Report on the sixth blind test of organic crystal structure prediction methods.

The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations. All of the targets, apart from a single potentially disordered Z' = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms.

Do solid-to-solid polymorphic transitions in DL-norleucine proceed through nucleation?

DL-Norleucine is a molecular crystal exhibiting two enantiotropic phase transitions. The high temperature α ↔ γ transition has been shown to proceed through nucleation and growth [Mnyukh et al., J. Phys. Chem. Solids, 1975, 36, 127]. We focus on the low temperature ß â†” α transition in a combined computational and experimental study. The temperature dependence of the structural and energetic properties of both polymorphic forms is nearly identical. Molecular dynamics simulations and nudged elastic band calculations of the transition process itself, suggest that the transition is governed by cooperative movements of bilayers over relatively large energy barriers.