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Communication Dans Un Congrès Année : 2012

Crystal structure determination from high-resolution proton NMR and crystal structure prediction

Résumé

A protocol for ab initio structure determination of powdered solids at natural isotopic abundance by combining solid-state NMR spectroscopy, crystal structure prediction and DFT chemical shift calculations is used to determine the crystal structures of a series of drug molecules: flutamide, flufenamic acid, cocaine and theophylline. For flutamide and flufenamic acid we find that assigned 1H isotropic chemical shifts provide sufficient discrimination so as to determine the correct structures from a set of predicted structures using the root-mean-square deviation between experimentally determined and calculated chemical shifts. In both cases neither unassigned 1H shifts nor 13C shifts could be used to determine the structures. The correct structures were determined to within an atomic rmsd of less than0.12 Å with respect to the known structures. For theophylline the NMR spectrum is too simple to allow unambiguous structure selection. We show how the information contained in the NMR chemical shifts is complementary (orthogonal) to PXR D. Combining 1 H NMR chemical shift, CSP/DFT and PXRD leads to a very robust structure determination protocol, with no hypothesis, and no bias. We also use this procedure to determine for the first time the crystal structure of a pharmaceutically pertinent molecule with previously unknown structure, where previous attempts by X-ray diffraction alone had not been successful. Combining 1H solid-state NMR spectroscopy with first-principles calculations can also be applied to the crystal structure determination of metal organic frameworks. We demonstrate this by reporting the discovery of the previously unknown crystal structure of a novel porous imidazolate substituted metal organic framework with possible applications as a H2 storage material. 1H NMR experiments provided a description of the proton environments within the MOF, which in combination with DFT chemical shift calculations and PXRD led to the elucidation of the complete crystal structure.
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Dates et versions

hal-00917019 , version 1 (11-12-2013)

Identifiants

  • HAL Id : hal-00917019 , version 1

Citer

Maria Baias, Jean-Nicolas Dumez, Graeme M. Day, Elodie Salager, Sonia Augado, et al.. Crystal structure determination from high-resolution proton NMR and crystal structure prediction. Small Molecule NMR Conference 2012 (SMASH 2012), Sep 2012, Providence, United States. ⟨hal-00917019⟩
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