Encapsulated nanodroplet crystallization of organic-soluble small molecules.

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