How many more polymorphs of ROY remain undiscovered
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
With 12 crystal forms, 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecabonitrile (a.k.a. ROY) holds the current record for the largest number of fully characterized organic crystal polymorphs. Four of these polymorph structures have been reported since 2019, raising the question of how many more ROY polymorphs await future discovery. Employing crystal structure prediction and accurate energy rankings derived from conformational energy-corrected density functional theory, this study presents the first crystal energy landscape for ROY that agrees well with experiment. The lattice energies suggest that the seven most stable ROY polymorphs (and nine of the twelve lowest-energy forms) on the Z′ = 1 landscape have already been discovered experimentally. Discovering any new polymorphs at ambient pressure will likely require specialized crystallization techniques capable of trapping metastable forms. At pressures above 10 GPa, however, a new crystal form is predicted to become enthalpically more stable than all known polymorphs, suggesting that further high-pressure experiments on ROY may be warranted. This work highlights the value of high-accuracy crystal structure prediction for solid-form screening and demonstrates how pragmatic conformational energy corrections can overcome the limitations of conventional density functionals for conformational polymorphs.
Date Issued
2022-02-07
Date Acceptance
2021-12-10
Citation
Chemical Science, 2022, 13 (5), pp.1288-1297
ISSN
2041-6520
Publisher
The Royal Society of Chemistry
Start Page
1288
End Page
1297
Journal / Book Title
Chemical Science
Volume
13
Issue
5
Copyright Statement
© 2022 The Author(s). Published by the Royal Society of Chemistry Open Access Article. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35222912
PII: d1sc06074k
Subjects
AB-INITIO GENERATION
ACCURATE ENERGY RANKING
Chemistry
Chemistry, Multidisciplinary
CRYSTALLIZATION
CRYSTAL-STRUCTURE PREDICTION
DIPOLE DISPERSION MODEL
EFFICIENT REPRESENTATION
FORM
INTRAMOLECULAR ENERGY
LANDSCAPES
MOLECULAR-CRYSTALS
Physical Sciences
Science & Technology
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2021-12-13