CT-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... 

The approach of Furihata and Seto was to introduce a constant time evolution period in the CT-HMBC-1 pul.se sequence shown in Fig. 9(a). Thus, rather than a sequence in which evolution is represented by... 

The CT-HMBC-2 pulse sequenee utilizes a decremented delay prior to the evolution period, with a 180° proton pulse midway through it of the type... 

Again, the (A3 - ti/2) terms are deeremented as the evolution periods t 2 are correspondingly incremented, keeping the overall evolution time in the experiment constant. The authors note that this modification not only suppresses J-modulation due to homonuclear coupling, but also heteronuclear coupling as well, thereby improving resolution further relative to the CT-HMBC-1 experiment. 

The concepts of the CT-HMBC experiments are fundamentally quite important, and have been exploited in the development of some of the accordion-optimized experiments described below (see Section 3.3..3). To date there have not been any reported applications of either of the experiments described in this section. 

Fig. 9. Pulse sequence for the constant time CT-HMBC experiments devised by Furihata and Seto. The authors reported two variants of the experiment, the CT-HMBC-1 pulse sequence shown in Panel (a) and the more complex CT-HMBC-2 pulse sequence shown in Panel (b). (a) The CT-HMBC-1 sequence utilizes a pair of decremented delays (A , — / /2) flanking the incremented duration of the evolution period. As the delays u.sed for the evolution period (t ) are incremented from zero to the delay intervals — I I2 are correspondingly decremented from A = q" to zero, thereby keeping the overall duration of the CT-HMBC-1 pulse sequence constant. This approach has the beneficial effect of suppressing J-modulation due to homonuclear couplings, thereby improving resolution in the indirectly detected frequency domain, (b) The CT-HMBC-2 pul.se sequence utilizes a decremented delay with a 180° H pulse midway through it prior to the evolution period of the type (A - t /2) — 180° H - (A,i — /i/2). The authors note that this modification, in addition to suppressing J-modulation due to homonuclear coupling also suppresses heteronuclear couplings to provide a further improvement in re.solution relative to the CT-HMBC-1 pulse sequence.

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.

To obtain information about the glycosidic linkage, 1H—1H NOESY/ROESY and/or long-range 1H—13C correlated spectra, heteronuclear multiple bond correlation (HMBC) or CT (constant time)-HMBC,12 are recorded. The combined 2D HSQC(HMQC)-NOESY(ROESY) experiments could also be helpful, but have limited applications due to their low sensitivity in samples with natural abundance of 13C. 

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.

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