Heteronuclear multiple-quantum sensitivity

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. 

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. 

HMQC Heteronuclear multiple quantum coherence, e.g. inverse CH correlation via one-bond carbon proton-coupling, same format and information as described for ( C detected) CH COSY but much more sensitive (therefore less time-consuming) because of H detection... 

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 ... 

Inverse-detected experiments have had the greatest effect in making 15N NMR experiments feasible for small samples. These experiments take advantage of the higher sensitivity of NMR to facilitate the observation of insensitive nuclei like 13C and 15N. The H-13C heteronuclear multiple quantum coherence (HMQC) and the related heteronuclear multiple-bond correlation (HMBC) experiments are important in contemporary natural products... 

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). 

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 sensitivity gain of proton detected Heteronuclear Multiple-Quantum Coherences (HMQ.C) experiments, as compared with direct heteronuclear detected ones and with polarization transfer techniques like INEPT [22-24] using heteronuclear detection, can be calculated [27,28] for the Sn, Sn and Sn isotopes (Table 3). 

For smaller quantities of compounds more sensitive inverse detected techniques are available, such as HMQC ( IH-I C one bond correlation via heteronuclear multiple quantum coherence, analogous to HETCOR) and HMBC (proton detected heteronuclear multiple bond correlation spectroscopy) (15). The last provide, in addition to the intraresidue multiple bond correlations, interresidue correlations between the anomeric carbon and the aglycone protons.We follow this general strategy for the structural determination of tri terpenoid saponins of Bupleurum fruticosum (16) andArdisia japonica (9). 

The inverse detection heteronuclear multiple quantum coherence (HMQC) experiment is another approach to two-dimensional NMR techniques, which consists of a transfer of chemical shift and coupling information from relatively insensitive nuclei such as and some metals, to more sensitive nuclei such as H. The advantage of this method is a substantial increase in the sensitivity obtained, due to the greater natural abundance of H (Kingery et al., 2001). 

Muller, L. (1979). Sensitivity enhanced detection of weak nuclei using heteronuclear multiple quantum coherence, J. Am. Chem. Soc., 101 4481. 

The domain is concerned with mainly two varieties of CH 2D experiments the one-bond correlation and the long range (two- or three-bond) correlation. These experiments were formerly run in the so-called normal mode acquisition with modulation) and were named CH COSY (XH CORR or HETCOR) and COLOC (long range). These acron rms are now being replaced with HMQC ( Heteronuclear Multiple Quantum Correlation) and HMBC (Heteronuclear Multiple Bond Correlation) and they are run in the reverse mode ( H acquisition with C modulation). The differences between normal and reverse experiments are sensitivity (a factor of 5) and resolution (in the dimension of acquisition ). 

Heteronuclear Multiple Quantum Correlation) and HMBC (Heteronuclear Multiple Bond Correlation). Application of nuclear Overhauser effect (nOe) difference spectroscopy and nuclear Overhauser effect spectroscopy (NOESY) complete the analysis, giving atomic spatial relationships. Sensitivity problems can be alleviated using Homo Hartmann-Hahn spectroscopy (HOHAHA or TOCSY, Total Correlation Spectroscopy). For weak nOes a rotating frame experiment, i.e. ROESY (Rotating frame Overhauser Effect Spectroscopy) is useful, and may be the best experimental method to sequence chains of sugars [5]. 

In practice, however, we rarely collect a H-coupled spectrum because of the poor sensitivity associated with this experiment. More elegant experiments that require less instrument time are available to provide similar information. These experiments include the attached proton test (APT) [1] and the distortionless enhancement through polarization transfer (DEPT) [2] experiments. Careful examination of data generated by the heteronuclear multiple quantum... 

The heteronuclear multiple quantum correlation (HMQC) and heteronuclear single quantum correlation (HSQC) experiments both correlate H resonances with the resonances of some other nuclide, usually C or N. Both the HMQC and HSQC experiments can be run in the phase-sensitive or nonphase-sensitive mode. As in... 

Figure 9. The Pb(II) complex [Pb -EDTA-N4] + has been characterized both (a) crystal-lographically and (h) by two-dimensional Pb— H heteronuclear multiple quantum (HMQC) NMR spectroscopy. The technique is sensitive enough to detect Pb(ll) coupling to methylene protons through three bonds to the protons on the acetoamido arms (—CH2CONH2) and ethylene backbone (—NCH2). [Reprinted with permission from E. S. Claudio, M. A. ter Horst, C. E. Forde, C. L. Stern, M. K. Zart, and H. A. Godwin, Inorg. Chem., 39, 1391-1397 (2000). Copyright 2000 American Chemical Society.]...

HMQC (heteronuclear multiple quantum correlation) or HSQC (heternuclear single quantum correlation) Provides 1 bond or correlation Can identify all the protonated carbons and nitrogens in a molecule Less sensitive experiment due to low sensitivity of C and N Compound requirement is high Minimum 20 p-g or more Can assist in identifying complete unknowns, unexpected products or metabolites... 

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