Basic HMQC Pulse Sequence

The most popular pulse sequences for proton detected heteronuclear spectroscopy are derived from the one initially proposed by Muller [29] in 1979 and 

The main problem for the proton detection of low natural abundance heteronuclei turns out to be the suppression of the undesired proton resonances from H nuclei not coupled to the magnetically active heteronucleus of interest. Basically, the central intense resonance is of course much more difficult to suppress than the H- Sn (and H- Sn) satellites. However, the suppression of undesired signals is far less problematic in H- Sn than in HMQC 

The 180° proton pulse exchanges the ZQ and DQ frequencies in the middle of the evolution period and thus eliminates the proton chemical shift term yielding, after Fourier transform in t, crosspeaks at the frequency tox on the Fi scale of the heteronucleus. 

In addition to the correlation between the mutually coupled H and Sn nuclei to be evidenced, the value of that V( Sn, H) heteronuclear coupling can be determined in the Fi dimension. This may prove very useful in cases where the standard ID proton spectrum is too overcrowded to extract these y( Sn, H) coupling constants from the satellites. This is especially the case when the coupling constants are very small, as they disappear at the foot of the 

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The basic HMQC pulse sequence (Figure 13) is the shortest, simplest HMQC experiment and gives the best sensitivity, ft is used both to determine the chemical shifts of an insensitive nuclide (spin S) coupled to a nuclide of higher sensitivity (spin I) and to correlate the coupled pairs of I and S spins. The experiment is not phase sensitive hence lineshapes are not Lorentzian and coupling constants cannot... 

Figure 10 Folding in the Fj dimension of the 2D H- Sn HM( spectrum which may reduce the total experiment time without coarse digitization in F,. It should be noted that for the basic HMQC pulse sequence presented above this folding occurs from the opposite spectrum edge...

Figure 2 Basic four-pulse sequence for the proton detected HMQC-COSY experiment [91...

An interesting alternative to three dimensional NMR techniques is to suppress one of the evolution times while retaining the basic 3D pulse sequence. The spectral resolution is no longer increased, which is usually not a problem with smaller molecules, but the extra information is still available. The gs-HMQC-TOCSY experiment represents one such experiment. The combination of the HMQC method with the TOCSY sequence leads, in principle, to a 3D technique. However, if the tj evolution period of the TOCSY part is omitted, a 2D sequence is obtained which provides a 13C edited TOCSY spectrum. Starting from each HMQC cross-signal, one finds in the same row additional signals which are caused by a TOCSY transfer. When the structure elucidation is difficult, this experiment can fruitfully complement the HMBC experiment. 

Similar spectra can be obtained more rapidly and with less sample if the data are acquired through the proton signals, which are much more intense. Basically, the H NMR data are acquired and the H- C coupling constant used as the delay in a pulse sequence, which enables us to obtain the carbon spectrum. This method of obtaining the data is called inverse-mode , since the carbon atoms are detected through their attached hydrogen atoms rather than by direct detection, with obvious benefits in the sensitivity and the time taken to obtain a spectrum. HMQC and HMBC are both examples of inverse-mode spectra and this method is so much quicker than CH COSY that an entire HMQC spectrum can be obtained in much less time than it takes to obtain the proton-decoupled C... 

Choice of Pulse Sequence. Many variants of these basic pulse sequences exist. HMQC sequences are often preferred in studies of low-y metal nuclei, while HSQC sequences are preferred by authors interested in N. The present authors experience is in line with these prejudices . We have found versions incorporating adiabatic decoupling of third nuclei (eg., H, N HSQC with adiabatic decoupling of P) particularly useful (Figure 19). 

Fig. 3. Basic pulse sequences for 2D- X,"T H correlations. Tbe same notation as in Hg. 1 is used. Minimum phase cycles for selection of correlation signals are given, more elaborate schemes for quadrature detection in FI and phase-sensitive spectra may be applied following standard rules. (a) HETCOR (without 180° pulses)/INEPT (with 180° pulses), the refocusing delays A are optional in both experiments setting the mixing pulses 8 to 45°/135° instead of 90° allows to determine coupling signs in ABX-type spectra. (b), HSQC. (c), HMQC the refocusing delay A2 is optional.

Despite the slightly foreboding title, the basic HMQC sequence is rather simple, comprising only four rf pulses (Fig. 6.3), the operation of which is considered here for a simple H- C spin pair. The sequence starts with proton excitation followed by evolution of proton magnetisation under the influence... 

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