Why is HMBC superior to LR-HSQC? Influence of homonuclear couplings JHH′ on the intensity of long-range correlations

Long-range heteronuclear single quantum correlation (LR-HSQC) experiments may be applied as an alternative to heteronuclear multiple-bond correlation (HMBC) experiments for detecting long-range correlations but has never enjoyed popularity for that purpose. To the best of our knowledge, the exact reasons have not yet been fully established. For both experiments, it is widely accepted that the evolution of proton-proton homonuclear couplings J(HH ') during the polarization transfer delays leads to significant losses, and that the intensity of the observable coherence is zero when J(HH ') matches the condition Delta = 0.5/J(HH '). Here, we analyze the influence of J(HH ') on the intensity of long-range correlations in HMBC and LR-HSQC spectra. We show that for both experiments long-range correlations will not be canceled because of homonuclear couplings J(HH '). Our theoretical and experimental results definitely establish and validate the superiority of HMBC-based experiments among the family of heteronuclear long-range correlation experiments: (a) the overall cross peak's intensity is higher, and (b) in LR-HSQC experiments, the intensity of the long-range cross peaks is additionally influenced in an unwanted way by the magnitude and number of passive homonuclear proton-proton couplings J(HH ').