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

Abstract

The long‐range heteronuclear single quantum multiple bond correlation (LR‐HSQMBC) experiment is the experiment of choice for visualizing heteronuclear long‐range coupling interactions nJCH across 4–6‐bonds and is experimentally superior to the decoupled heteronuclear multiple‐bond correlation (D‐HMBC) experiment. Yet, the exact reasons have not been fully understood and established. On the basis of our recent investigation of the nonrefocused variants LR‐HSQC and HMBC, we have extended a JHH′‐dedicated investigation to the D‐HMBC and LR‐HSQMBC experiments. Unlike the nonrefocused variants, the influence of homonuclear couplings JHH′ on the intensity of long‐range nJCH cross‐peaks is not easily predictable and may be summarized as follows: (a) irrespective of the magnitude and number of JHH′ interactions long‐range nJCH cross‐peaks are more intense in D‐HMBC spectra as long as the evolution delay Δ is not too large, because in contrast to LR‐HSQMBC no JHH′‐caused intensity zeroes will occur. (b) If JHH′ is small and Δ large, the intensity of cross peaks in D‐HMBC spectra may be weakened or may even vanish at Δ = (0.25+0.5k)/JHH′, whereas for the LR‐HSQMBC this unwanted effect occurs at Δ = k + 0.5/JHH′. Consequently, when Δ is adjusted to visualize weak nJCH long‐range correlations, our findings corroborate that there are potentially more cross‐peaks expected to show up in a LR‐HSQMBC spectrum compared with a D‐HMBC spectrum. This has been indeed noticed experimentally, even though the intensity of a many long‐range nJCH cross‐peaks may still be higher in the spectra of the D‐HMBC experiment correspondingly adjusted for detecting weak nJCH correlations.

Simplifying LR‐HSQC spectra using a triple‐quantum filter: The LR‐HTQC experiment

“…and proved to be the best choice for detecting very weak long-range correlations. [4,9,[18][19][20][21][22][23] However, and despite the absence of J HH 0 -modulation our recent findings demonstrate that in LR-HSQC experiments, the intensity of the long-range cross peaks is influenced in an unwanted way by the magnitude and number of passive homonuclear proton-proton couplings J HH 0 . [24] In addition, there are two other, long known, disadvantages associated with LR-HSQC spectra: (i) The information density in LR-HSQC spectra due to the large number of detectable n J CH correlations can be too high and therefore confusing.…”

“…Of note, selective and nonselective versions of the LR‐HSQMBC pulse sequence, a refocused variant of the LR‐HSQC experiment, have been recently proposed and proved to be the best choice for detecting very weak long‐range correlations. [ 4,9,18–23 ]…”

LR-HSQMBC versus LR-selHSQMBC: Enhancing the Observation of Tiny Long-Range Heteronuclear NMR Correlations

“…Although it is not detailed here, a similar behavior would also occur with the refocused version of the HMBC experiment. 6 Other illustrative simulations with other spin systems can be found in the Supporting Information (Figures S1 and S2). In analogy, Figure S3 shows the theoretical signal behavior for cross-peaks with an n J CH of 2 and 8 Hz as a function of the passive J HH′ in HSQMBC and selHSQMBC.…”

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

“…The use of refocused versions of these experiments has been reported to improve the observation of IP magnetization components that can be detected under heteronuclear decoupling. Recently, a comparative study focusing on the effects of J HH modulation in D‐HMBC versus LR‐HSQMBC pulse schemes concluded that more cross‐peaks are expected to show up in an LR‐HSQMBC spectrum compared with a D‐HMBC spectrum . In particular, the use of ultra‐long‐range correlations observed in LR‐HSQMBC spectra has shown its usefulness in computer‐assisted structure elucidation (CASE) analysis of proton‐deficient natural products .…”

“…Recently, a comparative study focusing on the effects of J HH modulation in D-HMBC [4] versus LR-HSQMBC [5][6] pulse schemes concluded that more cross-peaks are expected to show up in an LR-HSQMBC spectrum compared with a D-HMBC spectrum. [7][8] In particular, the use of ultra-long-range correlations observed in LR-HSQMBC spectra has shown its usefulness in computer-assisted structure elucidation (CASE) analysis of proton-deficient natural products. [9] On the other hand, HSQMBC-TOCSY [10] and ADEQUATE experiments [11][12] are alternative NMR tools to detect such longer-range correlations, although the limitations in sensitivity due to additional relaxation effects or the required 13 C-13 C selection at natural abundance are challenges to overcome.The advantages of using a 1 H frequency-selective version of the HSQMBC experiment (selHSQMBC) that has been previously reported to measure n J CH coupling constants from pure absorption IP coupling J patterns is analyzed herein.…”