| Title: |
A Prolific Solvate Former, Galunisertib, under the Pressure of Crystal Structure Prediction, Produces Ten Diverse Polymorphs |
| Authors: |
Bhardwaj, RM; McMahon, JA; Nyman, J; Price, LS; Konar, S; Oswald, IDH; Pulham, CR; Price, SL; Reutzel-Edens, SM |
| Source: |
Journal of the American Chemical Society , 141 (35) pp. 13887-13897. (2019) |
| Publication Year: |
2019 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
galunisertib; solid form screening; polymorphism; hydrate; solvate; crystal structure prediction; solid state NMR; crystal structure; thermal analysis |
| Description: |
The solid form screening of galunisertib produced many solvates, prompting an extensive investigation into possible risks to the development of the favored monohydrate form. Inspired by crystal structure prediction, the search for neat polymorphs was expanded to an unusual range of experiments, including melt crystallization under pressure, to work around solvate formation and the thermal instability of the molecule. Ten polymorphs of galunisertib were found; however, the structure predicted to be the most stable has yet to be obtained. We present the crystal structures of all ten unsolvated polymorphs of galunisertib, showing how state-of-the-art characterization methods can be combined with emerging computational modeling techniques to produce a complete structure landscape and assess the risk of late-appearing, more stable polymorphs. The exceptional conformational polymorphism of this prolific solvate former invites further development of methods, computational and experimental, that are applicable to larger, flexible molecules with complex solid form landscapes. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10080781/9/Price%20Galunisertib_JACS_revision.pdf; https://discovery.ucl.ac.uk/id/eprint/10080781/3/GAL_ESI_revision.pdf; https://discovery.ucl.ac.uk/id/eprint/10080781/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10080781/9/Price%20Galunisertib_JACS_revision.pdf; https://discovery.ucl.ac.uk/id/eprint/10080781/3/GAL_ESI_revision.pdf; https://discovery.ucl.ac.uk/id/eprint/10080781/ |
| Rights: |
open |
| Accession Number: |
edsbas.D43C5071 |
| Database: |
BASE |