Heteronuclear Chemical Shift Correlation Methods

Direct Heteronuclear Chemical Shift Correlation Methods 

The direct heteronuclear shift correlation experiments exploit the one-bond ( Vch) heteronuclear coupling as the basis of establishing chemical shift correlations. The concept of using multiple quantum coherence was developed by Muller in 1979 [83] that of using single quantum coherence came out of the work of Bodenhausen and Ruben in 1980 [111]. 

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Direct Heteronuclear Chemical Shift Correlation Methods... 

Heteronuclear chemical shift correlation methods establish the direct link between protons and the respective, directly attached carbons (or nitrogens). In the case of methylenes with inequivalent (anisochronous) protons, the "multiplicity of the carbon in question is irrefutably obvious. For isotropic methylenes and other resonances, the multiplicity of the resonance (CH, CH2 or CH3) in question may be less obvious. Early work by Kessler and co-workers addressed this issue via the development of the DEPT-HMQC experiment. [120] Multiplicity editing is also available for experiments such as GHSQC. An extra pair of delays and pulses, with the flip angle of the proton pulse being adjustable, allow the acquisition of data in... 

A second 2D NMR method called HETCOR (heteronuclear chemical shift correlation) is a type of COSY in which the two frequency axes are the chemical shifts for different nuclei usually H and With HETCOR it is possible to relate a peak m a C spectrum to the H signal of the protons attached to that carbon As we did with COSY we 11 use 2 hexanone to illustrate the technique... 

LC-NMR plays a central role in the on-line identification of the constituents of crude plant extracts (Wolfender and others 2003). This technique alone, however, will not provide sufficient spectroscopic information for a complete identification of natural products, and other hyphenated methods, such as LC-UV-DAD and LC-MS/MS, are needed for providing complementary information. Added to this, LC-NMR experiments are time-consuming and have to be performed on the LC peak of interest, identified by prescreening with LC-UV-MS. NMR applied to phenolic compounds includes H NMR,13 C NMR, correlation spectroscopy (COSY), heteronuclear chemical shift correlation NMR (C-H HECTOR), nuclear Overhauser effect in the... 

Figure 6-21 illustrates this procedure for an adamantane derivative. The H frequencies are on the vertical axis and the C frequencies are on the horizontal axis. The respective spectra are illustrated on the left and at the top. The 2D spectrum is composed only of cross peaks, each one relating a carbon to its directly bonded proton(s). There are no diagonal peaks (and no mirror symmetry associated with a diagonal), because two different nuclides are represented on the frequency dimensions. Quaternary carbons are invisible to the technique, as the fixed times A and A2 normally are set to values for one-bond couplings. This experiment often is a necessary component in the complete assignment of H and resonances. Its name, HETeronuclear chemical Shift CORrelation, usually is abbreviated as HETCOR, but other acronyms (e.g., HSC, for Heteronuclear Shift Correlation, and H, C-COSY, also are used. The method may be applied to protons coupled to many other nuclei, such as Si, and P, as well as C. 

A new mathematical technique for processing 2D data, known as the filter diagonaliza-tion method (FDM), was recently developed by A. J. Shaka. The technique accomplishes goals similar to those aimed at in LP. In this method, even fewer time-incremented spectra, namely, two to four increments for an HMQC or HSQC experiment, are collected than with LP. FDM appears to be best suited for those heteronuclear chemical-shift-correlated experiments for which there are a limited number of v signals for any particular frequency V2 [e.g., for HMQC or HSQC spectra when the maximum number of v ( C) signals per U2( H) frequency is unity]. 

Bax A, Morris GA (1981) An Improved Method for Heteronuclear Chemical Shift Correlation by Two-Dimensional NMR. J Magn Reson 42 501... 

Bax, A. and Morris, G. A. An improved method for heteronuclear chemical shift correlation by two-dimensional NMR./. Magn. Reson. 42 501-505, 1981. 

Bax [62] gives a detailed discussion of the experimental aspects of this 2D heteronuclear chemical-shift correlation experiment and suggests methods for the suppression of the axial peaks as well as of errors resulting from quadrature H detection. 

In the case of an unknown chemical, or where resonance overlap occurs, it may be necessary to call upon the full arsenal of NMR methods. To confirm a heteronuclear coupling, the normal H NMR spectrum is compared with 1H 19F and/or XH 31 P NMR spectra. After this, and, in particular, where a strong background is present, the various 2-D NMR spectra are recorded. Homonuclear chemical shift correlation experiments such as COSY and TOCSY (or some of their variants) provide information on coupled protons, even networks of protons (1), while the inverse detected heteronuclear correlation experiments such as HMQC and HMQC/TOCSY provide similar information but only for protons coupling to heteronuclei, for example, the pairs 1H-31P and - C. Although interpretation of these data provides abundant information on the molecular structure, the results obtained with other analytical or spectrometric techniques must be taken into account as well. The various methods of MS and gas chromatography/Fourier transform infrared (GC/FTIR) spectroscopy supply complementary information to fully resolve or confirm the structure. Unambiguous identification of an unknown chemical requires consistent results from all spectrometric techniques employed. 

Of the many techniques available to the NMR spectroscopist in structural elucidations, none is so valuable as the indirect chemical-shift correlation experiment, such as HMBC, TOCSY (both homo- and heteronuclear varieties), and FLOCK. Once molecular fragments have been identified by the COSY and HSQC experiments, the spectroscopist attempts to combine these fragments by means of the preceding techniques. As indispensable as these methods have become to NMR spectroscopists, they nonetheless suffer a common... 

In the following, we will discuss heteronuclear polarization-transfer techniques in four different contexts. They can be used as a polarization-transfer method to increase the sensitivity of a nucleus and to shorten the recycle delay of an experiment as it is widely used in 1H-13C or 1H-15N cross polarization. Heteronuclear polarization-transfer methods can also be used as the correlation mechanism in a multi-dimensional NMR experiment where, for example, the chemical shifts of two different spins are correlated. The third application is in measuring dipolar coupling constants in order to obtain distance information between selected nuclei as is often done in the REDOR experiment. Finally, heteronuclear polarization transfer also plays a role in measuring dihedral angles by generating heteronuclear double-quantum coherences. 

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