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.

Model for the crystal packing and conformational changes of biphenyl in incommensurate phase transitions.

Standard atom-atom potentials for hydrocarbons and a torsional potential to account for the pi-electron conjugation energy were used to model the crystal structures and phase transitions of biphenyl. The model describes the high-temperature phase (I) with its planar molecule as a stationary point of the energy hypersurface. Phase I represents a low-energy barrier between the symmetry minima of the ground state (phase III), in which the molecule is twisted with torsion angles of opposite sign. Global-energy minimization was carried out by considering both regular structures, with one or two independent molecules, and quasi-one-dimensional superstructures built of N cells (N up to 16) of the high-temperature structure. The various energy-minimized biphenyl structures demonstrate remarkable similarity in their crystal packing; in particular, there are characteristic rows of cooperatively twisted molecules parallel to the superstructure dimension b. The structures built of centrosymmetric rows (P1, Z = 4 and 8) are almost as low in energy as the basic structure (an N = 2 superstructure, Pa, Z = 4); moreover, one of them is isostructural with the low-temperature p-quaterphenyl structure. With N > 8, structures of lower energy than that of the basic structure (N = 2) were found; their common feature is an M-fold modulation of the twist angle over the supercell period, with M smaller than N and generally not a simple fraction of it. The global minimum was found to conform to the ratio k = M/N = 6/14, which is close to the experimentally observed k = 6/13 in the incommensurate phase III. Enthalpy minimization showed an overall decrease in the magnitude of the twist angle down to tau approximately 0 degrees, as well as the evolution of the modulated structures towards the high-temperature structure with increasing pressure, in agreement with evidence for the high-pressure limit of the incommensurate biphenyl phases.

Crystal structure prediction of small organic molecules: a second blind test.

The first collaborative workshop on crystal structure prediction (CSP1999) has been followed by a second workshop (CSP2001) held at the Cambridge Crystallographic Data Centre. The 17 participants were given only the chemical diagram for three organic molecules and were invited to test their prediction programs within a range of named common space groups. Several different computer programs were used, using the methodology wherein a molecular model is used to construct theoretical crystal structures in given space groups, and prediction is usually based on the minimum calculated lattice energy. A maximum of three predictions were allowed per molecule. The results showed two correct predictions for the first molecule, four for the second molecule and none for the third molecule (which had torsional flexibility). The correct structure was often present in the sorted low-energy lists from the participants but at a ranking position greater than three. The use of non-indexed powder diffraction data was investigated in a secondary test, after completion of the ab initio submissions. Although no one method can be said to be completely reliable, this workshop gives an objective measure of the success and failure of current methodologies.