Resolution Enhancement in Multiple-Quantum MAS NMR Spectroscopy

Solid‐State NMR Studies on Supramolecular Chemistry

“…20 By means of its CRAMPS analogue, 1 H DQ CRAMPS, the observation of correlation peaks in 2D spectra are indicative of H-H proximities under 3.5Å. 21 2D heteronuclear correlation (HETCOR) spectroscopy is a cornerstone technique for many assignment strategies and is the method of choice for distance measurements through time-oscillatory magnetization build-up curves, REDOR (rotational echo double resonance) dephasing curves or rotor-encoded SSB analysis.…”

Probing Intermolecular Crystal Packing in γ-Indomethacin by High-Resolution 1H Solid-State NMR Spectroscopy

“…[21][22][23] In particular, 1 H-1 H double-quantum spectroscopy is a powerful method for identifying proton-proton proximities up to~3.5 Å, be they intra-or intermolecular proximities. 24,25 By employing advances in homonuclear 1 H decoupling that deliver high-resolution 1 H spectra, 26,27 the 1 H-1 H DQ CRAMPS technique [28][29][30][31][32] has been applied to the potassium salt of penicillin characterised anhydrous polymorphs (that are labelled ,  and )  crystal structures are available for the  and  forms. 38,39 13 C CP MAS spectra have been reported for the crystalline polymorphs as well as amorphous forms of indomethacin, 13,[40][41][42] while a recent study has presented 1 H- 13 C and 1 H-1 H DQ twodimensional spectra for an indomethacin-polymer dispersion together with a 1 H-1 H DQ MAS spectrum of -indomethacin.…”

Distinguishing Anhydrous and Hydrous Forms of an Active Pharmaceutical Ingredient in a Tablet Formulation Using Solid‐State NMR Spectroscopy

“…[13][14][15][16] Herein, we show how the presence of a specific pseudopolymorph of an API containing about 20 carbon atoms is identified in a tablet formulation using 1 H DQ CRAMPS NMR spectroscopy. This is demonstrated for an API currently under development, using only 30 mg of sample, and with no need for special preparation (that is, isotopic labeling).…”

“…[2] Identification and characterization of (pseudo-)polymorphs is therefore essential during all stages of the development and manufacture of pharmaceuticals; of key importance is the form adopted in a tablet formulation in which the API is combined with a mixture of filler compounds (excipients). 13 C cross-polarization (CP) magic-angle spinning (MAS) solid-state NMR spectroscopy has proven itself as a powerful workhorse experiment for this purpose; [3][4][5] however, very little use has been made of 1 H solid-state NMR spectroscopy due to the large anisotropic broadening that results from extensive dipolar-coupled proton networks. However, advances such as fast MAS and improved homonuclear decoupling techniques have led to increased resolution for organic compounds.…”

“…However, advances such as fast MAS and improved homonuclear decoupling techniques have led to increased resolution for organic compounds. [6] In particular, 1 H double-quantum (DQ) MAS NMR spectroscopy [6][7][8] has become a powerful approach, providing valuable information about, for example, a molecular tweezer host-guest complex, [9] intramolecular hydrogen-bonding in a biological molecule, [10] water and hydroxy-group environments in polyoxoniobate materials, [11] and surface organometallic species.[12] More recently, the 1 H DQ CRAMPS (combined rotation and multiple-pulse spectroscopy) technique [13][14][15] has been shown to dramatically increase resolution, thus allowing well-resolved spectra to be obtained for model compounds. [13][14][15][16] Herein, we show how the presence of a specific pseudopolymorph of an API containing about 20 carbon atoms is identified in a tablet formulation using 1 H DQ CRAMPS NMR spectroscopy.…”