A comprehensive discussion of HMBC pulse sequences. III. Solving the problem of missing and weakly observed long‐range correlations

Abstract

The intensity of long‐range correlations observed with the classical HMBC pulse sequence using static optimization of the long‐range coupling delay is directly related to the size of the coupling constant and is often set as a compromise. As such, some long‐range correlations might appear with a reduced intensity or might even be completely absent from the spectra. After a short introduction, this third manuscript will give a detailed review of some selected HMBC variants dedicated to improve the detection of long‐range correlations, such as the ACCORD‐HMBC, CIGAR‐HMBC, and Broadband HMBC experiments. Practical details about the accordion optimization, which affords a substantial improvement in both the number and intensity of the long‐range correlations observed, but introduces a modulation in F1, will be discussed. The incorporation of the so‐called constant time variable delay in the CIGAR‐HMBC experiment, which can trigger or even completely suppress 1H–1H coupling modulation inherent to the utilization of the accordion principle, will be also discussed. The broadband HMBC scheme, which consists of recording a series of HMBC spectra with different delays set as a function of the long‐range heteronuclear coupling constant ranges and transverse relaxation times T2, is also examined. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part A 43A: 177–206, 2015.

A Comprehensive Discussion of HMBC Pulse Sequences: 4. Establishing Two‐Bond Correlations from HMBC and Related Experiments

“…). This aspect of the 2 J , 3 J ‐HMBC experiment is analogous to the scaling factor, N , used in the EXSIDE experiment described by Krishnamurthy and in the previous part for the ACCORD‐HMBC experiment .…”

“…Thus, for both 2 J CH and 3 J CH correlations, the 1 H‐ 13 C heteronuclear coupling is refocused during Δ1, Δ2, and D , but evolves during the variable‐delay, vd . As such, for long‐range 1 H‐ 13 C heteronuclear couplings, the STAR pulse element acts as a simple accordion optimization .…”

D‐HMBC versus LR‐HSQMBC: Which experiment provides theoretically and experimentally the best results?

“…We utilized strychnine (Figure ) as the classical model compound to compare the performance of the LR‐HSQMBC and the D‐HMBC sequences (Figures and S3–S8). Strychnine is readily available and has been used as a standard in many NMR studies …”

LR‐selHSQMBC: Simultaneous Detection and Quantification of Very Weak Long‐Range Heteronuclear NMR Correlations

“…Two‐dimensional HMBC and HSQMBC experiments are fundamental NMR techniques to trace out through‐bond long‐range proton‐carbon ( n J CH ) connectivities in structural elucidation studies of small and medium‐sized molecules . The interpulse evolution delays in these experiments are routinely optimized to J ° pt =6–10 Hz to observe most of the short‐range two‐bond and three‐bond heteronuclear correlations.…”