Abstract
One of the most consequential assumptions of the classical theories of crystal nucleation and growth is the Szilard postulate, which states that molecules from a supersaturated phase join a nucleus or a growing crystal individually. In the last 20 years, observations in complex biological, geological, and engineered environments have brought to light violations of the Szilard rule, whereby molecules assemble into ordered or disordered precursors that then host and promote nucleation or contribute to fast crystal growth. Nonclassical crystallization has risen to a default mode presumed to operate in the majority of the inspected crystallizing systems. In some cases, the existence of precursors in the growth media is admitted as proof for their role in nucleation and growth. With the example of olanzapine, a marketed drug for schizophrenia and bipolar disorder, we demonstrate that molecular assemblies in the solution selectively participate in crystal nucleation and growth. In aqueous and organic solutions, olanzapine assembles into both mesoscopic solute-rich clusters and dimers. The clusters facilitate nucleation of crystals and crystal form transformations. During growth, however, the clusters land on the crystal surface and transform into defects, but do not support step growth. The dimers are present at low concentrations in the supersaturated solution, yet the crystals grow by the association of dimers, and not of the majority monomers. The observations with olanzapine emphasize that detailed studies of the crystal and solution structures and the dynamics of molecular association may empower classical and nonclassical models that advance the understanding of natural crystallization, and support the design and manufacture of promising functional materials.
Highlights
The formation of crystal nuclei in a supersaturated “old” phase overcomes a free energy barrier due to the formation of a new surface [1]
We examine the role of the clusters in crystal growth and, surprisingly, discover that the clusters integrate in the crystals as foreign bodies and do not contribute to growth, either as preformed building blocks. nor as a source of solute supply as they decay
The presented kinetic scheme reveals that if crystals grow by incorporation of solute dimers that exist in equilibrium with monomers, the step velocity woulddepend on the analytical concentration of the solute C as v = β D K D ΩD C2 − Ce2, where β D = DD /Λ D, the subscript D denotes dimer, and KD is the dimerization equilibrium constant
Summary
The formation of crystal nuclei in a supersaturated “old” phase overcomes a free energy barrier due to the formation of a new surface [1]. A solution supersaturated with respect to a crystal overcomes the nucleation barrier via fluctuations that bring the local concentration and structure close to those of the incipient phase [1]. We examine the roles of two structures extant in olanzapine (OZPN) solutions, mesoscopic solute-rich clusters and molecular dimers, in the nucleation, crystal form transformations, and growth of OZPN crystals (Figure 1). The mechanism of transition between solid forms is among the major unsolved problems of modern materials science [31,32] To partially fill this knowledge gap, we demonstrate that the OZPN-rich mesoscopic clusters facilitate the nucleation of a crystal hydrate, OZPN DD, during its transformation from the anhydrous OZPN I.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
