Mechanical Deformation Chemistry of Crystals: Designing Mechanical Performance

Abstract

Crystal engineering approaches can be useful to understand, predict and design mechanical properties of the active pharmaceutical ingredients (APIs) for their improved performance in various stages of production. For example, the understanding of correlation among structure, mechanical property and powder compaction would allow prediction and design of powder tabletability of APIs. A design approach to achieve mechanically flexible plastic and elastic molecular crystals has recently been proposed. This involves the introduction of active slip planes (with minimal ruggedness) into the crystal structure by making different non-interfering weak interactions such as van der Waals (vdW), π-stacking and hydrogen bonding. By analyzing the reported crystal structures of plastically flexible crystals it can be hypothesized that the spherical hydrophobic groups will assemble via shape complementarity (shape synthons) to reliably form low energy slip planes. As these groups do not interfere with the π-stacking or hydrogen bonding groups, they can pack in a predictable manner and thus form slip planes to facilitate mechanical flexibility, as successfully demonstrated in a series of naphthalene diimide derivatives. Such studies can allow the preparation of exotic plastic crystals by design and through this demonstrate the potential for using soft interactions for tuning mechanical behaviour of ordered molecular materials. A comment is made on the prospects and ramifications of this emerging field, in the context of pharmaceutical solids.