In the last century, molecular crystals functioned predominantly as a means for determining the molecular structures via X-ray diffraction, albeit as the century came to a close the response of molecular crystals to electric, magnetic, and light fields revealed that the physical properties of molecular crystals were as rich as the diversity of molecules themselves. In this century, the mechanical properties of molecular crystals have continued to enhance our understanding of the colligative responses of weakly bound molecules to internal frustration and applied forces. Here, the authors review the main themes of research that have developed in recent decades, prefaced by an overview of the particular considerations that distinguish molecular crystals from traditional materials such as metals and ceramics. Many molecular crystals will deform themselves as they grow under some conditions. Whether they respond to intrinsic stress or external forces or interactions among the fields of growing crystals remains an open question. Photoreactivity in single crystals has been a leading theme in organic solid-state chemistry; however, the focus of research has been traditionally on reaction stereo- and regio-specificity. However, as light-induced chemistry builds stress in crystals anisotropically, all types of motions can be actuated. The correlation between photochemistry and the responses of single crystals—jumping, twisting, fracturing, delaminating, rocking, and rolling—has become a well-defined field of research in its own right: photomechanics. The advancement of our understanding requires theoretical and high-performance computations. Computational crystallography not only supports interpretations of mechanical responses, but predicts the responses itself. This requires the engagement of classical force-field based molecular dynamics simulations, density functional theory-based approaches, and the use of machine learning to divine patterns to which algorithms can be better suited than people. The integration of mechanics with the transport of electrons and photons is considered for practical applications in flexible organic electronics and photonics. Dynamic crystals that respond rapidly and reversibly to heat and light can function as switches and actuators. Progress in identifying efficient shape-shifting crystals is also discussed. Finally, the importance of mechanical properties to milling and tableting of pharmaceuticals in an industry still dominated by active ingredients composed of small molecule crystals is reviewed. A dearth of data on the strength, hardness, Young's modulus, and fracture toughness of molecular crystals underscores the need for refinement of measurement techniques and conceptual tools. The need for benchmark data is emphasized throughout.

By the formation of a 1:1 cocrystal of caffeine and methyl gallate, we demonstrated that powder compaction properties could be profoundly improved. The selection criterion for cocrystal exhibiting superior compaction properties was the presence of slip planes in crystal structure. Bulk cocrystal was prepared by suspending powders of the two pure compounds in ethanol. Fine powders of similar particle size distribution were compressed. Within the whole range of compaction pressure, the tablet tensile strength of methyl gallate was very poor (<0.5 MPa) and severe lamination and sticking occurred in almost all tablets. Tabletability of caffeine was acceptable at 180 MPa, severe lamination of caffeine tablets suddenly occurred. Tablet tensile strength dropped sharply at >240 MPa. In contrast, the tabletability of the cocrystal was excellent over the entire pressure range. Tablet tensile strength of the cocrystal was ∼2 times that of caffeine at <200 MPa, and the ratio gradually increased with increasing pressure, e.g., ∼8 fold at 350 MPa. Poor tablet tensile strength was always associated with high elastic recovery and low plasticity. The good plasticity and tabletability of the cocrystal validated the selection criterion, i.e., the presence of slip planes in crystal structure.

Tabletability, the ability to make a tablet of adequate mechanical strength by powder compaction, is of paramount importance in the successful manufacture of tablet products. Poor tabletability is ...