Atomic-level structure determination of amorphous molecular solids by NMR

DOI

Structure determination of amorphous materials remains challenging, owing to the disorder inherent to these materials. Nuclear magnetic resonance (NMR) powder crystallography is a powerful method to determine the structure of molecular solids, but disorder leads to both a high degree of overlap between measured signals, resulting in challenges for spectral assignment, and prevents the unambiguous identification of a single modelled periodic structure as representative of the whole material. Here, we determine the atomic-level ensemble structure of the amorphous form of the drug AZD4625 by combining solid-state NMR experiments with molecular dynamics (MD) simulations and machine-learned chemical shifts. By considering the combined shifts of all 1H and 13C atomic sites in the molecule, we determine the structure of the amorphous form by identifying an ensemble of local molecular environments that are in agreement with experiment. We then extract preferred conformations and intermolecular interactions in the amorphous sample, and analyze the structure in terms of the hydrogen bonding and conformational factors that stabilize the amorphous form of the drug.

Identifier
DOI https://doi.org/10.24435/materialscloud:gk-51
Related Identifier https://doi.org/10.1038/s41467-023-40853-2
Related Identifier https://archive.materialscloud.org/communities/mcarchive
Related Identifier https://doi.org/10.24435/materialscloud:k0-j1
Metadata Access https://archive.materialscloud.org/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai:materialscloud.org:1832
Provenance
Creator Cordova, Manuel; Moutzouri, Pinelopi; Nilsson Lill, Sten O.; Cousen, Alexander; Kearns, Martin; Norberg, Stefan T.; Svensk Ankarberg, Anna; McCabe, James; Pinon, Arthur C.; Schantz, Staffan; Emsley, Lyndon
Publisher Materials Cloud
Contributor Cordova, Manuel; Schantz, Staffan; Emsley, Lyndon
Publication Year 2023
Rights info:eu-repo/semantics/openAccess; Creative Commons Attribution Share Alike 4.0 International; https://creativecommons.org/licenses/by-sa/4.0/legalcode
OpenAccess true
Contact archive(at)materialscloud.org
Representation
Language English
Resource Type info:eu-repo/semantics/other
Format application/zip; text/markdown
Discipline Materials Science and Engineering