Journal article
Polymorphs of Theophylline Characterized by DNP Enhanced Solid-State NMR.
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Pinon AC
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) , 1015 Lausanne, Switzerland.
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Rossini AJ
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) , 1015 Lausanne, Switzerland.
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Widdifield CM
Institut de Sciences Analytiques (CNRS/ENS de Lyon/UCB-Lyon 1), Centre de RMN à Très Hauts Champs, Université de Lyon , 69100 Villeurbanne, France.
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Gajan D
Institut de Sciences Analytiques (CNRS/ENS de Lyon/UCB-Lyon 1), Centre de RMN à Très Hauts Champs, Université de Lyon , 69100 Villeurbanne, France.
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Emsley L
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) , 1015 Lausanne, Switzerland.
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Published in:
- Molecular pharmaceutics. - 2015
English
We show how dynamic nuclear polarization (DNP) enhanced solid-state NMR spectroscopy can be used to characterize polymorphs and solvates of organic solids. We applied DNP to three polymorphs and one hydrated form of the asthma drug molecule theophylline. For some forms of theophylline, sample grinding and impregnation with the radical-containing solution, which are necessary to prepare the samples for DNP, were found to induce polymorphic transitions or desolvation between some forms. We present protocols for sample preparation for solid-state magic-angle spinning (MAS) DNP experiments that avoid the polymorphic phase transitions in theophylline. These protocols include cryogrinding, grinding under inert atmosphere, and the appropriate choice of the impregnating liquid. By applying these procedures, we subsequently demonstrate that two-dimensional correlation experiments, such as (1)H-(13)C and (1)H-(15)N HETCOR or (13)C-(13)C INADEQUATE, can be obtained at natural isotopic abundance in reasonable times, thus enabling more advanced structural characterization of polymorphs.
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Language
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Open access status
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hybrid
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/80158
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