. Maleev, A. J. Misquitta, S. Mohamed, R. J. Needs, M. A.Neumann, D. Nikylov, A. M. Orendt, R. Pal, C. C.Pantelides, C. J. Pickard, L. S. Price, S. L. Price, H. A.Scheraga, J. van de Streek, T. S. Thakur, S. Tiwari, E.Venuti and I. K. Zhitkov, Acta Cryst. B (2011) 67,535-551. 10.1107/S0108768111042868

Data-Driven High-Throughput Prediction of the 3-DStructure of Small Molecules: Review and Progress. AResponse from The Cambridge Crystallographic DataCentre C. R. Groom, J. Chem. Inf. Model. (2011) 51,2787–2787. 10.1021/ci2002523

The Ensemble Performance Index: An ImprovedMeasure for Assessing Ensemble Pose PredictionPerformance O. Korb, P. McCabe, J. C. Cole, J. Chem. Inf. Model.(2011) 51, 2915–2919. 10.1021/ci2002796

Amplitude-phase calculations of Regge polesobtained from coupled radial Dirac equationsK.-E. Thylwe, P. McCabe, J. Phys. A: Math. Theor.(2011) 44, 275305. 10.1088/1751-8113/44/27/275305

Learning about Intermolecular Interactions from theCambridge Structural Database G. M. Battle, F. H. Allen, J. Chem. Ed. (2012) 89, 38-44. 10.1021/ed200139t

A study of dimethylsulfoxide solvates using theCambridge Structural Database (CSD) M. Brychczynska, R. J. Davey, E. Pidcock,CrystEngComm (2012) 14, 1479-1484.10.1039/C1CE05464C

The Cambridge Structural Database System and itsapplications in supramolecular chemistry andmaterials design F. H. Allen, J. A. Chisholm, P. A. Wood, P. T. A. Galek, L.Fábián, O. Korb, A. J. Cruz-Cabeza, J. W. Liebeschuetz,C. R. Groom, E. Pidcock, in ‘SupramolecularChemistry: From Molecules to Nanomaterials’ JohnWiley & Sons Ltd, Chichester, UK (2012) 2927-2946. 10.1002/9780470661345

One in half a million: a Solid Form Informatics studyof a pharmaceutical crystal structure P. T. A. Galek, E. Pidcock, P. A. Wood, I. J. Bruno, C. R.Groom, CrystEngComm (2012) 14, 2391-2403.10.1039/C2CE06362J

Isostructurality in Pharmaceutical Salts: How Oftenand How Similar? P. A. Wood, M. A. Oliveira, A. Zink, M. B. Hickey,CrystEngComm (2012) 14, 2413-2421.10.1039/C2CE06588F

Synthon preferences in cocrystals ofciscarboxamides:carboxylic acids A. M. Moragues-Bartolome, W. Jones, A. J. Cruz-Cabeza, CrystEngComm (2012) 14, 2552-2559.10.1039/C2CE06241K

The good, the bad and the twisted: A survey ofligand geometry in protein crystal structures J. W. Liebeschuetz, J. Hennemann, T. Olson, C. R. Groom,J. Comput. Aid. Mol. Des. (2012) 26, 169-183.10.1007/s10822-011-9538-6

Are Predefined Decoy Sets of Ligand Poses Able toQuantify Scoring Function Accuracy? O. Korb, T. ten Brink, F. R. Devadoss, M. Keil, T. Exner, J. Comput. Aid. Mol. Des. (2012) 26, 185-197. 10.1007/s10822-011-9539-5

Coupled radial Schrödinger equations written asDirac-type equations: application to an amplitude-phase approach K.-E. Thylwe, P. McCabe, J. Phys. A: Math. Theor.(2012) 45, 135302.

Geometry and conformation of cyclopropylderivatives having σ-acceptor and σ-donorsubsMtituents: a theoretical and crystal structuredatabase study A. J. Cruz-Cabeza, F. H. Allen, Acta Cryst. B (2012) 68,182-188. 10.1107/S0108768111054991

The Hydrogen Bond Environments of 1H-Tetrazoleand Tetrazolate Rings: The Structural Basis forTetrazole-Carboxylic Acid BioisosterismF. H. Allen, C. R. Groom, J. W. Liebeschuetz, D. A.Bardwell, T. S. G. Olsson, P. A. Wood, J. Chem. Inf.Model. (2012) 52, 857-866. 10.1021/ci200521k

How will I find you on YouTube?Just search for ccdccambridge and you’ll find us.Make sure you’re following us on Facebook andTwitter and that you subscribe to our channel tobe the first to know when a new video is posted!

Lauren Thomas, Account and Marketing Manager

Will they take me ages to watch?Whilst the webinars are around 30 minutes long,the “how-to” videos are only around 1 minutelong, and the demos are around 8 minutes onaverage.

Can I request a video on a specific subject?Of course! The purpose of our YouTube channel isto provide you with the material you want to see,and to help you understand how to make themost out of the product you’ve purchased. Youcould request demos and tutorials bycommenting on the current videos, emailingadmin@ccdc.cam.ac.uk or by getting in touch viaour Facebook page(www.facebook.com/ccdc.cambridge) or onTwitter (www.twitter.com/ccdc_cambridge).

Why does the CCDC have a YouTubeChannel?The CCDC has a global user base, and while wewould love to be able to give all of our users one-on-one training, with an institute of less than 50employees this is a big ask. So, we thought thatby having our own YouTube channel, we would beable to provide our users with webinars and“How-To” videos that would enhance their use ofour products, and enable them to get the best outof them.

What sort of videos will I find on there?So far we’ve posted webinars, teaching demos andhow-to videos using Mogul and Mercury, such as“How to visualise the void space of a functionalstructure in Mercury”, but we have plans to postmany more, covering our entire product base.

CCDC Publications Nov 2011 to May 2012

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