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

Abstract

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 during the polarization transfer delays Δ leads to significant losses, and that the intensity of the observable coherence is zero when J matches the condition Δ = 0.5/J . Here, we analyze the influence of J 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 . 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 .

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

“…On the other hand, for the D‐HMBC, according to theory (Equations and in Table and specific values in Table ) and in agreement with the results found for the nonrefocused variants, the intensities are generally higher. Most noteworthy and in contrast with LR‐HSQMBC no J HH ‐caused zeroes arise and the unique zero in the spectra occurs for Δ = 250 ms, that is at Δ = 1/ n J CH . Note also that in accordance with theory (Table ) a pure in‐phase component H r X results for the LR‐HSQMBC experiment exclusively at Δ = k / J HH′ .…”

“…The Equations and show that the in‐phase (H r − ) multiplets have a numerical coefficient that is identical in both experiments, whereas the coefficients of the antiphase ( H r − H′ Z ) multiplets have a numerical coefficient that is two times as large for D‐HMBC compared with LR‐HSQMBC. The same behavior applies to their nonrefocused experiment counterparts …”

“…The observable magnetization present at stage a for a general CHH' spin system is identical to that present before acquisition in the classical HMBC sequence (the effect of the low‐pass J filter for suppressing 1 J CH correlations can be neglected, as it only marginally reduces the intensity of the long‐range coupling magnetization) : …”

“…To analyze the performance and the characteristics of the refocused LR‐HSQMBC and the D‐HMBC experiments, the observable coherences present before data acquisition are listed below (Table ). For comparison, the corresponding coherences found for the nonrefocused variants LR‐HSQC and HMBC have been included …”

“…Long‐range heteronuclear single quantum correlation (LR‐HSQC) experiments may be applied as an alternative to HMBC experiments for detecting long‐range correlations, but these experiments are actually almost exclusively employed for the measurements of long‐range coupling constants . Recently, we have shown both theoretically and experimentally that the classical sensitivity‐enhanced HMBC experiment (HMBC‐SE) is superior to the LR‐HSQC for detecting long‐range correlations for the two main reasons: (a) long‐range cross peaks are generally more intense in HMBC spectra, and (b) the intensity of the long‐range cross peaks in LR‐HSQC spectra is influenced not only by the size of n J CH but additionally and in an unwanted way by the magnitude and number of passive homonuclear proton–proton couplings J HH′ …”