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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.

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Andrew R. Tyler

Ronnie Ragbirsingh

Charles J. McMonagle

Paul G. Waddell

Paul Thaw

Michael J. Hall

Michael R. Probert


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.


Tyler, A. R., Ragbirsingh, R., McMonagle, C. J., Waddell, P. G., Heaps, S. E., Steed, J. W., …Probert, M. R. (2020). Encapsulated Nanodroplet Crystallization of Organic-Soluble Small Molecules. Chem, 6(7), 1755-1765.

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


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