Issue 5, 2022

How many more polymorphs of ROY remain undiscovered


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.

Graphical abstract: How many more polymorphs of ROY remain undiscovered

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Article information

Article type
Edge Article
02 Nov 2021
10 Dec 2021
First published
13 Dec 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2022,13, 1288-1297

How many more polymorphs of ROY remain undiscovered

G. J. O. Beran, I. J. Sugden, C. Greenwell, D. H. Bowskill, C. C. Pantelides and C. S. Adjiman, Chem. Sci., 2022, 13, 1288 DOI: 10.1039/D1SC06074K

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