Molecular crystals structure predictions

Table 11.3 Sensitivity of molecular crystal structure predictions to the electrostatic model. 

Further improvements in our model potentials and simulation methods will therefore undoubtedly increase the detailed accuracy of molecular crystal structure predictions and will be required for crystal structures that correspond to weakly defined minima. However, for a routine transferable scheme, the addition of a realistic ab initio based electrostatic model clearly improves the range of molecules where a minimum in the lattice energy is close to the observed structure. The use of a theoretically derived, rather than an empirical potential, also increases confidence in the extrapolation of the potential to regions sampled in hypothetical crystal structures. 

There have been significant recent advances in both the model potentials that can be used in molecular crystal structure prediction and new methods of searching for hypothetical structures. We may expect that these will come together over the next decade, so that the prediction of a molecular crystal structure from first principles becomes possible. This should lead to an understanding of polymorphism. 

O Keeffe M, Hyde BG (1985) An Alternative Approach to Non-Molecular Crystal Structures with Emphasis on the Arrangements of Cations. 61 77-144 O Keeffe M (1989) The Prediction and Interpretation of Bond Lengths in Crystals. 71 161-190... 

Gao, D. and Williams, D. E. (1999). Molecular packing groups and ab initio crystal structure prediction. Acta Cryst. A55, 621-7. 

The statistical thermodynamic method discussed here provides a bridge between the molecular crystal structures of Chapter 2 and the macroscopic thermodynamic properties of Chapter 4. It also affords a comprehensive means of correlation and prediction of all of the hydrate equilibrium regions of the phase diagram, without separate prediction schemes for two-, three-, and four-phase regions, inhibition, and so forth as in Chapter 4. However, for a qualitative understanding of trends and an approximation (or a check) of prediction schemes in this chapter, the previous chapter is a valuable tool. 

A supramolecular synthon represents a reproducible, frequently occurring kind of non-covalent interaction found in molecular crystal structures. It has predictive power and may be used in crystal design. Supramolecular synthons are distinct from tectons, the molecules or the building blocks of the crystal. 

When applying a SA approach to crystal structure prediction, a Metropolis Monte Carlo scheme [20], rather than molecular dynamics [28], is usually chosen to sample the configurational space (different possible candidate structures). In practice, this scheme proceeds by comparing the quality (value of the cost function) of a new candidate structure with the current candidate structure. The new candidate is either rejected or used to replace the current candidate struc-... 

However, crystal engineering did not become synonymous with supramolecular synthesis until die 1990s. As noted by J. S. Maddox in 19883 and more recendy by Gavezzotd17 and Ball,18 crystal structure prediction remains in its infancy. However, prediction is fundamentally very different from engineering and design. Predicting a crystal structure requires an analysis of the recognition features present in the molecular component in such... 

Gdanitz, R. J. (1992). Prediction of molecular crystal structures by Monte Carlo simulated annealing without reference to diffraction data. Chem. Phys. Fett, 190, 391-6. [185]... 

Gdanitz, R. J. (1998). Ab initio prediction of molecular crystal structure. Curr. Opin. Solid State Mater. ScL, 3,414-18. [182, 185]... 

R693 Y, Tozuka, Is Crystal Structure Predictable even when a Single Crystal is Not Available , Farumashia, 2000, 36, 995 R694 K. Tsuji, Studies in Organic-Functionalized Molecular Sieves (OFMSs) , Zeoraito, 2000,17, 162... 

Since many critical physical and mechanical properties of pharmaceutical compounds are in large part dependent on crystal form, accurate prediction of crystal structure would be a highly valued tool in the pharmaceutical industry. Unfortunately, to date, reliable crystal structure prediction is only feasible for rigid, low molecular weight molecules, which do not represent the size and flexibility of pharmaceutical molecules. 

The type of model potential that is sufficient to predict a molecular crystal structure is very dependent on the shape of the molecule. If the shape has many well-defined protrusions and cavities, so that there is only one way that it can pack densely with a tight fitting of the protrusions of one molecule into the cavities of its neighbours, then any potential which represents this shape and has an attractive component will be acceptable. However, many shapes, such as discs or cylinders, can close pack in many ways, each generating a range of structures with differing tilt angles, etc. In these cases, the chemical nature of the atoms and resultant intermolecular forces determine which of the reasonably close-packed structures is adopted. 

Table 11.2 Prediction of molecular crystal structures using distributed multipole electrostatic models. 

Errors (/>(calc)-/>(expt)) in the predicted molecular crystal structures, calculated by minimizing the static lattice energy, starting from the experimental structure, for a model potential which includes a distributed multipole electrostatic model. The electrostatic term uses a DMA of a 6-31G SCF wave function, with all multipoles scaled by a factor of 0.9. The repulsion-dispersion potentials are taken from the literature (see text). The r.m.s. % error is calculated over the three cell edge lengths. Us is the calculated lattice energy, given at both the experimental and relaxed crystal structures. This can be compared with the experimental heat of sublimation AHsub (Chickos, 1987), where available. 

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