The HETCOR Technique

Protons and carbon atoms interact in two very important ways. First, they both have magnetic properties, and they can induce relaxation in one another. Second, the two types of nuclei can be spin-coupled to each other. This latter interaction can be very useful, since directly bonded protons and carbons have a J value that is at least a power of 10 larger than nuclei related by two-bond or three-bond 

To obtain a correlation between carbons and attached protons in a two-dimensional experiment, we must be able to plot the chemical shifts of the atoms along one axis and the chemical shifts of 

To obtain a correlation between carbons and attached protons in a two-dimensional experiment, we must be able to plot the chemical shifts of the atoms along one axis and the chemical shifts of the protons along the other axis. A spot of intensity in this type of two-dimensional spectrum would indicate the existence of a C—H bond. The heteronuclear chemical shift correlation (HETCOR) experiment is designed to provide the desired spectrum. 

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Of the many types of two-dimensional experiments, two find the most frequent application. One of these is H—H Correlation Spectroscopy, better known by its acronym, COSY. In a COSY experiment, the chemical shift range of the proton spectrum is plotted on both axes. The second important technique is Heteronuclear Correlation Spectroscopy, better known as the HETCOR technique. In a HETCOR experiment, the chemical shift range of the proton spectrum is plotted on one axis, while the chemical shift range of the C spectrum for the same sample is plotted on the second axis. 

Methyl-2-Pentanol. Figure 10.17 is a final example that illustrates some of the power of the HETCOR technique for 4-methyl-2-pentanol. Lines have been drawn on the spectrum to help you find the correlations. 

FIGURE 12.9 Example of heteronuclear single quantum coherence (HSQC) applied to allylbutyl ether (300 MHz).The correlations of H and 1 C chemical shifts are clearly shown. Note the similarity to Fig. 10.10, which displays a HETCOR spectrum. For a sample of this sort, where signal/noise ratio is no problem, there is little to choose between the two techniques, but HSQC is inherently much more sensitive. 

It is possible to separate and assign the H signals of the PPs using 2D HETCOR spectra, because the correlations are clearly resolved in the two-dimensional spectra for proton-carbon pairs. The 2D HETCOR technique allows resolution of H CRAMPS to be tied to the higher resolution associated with - C chemical shifts. - ... 

Thus, the 2D HETCOR technique allows the resolution of H CRAMPS to be tied to the higher resolution associated with C chemical shifts. However,... 

We can thus assign carbon atoms on the basis of known proton chemical shifts, or we can assign protons on the basis of known carbon chemical shifts. For example, we might have a crowded proton spec-tmm but a carbon spectrum that is well resolved (or vice versa). This approach makes the HETCOR experiment particularly useful in the interpretation of the spectra of large, complex molecules. An even more powerful technique is to use results from both the HETCOR and COSY experiments together. 

Solid state NMR techniques, such as CP, RAMP CP, CP TOSS, MQ DEPT, 2D HETCOR, which are relevant to the characterisation of natural organic matter have been reviewed by Cook. The pros and cons of many of the techniques are compared in an effort to provide guidance to the most beneficial utilisation of the NMR techniques for researchers interested in natural organic matter. 

The MQMAS technique has been combined with other NMR techniques to provide correlation information. For example, lijima et recently used P A1 MQMAS/HETCOR NMR to study the structure of amorphous... 

The latter technique unfortunately has two substantial disadvantages, i) significant amounts of material (at least 30 mg) are normally required, which may be impossible for a new natural product, and ii) the assignment of carbon signals with close (5 0.2 ppm) chemical shifts may be difficult because the digital resolution required cannot normally be achieved in a hetcor experiment. In addition, unless the hetcor experiment can be run under conditions where the J value emphasized is 4 - 8 Hz, no information concerning the assignment of quaternary carbons is possible. 

Though much of the HETCOR data bear out the details of the simulated unit cell, it differs in that the unit cell su ests that the PC7 iBM handles are at a 180° away from the polymer backbone. The fact that the 2D HETCOR suggests the existence of an orientation that is opposite to this shows the ability of the technique to provide direct proof of the intrinsic local structural disorder that is present in the system. The authors surest that this orientational disorder may result in disrupting the ID fijUerene channels and thus decrease the electron transport efficiency in these pathways. 

In the HETCOR experiment the peaks of an insensitive nucleus ( C. " N) are correlated with those of a sensitive nucleus ( H, F, " P). In Figure 27 the aliphatic part of the HETCOR spectrum of camphor (2) shows the specific resonances of the protons which are attached to each C nucleus. The relevant parts of the corresponding 1 D spectra are plotted along the axes. A correlation is observed as a cross-peak at the intersection of two lines drawn from a proton resonance and from a carbon peak, respectively. The three pairs of diastereotopic methylene protons H-3e do/exc H-5endo/e o and H-6c do/exo give individual cross peaks at the same carbon resonance, respectively. Correlations are not observed for quaternary carbon atoms. The technique is an important tool for chemical shift assignment and thus structure elucidation. 

Overlapping resonances in 2D NMR have limited protein-structure elucidation to fairly small proteins. However, three- and four-dimensional methods have been developed that enable NMR spectroscopy to be further extended to larger and larger protein structures. A third dimension can be added, for example, to spread apart a H- H two-dimensional spectrum on the basis of the chemical shift of another nucleus, such as N or - C. In most three-dimensional experiments, the most effective methods for large molecules are used. Thus, COSY is not often employed, but experiments like NOESY-TOeSY and TOCSY-HMQC are quite effective. In some cases, the three dimensions all represent different nuclei such as H- C- N. These are considered variants of the HETCOR experiment. Multidimensional NMR is now capable of providing complete solution-phase structures to complement crystal structures from X-ray crystallography. Hence. NMR spectroscopy is now an important technique for determining structure.s and orientation.s of complex molecules in solution. 

There are other two-dimensional techniques, more sensitive than HETCOR, that make use of polarization transfer (Section 4.12.2). Even greater enhancement can be obtained if the magnetization is generated at the insensitive nucleus and then transferred back to the sensitive nucleus for detection. Procedures making use of this principle are called inverse techniques and lead to a great reduction of sample concentration or measurement time. Typical experiments involve recording spectra for insensitive nuclei such as C, Si and N, which are recorded in inverse, proton-detected procedures. The information given by such experiments is the same as that from the HETCOR experiments, but the experiments are much more sensitive and are quicker to perform. 

HETCOR experiment particularly useful in the interpretation of the spectra of large, complex molecules. An even more powerful technique is to use results from both the HETCOR and COSY experiments together. 

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... 

Section 13 19 2D NMR techniques are enhancements that are sometimes useful m gam mg additional structural information A H H COSY spectrum reveals which protons are spin coupled to other protons which helps m deter mining connectivity A HETCOR spectrum shows the C—H connections by correlating C and H chemical shifts... 

HETCOR (Section 13 19) A 2D NMR technique that correlates the H chemical shift of a proton to the chemical shift of the carbon to which it is attached HETCOR stands for heteronuclear chemical shift correlation Heteroatom (Section 1 7) An atom in an organic molecule that IS neither carbon nor hydrogen Heterocyclic compound (Section 3 15) Cyclic compound in which one or more of the atoms in the nng are elements other than carbon Heterocyclic compounds may or may not be aromatic... 

An alternative way of acquiring the data is to observe the signal. These experiments are referred to as reverse- or inverse-detected experiments, in particular the inverse HETCOR experiment is referred to as a heteronuclear multiple quantum coherence (HMQC) spectmm. The ampHtude of the H nuclei is modulated by the coupled frequencies of the C nuclei in the evolution time. The principal difficulty with this experiment is that the C nuclei must be decoupled from the H spectmm. Techniques used to do this are called GARP and WALTZ sequences. The information is the same as that of the standard HETCOR except that the F and F axes have been switched. The obvious advantage to this experiment is the significant increase in sensitivity that occurs by observing H rather than C. 

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