Hall MJ

Heaps SE

McMonagle CJ

Probert MR

Ragbirsingh R

Steed JW

Thaw P

Tyler AR

Waddell PG

Single crystal X-ray diffraction analysis (SCXRD) constitutes a universal approach for the elucidation of molecular structure and the study of crystalline forms. However, the discovery of viable crystallisation conditions remains both experimentally challenging and resource intensive, in time and quantity of analyte(s). We report a robot-assisted, high-throughput method for the crystallisation of organic-soluble small molecules, employing only micrograms of analyte per experiment. This allows hundreds of crystallisation conditions to be screened in parallel, with minimal overall sample requirements. Crystals suitable for SCXRD are grown from nanolitre droplets of a solution of analyte in organic solvent(s), each of which is encapsulated within an inert oil to control the rate of solvent loss. This encapsulated nanodroplet crystallisation methodology can also be used to search for new crystal forms, as exemplified through both our discovery of a new (thirteenth) polymorph of the olanzapine precursor ROY and SCXRD analysis of the “uncrystallisable” agrochemical dithianon

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Encapsulated Nanodroplet Crystallization of Organic-Soluble Small Molecules

Encapsulated Nanodroplet Crystallization of Organic-Soluble Small Molecules

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