Crystal Structure Searching

Once a molecular geometry, or ensemble of conformers, has been produced, the central computational step involved in CSP is the generation of trial crystal structures (Fig. 5.1). The goal of crystal structure generation methods is to produce aU possible, physically reasonable arrangements of molecules in a translationaUy repeating arrangement. 

---

Yui, T, Taki, N., Sugiyama, J., and S. Hayashi. 2007. Exhaustive crystal structure search and crystal modeling of P-chitin. International Journal of Biological Macromolecules 40 336-344. 

The parameters defining the repulsion and dispersion non-bonded interactions for 4-aminobenzoic acid in the second paper were modified to use those of Williams, with a specific modification of the Williams carboxylic proton-pyridine nitrogen repulsion potential for the 4-aminobenzoic acid-2,2 -bipyridine co-crystal. Calculations now predicted that the P polymorph of 4-aminobenzoie aeid was 1.3 kcal moP more stable than the a polymorph, which was in much better accord with experiment. Crystal structure searching was performed for eo-crystals and for the single component crystals using Crystal Predictor.The search algorithm successfully found the experimental structures for the single component systems considered. 

W. Klyne and V. Prelog, Experimentia, 1960, XVI, 521-523. CERIUS2 User Manual CERIUS Version 3.1, Molecular Simulations , Cambridge, UK, Massachusetts USA, 1993. Crystal Structure Search and Retrieval Instruction Manual , SERC Daresbuty Laboratory, Wanington, England, 1984. 

It may be desirable to predict which crystal structure is most stable in order to predict the products formed under thermodynamic conditions. This is a very difficult task. As of yet, no completely automated way to try all possible crystal structures formed from a particular collection of elements (analogous to a molecular conformation search) has been devised. Even if such an effort were attempted, the amount of computer power necessary would be enormous. Such studies usually test a collection of likely structures, which is by no means infal-... 

In conclusion, it is likely that computational approaches for metabolism prediction will continue to be developed and integrated with other algorithms for pharmaceutical research and development, which may in turn ultimately aid in their more widespread use in both industry and academia. Such models may already be having some impact when integrated with bioanalytical approaches to narrow the search for possible metabolites that are experimentally observed. Software that can be updated by the user as new metabolism information becomes available would also be of further potential value. The held of metabolism prediction has therefore advanced rapidly over the past decade, and it will be important to maintain this momentum in the future as the hndings from crystal structures for many discrete metabolic enzymes are integrated with the diverse types of computational models already derived. 

An experimental study of barbituric acid found one new polymorph where molecules in the asymmetric unit adopted two different conformations [10]. The conformational aspect was investigated through the use of ab initio calculations, which permitted the deduction that the new form found would have a lower lattice energy than would the known form. It was also found that many hypothetical structures characterized by a variety of hydrogen-bonding structures were possible, and so the combined theoretical and experimental studies indicated that a search for additional polymorphs might yield new crystal structures. 

Nearly 50 crystal structure determinations of examples of 5 and 6 have now been determined and reveal that the geometry at the five-coordinate metal centres can be anywhere between square-pyramidal and trigonal bipyramidal (CSD search April 2008). For example, in [2,6-(ArN=CMe)2C5H3N]FeCl2 (5 Ar = 2,6-i-Pr2C6H3) a distorted square-pyramidal geometry at the metal is exhibited with the arylimino groups almost perpendicular to the plane of the bis(imino)pyridine backbone (Fig. 5) [5, 6], The overall result is that the metal centre is protected both above and below... 

Recent developments and prospects of these methods have been discussed in a chapter by Schneider et al. (2001). It was underlined that these methods are widely applied for the characterization of crystalline materials (phase identification, quantitative analysis, determination of structure imperfections, crystal structure determination and analysis of 3D microstructural properties). Phase identification was traditionally based on a comparison of observed data with interplanar spacings and relative intensities (d and T) listed for crystalline materials. More recent search-match procedures, based on digitized patterns, and Powder Diffraction File (International Centre for Diffraction Data, USA.) containing powder data for hundreds of thousands substances may result in a fast efficient qualitative analysis. The determination of the amounts of different phases present in a multi-component sample (quantitative analysis) is based on the so-called Rietveld method. Procedures for pattern indexing, structure solution and refinement of structure model are based on the same method. 

---