Cambridge Crystallographic Data Centre Archives 500,000th Crystal Structure.

 

The Cambridge Crystallographic Data Centre (CCDC) is proud to announce an important milestone in the history of crystallography - the archiving of the 500,000th small molecule crystal structure to the Cambridge Structural Database (CSD). This unique, scientifically rigorous database, built over 45 years, is the international de facto standard for small-molecule chemical structures and has become an essential resource to scientists around the world.


Professor Sir David King, former Chief Scientific Adviser to the UK Government, and Chairman of the CCDC Board of Governors 1998-2000, notes that "The timely development of CCDC and the Cambridge Structural Database from very humble beginnings 45 years ago to become the key global source for crystal structures makes a remarkable story. The user-friendliness and versatility of the database has become the major resource for the chemical and pharmaceutical industries, and in the process has transformed their capability".


The CSD System incorporates a suite of flexible search and analysis tools allowing chemical knowledge to be extracted from the raw crystallographic data. Information derived from small-molecule crystal structures is vital to structural chemistry research in its broadest sense, and in particular to pharmaceutical drug discovery, materials design, drug development and formulation. The database is also a rich resource for teachers and has application across the entire span of the chemistry curriculum. There are clear indications that this knowledge will be equally vital in the development of future materials, such as gas-storage systems, and will play a key role in the development of nano- and green-technologies.
Dr Colin Groom, Executive Director of the CCDC says that "the determination of 500,000 crystal structures is a remarkable achievement. However, the scientific community is hungry for the next 500,000 and the knowledge these will undoubtedly bring. As the CSD grows both in size and in the complexity of structures it contains, the database not only helps us to answer our questions about molecular structure and interactions, but tells us what those questions should be".

 

The CSD's 500,000th structure is the anti-convulsant drug Lamotrigine, published in Acta Crystallographica, C65, o460-o464, 2009, by Balasubramanian Sridhar and Krishnan Ravikumar of the Indian Institute of Chemical Technology in Hyderabad. The CSD reference code for the structure is EFEMUX01. Lamotrigine (Lamictal®) was discovered by GlaxoSmithKline and approved by the US FDA for the treatment of epilepsy in 1994 and additionally for the treatment of bipolar I disorder in 2003. Lamotrigine is chemically unrelated to other anticonvulsant or mood regulating medications, and is distinguished by its relatively benign side effects. It is frequently effective in patients who have not responded to antidepressants or other mood stabilisers. The CSD contains chemical structure information on several close variants of the compound, all of which, when used together, provide invaluable information to the life sciences community in their quest to optimise the efficacy of such medicines.


 

Fig. 1 Crystal structure of Lamotrigine (CSD reference code EFEMUX01). The structure can be viewed using WebCSD - the online search interface to the CSD at www.ccdc.cam.ac.uk/halfmillionthstructure

 

 

History of Crystallography and the Cambridge Structural Database


The development of X-ray crystallography has been rapid, and since the diffraction of X-rays by crystals was discovered by von Laue in 1912 the technique has attracted 24 Nobel Prizes. Indeed, crystal structure analysis is now central to modern chemistry - it is the method of choice for the characterisation of newly discovered compounds - and it is distinguished from other analytical methods by the sheer richness of the information that it provides: not only does it give the precise three-dimensional structure and geometry of individual molecules, but also vital information about how molecules interact with each other. In the words of Professor Chet Raymo in the Boston Globe, "Crystals are windows on the world of atoms".


While individual determinations of organics and metal-organics have value, taken collectively crystal structures provide knowledge that transcends individual results and is key to our understanding of chemical and biological processes. For this reason a high quality, fully curated database is a unique scientific resource. The CCDC began operations in 1965 with a brief to build the Cambridge Structural Database (CSD) - the worldwide repository of carbon-containing small-molecule crystal structures. One of the world's first numerical database systems, compilation of the CSD began with just a few hundred structures.


Today, the CCDC archives approximately 150 new experimentally determined structures each working day. Each structure is fully checked and validated by expert chemists and crystallographers, and entries are further enriched with valuable chemical data. As the world's output of crystal structures continues to accelerate, the CSD has doubled in size in the last 9 years and now contains a fully retrospective collection of half a million entries. Notable examples include the structures of amino-acids, steroids, alkaloids, antibiotics including penicillin, ferrocenes, fullerenes, catalysts, etc. Within this massive structural diversity, normal molecules are abundant and unusual molecules are commonplace.

 


About The Cambridge Crystallographic Data Centre


Originating in the Department of Chemistry at the University of Cambridge, and with UK Government funding principally from SERC (now EPSRC), the CCDC is now a fully independent institution constituted as a non-profit company and a registered charity since 1989. The CCDC is financially independent, through annual subscriptions received for CSD System access from academia and industry. The CCDC has a strong track record in basic research through more than 700 peer-reviewed publications, and these papers have attracted more than 18,000 citations in the international scientific literature. More than 1,500 CSD applications papers by non-CCDC authors have been similarly well received.
For more information, please contact:


Dr Gary M. Battle
The Cambridge Crystallographic Data Centre
12 Union Rd, Cambridge, CB2 1EX
Phone: +44 1223 336408
Email: b[email protected]
Web: www.ccdc.cam.ac.uk

 

 

Halfmill Structure Details

 

 The CSD's 500,000th structure is the anti-convulsant drug Lamotrigine, published in Acta Crystallographica, C65, o460-o464, 2009 by Balasubramanian Sridhar and Krishnan Ravikumar of the Indian Institute of Chemical Technology in Hyderabad. The CSD reference code for the structure is EFEMUX01.

 

Lamotrigine (Lamictal®) was discovered by GlaxoSmithKline and approved by the US FDA for the treatment of epilepsy in 1994 and additionally for the treatment of bipolar I disorder in 2003. Lamotrigine (I) is chemically unrelated to other anticonvulsant or mood regulating medications, and is distinguished by its relatively benign side effects. It is frequently effective in patients who have not responded to antidepressants or other mood stabilisers. The crystal structure of the methanol solvate of Lamotrigine (CSD refcode KADPAG) was reported by Janes et al., in Acta Cryst., C45, 129-132, 1989, and these authors also reported crystal data (EFEMUX) for a second form of the compound, possibly the parent molecule or another solvate. However, the current report by Sridhar and Ravikumar presents a different set of crystal data and a complete structure determination at R = 0.028. Their paper in Acta Cryst., C65, o460-o464, 2009 also reports the structures of two salts of lamotrigine: lamotriginium chloride and lamotriginium nitrate.

 

Other Lamotrigine structures available in the CSD are the monohydrate (XUVLOP: J.Mol.Struct., 570, 53-60, 2001), the 2-hydroxyethanesulfonic acid solvate (QEJHUI: J.Chem.Cryst., 29, 701-706, 1999), the dimethylformamide solvate (YERTAR: Acta Cryst., E62, o4752-o4754, 2006), the dimethylformamide solvates of the benzoate (GAVLEV: Acta Cryst., E61, o3805-o3807, 2005) and phthalate (YEXFUD: Mol.Cryst.Liq.Cryst., 461, 131-141, 2007).

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