Heteronuclear multiple-quantum correlation HMQC

The HMQC (Heteronuclear Multiple-Quantum Correlation) experiment is one of the two commonly employed proton-detected single-bond correlation experiments. Although this was suggested many years ago [1, 2], the experiment lacked widespread use until a scheme that was able to overcome the technical difficulties associated with proton observation described above was presented [3]. Since then, and particularly since the advent of PFGs, the technique has come to dominate organic NMR spectroscopy. 

The 2D spectrum provides a simple map of connectivities in which a crosspeak correlates two attached nuclei, as seen in the HMQC spectrum of menthol 6.1 

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 of the one-bond carbon-proton coupling. 

The HMQC sequence aims at detecting only those p-otons that are bound to a spin-Vi heteronucleus, or in other words, only the satellites of the conventional proton spectrum. In the case of this means that only 1 in every 100 proton spins contribute to the 2D spectrum (the other 99 being attached to NMR-inactive whilst for 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). By inverting the first C pulse on alternate scans, the phase of the C satellites is inverted whereas the C-bound protons remain unaffected (Fig. 6.5). Simultaneous inversion of the receiver will thus 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. 

The 2D spectrum provides a simple map of connectivities in which a crosspeak correlates two attached nuclei, as seen in the H- C HMQC spectrum of menthol 6.1 (Fig. 6.2). This illustrates three of the most significant features of the experiment when applied to routine structural problems. The 

This coherence is, in fact, a combination of both heteronuclear double- and zero-quantum coherence, as represented on the coherence transfer pathway of Fig. 6.3. Thus, for example, Hp = -1-1 and = -f-1 corresponds to (ioub/e-quantum coherence (Ep = 2), whilst Hp = - -1 and Cp = —1 is zero-quantum coherence (Ep = 0). The salient point at this stage is how such coherences evolve during the subsequent ti period. Since they contain terms for both transverse proton and carbon magnetisation, they will evolve under the influence of both proton and carbon chemical shifts (although a feature of multiple-quantum coherences is that they will not evolve under the active coupling, so Jch need not be considered at this point). What is ultimately 

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A variety of examples of 2D-NMR experiments is provided in reference [21]. The structure elucidation of the di-rhodium compound shown in Figure 11.3 was mostly carried out in this way. For example, 2D 11 l-31P heteronuclear multiple quantum correlation (HMQC) experiments were used to show that two rhodium-coupled hydride resonances are connected to a single type of 31P nucleus. 

The first of the proton-detected experiments is the Heteronuclear Multiple Quantum Correlation HMQC experiment of Bax, Griffey and Hawkins reported in 1983, which was first demonstrated using 1H-15N heteronuclear shift correlation [42]. The version that has come into wide-spread usage, particularly among the natural products community, is that of Bax and Subramanian reported in 1986 [43]. A more contemporary gradient-enhanced version of the experiment is shown in Fig. 10.14 [44],... 

The structural assignment of both 29 and 30 was accomplished through extensive two-dimensional (2-D) NMR heteronuclear multiple quantum correlation (HMQC) and heteronuclear multiple bond correlation (HMBC) spectroscopic studies <2004T8189>. In the HMBC spectrum of 29, the proton at 8.64p.p.m. shows a strong correlation Jq-h with the carbonyl carbon (C-10) at 180.9 ppm and the proton at 8.82p.p.m. with the carbonyl carbon (C-5) at 181.7 ppm. The HMBC spectrum of 30 shows a significant strong correlation Vq h of the C-5 carbonyl carbon with the H-6 proton at 8.52 ppm and the H-4 proton at 8.52p.p.m. 

The vast literature associated with flavanoid chemistry precludes a discussion here but two valuable reviews have been published. The first reviews a number of spectroscopic techniques used for flavonoid analysis, with a strong emphasis on NMR spectroscopy (plus also mass spectrometry, vibrational spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, X-ray crystallography, and circular dichrosim (CD)) . The second review deals with NMR methods that have been successful in the characterization of phenolic acids and flavonoids from plant extracts that have not been separated or isolated as single components. The emphasis of the article is 2-D NMR methodology and a variety of experiments such as total correlated spectroscopy (TOCSY), COSY, nuclear Overhauser enhancement spectroscopy (NOESY) and heteronuclear multiple quantum correlation (HMQC) are discussed . 

Similar to the HSQC experiment, multiple quantum coherences can be used to correlate protons with Q-coupled heteronuclei. The information content of the Heteronuclear Multiple Quantum Correlation (HMQC) experiment (56) is equivalent to the HSQC, but the sensitivity can be improved in certain cases. Additionally, by proper tuning of delays and phase cycling, it can be transformed into the heteronuclear multiple bond correlation experiment (57-59), which results in correlations between J- and J-coupled nuclei. 

The addition of a HOHAHA mixing step to a heteronuclear multiple-quantum correlation (HMQC) experiment (Bax et al., 1983) yields two-dimensional HMQC-HOHAHA experiments (Lerner and Bax, 1986 Davis, 1989b Oh et al., 1989 Gronenborn et al., 1989b John et al., 1991 Willker et al., 1993a). Domke and McIntyre (1992) combined heteronuclear Hartmann-Hahn transfer with multiplicity editing techniques. 

The Si NMR spectrum of pentaorganosilicate 25 was recorded at —50°C to minimize signal broadening <2004AGE3440>. H NMR, NMR, heteronuclear multiple quantum correlation (HMQC), and heteronuclear multiple bond correlation (HMBC) spectroscopic measurements were also performed. The observed 7c2,si value of 86 Hz was similar to that of a typical Si(sp )-C(sp ) bond, while the /c 2, si value of 30 Hz was much smaller than that of a Si(sp )-C(sp ) bond (64-70 Hz). 

The two-dimensional, heteronuclear multiple quantum correlation (HMQC) and heteronuclear multiple bond correlation (HMBC) spectra were taken with standard Bruker pulse programs. The HMQC and HMBC spectra are given in Figures 8 and 9 (9). The chemical shifts and spectral assignments are provided in Table 2 (9,10). The effect of Al3+ on the carbon spectrum of lomefloxacin is shown in Figure 10 (9). 

Figure 8. Heteronuclear multiple quantum correlation (HMQC) spectrum of Lomefloxacin mesylate.

HSQC) or heteronuclear multiple quantum correlation (HMQC). The combined experiments such as 2D HSQC(HMQC)-TOCSY experiments are powerful tools for the assignment of the 13C and 11 resonances belonging to the same sugar residue providing enhanced dispersion of TOCSY correlations in the carbon dimension. More recendy, different carbon multiplicity editing methods, for example, DEPT (distortionless enhanced polarization transfer)-HMQC and E-HSQC, have been developed to reduce the complexity of proton-carbon correlation spectra and to enhance the resolution by narrowing the applied spectral window.11... 

C NMR was a reliable source of detection and identification of carbon nuclei in the saccharide molecule. However, greater quantities were requiredfor ID experiments as compared with H NMR spectroscopy and often extended periods for acquisition (sometimes 3 days) were required. The H- C heteronuclear multiple quantum correlation (HMQC) was one experiment that allowed the assigiunent of carbon resonances, by correlation with their proton nuclei, and where smaller quantities were used. A conscious ID P NMR investigation quickly revealed the presence of phosphate or a 2-aminoethyl phosphate unit in the core OS. 2D H-3 P HMBC NMR spectroscopy was a reliable method for efficient detection and sometimes placement of the phosphate substituents. 

The main emphasis of current carbohydrate structural analysis is the applicability of modern multi-dimensional NMR for solving the two crucial problems in complex carbohydrate structural analysis, namely, the elucidation of the sequence of glycosyl residues and the solution conformation and dynamics of a carbohydrate (150). Techniques include 2D Total Correlation Spectroscopy (TOCSY), Nuclear Overhauser effect spectroscopy (NOESY), rotational nuclear Overhauser effect spectroscopy (ROES Y),hetero-nuclear single quantum coherence (HSQC), heteronuclear multiple quantum correlation (HMQC), heteronuclear multiple bond correlation (HMBC), and (pseudo) 3D and 4D extensions. 

In the heteronuclear experiment category, the experiments of interest are the heteronuclear multiple quantum correlation (HMQC) experiment, the heteronuclear single quantum correlation (HSQC) experiment, and the heteronuclear multiple bond correlation (HMBC, including the gradient-selected version gHMBC) experiment. Both the HMQC and HSQC produce similar results, but each has its own unique advantages and disadvantages. 

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. 

The complete PMR and C assignments for a series of differently substituted thiadiazin-2//-thiones 30-32, having different groups on the two heterocyclic nitrogen atoms, have been presented <2001MRC222>. To assign all of the NMR signals unequivocally, 1-D and 2-D techniques such as distortionless enhancement of polarization transfer (DEPT 135), heteronuclear multiple quantum correlation (HMQC), and heteronuclear multiple bond... 

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