For meaningful crystal structure predictions (CSP) of practically relevant molecular crystals, it is imperative to calculate relative lattice energies with an accuracy of about 1 kJ/mol since it is necessary to correctly rank the stabilities of numerous low-energy polymorphs. Accurate results can be obtained by utilizing density-functional theory (DFT) supplemented by a high-level van der Waals (vdW) model, such as the many-body dispersion (MBD) method. Since relative stabilities have to be determined at finite temperatures, vibrational free energies have to be considered as well. Furthermore, vdW interactions are not only important for lattice energies, but also crucial for the actual structure of molecular crystals and all related response properties. We present a hierarchical DFT approach for the re-optimization and re-ranking of polymorph structures which is applicable to pharmaceutically relevant systems, i.e. for unit cell sizes of up to circa 1000 atoms. The quality of this approach is discussed for the systems studied in the most recent CSP blind test of the Cambridge Crystallographic Data Centre, with a particular focus on a challenging case of a highly polymorphic system. It is shown that collective many-body vdW interactions considerably improve the relative stabilities of the studied polymorphs in comparison to a pairwise-additive approach. Furthermore, the inclusion of thermal fluctuations within the harmonic approximation also leads to a significant improvement of the relative stabilities. Moreover, we discuss how the results for a selected group of structures can be further improved on a DFT level by going beyond the harmonic approximation for vibrational free energies. The thermal expansion of a molecular crystal can be modeled by the quasi-harmonic approximation, which allows for the description of the unit cell volume corresponding to finite temperatures rather than optimized structures at 0 K without zero-point fluctuations. Finally, we also estimate the anharmonicity of the phonon modes by replacing the system of independent harmonic oscillators with morse oscillators. Overall, the CSP approach based on DFT+MBD provides remarkably accurate structures and stability rankings for practically relevant molecular crystals.

Molecular crystal structure prediction from large-scale first-principles calculations

255th National Meeting (2018)

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