Crystal structure prediction applications

Abstract Methods, evolutionary and systematic search approaches, and applications of crystal structure prediction of closest-packed and framework materials are reviewed. Strategies include developing better cost functions, used to assess the quality of the candidate structures that are generated, and ways to reduce the set of candidate structures to be assessed. The crystallographic coordinates for new materials, available only as a powder sample, are often intractable from diffraction data alone. In recent years, steady progress has been made in the ability to solve previously unknown crystal structures of such compounds, the generation of known structures (inferring more confidence in such approaches) and the prediction of hypothetical yet-to-be-synthesised structures. 

The lattice energy based on the Born model of a crystal is still frequently used in simulations [14]. Applications include defect formation and migration in ionic solids [44,45],phase transitions [46,47] and, in particular, crystal structure prediction whether in a systematic way [38] or from a SA or GA approach [ 1,48]. For modelling closest-packed ionic structures with interatomic force fields, typically only the total lattice energy (per unit cell) created by the two body potential,... 

C.M. Freeman, Inorganic Crystal-Structure Prediction Using Simplified Potentials and Experimental Unit Cells - Application to the Polymorphs of Titanium-Dioxide. J. Mater. Chem., 1993, 3, 531-535. 

The aim of this chapter is to give a brief description of the methods currently used for the ab initio prediction of crystal structures, to provide an examination of the reliability of these methods and to show how such in silico examinations of crystal packing can complement experimental studies in developing our understanding of the crystal packing of small organic molecules. The examples of applications are taken from pharmaceutical materials science, which is one of the main industrial interests in crystal structure prediction. 

While much of the development of methods has necessarily focussed on the simplest small, rigid molecules, the focus of recent crystal structure prediction studies has noticeably shifted to more complex molecular systems. This shift in the nature of targets for structure prediction somewhat reflects the feeling that, for small rigid molecules, current methods are already useful and, while they still require further refinement, there is a pressing need to extend the applicability of what has been learnt from rigid molecules to more general, flexible molecules. 

Computational assessment of the likelihoods of occurrence and the relative stabilities of polymorphs is not necessarily more effective than the experimental approach. Whilst great advances have been made in the field of ab initio crystal structure prediction (CSP), as documented in five international blind tests spanning the years 1999-2010 [5], it is still not routinely possible to predict whether a molecule is likely to be polymorphic or to confirm whether the most thermodynamically stable structure has been found experimentally, especially for molecules of the complexity of a typical drug. It is possible to compute the polymorph landscape for a specific flexible molecule, but the calculations require considerable expertise, and the timescales and computing resources can render CSP impractical for application to even a limited portfolio of candidate APIs. 

ADVANCES IN CRYSTAL STRUCTURE PREDICTION AND APPLICATIONS TO PHARMACEUTICAL MATERIALS... 

I thank all of my colleagues who have contributed to the development and application of methods used in crystal structure prediction and the Royal Society for current funding of a University Research Fellowship. 

Cocrystals Synthesis, Structure, and Applications Crystal Structure Prediction Noncovalent Interactions in Crystais X-Ray Diffraction Addressing Structural Complexity in Supramolecular Chemistry... 

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