ACCORD-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... 

To provide the means of sampling a wider range of potential long-range heteronuclear coupling constants, an alternative version of this heteronuclear shift correlation experiment is called the accordion-optimized HMBC, or ACCORD-HMBC [50]. Additional modifications of this experiment are also available [51]. 

Wagner, R. and Berger, S., ACCORD-HMBC a superior technique for structural elucidation, Magn. Reson. Chem., 36, S44, 1998. 

If, on the other hand, one has an isolated sample of limited mass and/or a limited amount of time, an alternative approach should be taken. Carbon resonances and their corresponding multiplicity should be detected indirectly to maximize sensitivity and minimize acquisition times. Therefore, instead of acquiring an APT plus an HSQC spectrum, the more time-efficient DEPT-HSQC can be used. COSY affords improved sensitivity over DQFCOSY at the cost of resolution along the diagonal. Similarly, ACCORD-HMBC can be replaced with the more sensitive HMBC. This approach is recommended for time-limited situations or for the nominal mass range of lOOpg-lOmg. 

The first step in optimizing the ACCORD-HMBC sequence and removing the tilt of the correlation peaks, is the IMPEACH experiment [5.173] which utilizes a constanttime variable delay element to remove the skewed shape of the correlation peaks. The constant-time variable delay element discriminates between IH-IH and DC-lH coupling... 

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... 

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. 

Aside from the advantage of the ACCORD-HMBC spectrum shown by Fig. 11. Martin and co-workers - examined various aspects of the accordion-optimization process on the character of the spectrum. Modulation in the ACCORD-HMBC experiment is affected by both the optimization range selected and the number of increments of the evolution time (ni) used to digitize the indirectly detected time domain, t]. F skew is governed by a scaling factor, N, which is defined by... 

This facet of the experiment is similar to the EXSIDE experiment developed by Krishnamurthy. Modulation is illustrated by the nature of the responses in the four panels presented in Fig. 12. Segments are shown from four ACCORD-HMBC spectra, each acquired with ni = 128. Panels (a)-(d) were acquired with optimization ranges of 6-10, 4-12, 2-16, and 2-25 Hz, respectively. In Panel (a), no response is observed for the H-I la proton resonating at 3.05ppm. The response correlating H-1 la/C12 is observed in the 4-12 Hz data shown in Panel (b). Note that in the 3-16 and 2-25 Hz data shown in Panels (c) and... 

Fig. 13. Panels taken from a series of 2 25 Hz optimized ACCORD-HMBC spectra in which the number of increments of the evolution time, t], was varied from 64 to 512. The response shown is the Jch correlation of the H12 resonance to the C23 methylene carbon across the ether linkage of the seven-membered oxepin ring of strychnine (14).

In addition to the importance of parameter selection on F skew, the ACCORD-HMBC experiment has also been shown to exhibit strong coupling artifact responses similar to those observed in heteronuclear 2D J-resolved spectra. - Finally, the triplet character of responses in the second frequency domain superimposed over the Fi skew was mathematically accounted for by Zangger and Armitage in their development of the ACCORD-HMQC experiment. "... 

There have been no applications of the ACCORD-HMBC experiment reported in the literature to date. 

In an effort to address the essentially uncontrolled F skew inherent to the ACCORD-HMBC, the author and co-workers next reported the development of the IMPEACH-MBC experiment, the pulse sequence for which is shown in Fig, 14. Recognizing that F skew arises due to homonuclear scalar coupling modulation for which the variable duration accordion-optimized delay serves as an evolution time, the variable delay, vd, was modified in the IMPEACH-MBC experiment. The variable delay can be made into a constant time delay for homonuclear components of magnetization by adding a new segment to the overall delay centered about a 180° X pulse to refocus heteronuclear magnetization. The thus modified constant time variable delay is given by... 

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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