HMBC pulse sequence

Recent results have been summarized in a number of articles, especially in this journal.17-19 This review will focus on newly developed HMBC pulse sequences and application on small to medium-sized organic molecules. After a short introduction into basic theory, a selection of pulse sequences and a look at the large variety of applications will complete the overview of the HMBC experiment. Finally, a brief summary and outlook to future perspectives of HMBC will be given. 

Analysis of the basic HMBC pulse sequence residual Vch signals... 

Analysis of the standard HMBC pulse sequence missing and weak long-range correlations... 

Figure 2 HMBC spectrum recorded on a sample of 50 mmol cyclosporine dissolved in C6D6 using the standard HMBC pulse sequence depicted in Figure 1 and recommended acquisition and processing parameters.27...

In its standard implementation, the suppression of the undesired one-bond correlations is far from complete using a one-step low-pass J filter HMBC pulse sequence. Effective modifications are needed to achieve this goal when there is a wide range of Vch values. There are several kinds of pulse... 

Figure 9 Timing diagram of the BIRD-HMBC pulse sequence for the detection of nJch correlations, including an additional two-step low-pass J filter. Thin and thick bars represent 90° and 180° pulses, respectively. 13C180° pulses are replaced by 90°y — 180°x — 90°y composite pulses. <5 is set to 0.5/(Vch) and A is set to 0.5/("JCH). Phases are cycled as follows fa = y, y, —y, —y 4>j = x, —x fa — 8(x), 8(—x) fa = 4(x), 4(— x) ( rec = 2 (x, — x), 4(—x, x), 2(x, —x). Phases not shown are along the x-axis. Gradient pulses are represented by filled half-ellipses denoted by Gi-G3. They should be applied in the ratio 50 30 40.1.

Figure 20 Timing diagram of the suggested 2y,3y-HMBC experiment, including a LPJF3 for efficient 1JCH suppression. The sequence is virtually identical to the CIGAR-HMBC pulse sequence. The STAR operator is also a constant-time variable element. In this fashion, scalable F, modulation can be specifically introduced for 2JCH cross-peaks into the spectrum independently of the digitization employed in the second frequency domain.

B) up-down HMBC pulse sequence inverting BCH and 13CH3 peaks relative to the standard sequence. (C) up-down + HMBC pulse sequence inverting 13CH and 13CH3 peaks relative to the standard sequence and in the opposite sense to the up-down sequence. The data of the different pulse sequences are recorded in an interleaved manner. After formation of the required two linear combinations in the time domain, the data are processed in the same way as other HMBC-type data. 

Figure 28 Excerpts of an HMBC (top), BS-HMBC (middle) and CT-BS-HMBC (bottom) spectra showing the carbonyl part of cyclosporine using the standard HMBC pulse sequence and the CT-BS-HMBC of Claridge.73 The conventional non-selective HMBC was acquired with a 200-ppm, 3C window. The band-selective (middle) and the constanttime band-selective (bottom) HMBC were acquired with a 6-ppm window cantered at 172 ppm. Selective excitation was achieved with a 13C 1 ms 180° seduce-1 pulse.

In practice, any available HMBC pulse sequence could be used to record fast-HMBC spectra.88 As HMBC are recorded without broadband heteronuclear decoupling, the duty cycle is no longer an issue with FAST-HMBC schemes, as it is using the standard SOFAST-HMQC or FAST-HMQC pulse sequences. 

The potential advantages of the IMPACT-HMBC experiment are readily shown in Figures 34 and 35. In Figure 34, the full-width HMBC spectrum, recorded using the standard HMBC pulse sequence, is shown on the left. This spectrum combines strong residual a/CH correlations and F, ridges... 

Figure 34 Excerpts of two-dimensional HMBC spectra of cholesteryl acetate recorded on a Bruker Avancell 400 MHz spectrometer (A) with the standard HMBC pulse sequence (Figure 1), and (B) with the IMPACT-HMBC experiment depicted in Figure 30. The same contour levels are used for all spectra. In (A), F, ridges are still visible (indicated by a vertical arrow), while they are very efficiently suppressed in (B). The proposed sequence results in signals with no coupling structure, as a result of the incorporation of a constant-time period. The improved peak dispersion is shown for the correlation between C-3 and H-2 (expanded in the small boxes). Asterix and the dashed box indicate residual Vch signals. The measurement duration was 22 min for both experiments.

For D-HMBC experiments, we usually omit the low pass J-filter (the first 90° pulse for C nucleus in the HMBC pulse sequence) aiming to suppress the cross peaks due to the direct Jc-h correlation, but it can be implemented if desirable. In the D-HMBC spectra, the cross peaks between directly bonded C and H do not, in most cases, hinder the easy analysis of the spectra, because these cross peaks appear as singlets. On the contrary, these peaks even contribute to easy NMR spectral analysis when HMQC spectral data are not in hand. 

The D-HMBC pulse sequence can also be used in combination with the pulse field gradient (PFG) technique [12]. Figure 5(c) shows the successful observation of cross peaks between the methyl group at C-5 of an oxazole unit and adjacent carbons in promothiocin. These cross peaks are hidden by the strong t noise of the solvent peak in the HMBC and D-HMBC spectra. The above results clearly indicate that D-HMBC is a quite useful technique for structural studies of complicated natural products. 

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

Figure 7-17 The gradient HMBC pulse sequence. The relative strengths of gradients G, G2, and G3 are 5,3, and 4 G cm, respectively, as shown, when X =...

HMBC pulse sequence. The relative strengths of the 10 gradients are as follows (i) dual-stage, low-pass 7-filter (G1-G3) 10, -6.63,-3.37 (ii) STAR operator (G4-G7)... 

Open the configuration file ch5731.cfg. Create the HMBC pulse sequence as shown in the scheme below saving the new sequence files with the name myhmbc2.seq. Check the new pulse sequence using the test spin system chlongrg.ham (calculation time approximately 3 minutes). 

Retrospectively, after demonstrating in the implementation of the IMPEACH-MBC experiment that it is possible to suppress F skew, it was evident that the skew of responses in F, while a nuisance if uncontrolled, could serve as a useful means of response authentication if Fi skew was under user control. The CIGAR-HMBC experiment aeeomplishes this task. While the constant time variable delay of the IMPEACH-MBC experiment (see Eq. (8)) renders the duration of the variable delay constant, the CIGAR-HMBC pulse sequence modifies the variable delay interval of the experiment still further, as shown below the complete puLse sequence is shown in Fig. 17. 

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