The results of the sixth blind test of organic crystal structure prediction methods are presented and discussed, highlighting progress for salts, hydrates and bulky flexible molecules, as well as on-going challenges.

The results of the fifth blind test of crystal structure prediction, which show important success with more challenging large and flexible molecules, are presented and discussed.

We report on the organization and outcome of the fourth blind test of crystal structure prediction, an international collaborative project organized to evaluate the present state in computational methods of predicting the crystal structures of small organic molecules. There were 14 research groups which took part, using a variety of methods to generate and rank the most likely crystal structures for four target systems: three single-component crystal structures and a 1:1 cocrystal. Participants were challenged to predict the crystal structures of the four systems, given only their molecular diagrams, while the recently determined but as-yet unpublished crystal structures were withheld by an independent referee. Three predictions were allowed for each system. The results demonstrate a dramatic improvement in rates of success over previous blind tests; in total, there were 13 successful predictions and, for each of the four targets, at least two groups correctly predicted the observed crystal structure. The successes include one participating group who correctly predicted all four crystal structures as their first ranked choice, albeit at a considerable computational expense. The results reflect important improvements in modelling methods and suggest that, at least for the small and fairly rigid types of molecules included in this blind test, such calculations can be constructively applied to help understand crystallization and polymorphism of organic molecules.

Following the interest generated by two previous blind tests of crystal structure prediction (CSP1999 and CSP2001), a third such collaborative project (CSP2004) was hosted by the Cambridge Crystallographic Data Centre. A range of methodologies used in searching for and ranking the likelihood of predicted crystal structures is represented amongst the 18 participating research groups, although most are based on the global minimization of the lattice energy. Initially the participants were given molecular diagrams of three molecules and asked to submit three predictions for the most likely crystal structure of each. Unlike earlier blind tests, no restriction was placed on the possible space group of the target crystal structures. Furthermore, Z' = 2 structures were allowed. Part-way through the test, a partial structure report was discovered for one of the molecules, which could no longer be considered a blind test. Hence, a second molecule from the same category (small, rigid with common atom types) was offered to the participants as a replacement. Success rates within the three submitted predictions were lower than in the previous tests - there was only one successful prediction for any of the three ;blind' molecules. For the ;simplest' rigid molecule, this lack of success is partly due to the observed structure crystallizing with two molecules in the asymmetric unit. As in the 2001 blind test, there was no success in predicting the structure of the flexible molecule. The results highlight the necessity for better energy models, capable of simultaneously describing conformational and packing energies with high accuracy. There is also a need for improvements in search procedures for crystals with more than one independent molecule, as well as for molecules with conformational flexibility. These are necessary requirements for the prediction of possible thermodynamically favoured polymorphs. Which of these are actually realised is also influenced by as yet insufficiently understood processes of nucleation and crystal growth.

This paper presents data on the 15N chemical shift tensor principal values in a series of 15N-enriched heterocycles. Compounds that are liquids at room temperature were frozen, and the principal values of all compounds studied were measured from static powder patterns. Four different types of nitrogen tensors are described, consisting of protonated and nonprotonated nitrogens in both five- and six-membered rings. The principal values were oriented on the molecular frame using the DFT quantum mechanical calculations of the 15N chemical shielding tensors. The agreement between the calculated and experimental principal values is adequate to make these assignments, but the relative scatters are greater than those observed in similar 13C chemical shift calculations. The largest shift component, δ11, is always oriented in the radial direction to the ring for substituted nitrogens but is tangential to the ring for the nonsubstituted nitrogens. The large variations observed in the nitrogen chemical shift tensors upon changing the nitrogen hybridization can be explained using qualitative arguments on the localization of the smallest bonding-antibonding or HOMO−LUMO gap in the molecule. The orientation of the largest shift component is always found in the plane of the molecule and is approximately perpendicular to the plane containing the bonding−antibonding or HOMO−LUMO pair of orbitals with the smallest energy gap.