Heteronuclear multiple-quantum pulse sequence

Fig. 20. Heteronuclear multiple quantum pulse sequence used for 2H-13C correlation.

HC HMQC (heteronuclear multiple quantum coherence) and HC HSQC (heteronuclear single quantum coherence) are the acronyms of the pulse sequences used for inverse carbon-proton shift correlations. These sensitive inverse experiments detect one-bond carbon-proton connectivities within some minutes instead of some hours as required for CH COSY as demonstrated by an HC HSQC experiment with a-pinene in Fig. 2.15. 

To be fair, we must point out that this type of experiment is extremely sensitive to the parameters chosen. Various pulse sequences are available, including the original COLOC (Correlation by means of Long range Coupling) as well as experiments variously referred to as HMBC (Heteronuclear Multiple-Bond Correlation) and HMQC (Heteronuclear Multiple-Quantum Correlation). Depending on the parameters chosen, it is often not possible to suppress correlations due to one-bond coupling ... 

J splittings cannot be directly resolved. In addition to the obvious advantage of providing a map of chemical bonds between the spins, /-based transfers do not require spin-locking and are not disturbed by molecular motions. The major drawback of polarization transfer through J coupling is that the delays involved in the pulse sequences, such as insensitive nuclei enhanced by polarization transfer (INEPT) [233] or heteronuclear multiple-quantum coherence (HMQC)... 

Fig. 10.14. Gradient-enhanced HMQC pulse sequence described in 1991 by Hurd and John derived from the earlier non-gradient experiment of Bax and Subramanian. For 1H-13C heteronuclear shift correlation, the gradient ratio, G1 G2 G3 should be 2 2 1 or a comparable ratio. The pulses sequence creates heteronuclear multiple quantum of orders zero and two with the application of the 90° 13C pulse. The multiple quantum coherence evolves during the first half of ti. The 180° proton pulse midway through the evolution period decouples proton chemical shift evolution and interchanges the zero and double quantum coherence terms. Antiphase proton magnetization is created by the second 90° 13C pulse that is refocused during the interval A prior to detection and the application of broadband X-decoupling.

Heterocorrelations can be detected both in direct and reverse modes. In the latter mode, dramatic enhancements of sensitivity can be achieved owing to the larger sensitivity of protons with respect to heteronuclei. In the most common heterocorrelation pulse sequences for reverse detection, called heteronuclear multiple quantum coherence (HMQC) (Fig. 8.2G) [25,26], H-I3C MQ (multiple quantum) coherence is generated by first applying a 90° pulse on protons and, after a time t chosen equal to 1/2 J[j, by applying a 90° pulse on carbon (Fig. 8.19). 

FIGURE 12.10 Pulse sequence for the heteronuclear multiple quantum coherence experiment. See text for discussion of the state of the spin system at the times indicated. 

Heteronuclear multiple-quantum coherence (HMQC) allows one to edit all of the different isotopomers of a Pt cluster using the sequence described in ref. [20] with the preparation pulse only being cycled between +x and —x. More sophisticated phase cycling procedures lead to the selective editing of the different isotopomers. An example of Pt3(CO)3(PPh2 Pr)3 is presented in Figure 2. 

The DEPT pulse sequence is illustrated in Fig. 4.31. To follow events during this, consider once more a H- C pair and note the action of the two 180 pulses is again to refocus chemical shifts where necessary. The sequence begins in a similar manner to INEPT with a 90 (H) pulse after which proton magnetisation evolves under the influence of proton-carbon coupling such that after a period 1 /2J the two vectors of the proton satellites are antiphase. The application of a 90 (C) pulse at this point produces a new state of affairs that has not been previously encountered, in which both transverse proton and carbon magnetisation evolve coherently. This new state is termed heteronuclear multiple quantum coherence (hmqc) which, in general, cannot be visualised with the vector model, and without recourse to mathematical formalisms it is... 

FIGURE 6.11 An abbreviated version of the heteronuclear multiple quantum correlation (HMQC) pulse sequence. The state of the net magnetization is discussed for five points corresponding to the five numbers in the dashed circles. 

An additional option is the use of relaxation-compensating pulse sequences. This is the domain of the pulse-sequence developers. At the moment, there are two approaches available. One uses heteronuclear multiple-quantum coherences, in which the dipolar relaxation is removed [17]. The achieved gain in intensity is shown on the example of an RNA. 

Fig. 8.19 Schematic representation of the gradient heteronuclear multiple quantum coherence or GHMQC pulse sequence. The gradient version of this experiment now in use [114] is derived from the earlier non-gradient experiment described by Bax and Subramanian [113]. Coherence pathway selection is obtained by the application of gradients in a ratio of 2 2 1 as shown. Other ratios are also possible, as considered in the reports of Ruiz-Cabello et al. [115] and Parella [116]. The experiment creates heteronuclear multiple quantum coherence with the 90° C pulse that precedes evolution. Both zero and double quantum coherences are created and begin to evolve through the first half...

Some readers may be surprised to learn that inverse-detected two-dimensional NMR experiments are not a recent addition to the pulse sequence libraries of the NMR spectroscopist. The HMQC (Heteronuclear Multiple-Quantum Correlation) experiment of Bax and Subramanian (1986), now in widespread use, was preceded by the pioneering work of MiilleF (1979) 7 years earlier. Muller described a pulse sequence that is not substantially different from the HMQC experiment of Bax and Subramanian (1986). 

Fig. 5. HMBC pulse sequence of Bax and Summers (1986). The first 90° pulse serves as a low-pass J-filter (Kogler et al. 1983), as discussed in the text. Heteronuclear multiple-quantum coherence of order zero and two is created by the second 90° pulse. The 180° H pulse interchanges zero- and double-quantum coherences and decouples proton chemical shift evolution during tp Observable proton single-quantum coherence is recreated by the final 90° pulse and detected...

Figure 1 Heteronuclear multiple quantum correlation (HMQC) pulse sequences (a) sequence for small J(I,S) values (b) for larger, resolved J(1,S) values and phase-sensitive presentation (c) zero or double quantum variant for the determination of the /-spin-multiplicity (d) with refocusing and optional 5-spin...

The D-HMQC (dipolar heteronuclear multiple-quantum coherence) technique is a recently developed NMR pulse sequence particularly suitable for the investigation of spatial proximity between quadrupolar and spin-1/2 nuclei. Compared to the crosspolarisation magic-angle spinning technique applied to a quadrupolar nucleus, D-HMQC does not require time-consuming optimisations and exhibits on the quadrupolar spin a better robustness to irradiation offset and to Cq values and... 

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