Nuclei other than the proton

NMR data are usually a must have in stmcture elucidations where little is known about the molecule. In analysis of degradants and metabolites, H data may be sufficient to relate the unknown to the parent drug molecule but in other cases, data will usually prove essential to obtain sufficient connectivity data. Apart from and there are several other elements commonly found in drugs which can be detected and quantitated directly by NMR. Table 4.3 lists some of these basic properties for nuclei of significant utility in pharmaceutical NMR. The relative sensitivity for these nuclei gives some indication of the potential problems that are encountered in heteronuclear NMR. For 

Nuclide Spin Natural abundance (%) Magnetogyric ratio ())x lO radT s NMR frequency at 9.4T (MHz) Relative sensitivity compared to 

As noted above, detection of carbon is usually critical to stmcture elucidation. In particular, the long-range couplings (over 2-4 bonds) between and nuclei, expressed as HC, are often key to elucidating the framework of an organic molecule. The one bond coupling ( HC) may also contribute to assignment of the spectrum. 

A is a term representing the abundance of the NMR-active spins involved in the experiment  

Modern inverse-detection experiments achieve increased S/N relative to direct detection by both exciting and detecting the high y proton nucleus. These methods require the suppression of the 98.9% of signal in favour of 

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Nuclear relaxation of different nuclei other than the proton can also be used to determine the rotational correlation time. The longitudinal relaxation of the 170 is governed by quadrupolar [68] and dipolar mechanisms [69], 1 /Tlq and 1 /Tld, respectively, both dependant on rotation ... 

In everyday practice, a restricted view is normally taken basicity refers to the proton and is determined in equilibrium processes, although one can and does speak of kinetic basicity and acidity (10), which do not necessarily parallel the corresponding thermodynamic, or equilibrium, quantities (11). Likewise, nucleophilicity refers to all nuclei other than the proton and is a kinetic parameter, although, again, one can speak of equilibrium nucleophilicity (12). These practical meanings of basicity and nucleophilicity are used in this paper. 

This work was done while Roberts was at MIT. He later moved to the California Institute of Technology, where he became a leader in applying NMR spectroscopy to nuclei other than protons, especially Cand N. 

Pulsed FT-NMR has facilitated the study of nuclei other than H where the sensitivity obtainable from a CW instrument is totally inadequate. In particular, 13C NMR, the sensitivity of which is nearly 10-4 less than that of the proton (Table 9.9), is now a well-established technique that yields information on the skeletal structure of complex molecules. The pulsed technique also enables proton spectra to be obtained from samples as small as a few micrograms. 

In the ENDOR literature, the tensor ADD has been treated at several levels of approximation. For ligand nuclei other than protons, the largest coupling generally arises from the one-centre contribution... 

For nuclei other than protons, the one-center contribution (5.4) has to be added to (5.14). If the principal axes of (Add)j do not coincide with the axes of the tensor T, the contributions arising from the term aF, T and (ADD)i cannot be individually determined from the experimental A tensor without using additional assumptions concerning the orientations of T and (ADD)i. 

ENDOR on transition metal complexes in solutions is only attainable if no other nuclei possessing a much larger hf anisotropy than the protons are present. Moreover, the deviation of the g tensor principal values from g should be small, so that Tr(g - gel)2 < 3 10-3. Solvent and temperature, however, appear to have minor influence on optimum ENDOR detection conditions. 

Because the sensitivity of NMR is the highest for protons compared to other nuclei, all examples of quantitation work described in this chapter are based on proton NMR data. The signals from other NMR active nuclei such as 19F or 13C may also be used for quantitation. The quantification of TFA using 19F NMR is a good example. However, except for 19F, the sensitivities and detection limits are usually compromised in these measurements because nuclei other than H and 19F typically have a lower natural abundance and a lower magnetogyric ratio. 

For nuclei other than protons the dipolar term is smaller, due to the smaller value of yjv, a.nd the contact term may be larger, in case of directly coordinated nuclei. Therefore, contact relaxation may more often be the dominant contribution to nuclear relaxation. 

The new avenues in NMR imaging may be focused on (a) improving spatial resolution, (b) imaging protons with short relaxation timeT2, and (c) imaging nuclei other than proton. 

As EXSY cross peak intensities can be as strong as the diagonal peak intensities in favorable cases, EXSY experiments can be performed with relative ease also on nuclei other than protons. 

The envelope curve depicted in Fig. 116 also applies to anisotropies caused by nuclei other than protons. As has been stressed already, such anisotropy generally arises from dipole-dipole interactions between electrons in p- or d-levels on the atom concerned. In that case, the hyper-fine coupling tensor should have axial symmetry, so that two of the three elements of the hyperfine tensor will be equal, and components similar to that in Fig. 106 will be detected. 

Axenrod, T., Structural effects on the one-bond 15N-H coupling constant, in NMR Spectroscopy of Nuclei Other Than Protons, Axenrod, T. and Webb, G.A., Eds., Wiley Interscience, New York, 1974. 

Use of the complexation shift as a measure of donor-acceptor interaction is especially treacherous with nuclei other than protons, because chemical shifts of these nuclei are more dependent on the paramagnetic than on the diamagnetic term of the screening tensor (52, 53). Both 19F and 11B resonances of the boron trihalides do shift to high field on complexation, as expected if the complexation shift were due to the increase in electron density on the boron trihalide, and early work indicated that 19F complexation shifts of BF3 could be correlated with enthalpies of formation of the complexes. Although this is true for BF3 adducts of some series of closely related donors (42, 91, 151), such correlations do not occur in other series (169). Table II illustrates that, although there is a tendency for the strongest... 

The first Chapter on nuclear magnetic resonance2 in this Series was devoted principally to p.m.r. spectroscopy, because, up to 1964, virtually no magnetic resonance studies of other nuclei in carbohydrates and their derivatives had been made. The present Chapter is also concerned mainly with the p.m.r. technique, in the expectation that the broad subject of nuclei other than protons will be treated separately in this Series. 

When magnetic nuclei other than protons are present, it should be recalled that some values of J might be as large as many proton chemical shifts. For example, in Fig. 13.3, 2 /HF = 48 Hz, accounting for the widely spaced 1 3 3 1 quartets due to the CH that is coupled to both the fluorine and the adjacent methyl group. Because 3Jhf = 21 Hz and 3JhH = 7 Hz, the CH3 resonance is a doublet of doublets. 

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