Quantum chemical modeling of molecular crystal deformations

Polymorphism is the phenomenon of the existence of different arrangements of molecules in the crystal phase. Molecules can differ in conformations (conformational polymorphism) and / or in intermolecular interactions between them in the crystal (orientational polymorphism). The influence of molecular packing on the properties of materials cannot be overestimated, thus, the choice of the most suitable polymorphic form is crucial for manufacture. However, a lot of crystal structures are not stable and can undergo polymorphic transformation due to different reasons.

We present a multistage method for the analysis of mechanisms of polymorphic transformations based on shear slips of strongly bound fragments in structures that differ mainly in packing on the example of pharmaceutical compounds aspirin, piracetam and ibuprofen. The first stage consists in the computation of pairwise interaction energies between molecules in a crystal using quantum chemical methods. It reveals the most strongly bound structural fragments (building units and basic structural motifs) and the planes between which the binding of structural fragments is the least. In the second stage, parts of two adjacent structural motifs are displaced in different directions within the planes separated out earlier. The most probable shift directions are chosen based on a geometric estimate of minimum distances during translations and, further, shift energy profiles and barriers inherent to them are calculated. Inexpensive and efficient, our method allows to determine probabilities of molecular translations with high accuracy.