CIGAR-HMBC

Key Words NMR, Heteronuclear Long-range correlation, HMBC, CT-HMBC, ACCORD-HMBC, IMPEACH-MBC, BIRD-HMBC, G-BIRD-HMBC, CIGAR-HMBC, IMPACT-HMBC, TS-HMBC, Broadband-HMBC, H2BC, edited HMBC, 10-ppm HMBC, /CH artefacts suppression, Spectral editing... 

In 2000, Krishnamurthy et al. have presented the 2/,3/-HMBC experiment (Figure 20), that affords for the first time the means of unequivocally differentiating between 2/ch from 3Jch correlations.59 Their approach is based on a further derivative of the constant-time variable delay introduced in the IMPEACH-MBC experiment. The user-definable /-scaling factor of the CIGAR-HMBC is used in the new experiment, the 2J,3J-HMBC experiment, to differentiate between 2/CH from 3Jch correlations. This new pulse sequence element has been given the acronym STAR (Selectively Tailored Accordion F1 Refocused) operator. 

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.

As a final piece of data to further support the structure of 15, a 3-6-Hz optimized CIGAR-HMBC experiment was also acquired over a weekend... 

Hadden, C.E., Martin, G.E., and Krishnamurthy, V.V., Constant time inverse-detection gradient accordion rescaled heteronuclear multiple bond correlation spectroscopy CIGAR-HMBC, Magn. Reson. Chem., 38, 143, 2000. 

One of the examples shown by Kline and Cheatham compares the correlations observed in a GNHMBC experiment with those from a N-optimized CIGAR-HMBC experiment performed on 5-chloro-l,3-dimethylpyrazole (2). When conventional, statically optimized GNHMBC data were acquired, then only a correlation from the H4 resonance to the NMe N1 resonance at 196.7 ppm was observed. In contrast, when a 3-10 Hz optimized CIGAR-HMBC spectrum was recorded, a correlation was also observed to the N2 resonance at 309.5 ppm. 

From the start of data interpretation to the completion of the strucmre elucidation, including the quantum leap provided by the recognition that the structure contained an 11-cryptolepinyl moiety based on the observed color and then confirmed by the data assignment, a highly competent spectroscopist required 72 h to assemble the structure. Using the same data, including the CIGAR-HMBC data, which afforded correlations to... 

Investigation of the robustness of optimized CIGAR-HMBC. Kline and Cheatham in developing a N-optimized variant of CIGAR-HMBC (see Section 2.2) extensively applied the experiment in an effort to determine its robustness relative to conventional HMBC for structural characterization. assignments reported by... 

Table 11. chemical shifts for a series of primary and secondary amines measured using N-optimized CIGAR-HMBC ... 

HMBC experiment. However as already discussed decreasing the corresponding free precession period prior to the coherence transfer reintroduces splitting due to IH, IH coupling in the fl dimension. So alternative experiments such as IMPEACH-HMBC and CIGAR-HMBC experiment have been designed to suppress this splitting [5.173, 5.174, 5.175]. 

To simulate the 2D [13C, 1H] CIGAR-HMBC spectrum for the spin system used in the Check its 5.S.2.3 and 5.5.2A, load the file ch5525.cfg. Process the data in 2D WIN-NMR. To examine the signal modulation in f1 by the 1H- >H coupling, run a series of simulations using different values of id23 starting with the current Jscale value of 8 [Hz]. 

In the early days of heteronuclear correlation spectroscopy, a gradient free version of the double low-pass filter was proposed [5.212, 5.213], but the necessity to suppress unwanted coherences, particularly in INADEQUATE experiments, has forced the design of a gradient version [5.214]. The application of this filter is not just restricted to INADEQUATE experiments it has also become the element of choice in ACCORD-HMBC and ACCORD-CIGAR-HMBC experiments to reduce residual one-bond correlations. These experiments are very sensitive to the suppression of one-bond... 

CIGAR-HMBC - Constant time Inverse-detected Gradient Accordion Rescaled Heteronuclear Multiple Bond Correlation... 

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. 

Fig. 18. H4/C3 JcH response in three CIGAR-HMBC spectra of 2-pentanone showing the effect of varying the parameter /scale- The response shown in Panel (a) was acquired with /s -iie = 0. As expected, no skew is observed in F. When is increased to 6, a modest degree of skew is introduced as shown in Panel (b). Finally, when /scale = 24, a considerable degree of F skew is introduced. In practice, we have found it useful in the author s laboratory to use /scale = 15 to afford an adequate degree of F skew for long-range response authentication.

Fig. 19. Pulse sequence for the J, J-HMBC experiment described by Krishnamurthy ei This experiment represents the most refined version of the accordion-optimized experiments to be developed thus far and allows the differentiation of Jxh from Jxh long-range correlations to protonated heteroatoms ( - C and N). The experiment further modifies the concept of the constant time variable delay used in the IMPEACH-MBC and CIGAR-HMBC experiments to even more selectively manipulate various components of magnetization. This is done using the pulse sequence operator given the acronym STAR (Selectively Tailored Accordion F Refocusing) (.see also Fig. 20). Differentiation of various components of heteronuclear long-range magnetization is accomplished within the STAR operator, with the balance of the pulse sequence similar to that of the IMPEACH-MBC and CIGAR-HMBC experiments.

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