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 (n)J(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 (n)J(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 (n)J(CH) cross-peaks are more intense in D-HMBC spectra as long as the evolution delay Delta 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 Delta large, the intensity of cross peaks in D-HMBC spectra may be weakened or may even vanish at Delta = (0.25+0.5k)/J(HH)', whereas for the LR-HSQMBC this unwanted effect occurs at Delta = k + 0.5/J(HH '). Consequently, when Delta is adjusted to visualize weak (n)J(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 (n)J(CH) cross-peaks may still be higher in the spectra of the D-HMBC experiment correspondingly adjusted for detecting weak (n)J(CH) correlations.