Solid state nuclear magnetic resonance SSNMR spectroscopy

In terms of the structural features that are probed with various analytical methods, solid state nuclear magnetic resonance (SSNMR) may be looked upon as representing a middle ground between IR spectroscopy and X-ray powder diffraction methods. The former provides a measure of essentially molecular parameters, mainly the strengths of bonds as represented by characteristic frequencies, while the latter reflect the periodic nature of the structure of the solid. For polymorphs differences in molecular environment and/or molecular conformation may be reflected in changes in the IR spectrum. The differences in crystal structure that define a polymorphic system are clearly reflected in changes in the X-ray powder diffraction. Details on changes in molecular conformation or in molecular environment can only be determined from full crystal structure analyses as discussed in Section 4.4. 

Solid state nuclear magnetic resonance spectroscopy provides information on the environment of individual atoms. In essence, the change in environment of any atom can arise from two factors, which usually are not separable in the interpretation of the SSNMR spectra, but are conceptually independent. Since different polymorphs are different crystal structures, it is expected that the crystal environment of at least some atoms will differ from polymorph to polymorph (Section 2.4.2). In addition, since the molecular conformation may also vary among polymorphs (Section 5.6), the change in the environment of an atom due to conformational differences will also be reflected in the SSNMR (Levy et al. 1980 Bugay 2001 Strohmeier et al. 2001). 

The theoretical basis and practical considerations for the application of SSNMR to the smdy of polymorphism may be found in a number of references, which themselves contain additional primary sources (for instance Yannoni 1982 Fyfe 1983 Komorski 1986 Bugay 1993 Harris 1993 Brittain 1997 Byrn etal. 1999). As with many of the analytical techniques described in this chapter, SSNMR is a rapidly developing field with great potential in the investigation of polymorphic systems. It is not limited to a single nucleus (although most studies to date have concentrated on the nucleus) and it is being adapted for quantitative analysis of polymorphic mixtures and other multicomponent systems. 

The original development of the basis for SSNMR by Schaefer and Stejskal (1976) through the combination of high power proton decoupling with magic angle spinning and cross-polarization SSNMR techniques for is demonstrated in Fig. 4.32. 

Perhaps the first application of this technique directly to polymorphic systems was by Ripmeester (1980), and Threlfall (1995) has more recently reviewed the subject in addition to references cited above. For the study of polymorphic systems SSNMR has a number of advantages. The signal is not influenced by particle size which may eliminate the complications of possibie polymorphic transformations due to the grinding required in, say IR and X-ray powder diffraction techniques. The intensity of the signal is directly proportional to the number of nuclei producing it, so that 

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Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a powerful technique used in the analysis of solids, and is currently finding more and more applications, particularly in the analysis of pharmaceutical formulations. It is a non-destructive, non-invasive technique that can be employed to simultaneously examine the physical and chemical states of both the active pharmaceutical ingredient (API) and the excipients present as they exist within the formulation. It is also highly selective, as nuclei of the API often have different chemical shifts than do common excipients. 

Solid-state nuclear magnetic resonance (ssNMR) spectroscopy has emerged over the years as a powerful analytical method in solid-state chemistry, especially with the advancements in techniques that allow the acquisition of high-resolution spectra [47]. In the broadest sense, ssNMR is mostly applied in characterization of crystalline materials as a means to support PXRD structural analyses by providing information on the number of molecules in the asymmetric unit or the symmetry of the occupied positions within the unit cell. Another major field of application is the structural characterization of amorphous and disordered solids where standard X-ray diffraction-based techniques fail to give detailed structural information. When discussing ssNMR in the context of API polymorphism and synthesis of co-crystals,... 

Recent developments on acidity characterization of solid acid catalysts, specifically those invoking P solid-state nuclear magnetic resonance (SSNMR) spectroscopy using phosphorus-containing molecules as probes, have been summarized. In particular, various P SSNMR approaches using trimethylphosphine, diphosphines, and trialkylphosphine oxides (R3PO) will be Introduced, and their practical applications for the characterization of important qualitative and quantitative features, namely, type, distribution, accessibility (location/proximity), concentration (amount), and strength of acid sites in various solid acids, will be illustrated. 

In 2010, MacKenzie et al. succeeded in proving (using solid-state nuclear magnetic resonance (ssNMR.) spectroscopy) that the outer layer of The Bent Pyramid of Snefru was indeed synthetically manufactured from mixed gypsum (CaS04, -H2O), crushed limestone from the Tura diatomite quarry in... 

Solid state nuclear magnetic resonance (SSNMR) spectroscopy, which in many respects complements the most powerful tool for structure determination. X-ray crystallography, has become an indispensable tool for the characterization of both structure and dynamics in molecular materials.This nondestructive technique has the unique ability to probe electronic environments and the dipolar connectivity of NMR-active nuclei (e.g.,... 

Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a more advanced method for differentiating the polymorphs of a material. The substance is placed in a strong magnetic field and subjected to radiofrequency radiation. The individual nuclei experience different magnetic environments and thus show different changes in resonant frequency characterized by chemical shift. SSNMR spectra show sharp resonance at chemical shifts characteristic of the molecular and crystal structure. The polymorphs are differentiated by their characteristic spectra. 

The enantiomer and the racemic compound possess different crystal structures, which correspond to different intermolecular interactions, as mentioned in Sec. 3. Therefore the enantiomer and the racemic compound exhibit different powder x-ray diffraction (PXRD) patterns, different infrared (IR) and Raman spectra, and different solid-state nuclear magnetic resonance (SSNMR) spectra. However, the opposite enantiomers give identical PXRD patterns, and identical IR, Raman, and SSNMR spectra. Consequently, the PXRD patterns and the above spectra of a conglomerate, which is a physical mixture of opposite enantiomers, are identical to that of the pure enantiomers. In contrast, the diffraction pattern and the various corresponding spectra of the racemic compound usually differ significantly from those of the pure enantiomers. Therefore the type of racemate can be easily determined by comparing the diffraction patterns or the various spectra of the racemic species with that of one of the pure enantiomers (Figs. 3 5). The enantiomeric composition in a racemic mixture may be determined by PXRD, or by IR or SSNMR spectroscopy. Quantitative PXRD has been applied to determine the relative... 

Solid-state nuclear magnetic resonance spectroscopy (SSNMR) [13]... 

Several interesting review articles have been recently published focusing on the use of NMR methods to study peptide-lipid and small molecular weight molecule interactions in model and natural membranes. Maler as well as Kang and Li highlighted the unique possibilities of solution-state NMR to investigate the structure, dynamics and location of proteins and peptides in artificial bilayers and peptide-lipid interactions. On the other hand, Renault et reviewed recent advances in cellular solid-state nuclear magnetic resonance spectroscopy (SSNMR) to follow the structure, function, and molecular interactions of protein-lipid complexes in their cellular context and at atomic resolution. 

Co-crystal patents usually contain experimental examples that describe the preparation of the co-crystal and the characterization of the co-crystal. Characterization of the co-crystal describes the co-crystal itself and its various properties which include its sohd state characteristics and stoichiometry. Typically, the sohd state characteristics of a crystalline solid are shown by one or more of the foUowing analytical techniques X-ray powder diffraction pCRPD), single crystal X-ray diffraction (SCXD), Raman spectroscopy, infrared (IR) spectroscopy, sohd state nuclear magnetic resonance spectroscopy (SSNMR), and differential scanning calorimetry (DSC). The stoichiometry of a co-crystal may be estabhshed through solution techniques such as comparison of peak integrations in a solution NMR spectrum, data... 

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