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Enantiotropically-related polymorphs of {4-(4-chloro-3-fluorophenyl)-2-[4-(methyloxy)phenyl]-1,3-thiazol-5-yl} acetic acid: Crystal structures and multinuclear solid-state NMR

Enantiotropically-related polymorphs of {4-(4-chloro-3-fluorophenyl)-2-[4-(methyloxy)phenyl]-1,3-thiazol-5-yl} acetic acid: Crystal structures and multinuclear solid-state NMR
Enantiotropically-related polymorphs of {4-(4-chloro-3-fluorophenyl)-2-[4-(methyloxy)phenyl]-1,3-thiazol-5-yl} acetic acid: Crystal structures and multinuclear solid-state NMR
Single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), and solid-state NMR (SSNMR) techniques are used to analyze the structures of two nonsolvated polymorphs of {4-(4-chloro-3-fluorophenyl)-2-[4-(methyloxy)phenyl]-1,3-thia-zol-5-yl} acetic acid. These polymorphs are enantiotropically-related with a thermodynamic transition temperature of 35 +/- 3 degrees C. The crystal structure of Form 1, which is thermodynamically more stable at lower temperatures, was determined by SCXRD. The crystal structure of Form 2 was determined using PXRD structure solution methods that were assisted using two types of SSNMR experiments, dipolar connectivity experiments and chemical shift measurements. These experiments determined certain aspects of local conformation and intermolecular packing in Form 2 in comparison to Form 1, and provided qualitative knowledge that assisted in obtaining the best possible powder structure solution from the X-ray data. NMR chemical shifts for H-1, C-13, N-15, and F-19 nuclei in Forms 1 and 2 are sensitive to hydrogen-bonding behavior, molecular conformation, and aromatic-stacking interactions. Density functional theory (DFT) geometry optimizations were used in tandem with Rietveld refinement and NMR chemical shielding calculations to improve and verify the Form 2 structure. The energy balance of the system and other properties relevant to drug development are predicted and discussed. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4756-4782, 2008
0022-3549
4756-4782
Vogt, Frederick G.
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Katrincic, Lee M.
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Long, Stacey T.
e112b849-411f-4abd-a1d8-9731f3f7fdb5
Mueller, Ronald L.
cbe4600b-9c47-4662-86f3-1dfb59f4d785
Carlton, Robert A.
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Sun, Yan T.
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Johnson, Matthew N.
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Copley, Royston C. B.
681579f7-9350-488a-abe6-87a6746f9b2c
Light, Mark Edward
cf57314e-6856-491b-a8d2-2dffc452e161
Vogt, Frederick G.
7d079821-4529-4974-90a7-35fdc87a37d6
Katrincic, Lee M.
170417b3-5c8d-4dea-a9b1-b71bb4407db5
Long, Stacey T.
e112b849-411f-4abd-a1d8-9731f3f7fdb5
Mueller, Ronald L.
cbe4600b-9c47-4662-86f3-1dfb59f4d785
Carlton, Robert A.
5a3496f8-32d4-4fbc-bb1d-db23aded6607
Sun, Yan T.
e5619794-8ad0-4025-b768-e5220142151a
Johnson, Matthew N.
7df05506-9f8b-4dec-bd06-ae0a5366bac0
Copley, Royston C. B.
681579f7-9350-488a-abe6-87a6746f9b2c
Light, Mark Edward
cf57314e-6856-491b-a8d2-2dffc452e161

Vogt, Frederick G., Katrincic, Lee M., Long, Stacey T., Mueller, Ronald L., Carlton, Robert A., Sun, Yan T., Johnson, Matthew N., Copley, Royston C. B. and Light, Mark Edward (2008) Enantiotropically-related polymorphs of {4-(4-chloro-3-fluorophenyl)-2-[4-(methyloxy)phenyl]-1,3-thiazol-5-yl} acetic acid: Crystal structures and multinuclear solid-state NMR. Journal of Pharmaceutical Sciences, 97 (11), 4756-4782. (doi:10.1002/jps.21336).

Record type: Article

Abstract

Single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), and solid-state NMR (SSNMR) techniques are used to analyze the structures of two nonsolvated polymorphs of {4-(4-chloro-3-fluorophenyl)-2-[4-(methyloxy)phenyl]-1,3-thia-zol-5-yl} acetic acid. These polymorphs are enantiotropically-related with a thermodynamic transition temperature of 35 +/- 3 degrees C. The crystal structure of Form 1, which is thermodynamically more stable at lower temperatures, was determined by SCXRD. The crystal structure of Form 2 was determined using PXRD structure solution methods that were assisted using two types of SSNMR experiments, dipolar connectivity experiments and chemical shift measurements. These experiments determined certain aspects of local conformation and intermolecular packing in Form 2 in comparison to Form 1, and provided qualitative knowledge that assisted in obtaining the best possible powder structure solution from the X-ray data. NMR chemical shifts for H-1, C-13, N-15, and F-19 nuclei in Forms 1 and 2 are sensitive to hydrogen-bonding behavior, molecular conformation, and aromatic-stacking interactions. Density functional theory (DFT) geometry optimizations were used in tandem with Rietveld refinement and NMR chemical shielding calculations to improve and verify the Form 2 structure. The energy balance of the system and other properties relevant to drug development are predicted and discussed. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4756-4782, 2008

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Published date: 25 February 2008

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Local EPrints ID: 67662
URI: http://eprints.soton.ac.uk/id/eprint/67662
ISSN: 0022-3549
PURE UUID: 18ac1044-3ffa-4172-bb8f-3bd94f41998c
ORCID for Mark Edward Light: ORCID iD orcid.org/0000-0002-0585-0843

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Date deposited: 02 Sep 2009
Last modified: 10 Dec 2019 01:51

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Contributors

Author: Frederick G. Vogt
Author: Lee M. Katrincic
Author: Stacey T. Long
Author: Ronald L. Mueller
Author: Robert A. Carlton
Author: Yan T. Sun
Author: Matthew N. Johnson
Author: Royston C. B. Copley

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