|
Crystal structures describe the periodically repeating arrangement of
molecules in a material and determine many of a material�s properties,
such as solubility, dissolution rate, hardness, colour and external
shape. The ability to predict crystal structures could revolutionise
the design of materials with novel properties.
In particular, the pharmaceutical industry would benefit from reliable
methods of crystal structure prediction because pharmaceutical
molecules are prone to crystallise in more than one crystal structure
(or polymorph), depending on the conditions under which the molecule
is crystallised. The specific polymorph that goes into a formulation
must be strictly controlled to ensure consistency of delivery to the
patient.
Dr John Kendrick, Senior Researcher at the Institute of Pharmaceutical
Innovation at the University of Bradford, said: �We are tremendously
excited about this result. The success of our approach begins to
answer many questions which have been posed over the years, and opens
up several new avenues for leading-edge research.
�Having proven that the crystal structures of small organic compounds
can be predicted reliably, we now face the challenge of predicting the
relative stability of polymorphs as a function of crystallisation
conditions to really capture the effect of temperature and solvent.�
The team applied a new computer program, GRACE, recently developed by
Avant-garde Materials Simulation, and predicted the crystal structures
of all four test compounds correctly. Their results are a significant
improvement over the outcome of previous Blind Tests. The other 14
participants in the event, which included ETH Z�rich (Switzerland),
the Pfizer Institute at Cambridge University (UK), University College
London (UK), Cornell University (USA) and Purdue University (USA),
correctly predicted none, one or two of the crystal structures.
Many approaches to the problem have been developed and these have been
evaluated over the years in the Blind Tests. Fifteen research groups
who had been developing methods for predicting crystal structures of
organic molecules in the latest test were challenged to predict four
recently determined crystal structures given only the chemical diagram
of the molecules and conditions of crystallisation, with three
predictions allowed per crystal.
The results of previous blind tests, in 1999, 2001 and 2004,
demonstrated that the crystal structures of small organic molecules
are hard to predict, The rates of success were low and no one method
was consistently successful over the range of types of molecules
studied.
Dr Graeme Day of the University of Cambridge, who co-ordinated this
year�s challenge, said: �The results of this year�s test reflect
significant development over the past few years. Things looked much
less encouraging last time we held a blind test, but crystal structure
prediction can now be seen as a real tool to be used alongside
experimental studies, when designing new materials or developing a
pharmaceutical molecule.�
Dr Marcus Neumann, author of computer program GRACE for crystal
structure prediction, said: �Obviously we are delighted with these
results but there is still plenty of room for improvements. Over the
next few years the range of applicability will gradually extend
towards more and more complex compounds such as highly flexible
molecules, solvates and salts.�
|
