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High-throughput co-former screening and structural elucidation using resonant acoustic mixing and 3D electron diffraction

High-throughput co-former screening and structural elucidation using resonant acoustic mixing and 3D electron diffraction
High-throughput co-former screening and structural elucidation using resonant acoustic mixing and 3D electron diffraction
Integrating 3D electron diffraction (3D ED) analysis into the screening workflow of multicomponent systems facilitates direct structural determination from high-throughput resonant acoustic mixing (RAM). This screening method enables the investigation of a wide experimental landscape, including various co-formers and solvents, within a short timeframe. Consequently, it allows for the rapid and efficient generation of numerous potential novel materials. Hit identification from the screening process is conducted through high-throughput X-ray powder diffraction (XRPD) and Raman microscopy, followed by structural determination of selected novel phases by 3D ED. This workflow has been demonstrated using sulfasalazine as an example active pharmaceutical ingredient (API), encompassing a broad range of crystallisation conditions. Multiple distinct diffractograms were observed, leading to the discovery and structural characterisation of two novel multicomponent systems of sulfasalazine by 3D ED, one of which shows evidence of tautomerisation within a single crystal.
1466-8033
Danks, Jacob
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Rainer, Daniel N.
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Hamza, Ahmed S.
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Coles, Simon J.
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Carter, Anthony B.
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Benson, Joseph E.G.
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Danks, Jacob
8f476d6f-666b-4017-82f0-7f816bca92a3
Rainer, Daniel N.
ece5513b-0f92-4143-bddd-a4ae2802ae6d
Hamza, Ahmed S.
b3c6e15c-8c0b-4872-9ca8-9bb82bc528c7
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Carter, Anthony B.
933bbb3b-a4d9-4e6d-9968-6e4774b8a837
Benson, Joseph E.G.
c7bbead0-54ba-4a8f-b758-d41683b9eeac

Danks, Jacob, Rainer, Daniel N., Hamza, Ahmed S., Coles, Simon J., Carter, Anthony B. and Benson, Joseph E.G. (2026) High-throughput co-former screening and structural elucidation using resonant acoustic mixing and 3D electron diffraction. CrystEngComm. (doi:10.1039/D5CE01188D).

Record type: Article

Abstract

Integrating 3D electron diffraction (3D ED) analysis into the screening workflow of multicomponent systems facilitates direct structural determination from high-throughput resonant acoustic mixing (RAM). This screening method enables the investigation of a wide experimental landscape, including various co-formers and solvents, within a short timeframe. Consequently, it allows for the rapid and efficient generation of numerous potential novel materials. Hit identification from the screening process is conducted through high-throughput X-ray powder diffraction (XRPD) and Raman microscopy, followed by structural determination of selected novel phases by 3D ED. This workflow has been demonstrated using sulfasalazine as an example active pharmaceutical ingredient (API), encompassing a broad range of crystallisation conditions. Multiple distinct diffractograms were observed, leading to the discovery and structural characterisation of two novel multicomponent systems of sulfasalazine by 3D ED, one of which shows evidence of tautomerisation within a single crystal.

Text
RAM 3D ED article submitted - Accepted Manuscript
Available under License Creative Commons Attribution.
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More information

Accepted/In Press date: 16 March 2026
e-pub ahead of print date: 17 March 2026

Identifiers

Local EPrints ID: 510314
URI: http://eprints.soton.ac.uk/id/eprint/510314
ISSN: 1466-8033
PURE UUID: f2ba7677-e8a5-4e4a-aa59-3ecf545c836e
ORCID for Daniel N. Rainer: ORCID iD orcid.org/0000-0002-3272-3161
ORCID for Simon J. Coles: ORCID iD orcid.org/0000-0001-8414-9272

Catalogue record

Date deposited: 25 Mar 2026 17:40
Last modified: 26 Mar 2026 03:08

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Contributors

Author: Jacob Danks
Author: Daniel N. Rainer ORCID iD
Author: Ahmed S. Hamza
Author: Simon J. Coles ORCID iD
Author: Anthony B. Carter
Author: Joseph E.G. Benson

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