(M1030-12-72) Enhancement of Crystal Nucleation at a Liquid/Vapor Interface

Purpose: Molecules at a liquid/vapor interface have different organization and dynamics from those in the bulk. For multi-component systems, the surface composition can differ substantially from the bulk composition. These differences can potentially influence the crystal nucleation process, but the present understanding of the effect is limited. This work investigates the role of a liquid/vapor interface in crystal nucleation in one- and two-component systems.

Methods: Crystal nucleation rates were measured in liquid films without a free surface (sandwiched between two coverslips) and with an open surface (supported on one coverslip). The one-component systems were D-arabitol, posaconazole, acetaminophen, and nifedipine. The two-component systems were nifedipine doped with non-ionic surfactants (Tween 80, Span 80, Triton X-100, Poloxamer 407).

Results: In D-arabitol and posaconazole, crystal nucleation is vastly enhanced at the liquid/vapor interface, by 12 and 9 orders of magnitude, respectively, on a per-molecule basis, and selects a different polymorph from bulk nucleation. In both cases, the surface-nucleating polymorph features a layered structure with each layer containing molecules in parallel (as opposed to antiparallel) arrangement. This structure resembles the molecular packing at the liquid/vapor interface, leading to enhanced nucleation rate and polymorph switch. In contrast to these two systems, acetaminophen and nifedipine show a more modest surface enhancement of nucleation of 5 orders of magnitude with no polymorph switch. The surfactants have a similar effect on bulk nucleation when compared at a common concentration (10 wt %), but different effects on surface nucleation, possibly a result of the different surface concentrations of the surfactants.

Conclusion: This work has revealed a wide range of effects that a liquid/vapor interface can have on the crystal nucleation process. In all the systems tested, surface nucleation is enhanced, not suppressed, relative to bulk nucleation. The anisotropic molecular packing at an interface and its similarity to a latent polymorph can cause a vast surface enhancement of nucleation rate and polymorph switch. In a binary system, surface nucleation is controlled by the same factors described above, as well as the surface enrichment effect of different components. These results are important for controlling crystallization and polymorphism in all systems that have a significant liquid/vapor interface such as atmospheric water and amorphous drug particles.

References: Yao, X. et al. J. Am. Chem. Soc. 2022, ASAP. https://doi.org/10.1021/jacs.2c02623

Acknowledgments: XY and LY thank AbbVie Inc. and the Wisconsin-Puerto Rico Partnership for Research and Education in Materials (Grant NSF DMR-1827894) for supporting this work. HW thanks the Chinese Scholarship Council for financial support.