The Role of Weak Interactions in the Phase Transition and Distinct Mechanical Behavior of Two Structurally Similar Caffeine Co-crystal Polymorphs Studied by Nanoindentation

Abstract

Although weak interactions, such as C−H•••O and πstacking, are generally considered to be insignificant, it is their reorganization that holds the key for many a solid-state phenomenon, such as phase transitions, plastic deformation, elastic flexibility, and mechanochromic luminescence in solid-state fluorophores. Despite this, the role of weak interactions in these dynamic phenomena is poorly understood. In this study, we investigate two co-crystal polymorphs of caffeine:4-chloro-3-nitrobenzoic acid, which have close structural similarity (2D layered structures), but surprisingly show distinct mechanical behavior. Form I is brittle, but shows shearinduced phase instability and, upon grinding, converts to Form II, which is soft and plastically shearable. This observation is in contrast to those reported in earlier studies on aspirin, wherein the metastable drug forms are softer and convert to stable and harder forms upon stressing. To establish a molecular-level understanding, we have investigated the two co-crystal polymorphs I and II by single-crystal X-ray diffraction, nanoindentation to quantify mechanical properties, and theoretical calculations. The lower hardness (from nanoindentation) and smooth potential surfaces (from theoretical studies) for shearing of layers in Form II allowed us to rationalize the role of stronger intralayer (sp 2 )C−H•••O and nonspecific interlayer π-stacking interactions in the structure of II. Although the Form I also possesses the same type of interactions, its strength is clearly opposite, that is, weaker intralayer (sp 3 )C−H•••O and specific interlayer π-stacking interactions. Hence, Form I is harder than Form II. Theoretical calculations and indentation on (111) of Form I suggested the low resistance of this face to mechanical stress; thus, Form I converts to II upon mechanical action. Hence, our approach demonstrates the usefulness of multiple techniques for establishing the role of weak noncovalent interactions in solid-state dynamic phenomena, such as stress-induced phase transformation, and hence is important in the context of solid-state pharmaceutical chemistry and crystal engineering.

Unusually Large Young’s Moduli of Amino Acid Molecular Crystals

“…[10][11][12][13] Partly,this interest is driven by practical issues,asmechanical considerations affect the stability of molecular solids across ad iverse range of applications,from pharmaceuticals [3,[14][15][16] to energetic materials. [4,5] But the research is also driven by basic science,assome molecular solids exhibit Youngs moduli much higher than that expected from naive considerations.…”

Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

“…Cocrystals of carbamazepine (CBZ) with nicotinamide (NCT) and saccharin (SAC) are shown to exist as heterosynthon polymorphic forms. Two polymorphs of CBZ-NCT cocrystals and two polymorphs of CBZ-SAC cocrystals have been observed [122]. The CBZ-SAC (form II) cocrystal represents a heterosynthon polymorph (Fig.…”

“…The SCXRD technique determines the crystal unit cell dimensions and related space group. This also provides information on the complete three-dimensional arrangement, positions of atoms and packing of molecules in the unit cell [116,122,166,167]. Supramolecular synthons can be elucidated from this three-dimensional arrangement.…”

Mechanical Anisotropy in Austenitic NiMnGa Alloy: Nanoindentation Studies

“…Nanoindentation technique, because of its ability to probe mechanical properties of relatively small volume materials, allows for measuring mechanical properties along various crystallographic directions and hence estimates the anisotropy [11][12][13][14][15][16][17]. Some of the current authors have extensively utilized nanoindentation technique to characterize organic, pharmaceutical and metal-organic framework systems to correlate molecular-level properties such as interaction characteristics, crystal packing, and the inherent anisotropy with micro/macroscopic events [18][19][20][21][22][23][24][25][26][27][28][29]. This has been attempted in this work wherein the elastic and plastic properties of grains in an austenitic Ni 50 Mn 26.25 Ga 23.75 , which are oriented in different crystallographic directions, are evaluated by employing the nanoindentation technique.…”