The synthesis of high-value crystals, crucial for pharmaceuticals, organic semiconductors, and optical devices, often utilizes organic solvents. Unlike aqueous solutions dominated by strong hydrogen bonds and polar attractions, organic solute-solvent systems primarily rely on weaker van der Waals forces. This difference significantly impacts the fundamental processes of crystal growth, introducing a knowledge gap in understanding the molecular-level mechanisms involved. While macroscopic processes might exhibit similarities to aqueous systems, molecular-level processes are expected to differ due to the distinct nature of intermolecular interactions. The classical theories of crystal nucleation and growth assume sequential and individual molecular association to growing crystals. While confirmed under controlled conditions with moderate driving forces, numerous observations in more complex environments (proteins, biominerals) reveal significant deviations from these classical models, highlighting the emergence of nonclassical growth pathways. A prominent nonclassical pathway involves oriented attachment of nanocrystallites, but the vast majority of these observations are from aqueous solutions. This research investigates whether nonclassical growth occurs in organic crystals by studying etioporphyrin I crystallization in neat octanol. Etioporphyrin I's unique structure and low symmetry, similar to other porphyrins, make it an excellent model system, offering valuable insights into organic crystallization mechanisms.

Classical theories of crystal nucleation and growth posit that molecules individually and sequentially associate with growing nuclei or crystals. Experiments under controlled conditions with moderate driving forces have confirmed these assumptions or yielded results consistent with classical predictions. However, in recent years, studies on proteins, biominerals, and other complex systems have revealed significant deviations. Crystals have been observed to nucleate within disordered, liquid precursors and grow through the association of preformed molecular blocks. Oriented attachment of nanocrystallites, guided by short-range electrostatic and solvent-structuring interactions, represents another well-discussed nonclassical growth pathway. Most nonclassical growth observations are from aqueous solutions, leaving the question open for organic systems.

This study focuses on etioporphyrin I crystallization from neat octanol. The growth rates of individual crystal faces were measured using a microfluidics device, maintaining constant solute concentrations. In situ atomic force microscopy (AFM) was employed to monitor the crystal surface dynamics at various supersaturations. Oblique illumination microscopy (OIM) characterized the etioporphyrin I solutions, revealing the presence of aggregates. The optical properties of the crystals, specifically linear retardance and linear extinction, were assessed using transmission Mueller matrix polarimetry. The methods involved preparing supersaturated solutions, measuring concentrations via UV-Vis spectroscopy, analyzing crystal morphology using scanning electron microscopy (SEM), and monitoring crystal growth using AFM and microfluidics. OIM was used to identify mesoscopic solute-rich clusters. Transmission Mueller matrix polarimetry was used to analyze the optical properties of crystals grown via different mechanisms, allowing the comparison of crystalline quality.

Etioporphyrin I crystals exhibit a dual growth mode: classical growth at low supersaturations and nonclassical growth at higher supersaturations. The nonclassical growth is facilitated by mesoscopic liquid precursors (approximately 400 nm in diameter and 6–12 nm in height) which land on the crystal surface. These precursors, identified as mesoscopic etioporphyrin I-rich clusters via OIM, initially grow in height and width before developing flat tops parallel to the crystal surface and transforming into stacks of 25–50 layers that spread laterally. The observed superlinear correlation between growth rate and solute concentration is inconsistent with classical models (two-dimensional nucleation, step pinning, low kink density). AFM imaging revealed abundant kinks and spiral steps originating from screw dislocations, supporting the precursor-mediated growth model. The lateral spreading of the stacks occurs via direct incorporation of solute molecules from the solution, bypassing surface diffusion. The precursors' liquid-like nature allows for seamless lattice alignment with the growing crystal, with only moderate strain observed even at high growth rates. Not all particles that land on the surface integrate into the lattice; some amorphous particles dissolve, highlighting the importance of the liquid precursor phase for successful integration. Surprisingly, fast nonclassically grown crystals showed no significant differences in optical birefringence compared to those grown classically, indicating that the high-speed growth does not compromise crystal quality.

This study's findings provide crucial insights into organic crystal growth mechanisms. The observed dual growth mode, with its reliance on mesoscopic liquid precursors, is rarely documented and adds to the growing understanding of nonclassical crystallization. The direct incorporation pathway, bypassing surface diffusion, may be unique to organic systems where weak solute-solvent interactions dominate. The formation of mesoscopic clusters is attributed to weak intermolecular interactions, suggesting that the transition to nonclassical growth might be driven by subtle variations in system parameters. The observation that fast growth does not compromise crystal quality in terms of birefringence is technologically significant. The ability to obtain high-quality crystals at high growth rates is highly desirable for many applications.

This study demonstrates a novel dual growth mode in organic crystals, driven by mesoscopic liquid precursors that facilitate lateral layer stack spreading. Direct solute incorporation from the solution, bypassing surface diffusion, and the formation of mesoscopic clusters due to weak intermolecular interactions are key features distinguishing this mode of organic crystal growth. These findings provide essential insights into crystal growth mechanisms, with implications for various material synthesis strategies. Future research could explore the influence of solvent properties and solute structure on this unique dual growth mode, furthering our understanding of organic crystallization across diverse systems.

The study primarily focuses on etioporphyrin I in octanol. While this provides valuable insights, further research is needed to determine the generality of these findings to other organic molecules and solvent systems. The characterization techniques used have limitations in resolution; higher resolution techniques could provide further insights into the structure and dynamics of the precursors and their integration into the crystal lattice. The current study doesn't exhaustively explore the effects of variations in supersaturation and temperature on crystal quality. Further work is needed to fully determine the range of conditions where this dual growth mode is observed.