HR-MAS NMR spectroscopy

J. S. Fruchart, G. Lippens, C. Kuhn, H. Gras-Masse and O. Melnyk, Solid-phase enolate chemistry investigated using HR-MAS NMR spectroscopy, J. Org. Chem., 2002,67, 526-532. 

B. Combourieu, J. Inacio, A. M. Delort and C. Forano, Differentiation of mobile and immobile pesticides on anionic clays by 1H HR MAS NMR spectroscopy, Chemical Communications, 2001, 2214-2215. 

A. J. Simpson, W. L. Kingery, D. R. Shaw, M. Spraul, E. Humpfer and P. Dvortsak, The application of H HR-MAS NMR spectroscopy for the study of structures and associations of organic components at the solid-aqueous interface of a whole soil, Environ. 

Shintu, L., Caldarelli, S., and Franke, B. M. (2007). Pre-selection of potential molecular markers for the geographic origin of dried beef by HR-MAS NMR spectroscopy. Meat Sci. 76, 700-707. 

HR-MAS NMR spectroscopy. Applications to whole soils (Simpson et al., 2001b) are discussed in Section 15.3.3, and applications to organo-mineral interactions (Simpson et al., 2006b) are covered in Section 15.4.3. 

Figure 15.15. ll HR-MAS NMR spectra of a whole soil swollen in D20 and doped with trifluralin (A). II HR-MAS spectra whole soil swollen in D20 (B). For C-III and C-IV, dashed lines indicate the unbound trfluralin while solid lines with brackets indicate the bound trifluralin. protons II are masked by the ahphatic signals from the soil. Reprinted from Simpson, A. J., Kingery, W. L., Shaw, D. R., et al. (2001b).The apphcation of H HR-MAS NMR spectroscopy for the study of structures and associations of organic components at the solid—Aqueous interface of a whole soil. Environ. Sci. Technol. 35, 3321-3325, with permission from the American Chemical Society. 

Deshmukh, A. P., Simpson, A. J., and Hatcher, P. G. (2003). Evidence for cross-linking in tomato cutin using HR-MAS NMR spectroscopy. Phytochemistry 64,1163-1170. 

Kelleher, B. E, Simpson, M. J., and Simpson, A. J. (2006). Assessing the fate and transformation of plant residues in the terrestrial environment using HR-MAS NMR spectroscopy. Geochim. Cosmochim. Acta 70,4080 094. 

Hellriegel, C., Skogsberg, U., Albert, K., Laemmerhofer, M., Maier, N. M., Lindner, W. Characterization of a chiral stationary phase by HR/MAS NMR spectroscopy and investigation of enantioselective interaction with chiral ligates by transferred NOE, J. Am. Chem. Soc.,... 

Nevertheless, the primary tool used in solution-phase synthesis for structural elucidation is NMR spectroscopy. There has been some interest in developing NMR methods for analyzing resin-bound compounds and monitoring the progress of chemical reactions on solid-phase by on-bead analysis (without cleavage of the product from the resin). Many improvements have been achieved in NMR for SPS, but hmitations remain. On the one hand, the limited mobility of polymers, as well as the poor mobility of attached compounds, leads to broad bands with low spectral resolution. On the other hand, the broad signals due to the polymer matrix can mask or overlay with bands from the desired product. The main advantage of this technique is its nondestructive nature, as the sample can be easUy recovered. The next section will focus on the most powerful technique developed to monitor and characterize polymer-supported compounds gel-phase HR-MAS NMR spectroscopy. 

As with resin beads, gel-phase HR-MAS NMR spectroscopy can be used to analyze systems where the resin is grafted onto the base polymer units, known as crowns. The first example of HR-MAS NMR on crowns was demonstrated by Shapiro et al. The spectrum of a crown with the aldehyde 13 attached to the graft polymer has the characteristic peak at 10.2 ppm (Scheme 4.6). A Wittig reaction was performed on this substrate, and its... 

Other examples concerned the use of macroscopic systems such as Syn-phase lanterns. Lippens et compared the results they obtained using Wittig-Homer condensation on a macroscopic support with earlier results of the same reaction on a standard resin. As in all of the examples shown above, gel-phase HR-MAS NMR spectroscopy proved to characterize better the supported intermediates and final products and provide better understanding of the interactions between the polymer and the reagents. This is an important development in supported organic chemistry. 

In complex reactions on resins, one-dimensional gel-phase HR-MAS NMR spectroscopy does not always afford conclusive information to be obtained on the characterization of all the intermediates and final products. Two-dimensional HR-MAS NMR spectroscopy (COSY,TOCSY, HETCOR, and SECSY) provides crucial information on proton connectivity through / coupling information. With 2D HR-MAS NMR complete assignments can be made of spectra of complex bound-molecules, such as oligosaccharides and peptides, and even of noncovalent interactions between compounds connected to resins and receptor molecules. In sum, HR-MAS NMR spectroscopy has been successfully used for characterizing complex resin-bound products and intermediates. It has been used for analyzing biochemical compounds as well. Future work will adapt this technique to reaction monitoring and to routine quantitation besides its use as a characterization tool. 

Hence, this NMR technique allows us to record the NMR spectrum of a dissolved analyte in the presence of a chromatographic sorbent, and therefore mimic a static chromatographic situation. In the suspended-state HR/MAS NMR experiment, the resolution of the signals of the dissolved analyte will be comparable to that in a solution-state NMR experiment. HR/MAS NMR spectroscopy also allows the acquisition of H NMR spectra of stationary phases bonded to silica supports with high resolution compared to the corresponding solid-state NMR spectra. The HR/MAS H NMR spectrum of a (tert-butylcarbamoyl)quinine selector covalently bonded to silica, suspended in [DJmethanol, shows that a full structure elucidation of the selector is possible (see Fig. 4). 

The use of suspended-state HR/MAS NMR spectroscopy to study the interactions between chromatographic sorbents and analytes of interest is still in its infancy. 

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