Rationalizing Distinct Mechanical Properties of Three Polymorphs of a Drug Adduct by Nanoindentation and Energy Frameworks Analysis: Role of Slip Layer Topology and Weak Interactions

Abstract

Three concomitant polymorphs of 3-((4-chlorophenyl)­imino)­indolin-2-one, a Schiff’s base, are identified and sorted based on morphology and mechanical response of their crystals. Form I grows as blocks and shows brittle fracture, Form II has long needles and shows plastic bending, and Form III also has long needles and shows elastic bending under similar qualitative mechanical deformation tests. Furthermore, the brittle Form I was found to exhibit thermosalient behavior (jumping) when heated on a hot plate. The distinct mechanical behavior of the three forms is rationalized by analyzing intermolecular interaction energies from energy frameworks analysis, slip layer topology, Hirshfeld surface analysis, and nanoindentation. The quantitative nanoindentation studies unveiled that Form III has higher elastic modulus and stiffness than Forms I and II, while the hardness was lowest for the plastic Form II. Despite high structural similarity in Forms II (plastic) and III (elastic), the E of elastic Form III was found to be 3 orders of magnitude higher than that of plastic Form II crystals, which is attributed to the subtle differences in interaction energies and slip layer topology in the two cases. Consideration of slip layer topology and interaction energies from the structures are very useful for rationalizing mechanical properties, but may not be always sufficient, and one may also need to know the topology of the potential energy surface of the slip layers for understanding the distinct mechanical behavior.

Interactions in flavanone and chalcone derivatives: Hirshfeld surface analysis, energy frameworks and global reactivity descriptors

“…(iv) Most of the interactions found in the analysed structures are of the types C-HÁ Á ÁO, C-HÁ Á Á and -. For these, the interaction energy ranges from À19.5 to À57.4 kJ mol À1 ; these values are comparable with the corresponding interaction energies for other structures published in Bhowal et al (2019), Bal Raju et al (2018) and Bhandary et al (2019).…”

Temperature‐Reliant Dynamic Properties and Elasto‐Plastic to Plastic Crystal (Rotator) Phase Transition in a Metal Oxyacid Salt

“…However, the molecules across the slip planes are connected via the weak C−H⋅⋅⋅O interactions. The measurement of layer separation [16a] about the slip regions shows very closely placed columnar layers with only 0.032 Å separation at 100 K and 0.127 Å at 300 K (Supporting Information Figure S10). In previous studies, it has been shown that a larger separation is helpful for plastic deformation [16] .…”

“…In previous studies, it has been shown that a larger separation is helpful for plastic deformation [16] . An interdigitation of layers or rigid interactions may impede plastic deformation, [16a] leading to a degree of elastic deformation or brittleness. The weak C−H⋅⋅⋅O interactions and tightly packed ‐Me groups appear to provide some initial resistance to a permanent slippage of molecules along these planes, facilitating initial elasticity followed by plasticity at higher strains.…”

Indomethacin Polymorph δ Revealed To Be Two Plastically Bendable Crystal Forms by 3D Electron Diffraction: Correcting a 47‐Year‐Old Misunderstanding**

“…To the best of our knowledge, IDM is the first clinical drug with two phase-pure polymorphs displaying plasticity. Polymorphism that showcases various mechanical behaviors helps us to understand the relationship between crystal structure and solid-state properties [57][58][59][60] and also offers an excellent opportunity to tune or predict pharmaceutical-related mechanical properties. [61] For example, the compressibility of an active pharmaceutical ingredient plays an important role in the tabletability of the formulation, especially for high drug-load formulations.…”