Validation of a search technique for crystal structure prediction of flexible molecules by application to piracetam.
A new approach to the crystal structure prediction of flexible molecules is presented. It is applied to piracetam, whose conformational polymorphs exhibit a variety of hydrogen-bond motifs but lack the intramolecular hydrogen bond found in the gas-phase ab initio optimized conformer. Stable crystal packing can result when favourable intermolecular interactions are made possible when the molecule distorts from the gas-phase conformation. If the resulting intermolecular lattice energy is sufficiently favourable to compensate for the intramolecular energy penalty associated with the suboptimal gas-phase conformation, then the crystal structure may be experimentally feasible. The new approach involves searching for low-energy crystal structures using a large number of rigid conformers, firstly to systematically explore which regions of conformational space could give rise to low-energy hydrogen-bonded crystal structures, and then to refine the search using crystallographic insight to optimize particular intermolecular interactions. The timely discovery of a new polymorph (form IV) by an independent experimental team allowed this approach to be validated by way of a ;blind test' of crystal structure prediction. Form IV was successfully identified as the most favourable computed crystal structure with a conformation very distinct from that in the previously known polymorphs.
Nowell
Harriott
H
Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, England.
Price
Sarah L
SL
D002621:Chemistry / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D010889:Piracetam / Q000737:chemistry*; D011312:Pressure
D010889:Piracetam