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Modeling the interplay of inter- and intramolecular hydrogen bonding in conformational polymorphs

Karamertzanis, Panagiotis G., Day, Graeme M., Welch, Gareth W.A., Kendrick, John, Leusen, Frank J.J., Neumann, Marcus A. and Price, Sarah L. (2008) Modeling the interplay of inter- and intramolecular hydrogen bonding in conformational polymorphs The Journal of Chemical Physics, 128, (24), 244708-[17pp]. (doi:10.1063/1.2937446).

Record type: Article


The predicted stability differences of the conformational polymorphs of oxalyl dihydrazide and ortho-acetamidobenzamide are unrealistically large when the modeling of intermolecular energies is solely based on the isolated-molecule charge density, neglecting charge density polarization. Ab initio calculated crystal electron densities showed qualitative differences depending on the spatial arrangement of molecules in the lattice with the greatest variations observed for polymorphs that differ in the extent of inter- and intramolecular hydrogen bonding. We show that accounting for induction dramatically alters the calculated stability order of the polymorphs and reduces their predicted stability differences to be in better agreement with experiment. Given the challenges in modeling conformational polymorphs with marked differences in hydrogen bonding geometries, we performed an extensive periodic density functional study with a range of exchange-correlation functionals using both atomic and plane wave basis sets. Although such electronic structure methods model the electrostatic and polarization contributions well, the underestimation of dispersion interactions by current exchange-correlation functionals limits their applicability. The use of an empirical dispersion-corrected density functional method consistently reduces the structural deviations between the experimental and energy minimized crystal structures and achieves plausible stability differences. Thus, we have established which types of models may give worthwhile relative energies for crystal structures and other condensed phases of flexible molecules with intra- and intermolecular hydrogen bonding capabilities, advancing the possibility of simulation studies on polymorphic pharmaceuticals.

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Published date: 24 June 2008
Keywords: ab initio calculations, band structure, crystal structure, density functional theory, electron density, hydrogen bonds, polymorphism
Organisations: Organic Chemistry: Synthesis, Catalysis and Flow, Computational Systems Chemistry


Local EPrints ID: 343440
ISSN: 0021-9606
PURE UUID: e1f9ff9a-5040-45ac-b1de-1962c9bc4fac
ORCID for Graeme M. Day: ORCID iD

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Date deposited: 08 Oct 2012 10:12
Last modified: 18 Jul 2017 05:22

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Author: Panagiotis G. Karamertzanis
Author: Graeme M. Day ORCID iD
Author: Gareth W.A. Welch
Author: John Kendrick
Author: Frank J.J. Leusen
Author: Marcus A. Neumann
Author: Sarah L. Price

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