The HMQC Experiment

The gradient version of HMQC is performed in the absolute-value mode, whereas the nongradient experiment is conducted in the phase-sensitive mode. While the use of gradients does result in a 2 / decrease in sensitivity with respect to the nongradient version (Part C, introduction), this decrease is seldom important, because HMQC is inherently a relatively sensitive experiment. Sensitivity is, however, critical in other experiments, as will be seen in Section 7-9a. 

The following parameters are appropriate for phase-sensitive HMQC experiments  

steady-state scans = 32 (gradient and nongradient versions) 

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Figure 5.51 The pulse sequence employed for the HMQC experiment.

In contrast to the HMQC experiment, which provides connectivity information about directly bonded interactions (i.e., one-bond... 

The SELINCOR experiment is a selective ID inverse heteronuclear shift-correlation experiment i.e., ID H,C-COSYinverse experiment) (Berger, 1989). The last C pulse of the HMQC experiment is in this case substituted by a selective 90° Gaussian pulse. Thus the soft pulse is used for coherence transfer and not for excitation at the beginning of the sequence, as is usual for other pulse sequences. The BIRD pulse and the A-i delay are optimized to suppress protons bound to nuclei As is adjusted to correspond to the direct H,C couplings. The soft pulse at the end of the pulse sequence (Fig. 7.8) serves to transfer the heteronuclear double-quantum coherence into the antiphase magnetization of the protons attached to the selectively excited C nuclei. 

A ID analog of the HMQC experiment with TOCSY magnetization transfer has been reported (Crouch et al, 1990). The pulse sequence is... 

Because of the favorable cross-peak multiplet fine-structure, the HSQC experiment offers superior spectral resolution over the HMQC (heteronuclear multiple quantum coherence) experiment [13, 14], On the other hand, the HMQC experiment works with fewer pulses and is thus less prone to pulse imperfections. The real advantage of the HSQC experiment is for measurements of samples at natural isotopic abundance and without the use of pulsed field gradients, since the HSQC experiment lends itself to purging with a spin-lock pulse. Spin-lock purging in the HMQC experiment... 

The HMQC experiment gives exactly the same result as the HSQC, and the data is processed in the same way. There are some differences in sensitivity and peak shape that depend on the size and complexity of the molecule, and the pros and cons of the two experiments are the subject of some debate in the literature. Because it relies on double-quantum and zero-quantum coherences (DQC and ZQC) during the evolution (t ) period, the HMQC is more difficult to explain and understand than HSQC, which uses only the familiar singlequantum transitions that can be diagramed and analyzed using vectors. We discuss it here because it forms the basis of the HMBC (multiple-bond) experiment. 

It should be noted that the DQ-spectra presented here are obtained assuming ideal excitation. To accurately simulate the DQ projections from the HMQC experiments, real time rf-pulses should be included and the calculations should be performed for the indirect dimension of the HMQC sequence. 

A number of variations of both HSQC and HMQC have been developed. Both methods are widely used and are of comparable value. The HMQC experiment uses fewer pulses, hence can be somewhat shorter and is less dependent... 

C, Li3 spin systems). The HMQC experiment, which also allows a straightfoward determination of the involved C, Li coupling constants, is especially easy to perform with a triple resonance probehead which has, aside from the H and the lock channel, a fixed frequency for and a variable X frequency (see Chapter 2). It is of interest to note that Li, C cross peaks can also be observed in cases where the corresponding Li, C coupling is not resolved in the ID spectrum [14]. An example for an experiment using sequence (v) is shown in Figure 14 with the spectrum of isopropyllithium, where in hydrocarbon solvents solvation leads to the formation of tetramers and hexamers [76]. 

To conclude this section we mention an ingenious application of the HMQC experiment for Li, N doubly labelled organonitrogen compounds in the form proposed by Muller [138] and Bodenhausen and Ruben [143]. It was introduced by Gilchrist and Collum [149], who showed that the method allows, on the basis of homonuclear zero-quantum coherence selection, the... 

BIRD-HMQC. The most difficult aspect of implementing the HMQC experiment is the suppression of signals from protons attached to C (the center-band or single quantum coherences) in favor of the protons attached to C (the satellites or double quantum coherences). The use of pulse field gradients (PFG, Section 6-6) is the most effective technique, but relatively few spectrometers are equipped with the hardware required for their generation. Fortunately, there is an effective alternative for the suppression of center bands by means of the BIRD Bilinear Rotation Decoupling) sequence, which is outlined by the vector... 

The HMQC sequence aims to detect only those protons that are bond to a spin- A heteronucleus, or in other words only the satellites of the conventional proton spectrum. In the case of C, this means that only 1 in every 100 proton spins contribute to the 2D spectrum (the other 99 being attached to NMR inactive C) whilst for N with a natural abundance of a mere 0.37%, only 1 in 300 contribute. When the HMQC FID is recorded, all protons will induce a signal in the receiver on each scan and the unwanted resonances, which clearly represent the vast majority, must be removed with a suitable phase cycle if the correlation peaks are to be revealed (the notable exception to this is when pulsed field gradients are employed for signal selection, see Section 6.3.3 below). By inverting the first C pulse on alternate scans, the phase of the C satellites are themselves inverted whereas the C-bound protons remain unaffected (Fig. 6.5). Simultaneous inversion of the receiver will lead to cancellation of the unwanted resonances with corresponding addition of the desired satellites. This two step procedure is the fundamental phase-cycle of the HMQC experiment, as indicated in Fig. 6.3 above. 

F re 6.5. Selection of satellite resonances in the HMQC experiment through phase-cycling. The phase of the carbon-13 satellites can be inverted by inverting the phase of the first 90° carbon pulse (a vs b). Subtraction of these two data sets by inverting the receiver phase also, cancels the parent H- C resonance but reinforces the satellites (c). 

Figure 6.12. The BIRD variant of the HMQC experiment. The conventional HMQC sequence is employed, but is preceded by the BIRD inversion element and an inversion recovery delay, t. This procedure ultimately leads to saturation of the unwanted parent resonances.

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