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Structure prediction, disorder and dynamics in a DMSO solvate of carbamazepine

Structure prediction, disorder and dynamics in a DMSO solvate of carbamazepine
Structure prediction, disorder and dynamics in a DMSO solvate of carbamazepine
We have applied crystal structure prediction methods to understand and predict the formation of a DMSO solvate of the anti-convulsant drug carbamazepine (CBZ), in which the DMSO molecules are disordered. Crystal structure prediction calculations on the 1 : 1 CBZ : DMSO solvate revealed the generation of two similar low energy structures which differ only in the orientation of the DMSO molecules. Analysis of crystal energy landscapes generated at 0 K suggests the possibility of solvent disorder. A combined computational and experimental study of the changes in the orientation of the DMSO within the crystal structure revealed that the nature of the disorder changes with temperature. At low temperature, the DMSO disorder is static whilst at high temperature the DMSO configurations can interconvert by a 180° rotation of the DMSO molecules within the lattice. This 180° rotation of the DMSO molecules drives a phase change from a high temperature dynamically disordered phase to a low temperature phase with static disorder. Crystallisation of a DMSO solvate of the related molecule epoxycarbamazepine resulted in a different degree of DMSO disorder in the crystal structure, despite the similarity of the carbamazepine and epoxycarbamazepine molecules. We believe consideration of disorder and its contribution to entropy and crystal free energies at temperature other than 0 K is fundamental for the accuracy of future energy rankings in crystal structure prediction calculations of similar solvated structures.
1463-9076
12808-12816
Cruz-Cabeza, Aurora J.
6992b540-1934-4172-9655-7fcee52439ba
Day, Graeme M.
e3be79ba-ad12-4461-b735-74d5c4355636
Jones, William
3173abf0-1cfa-45f0-996e-2586b385c21e
Cruz-Cabeza, Aurora J.
6992b540-1934-4172-9655-7fcee52439ba
Day, Graeme M.
e3be79ba-ad12-4461-b735-74d5c4355636
Jones, William
3173abf0-1cfa-45f0-996e-2586b385c21e

Cruz-Cabeza, Aurora J., Day, Graeme M. and Jones, William (2011) Structure prediction, disorder and dynamics in a DMSO solvate of carbamazepine. Physical Chemistry Chemical Physics, 13 (28), 12808-12816. (doi:10.1039/C1CP20927B).

Record type: Article

Abstract

We have applied crystal structure prediction methods to understand and predict the formation of a DMSO solvate of the anti-convulsant drug carbamazepine (CBZ), in which the DMSO molecules are disordered. Crystal structure prediction calculations on the 1 : 1 CBZ : DMSO solvate revealed the generation of two similar low energy structures which differ only in the orientation of the DMSO molecules. Analysis of crystal energy landscapes generated at 0 K suggests the possibility of solvent disorder. A combined computational and experimental study of the changes in the orientation of the DMSO within the crystal structure revealed that the nature of the disorder changes with temperature. At low temperature, the DMSO disorder is static whilst at high temperature the DMSO configurations can interconvert by a 180° rotation of the DMSO molecules within the lattice. This 180° rotation of the DMSO molecules drives a phase change from a high temperature dynamically disordered phase to a low temperature phase with static disorder. Crystallisation of a DMSO solvate of the related molecule epoxycarbamazepine resulted in a different degree of DMSO disorder in the crystal structure, despite the similarity of the carbamazepine and epoxycarbamazepine molecules. We believe consideration of disorder and its contribution to entropy and crystal free energies at temperature other than 0 K is fundamental for the accuracy of future energy rankings in crystal structure prediction calculations of similar solvated structures.

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More information

e-pub ahead of print date: 14 May 2011
Published date: 2011
Organisations: Organic Chemistry: Synthesis, Catalysis and Flow, Computational Systems Chemistry

Identifiers

Local EPrints ID: 343419
URI: http://eprints.soton.ac.uk/id/eprint/343419
ISSN: 1463-9076
PURE UUID: 764fdf51-d67b-48a1-9c41-6932c93045f5
ORCID for Graeme M. Day: ORCID iD orcid.org/0000-0001-8396-2771

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Date deposited: 05 Oct 2012 15:36
Last modified: 15 Mar 2024 03:44

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Contributors

Author: Aurora J. Cruz-Cabeza
Author: Graeme M. Day ORCID iD
Author: William Jones

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