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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
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
0022-2860
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
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).

Record type: Article

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.

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PROPY_CD JMolStruct Final - Accepted Manuscript
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More information

Accepted/In Press date: 15 September 2020
e-pub ahead of print date: 16 September 2020
Published date: 15 January 2021
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
ORCID for Simon J. Coles: ORCID iD orcid.org/0000-0001-8414-9272

Catalogue record

Date deposited: 14 Oct 2020 16:30
Last modified: 16 Sep 2021 04:01

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