The University of Southampton
University of Southampton Institutional Repository

Exploring the multi-minima behavior of small molecule crystal polymorphs at finite temperature

Exploring the multi-minima behavior of small molecule crystal polymorphs at finite temperature
Exploring the multi-minima behavior of small molecule crystal polymorphs at finite temperature
The predicted ambient-temperature crystal structures of organic small molecules are often represented by a single energy-minimized configuration at zero Kelvin. This procedure effectively collapses the ensemble of configurations that would be present at ambient temperature into a single representative structure. This simplification is likely to break down if the crystal structure has multiple different lattice energy minima within the ambient temperature ensemble. In this paper, we explore the existence of multiple minima within finite-temperature crystal basins by sampling crystals at a range of temperatures followed by rapidly quenching the configurations. We then observe whether each crystal returns to the original minimum or to an ensemble of minima on the lattice energy landscape. Eight of the twelve compounds examined in this work have at least one polymorph with multi-minima behavior. These multi-minima basins have implications for crystal structure prediction studies, and it is therefore important to understand the factors that lead a crystal structure to have multiple minima. We find that in general, the existence of multiple minima within a crystal basin is more likely for the compounds that are larger and have more flexibility. We find that the number of minima found tends to increase with the sampling temperature, and the lattice energy of minima found from the same finite-temperature trajectory can vary by > 2.0 kJ/mol. Finally, we show that the lattice energy minima contained within a single ambient temperature basin can have different space groups and numbers of molecules in the asymmetric unit. Overall, the data suggest that many experimental crystal polymorphs are highly likely to have multi-minima behavior and are best described by an ensemble of structures encompassing many minima rather than by a single lattice-energy minimum.
1528-7483
5568-5580
Dybeck, Eric C.
c80a5868-1b4a-49af-a1d2-dd78f845c9fc
Mcmahon, David P.
026a4184-d048-4a12-964e-5c6d9da81c68
Day, Graeme M.
e3be79ba-ad12-4461-b735-74d5c4355636
Shirts, Michael R.
4950936b-cadb-4145-8a2f-c32404143e93
Dybeck, Eric C.
c80a5868-1b4a-49af-a1d2-dd78f845c9fc
Mcmahon, David P.
026a4184-d048-4a12-964e-5c6d9da81c68
Day, Graeme M.
e3be79ba-ad12-4461-b735-74d5c4355636
Shirts, Michael R.
4950936b-cadb-4145-8a2f-c32404143e93

Dybeck, Eric C., Mcmahon, David P., Day, Graeme M. and Shirts, Michael R. (2019) Exploring the multi-minima behavior of small molecule crystal polymorphs at finite temperature. Crystal Growth & Design, 19 (10), 5568-5580. (doi:10.1021/acs.cgd.9b00476).

Record type: Article

Abstract

The predicted ambient-temperature crystal structures of organic small molecules are often represented by a single energy-minimized configuration at zero Kelvin. This procedure effectively collapses the ensemble of configurations that would be present at ambient temperature into a single representative structure. This simplification is likely to break down if the crystal structure has multiple different lattice energy minima within the ambient temperature ensemble. In this paper, we explore the existence of multiple minima within finite-temperature crystal basins by sampling crystals at a range of temperatures followed by rapidly quenching the configurations. We then observe whether each crystal returns to the original minimum or to an ensemble of minima on the lattice energy landscape. Eight of the twelve compounds examined in this work have at least one polymorph with multi-minima behavior. These multi-minima basins have implications for crystal structure prediction studies, and it is therefore important to understand the factors that lead a crystal structure to have multiple minima. We find that in general, the existence of multiple minima within a crystal basin is more likely for the compounds that are larger and have more flexibility. We find that the number of minima found tends to increase with the sampling temperature, and the lattice energy of minima found from the same finite-temperature trajectory can vary by > 2.0 kJ/mol. Finally, we show that the lattice energy minima contained within a single ambient temperature basin can have different space groups and numbers of molecules in the asymmetric unit. Overall, the data suggest that many experimental crystal polymorphs are highly likely to have multi-minima behavior and are best described by an ensemble of structures encompassing many minima rather than by a single lattice-energy minimum.

Text
Minima_Interconversion - Accepted Manuscript
Restricted to Repository staff only until 25 July 2020.
Request a copy

More information

Accepted/In Press date: 25 July 2019
e-pub ahead of print date: 6 August 2019
Published date: 2 October 2019

Identifiers

Local EPrints ID: 433117
URI: http://eprints.soton.ac.uk/id/eprint/433117
ISSN: 1528-7483
PURE UUID: faaf5c96-785b-4084-acf4-5daa74020dcc
ORCID for Graeme M. Day: ORCID iD orcid.org/0000-0001-8396-2771

Catalogue record

Date deposited: 08 Aug 2019 16:30
Last modified: 17 Dec 2019 01:38

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×