Organic Molecular Crystals

Crystallization of molecular organic compounds is often hampered by the existence of a number of polymorphous structures which are very close in lattice energies. The packing and interaction of flexible organic molecules affords a large number of possible structures in the solid and many polymorphous crystals appear to be feasible. Enantiopure S-3-chloro mandelic acid and the R,S-racemate was chosen as an example system to explore the complex energy landscape of possible packings and structures. The energy ranking of possible structures from CSP is the most critical issue, in particular for chiral compounds.

The separation of an enantiomer from a racemic mixture is of primary relevance to the pharmaceutical industry. Accurate lattice energies of sparsely packed organic crystals are important i.e. for the chemical and pharmaceutical industries. Periodic DFT calculations with atom-centred Gaussian basis functions were used to calculate lattice energies for several non-covalently bound organic molecular crystals of the X23 benchmark set. The PBE-D3 and B97 calculations give a high accuracy to within ~5 kJ mol-1 of experimental data. The use of atom-localized GTOs allows an elegant and consistent treatment of molecules and periodic system of any dimensionality on equal footing. The calculated lattice energy differences between enantiopure and racemic crystal forms for a prototype set of chiral molecules (lactides, naproxen and 3-chloro-mandelic acid) are in good agreement with experimental results and allow the rationalization and computer-aided design of chiral separation processes.

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