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

The long-range heteronuclear single quantum multiple bond correlation (LR-HSQMBC) experiment is the experiment of choice for visualizing heteronuclear long-range coupling interactions ⁿJ_CH 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 J_HH′-dedicated investigation to the D-HMBC and LR-HSQMBC experiments. Unlike the nonrefocused variants, the influence of homonuclear couplings J_HH′ on the intensity of long-range ⁿJ_CH cross-peaks is not easily predictable and may be summarized as follows: (a) irrespective of the magnitude and number of J_HH′ interactions long-range ⁿJ_CH 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 J_HH′-caused intensity zeroes will occur. (b) If J_HH′ 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)/J_HH′, whereas for the LR-HSQMBC this unwanted effect occurs at Δ = k + 0.5/J_HH′. Consequently, when Δ is adjusted to visualize weak ⁿJ_CH 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 ⁿJ_CH cross-peaks may still be higher in the spectra of the D-HMBC experiment correspondingly adjusted for detecting weak ⁿJ_CH correlations.