Heteronuclear multiple bond correlation pulse sequence

Fig. 14. IMPEACH-MBC (IMproved PErformance ACcordion-optimized Heteionucicar multiple bond correlation) pulse sequence developed by Martin and co-workers. The experiment is a further modification of the ACCORD-HMBC experiment that utilizes a constant time variable delay in lieu of a simple variable delay. The con.stant time variable delay introduces the interval, D/2 — 180° "C — D/2, which precedes the variable delay interval, vd. As the evolution lime ti is incremented, the interval vd is decremented in the usual fashion. However, at the same time, the Dll (ct A) intervals are incremented in a manner to keep the overall duration of the period D + vd a constant time interval. Hence, homonuclear modulation, which plagues ACCORD-HMBC experiments, is suppressed by the constant time of the intcrv al D + vd. In contrast, evolving heteronuclear couplings arc refocused at time D by the 180° - C pulse located at DU. These couplings then evolve during the variable interval vd to be sampled in the usual, accordion manner. By using this approach, the constant time variable delay pulse sequence element is of constant duration for homonuclear components of magnetization while serving as a variable delay for heteronuclear components.

Figure 7.14 Pulse sequence for the HMBCS (heteronuclear multiple-bond correlation, selective) experiment, which uses advantageously a 270° Gaussian pulse for exciting the carbonyl resonances. It is also called the semisoft inverse COLOC. (Reprinted from Mag. Reson. Chem. 29, H. Kessler et al., 527, copyright (1991), with permission from John Wiley and Sons Limited, Baffins Lane, Chichester, Sussex P019 lUD, England.)...

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 ... 

UNDERSTANDING THE HETERONUCLEAR MULTIPLE-BOND CORRELATION (HMBC) PULSE SEQUENCE... 

Other strategies that show great promise in reducing NMR acquisition time utilise methods to obtain multiple sets of data from one experiment through a concept known as time-shared evolution. An example of this process that should find utility in natural products elucidation was demonstrated by a pulse sequence called CN-HMBC.93 Traditionally, a separate 13C-HMBC and 15N-HMBC were acquired independently. However, the CN-HMBC allows both 13C- and 15N-HMBC spectra to be obtained simultaneously. By acquiring both data sets simultaneously, an effective 50% time reduction can be achieved.93 This approach has also been demonstrated for a sensitivity-enhanced 2D HSQC-TOCSY (heteronuclear multiple bond correlation total correlation spectroscopy) and HSQMBC (heteronuclear single quantum... 

FIGURE 12.11 Pulse sequence for the heteronuclear multiple bond correlation experiment. A = 1 /(21/) and A = l/(2 7), where [J and "J are spin couplings between I and S through one and n bonds, respectively.The first S pulse, marked 90, is cycled through + x and —X. See text for discussion of the state of the spin system at the times indicated. 

The other common inverse-detection method, heteronuclear multiple quan-turn coherence (HMQC) relies on multiple-quantum coherence transitions during the pulse sequence. Due to the multiple-quantum coherence transitions it is more laborious to theoretically follow the course of magnetization, and the cross peak will be broader in the Fi dimension due to the /hh evolution. Unlike HSQC, HMQC can also be optimized for Jch couplings. This heteronuclear multiple bond correlation experiment, or HMBC, ° ° has lower sensitivity than HMQC/HSQC experiments, and the Jch correlations can appear as artefacts in the spectrum. However, the cross peak volume should follow the concentration of analyte, so with proper method validation HMQC and HMBC should also be applicable for quantification. 

When we collect a 2-D NMR spectrum, both the second frequency dimension data (fj or Fj) and the first frequency dimension data (f2 or F2) may be phase sensitive. (Note that fj and f2 appear to be reversed but this naming convention derives from the order of their time domain precedents, tj and t2, in the NMR pulse sequence.) Zero-and first-order phasing of the second dimension of a 2-D NMR data set is required in many cases. Some experiments, most notably the gradient-selected heteronuclear multiple bond correlation (gHMBC) experiment, use the absolute value of the signal and hence do not require phasing. 

To date, the only inverse-detected heteronuclear chemical shift correlation experiment available for multiple-bond correlation is the HMBC experiment of Bax and Summers (1986). The pulse sequence is shown in Fig. 5 and... 

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. 

There are two approaches to pulse sequence classification depending on the user s occupation. For the chemist who has to solve a structural question or characterize a new compound it is the spectra obtained from the pulse sequence that is of primary importance. The NMR spectroscopist is usually more concerned with the pulse sequence structure and choice of experimental parameters and whether a particular pulse sequence can be improved or modified to solve a specific problem. These two different approaches lead to confusion in pulse sequence nomenclature such that names are often a combination of the purpose of the experiment and the sequence layout. For example the commonly used acronyms HMQC, HSQC and HMBC imply a consistent abbreviation system yet HMQC and HSQC describe the coherence state during the evolution time whilst HMBC denotes an experiment to correlate nuclei using multiple bond heteronuclear scalar coupling. 

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