High-Pressure Influence on Piracetam Crystals: Studying by Quantum Chemical Methods

Abstract

The method developed previously for studying mechanical properties using quantum chemical calculations was applied to predict the most probable direction of deformation of the piracetam polymorphic Form II under pressure. By the analysis of the pairwise interaction energies between molecules in Form II, this structure was classified as columnar-layered. The shear deformation modeling of the strongly bound fragments in crystal packing predicted the [100] crystallographic direction with a shift energy barrier of 5.2 kcal/mol to be the most probable within the (001) crystallographic plane for Form II deformation. Comparison of Form II before the polymorphic transition and Form V after the crystal structure change confirmed the results of quantum chemical modeling. The analysis of the shift energy profile indicated the characteristic features (a local minimum near the starting point, negative interaction energies between layers during the displacement, and a low shift energy barrier) that can be used to predict a polymorphic transition. The study of the pairwise interaction energies in the piracetam Forms II and V under pressure has revealed that the crystal structure can be changed under pressure in two stages. In the first stage, the polymorphic transition occurs due to the shift of weakly bound layers without changing the columnar-layered type of the crystal structure from the energetic viewpoint. In the second stage, a change in the ratio of the interaction energies between BSM1 and BSM2 results in the transition of the crystal structure type from columnar-layered to columnar without changing the polymorphic form.

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“…Earlier, some features of the shift energy profile indicating the possibility of a polymorphic transition under pressure were found for the piracetam crystals. 38 These were a local energy minimum near the starting point, negative interaction energies between layers during the displacement, and a low shift energy barrier (Fig. 8, on the right).…”

“…According to the approach proposed earlier, 37,38 the next stage is the choice of a shear deformation direction with the plane defined using the results of the pairwise interaction energy study. A more detailed analysis of the layer recognized as BSM 1 showed that the neighboring DBUs differ in their slopes (Fig.…”

“…It was based on moving the mobile part in relation to the fixed part of the model system and measuring the shortest distances between them at each point. For piracetam crystals, 38 2D-maps of the shortest distances between atoms of the mobile and fixed parts were constructed as a function of the shortest distance between the atoms of the mobile and fixed parts and the position of the mobile part in relation to the fixed one. Some inaccuracy of this approach can be caused by using absolute values of the distances between the nearest atoms due to the fact that these values must be compared with the sum of the corresponding van der Waals radii.…”

“…Recently, we have proposed a new approach to analyzing the influence of pressure on a crystal structure. 37,38 It was assumed that any deformation of the crystal is caused by the shear of strongly bound fragments of the crystal packing to each other. This process can be studied using quantum chemical calculations in several stages.…”

“…37 Application of this approach to the analysis of piracetam crystals made it possible to indicate some prerequisites for a crystal–crystal polymorphic transition. 38 Both aspirin and piracetam molecules contain a functional group (carboxylic or carbamide) capable of forming a centrosymmetric dimer that can be considered as a building unit of the crystal structure. These dimers form strongly bound fragments, and the bonding between them is provided by weaker intermolecular interactions.…”