Broadband 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... 

It seems that the broadband HMBC is more effective for small molecules, as emphasized by Equations (24)-(26). For cyclosporine, indeed, as shown by Figures 15 and 16, there is no advantage in recording broadband and wZfra-broadband HMBC as compared to standard optimized HMBC schemes. On the contrary, the ultra-broadband HMBC spectrum shown in Figure 16 does not exhibit more cross-peaks than the standard HMBC (Figure 15A), and there is besides a severe sensitivity loss. 

Figure 15 HMBC and broadband HMBC spectra of cyclosporine in C6D6 recorded with the pulse sequence shown in Figure 14. (A) HMBC spectrum recorded with A = 65.0 ms and 32 scans. (B) HMBC spectrum where two subspectra of 16 scans each recorded with A = 65.0 ms and 120 ms, and co-added in absolute-value mode. (C) broadband HMBC spectrum where four subspectra of eight scans each were recorded with A = 96.7, 84.4, 81.8, and 80.8 ms, respectively, and co-added in absolute-value mode.

Figure 27 Edited broadband HMBC spectrum of cyclosporine using the pulse sequences shown in Figure 26 in an interleaved manner. The two subspectra, CH + CH3 (left) and C + CH2 (right), exemplify the editing properties. The spectrum in the bottom displays the two subspectra, CH + CH3 (black) and C + CH2 (grey) in the same frame. The number of scans was 32 for each of the 128fi increments, the relaxation delay was 1 s, and the range for the third-order low-pass. /-filter was 115 Hz < Vch < 165 Hz. The spectra were processed to maintain the absorptive profiles in F, while a magnitude mode was done in F2.

Additional heteronuclear long-range experiments include the BIRD-HMBC experiment and the broadband HMBC experiment [52]. Experimental variants capable of simultaneously recording direct and long-range heteronuclear correlations include the HMSQ and MBOB experiments [53]. 

HMBC data as well as some responses not observed in the conventional HMBC spectrum. Because of the long duration of the A intervals in the broadband HMBC experiment reported, in the opinion of this author losses due to spin-spin relaxation during the long delays would be problematic when dealing with either very small samples or in the acquisition of long-range data where signals are quite weak because of... 

Nearly simultaneously with the report of the BIRD-HMBC experiment, Meissner and Sprensen described another modification of the basic long-range hetero-nuclear shift correlation experiment that they refer to as broadband HMBC. The authors employ the gradient dual-stage low-pass J-filter used in the accordion-optimized experiments described above (Section 3.3.5) followed by a delay. A, which replaces the accordion-optimized delay or a normal fixed delay for the evolution of long-range heteronuclear components of magnetization. Instead, Meissner and Sprensen acquire a series of several experiments with different... 

Fig. 25. Pulse sequence for the broadband HMBC experiment proposed by Meissner and Sprensen." A series of experiments are acquired in which the delay, A, is varied and used in lieu of an accordion-optimized delay. This series of experiments is in some senses analogous to the processed result of the 3D-HMBC experiment proposed by Furihata and Seto. The authors used a series of four A values of 440.7, 343.4, 290.3, and 242.2 ms and claim uniform excitation to 20Hz. The authors also comment that the application of broadband HMBC requires higher numbers of transients/ti increment than conventional HMBC or accordion-optimized experiments, which is not surprising given the likelihood of considerable losses of magnetization due to relaxation proces,ses during the very long A delays that are employed to achieve broadband excitation in this approach.

Obviously, the one-step low-pass J filter produces the narrowest profile and is therefore the less efficient in removing direct correlations in HMBC spectra, while the five-step tuned low-pass J filter (f lps) offers the most broadband profile. For this filter, the intensity of the residual /ch signals remains below 0.11% for the range 125 < /ch < 225 Hz, which is remarkable. Interestingly, as long as the /ch couplings range of the molecule remains moderate (—60 Hz), the four- and five-step filters... 

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. 

Several new pulse sequences have been designed for the detection of hetero-nuclear long-range couplings. This includes a new 2D pulse sequence (BIRd-HMBC) proposed by Burger et and new broadband XLOC and /-HMBC experiments suitable for the measurement of /hh and /hx couplings in small molecules, designed by Meissner and Sorensen. ... 

Fig. 6. Pulse sequence for the refocused- or D-HMBC experiment. The idea of refocusing anti-phase proton single quantum coherence prior to acquisition to allow broadband heteronuclear decoupling during acquisition was first reported by Bermel et al in 1989. Evidently unaware of the initial report, Furihata and Seto again de.scribed this experiment in a 199.5 communication, giving it the acronym D-HMBC. There have been a number of applications of this experiment for the acquisition of both H- Cand long-range...

To keep the pulse sequence symmetric to allow broadband heteronuclear decoupling during acquisition, a second variable delay, vd, follows the recreation of antiphase single quantum proton magnetization. A reverse low-pass J follows to make ACCORD-HMBC sequence completely symmetric, followed by acquisition with broadband heteronuclear decoupling. 

In 2001, Meissner and Sprensen described methods for the measurement of Jhh anO "Jch couplings employing the broadband excitation approach (see Section 3.3.7) with the report of the broadband XLOC and broadband J-HMBC experiments, respectively. In a further extension of the idea of accordion optimization, Williamson ef reported the development of the J-IMPEACH-MBC pulse sequence. This approach is similar to the EXSIDE experiment previously described by Krishnamurthy and the J-resolved HMBC experiments of Furihata and Seto"- in its use of J-scaling to render small, long-range heteronuclear couplings conveniently measurable. Finally, Williamson e/ also described a new method, G-BIRDr-HSQMBC, that was reported in their survey of the available methods. 

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