title: Polymorphs of Theophylline Characterized by DNP Enhanced Solid-State NMR.
abstract: 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.
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) , 1015 Lausanne, Switzerland.|Institut de Sciences Analytiques (CNRS/ENS de Lyon/UCB-Lyon 1), Centre de RMN à Très Hauts Champs, Université de Lyon , 69100 Villeurbanne, France.
authors.forename: Arthur C
authors.initials: AC
authors.lastname: Pinon
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) , 1015 Lausanne, Switzerland.|Institut de Sciences Analytiques (CNRS/ENS de Lyon/UCB-Lyon 1), Centre de RMN à Très Hauts Champs, Université de Lyon , 69100 Villeurbanne, France.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Rossini
authors.affiliation: Institut de Sciences Analytiques (CNRS/ENS de Lyon/UCB-Lyon 1), Centre de RMN à Très Hauts Champs, Université de Lyon , 69100 Villeurbanne, France.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Widdifield
authors.affiliation: Institut de Sciences Analytiques (CNRS/ENS de Lyon/UCB-Lyon 1), Centre de RMN à Très Hauts Champs, Université de Lyon , 69100 Villeurbanne, France.
authors.forename: David
authors.initials: D
authors.lastname: Gajan
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) , 1015 Lausanne, Switzerland.|Institut de Sciences Analytiques (CNRS/ENS de Lyon/UCB-Lyon 1), Centre de RMN à Très Hauts Champs, Université de Lyon , 69100 Villeurbanne, France.
authors.forename: Lyndon
authors.initials: L
authors.lastname: Emsley
mesh_terms: D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008956:Models, Chemical; D013806:Theophylline / Q000737:chemistry*; D014665:Vasodilator Agents / Q000737:chemistry*
chemical_list: D014665:Vasodilator Agents; D013806:Theophylline
keywords: dynamic nuclear polarization; polymorphs; solid-state NMR; theophylline