Crystal regeneration: investigating the post-breakage growth phenomenon in organic crystals

This thesis investigates the 'crystal-regeneration' phenomenon, where a single macroscopic paracetamol crystal, broken along its cleavage plane (010), extrinsically regenerated into its pre-breakage shape before growing equivalently to its unbroken counterpart. Regeneration occurred via rapid growth along the cleavage plane, with facets on the intact crystal remaining dormant until the shape was restored. The extent and orientation of breakage influenced regeneration: breakage parallel to the cleavage plane promoted regeneration as opposed to perpendicular breakage, emphasising the importance of both particle size and shape evolution after breakage. Growth perpendicular to the cleavage plane was at least twice as fast as parallel growth, with most regeneration occurring in the experiment’s initial phase. These observations support a two-step mechanism consisting of a fast phase followed by a slower phase. The phenomenon was elucidated through intricate single crystal experiments, supported by advanced imaging setups and automated image analysis via MATLAB to measure facet-specific growth rates. Crystal regeneration was examined in three solvents—ethanol, acetone, and tetrahydrofuran (THF)—across various supersaturations (1.03 to 1.30) and under agitation. Regeneration was favourable under all tested conditions, with solutesolvent interactions, hydrodynamics, and thermodynamics influencing the process. Solutesurface interactions, driven by higher solubility, were preferred over unfavourable solventsurface interactions, resulting in higher regeneration rates. Regardless of conditions, regeneration led to accelerated growth kinetics strongly dependent on supersaturation, following power law kinetics. Cleaved crystals also enhanced secondary nucleation, showcasing their potential as a seeding strategy in batch crystallisation processes. Crystal regeneration challenges traditional morphological theories that emphasise the influence of slow-growing facets, as broken crystals behave differently. The preferred ‘switching off’ of facets during regeneration suggests a possible link between crystal ‘shape-memory’ effect and surface energetics. This thesis systematically explores crystal behaviour post-breakage and proposes mechanisms to explain these phenomena, offering critical insights into previously unexplored post-breakage crystal growth dynamics.