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Encapsulated nanodroplet crystallization of organic-soluble small molecules

DOI: 10.1016/j.chempr.2020.04.009 DOI Help

Authors: Andrew R. Tyler (Newcastle University) , Ronnie Ragbirsingh (Newcastle University) , Charles J. Mcmonagle (Newcastle University) , Paul G. Waddell (Newcastle University) , Sarah E. Heaps (Newcastle University) , Jonathan W. Steed (Durham University) , Paul Thaw (SPT Labtech) , Michael J. Hall (Newcastle University) , Michael R. Probert (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Chem

State: Published (Approved)
Published: May 2020
Diamond Proposal Number(s): 22240

Open Access Open Access

Abstract: 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 crystallization conditions remains both experimentally challenging and resource intensive in both time and the quantity of analyte(s). We report a robot-assisted, high-throughput method for the crystallization of organic-soluble small molecules in which we employ only micrograms of analyte per experiment. This allows hundreds of crystallization conditions to be screened in parallel with minimal overall sample requirements. Crystals suitable for SCXRD are grown from nanoliter 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 crystallization methodology can also be used to search for new crystal forms, as exemplified through both our discovery of a new (13th) polymorph of the olanzapine precursor ROY and SCXRD analysis of the “uncrystallizable” agrochemical dithianon.

Journal Keywords: ENaCtl; high-throughput; oil encapsulation; crystallization; single crystal; X-ray diffraction; small molecule; polymorph; ROY; dithianon

Subject Areas: Chemistry

Instruments: I19-Small Molecule Single Crystal Diffraction

Added On: 13/05/2020 10:20

Discipline Tags:

Organic Chemistry Chemistry

Technical Tags:

Diffraction Single Crystal X-ray Diffraction (SXRD)