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Solid-state NMR (SSNMR) is capable of providing detailed structural information about organic and pharmaceutical cocrystals and complexes. SSNMR nondestructively analyzes small amounts of powdered material and generally yields data with higher information content than vibrational spectroscopy and powder X-ray diffraction methods. These advantages can be utilized in the analysis of pharmaceutical cocrystals, which are often initially produced using solvent drop grinding techniques that do not lend themselves to single crystal growth for X-ray diffraction studies. In this work, several molecular complexes and cocrystals are examined to understand the capabilities of the SSNMR techniques, particularly their ability to prove or disprove molecular association and observe structural features such as hydrogen bonding. Dipolar correlation experiments between spin pairs such as 1H−1H, 1H−13C, and 19F−13C are applied to study hydrogen bonding, intermolecular contacts, and spin diffusion to link individual molecules together in a crystal structure and quickly prove molecular association. Analysis of the principal components of chemical shift tensors is also utilized where relevant, as these are more sensitive to structural effects than the isotropic chemical shift alone. In addition, 1H T1relaxation measurements are also demonstrated as a means to prove phase separation of components. On the basis of these results, a general experimental approach to cocrystal analysis by SSNMR is suggested. [ABSTRACT FROM AUTHOR]

An unusual pharmaceutical solid containing a pleuromutilin derivative, succinic acid and water is studied with a combination of physiochemical methods. The parent pleuromutilin derivative creates a host structure that contains large channels, which are occupied by variable amounts of both succinic acid and water. The inherent disorder of the system does not lend itself to detailed single-crystal X-ray diffraction studies; hence a combination of powder X-ray diffraction (PXRD) and solid-state NMR (SSNMR) techniques were used to characterize this system and understand its behavior. A variety of one and two-dimensional SSNMR experiments were used to understand the proton transfer and the hydrogen bonding network, including 1H− 13C heteronuclear correlation experiments and measurements of the principal components of 13C chemical shift tensors. This crystal system can exist as two distinct phases; a hemisuccinate phase containing a doubly ionized succinate molecule with two cations of the pleuromutilin derivative, and a succinic acid rich phase which contains a singly ionized succinate molecule hydrogen bonded to another fully protonated succinic acid for every mole of the pleuromutilin derivative. Individual particles can contain mixtures of these two phases, leading to a range of apparent stoichiometries between the succinic acid and pleuromutilin derivative. Both phases are variable hydrates and were characterized by gravimetric vapor sorption and variable humidity 13C SSNMR techniques. [ABSTRACT FROM AUTHOR]

A series of tantalum oxyfluoride materials containing the [Ta 4F 16O 4] 4−and [Ta 8F 24O 12] 8−anion clusters have been synthesized and characterized using X-ray diffraction (XRD) and solid-state nuclear magnetic resonance (SSNMR) spectroscopy. The structure of both tantalum oxyfluoride materials display octahedrally bonded tantalum atoms with bridging oxygen and terminal fluoride atoms. The [Ta 4F 16O 4] 4−cluster is an eight-membered ring, whereas the [Ta 8F 24O 12] 8-cluster forms a cagelike structure. Solid-state dynamics of these clusters were explored by monitoring the impact of temperature on the one-dimensional (1D) 19F magic angle spinning (MAS) NMR, 13C cross-polarization (CP) MAS NMR, and two-dimensional (2D) double quantum (DQ) 19F MAS NMR spectra. The DQ 19F NMR correlation experiments allowed the through space connectivity between the different resolved fluorine environments to be determined, thus aiding in the spectral assignment and structural refinement of these materials. Ab initio 19F NMR chemical shift calculations were used to assist in the interpretation of the 19F NMR spectra. The influence of scalar relativistic and Ta−F spin–orbit coupling on the 19F NMR shielding calculation arising from bonding to tantalum atoms is also addressed. [ABSTRACT FROM AUTHOR]