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.

Molecular crystals cannot be designed like macroscopic objects because they do not assemble according to simple, intuitive rules. Their structure results from the balance of many weak interactions, unlike the strong and predictable bonding patterns found in metal–organic frameworks and covalent organic frameworks. Hence, design strategies that assume a topology or other structural blueprint will often fail. Here, we combine computational crystal structure prediction and property prediction to build energy–structure–function maps describing the possible structures and properties available to a candidate molecule. Using these maps, we identify a highly porous solid with the lowest density reported for a molecular crystal. Both crystal structure and physical properties, such as the methane storage capacity and guest selectivity, are predicted using the molecular diagram as the only input. More generally, energy–structure–function maps could be used to guide the experimental discovery of materials with any target function that can be calculated from predicted crystal structures, such as electronic structure or mechanical properties.

Day, (2010) Modelling organic crystal structures using distributed multipole and polarizability-based model intermolecular potentials. Physical

A computational study of 1061 experimentally determined crystal structures of 508 polymorphic organic molecules has been performed with state-of-the-art lattice energy minimisation methods, using a hybrid method that combines density functional theory intramolecular energies with an anisotropic atom-atom intermolecular model. Rigid molecule lattice dynamical calculations have also been performed to estimate the vibrational contributions to lattice free energies. Distributions of the differences in lattice energy, free energy, zero point energy, entropy and heat capacity between polymorphs are presented. Polymorphic lattice energy differences are typically very small: over half of polymorph pairs are separated by less than 2 kJ/mol and lattice energy differences exceed 7.2 kJ/mol in only 5% of cases. Unsurprisingly, vibrational contributions to polymorph free energy differences at ambient conditions are dominated by entropy differences. The distribution of vibrational energy differences is narrower than lattice energy differences, rarely exceeding 2 kJ/mol. However, these relatively small vibrational free energy contributions are large enough to cause a re-ranking of polymorph stability below, or at, room temperature in 9% of the polymorph pairs.

Poor mechanical properties of paracetamol are improved through the strategy of cocrystal formation. Mechanochemical screening by liquid-assisted grinding generated four cocrystals of paracetamol that readily form tablets by direct compression. Computational studies reveal the mechanical properties can be related to structural features, before all the formation of hydrogen-bonded layers