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Encapsulated Nanodroplet Crystallization of Organic-Soluble Small Molecules

Lookup NU author(s): Andrew Tyler, Ronnie Ragbirsingh, Dr Charlie McMonagleORCiD, Dr Paul Waddell, Dr Sarah Heaps, Dr Michael HallORCiD, Professor Mike ProbertORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

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 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.

Publication metadata

Author(s): Tyler AR, Ragbirsingh R, McMonagle CJ, Waddell PG, Heaps SE, Steed JW, Thaw P, Hall MJ, Probert MR

Publication type: Article

Publication status: Published

Journal: Chem

Year: 2020

Volume: 6

Issue: 7

Pages: 1755-1765

Print publication date: 09/07/2020

Online publication date: 07/05/2020

Acceptance date: 15/04/2020

Date deposited: 03/07/2020

ISSN (print): 2451-9308

ISSN (electronic): 2451-9294

Publisher: Cell Press

URL: https://doi.org/10.1016/j.chempr.2020.04.009

DOI: 10.1016/j.chempr.2020.04.009

Data Access Statement: https://www.ccdc.cam.ac.uk/structures

Notes: https://www.sciencedirect.com/science/article/pii/S2451929420301777

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