Insights into the structure-property relationship of pharmaceutical co-crystals: charge density and quantum chemical approaches
Insights into the structure-property relationship of pharmaceutical co-crystals: charge density and quantum chemical approaches
A subset of co-crystal systems of the antipyretic and analgesic drug, propyphenazone, are used to probe the nature of the drug···co-former interactions. The experimental electron density distribution, based on very high-resolution single crystal diffraction, has been modelled and an analysis undertaken using Bader's Atoms in Molecules approach. Atomic charges, intermolecular interactions and their energies have been subsequently derived and compared between systems. Complementary theoretical calculations are used to derive interaction energies for intermolecular interactions beyond atom···atom contacts. These permit the deconvolution of the intermolecular interactions into their constituent energy components for a comprehensive analysis. This approach provides an insight into the factors affecting the assembly of the solid state, with the case of pharmaceutical co-crystals being highlighted in this work. Furthermore, this approach enables analysis of the effect of the co-former on various influencing factors that determine the physicochemical properties of these multi-component systems.
Interaction analysis, charge density, co-crystal
Mapp, Lucy Kristina
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Cadden, Joseph
86c93935-5d3e-4c0c-bd73-af51f60c9d1c
Klooster, Wim
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Aitipamula, Srinivasulu
e1ca2522-d14f-4f82-89ab-1996a021582a
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
15 January 2021
Mapp, Lucy Kristina
b90136ce-37b0-464a-8934-d44a8c2d7e48
Cadden, Joseph
86c93935-5d3e-4c0c-bd73-af51f60c9d1c
Klooster, Wim
64dc0111-f415-4226-9189-45764c0933d9
Aitipamula, Srinivasulu
e1ca2522-d14f-4f82-89ab-1996a021582a
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Mapp, Lucy Kristina, Cadden, Joseph, Klooster, Wim, Aitipamula, Srinivasulu and Coles, Simon J.
(2021)
Insights into the structure-property relationship of pharmaceutical co-crystals: charge density and quantum chemical approaches.
Journal of Molecular Structure, 1224, [129270].
(doi:10.1016/j.molstruc.2020.129270).
Abstract
A subset of co-crystal systems of the antipyretic and analgesic drug, propyphenazone, are used to probe the nature of the drug···co-former interactions. The experimental electron density distribution, based on very high-resolution single crystal diffraction, has been modelled and an analysis undertaken using Bader's Atoms in Molecules approach. Atomic charges, intermolecular interactions and their energies have been subsequently derived and compared between systems. Complementary theoretical calculations are used to derive interaction energies for intermolecular interactions beyond atom···atom contacts. These permit the deconvolution of the intermolecular interactions into their constituent energy components for a comprehensive analysis. This approach provides an insight into the factors affecting the assembly of the solid state, with the case of pharmaceutical co-crystals being highlighted in this work. Furthermore, this approach enables analysis of the effect of the co-former on various influencing factors that determine the physicochemical properties of these multi-component systems.
Text
PROPY_CD JMolStruct Final
- Accepted Manuscript
More information
Accepted/In Press date: 15 September 2020
e-pub ahead of print date: 16 September 2020
Published date: 15 January 2021
Additional Information:
Funding Information:
This research was funded by the Science and Engineering Research Council of A*STAR (Agency for Science, Technology and Research), Singapore. L. K. Mapp and J. Cadden thank A*STAR for a research fellowship jointly funded by the A*STAR Research Attachment Programme (ARAP) and The University of Southampton.
Funding Information:
This research was funded by the Science and Engineering Research Council of A*STAR (Agency for Science, Technology and Research), Singapore. L. K. Mapp and J. Cadden thank A*STAR for a research fellowship jointly funded by the A*STAR Research Attachment Programme (ARAP) and The University of Southampton.
Publisher Copyright:
© 2020
Keywords:
Interaction analysis, charge density, co-crystal
Identifiers
Local EPrints ID: 444358
URI: http://eprints.soton.ac.uk/id/eprint/444358
ISSN: 0022-2860
PURE UUID: 89572f9d-7ec9-49d8-992b-693e59c5e648
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Date deposited: 14 Oct 2020 16:30
Last modified: 17 Mar 2024 05:58
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Contributors
Author:
Lucy Kristina Mapp
Author:
Joseph Cadden
Author:
Wim Klooster
Author:
Srinivasulu Aitipamula
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