Solid-State NMR and X-Ray Crystallography: Complementary Tools for Structure Determination

Characterization of Racemic Species of Chiral Drugs Using Thermal Analysis, Thermodynamic Calculation, and Structural Studies

“…In Figure 5, the five ∆G°values within the range of -0.05 to 0.05 kcal‚mol -1 correspond to the four compounds (entries 6, 11, 20, 21 25 in Table 3) which are identified as racemic conglomerates; the fifth is the racemic compound a Numbers are given to identify the entries; code names are the acronyms explained in Table 1. b Enthalpy and entropy of formation were calculated according to eqs 4 and 5, respectively.…”

“…SSNMR spectra, on the other hand, can probe the short range order of the molecular environments in the solid and can effectively differentiate dynamic or static disorders. 25 The information from 13 C chemical shifts can be particularly useful for identifying conformational changes and structural differences, especially when they are difficult to recognize from the PXD patterns.…”

The Structure of N1‐Hydroxylophine N3‐Oxide (=1‐Hydroxy‐2,4,5‐ triphenyl‐1H‐imidazole 3‐Oxide) in the Solid State

“…6). Situation I corresponds to the very common case where the barrier is too high to observe the proton transfer within the NMR observational window (it can correspond to static disorder in crystallography [11]). The intermediate case II corresponds to the temperature-dependent dynamic behavior that can be studied by NMR [4 ± 6] [9], and that we have named ISSPT (the transfer often has a tunnelling component and corresponds to dynamic disorder in crystallography).…”

“…A multiple proton transfer along the H-bonds or, at least, a new example of a centred O ¥¥¥ H ¥¥¥ O H-bond could be expected. The study will need the concomitant use of X-ray crystallography and solid-state NMR (CPMAS) to eventually distinguish between static and dynamic disorder [11].…”

Approach to the Determination of Hydrate Form Conversions of Drug Compounds and Solid Dosage Forms by Near‐Infrared Spectroscopy

“…A wide range of analytical techniques is currently in use for the detection and quantitation of the hydration state of bulk solid samples. These methods include powder and single-crystal 10 X-ray diffraction, [10][11][12][13] thermal analysis techniques (differential scanning calorimetry and thermogravimetric analysis), 14 microscopy (optical, transmission electron microscopy, and scanning electron microscopy), 15 solid-state nuclear magnetic resonance, 16,17 Raman spectroscopy, 18 and mid-IR spectroscopy. These techniques have been reviewed extensively elsewhere.…”