Encapsulated Nanodroplet Crystallization of Organic-Soluble Small Molecules

Tyler, Andrew R.; Ragbirsingh, Ronnie; McMonagle, Charles J.; Waddell, Paul G.; Heaps, Sarah E.; Steed, Jonathan W.; Thaw, Paul; Hall, Michael J.; Probert, Michael R.

Abstract

Small molecules can form crystalline solids, in which individual molecules pack together into ordered three-dimensional arrays. Once a suitable crystal is grown, the packing and atomic connectivity of the constituent molecules can be studied by X-ray diffraction. However, the discovery of experimental conditions for successful crystal growth is often challenging. We have developed a nanoscale crystallization technique for organic-soluble small molecules by using high-throughput liquid-handling robotics to undertake multiple crystallization experiments simultaneously with minimal sample requirements and high success rates. We showcase our methodology through the crystallization of a diverse set of small molecules, including “uncrystallizables,” combined with structural analysis by X-ray diffraction. We anticipate that this rapid and reliable method for small-molecule crystallization will have far-reaching impact, facilitating academic and industrial research in the molecular sciences.

Citation

Tyler, A. R., Ragbirsingh, R., McMonagle, C. J., Waddell, P. G., Heaps, S. E., Steed, J. W., Thaw, P., Hall, M. J., & Probert, M. R. (2020). Encapsulated Nanodroplet Crystallization of Organic-Soluble Small Molecules. Chem, 6(7), 1755-1765. https://doi.org/10.1016/j.chempr.2020.04.009

• Journal Article Type: Article
• Acceptance Date: Apr 15, 2020
• Online Publication Date: Jul 9, 2020
• Publication Date: 2020-07
• Deposit Date: May 27, 2020
• Publicly Available Date: Jul 15, 2020
• Journal: Chem
• Print ISSN: 2451-9308
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 7
• Pages: 1755-1765
• DOI: https://doi.org/10.1016/j.chempr.2020.04.009
• Public URL: https://durham-repository.worktribe.com/output/1270006