Variable-temperature SSNMR

Variable-temperature SSNMR was used by Tozuka et to investigate the observed polymorphism in clarithromycin. Polymorphic interconversions were identified using both powder X-ray diffraction (PXRD) and CPMAS NMR. The authors performed quantitation of two polymorphs (forms I and II) using carbonyl resonances that exhibited 1 ppm resolution. Relaxation and CP rate constants were not taken into account instead, relative peak areas were adjusted using a term derived from the preparation and analysis of a known set of standard mixtures. The correlation coefficient of measured peak intensity and weight content was found to be >0.99. 

Different approaches can be made using SSNMR, the work presented by Apperley et al. [89] showed the apphcation of variable temperature SSNMR to the characterization of two compounds, indomethacin and nifedipine. Changes in the chemical shift of the indomethacin SSNMR spectrum... 

TunstaU et al. used variable-temperature SSNMR from 160 to... 

Figure 18 (a) Variable temperature SSNMR spectra of PRF-25(24C6) depictions of various modes of motion for the macrocyclic... 

As noted above, the characterization of polymorphs by SSNMR is by no means limited to spectra. For instance, Bauer et al. (1998), showed that CPMAS could easily distinguish between the two polymorphs of Irbesartan 4-1 and could be used to study the difference of the tautomeric behaviour in the tetrazole ring of the two polymorphic forms. Variable temperature spectra indicate that the ring in Form B is involved in an exchange process that does not occur in Form A (Fig. 4.37). 

In addition to the identification of crystal moditications, SSNMR has been used to monitor reactivity and phase changes in different polymorphic forms. For instance, Harris and Thomas (1991) followed the photochemical conversion of formyl-fran -cinnamic acid with SSNMR (see also Section 6.4). Variable temperature techniques have been used to study the interconversion of four polymorphic modifications of sulphanilamide (/ -amino-benzenesulphonamide), including interpretation of at least some of the molecular motions during the course of the transformation (Frydman et al. 1990). A similar combination was augmented with colourimetric techniques to study the coexistence of two phases in the course of a phase transition (Schmidt et al. 1999). Of course, differences between unsolvated and solvated or hydrated crystal moditications may also be readily characterized by the SSNMR technique, as was done with the anhydrous and monohydrate of oxyphenbutazone (Stoltz et al. 1991). Due to the availability of the crystal structures for both modifications the SSNMR results could be interpreted directly in terms of the different atomic environments, especially for the differences in hydrogen bonding in the presence... 

SSNMR spectroscopy. However, FTIR and Raman spectroscopy, thermal microscopy, variable-temperature x-ray diffractometry (VTXRD), and DSC may also be used to identify polymorphs. Solvates may be similarly characterized by the techniques mentioned above. In addition, the stoichiometric number of the solvent molecules in the crystal lattice of solvates may be determined by thermogravimetric analysis (TGA), gas chromatography, or, in the case of a hydrate, by Karl Fiseher titrimetry [37]. 

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