The University of Southampton
University of Southampton Institutional Repository

A strategy for predicting the crystal structures of flexible molecules: the polymorphism of phenobarbital

A strategy for predicting the crystal structures of flexible molecules: the polymorphism of phenobarbital
A strategy for predicting the crystal structures of flexible molecules: the polymorphism of phenobarbital
A computational exploration of the low energy crystal structures of the pharmaceutical molecule phenobarbital is presented as a test of an approach for the crystal structure prediction of flexible molecules. Traditional transferable force field methods of modelling flexible molecules are unreliable for the level of accuracy required in crystal structure prediction and we outline a strategy for improving the evaluation of relative energies of large sets of crystal structures. The approach involves treating the molecule as a set of linked rigid units, whose conformational energy is expressed as a function of the relative orientations of the rigid groups. The conformational energy is calculated by electronic structure methods and the intermolecular interactions using an atomic multipole description of electrostatics. A key consideration in our approach is the scalability to more typical pharmaceutical molecules of higher molecular weight with many more atoms and degrees of flexibility. Based on our calculations, crystal structures are proposed for the as-yet uncharacterised forms IV and V, as well as further polymorphs of phenobarbital.
1463-9076
1693-1704
Day, Graeme M.
e3be79ba-ad12-4461-b735-74d5c4355636
Motherwell, W.D.S.
0721bf42-563f-4292-a54d-fe3a282ae6d4
Jones, W.
c18f6cea-13e4-4c34-b280-f95cf8c6dd12
Day, Graeme M.
e3be79ba-ad12-4461-b735-74d5c4355636
Motherwell, W.D.S.
0721bf42-563f-4292-a54d-fe3a282ae6d4
Jones, W.
c18f6cea-13e4-4c34-b280-f95cf8c6dd12

Day, Graeme M., Motherwell, W.D.S. and Jones, W. (2007) A strategy for predicting the crystal structures of flexible molecules: the polymorphism of phenobarbital. Physical Chemistry Chemical Physics, 9 (14), 1693-1704. (doi:10.1039/B612190J).

Record type: Article

Abstract

A computational exploration of the low energy crystal structures of the pharmaceutical molecule phenobarbital is presented as a test of an approach for the crystal structure prediction of flexible molecules. Traditional transferable force field methods of modelling flexible molecules are unreliable for the level of accuracy required in crystal structure prediction and we outline a strategy for improving the evaluation of relative energies of large sets of crystal structures. The approach involves treating the molecule as a set of linked rigid units, whose conformational energy is expressed as a function of the relative orientations of the rigid groups. The conformational energy is calculated by electronic structure methods and the intermolecular interactions using an atomic multipole description of electrostatics. A key consideration in our approach is the scalability to more typical pharmaceutical molecules of higher molecular weight with many more atoms and degrees of flexibility. Based on our calculations, crystal structures are proposed for the as-yet uncharacterised forms IV and V, as well as further polymorphs of phenobarbital.

Full text not available from this repository.

More information

e-pub ahead of print date: 24 January 2007
Organisations: Organic Chemistry: Synthesis, Catalysis and Flow, Chemistry, Computational Systems Chemistry

Identifiers

Local EPrints ID: 343447
URI: http://eprints.soton.ac.uk/id/eprint/343447
ISSN: 1463-9076
PURE UUID: 8d17b761-a9f0-462d-8904-9283cf956548
ORCID for Graeme M. Day: ORCID iD orcid.org/0000-0001-8396-2771

Catalogue record

Date deposited: 05 Feb 2013 13:13
Last modified: 26 Nov 2019 01:37

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.

×