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Article
Polymorphs of Theophylline Characterized by DNP Enhanced Solid-State NMR
Molecular Pharmaceutics (2015)
  • Arthur C. Pinon, Institut des Sciences et Ingénierie Chimiques
  • Aaron J. Rossini, Institut des Sciences et Ingénierie Chimiques
  • Cory M. Widdifield, Institut de Sciences Analytiques
  • David Gajan, Institut de Sciences Analytiques
  • Lyndon Emsley, Institut des Sciences et Ingénierie Chimiques
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 1H–13C and 1H–15N HETCOR or 13C–13C INADEQUATE, can be obtained at natural isotopic abundance in reasonable times, thus enabling more advanced structural characterization of polymorphs.
Keywords
  • dynamic nuclear polarization,
  • solid-state NMR,
  • polymorphs,
  • theophylline
Publication Date
September 22, 2015
DOI
10.1021/acs.molpharmaceut.5b00610
Publisher Statement
Reprinted (adapted) with permission from Molecular Pharmaceutics, 12(11); 4146-4153. Doi: 10.1021/acs.molpharmaceut.5b00610. Copyright 2015 American Chemical Society.
Citation Information
Arthur C. Pinon, Aaron J. Rossini, Cory M. Widdifield, David Gajan, et al.. "Polymorphs of Theophylline Characterized by DNP Enhanced Solid-State NMR" Molecular Pharmaceutics Vol. 12 Iss. 11 (2015) p. 4146 - 4153
Available at: http://works.bepress.com/aaron-rossini/3/