Pure In‐Phase Heteronuclear Correlation NMR Experiments

Abstract

A general NMR approach to provide pure in-phase (PIP) multiplets in heteronuclear correlation experiments is described. The implementation of a zero-quantum filter efficiently suppresses any unwanted anti-phase contributions that usually distort the multiplet pattern of cross-peaks and can hamper their analysis. The clean pattern obtained in PIP-HSQMBC experiments is suitable for a direct extraction of coupling constants in resolved signals, for a peak-fitting process from a reference signal, and for the application of the IPAP technique in non-resolved multiplets.

Extending long-range heteronuclear NMR connectivities by HSQMBC-COSY and HSQMBC-TOCSY experiments

“…S8 in the SI). In this PIP-HSQMBC-TOCSY experiment, pure in-phase (PIP) signals are obtained, as previously reported for related HSQC-TOCSY [10] and PIP-HSQMBC [29] experiments. This can be particularly useful when determining n J(CH) coupling constants along the detected dimension.…”

“…In the case of non-resolved multiplets, n J(CH) can be extracted comparing linewidths in coupled/decoupled spectra [7]. In contrast to the PIP-HSQMBC experiment [29], a PIP-HSQMBC-TOCSY cross-peak can be the cumulative result of several and different coupling pathway contributions. This would preclude the extraction of n J(CH) using the IPAP methodology or the determination of the relative sign as reported for selective HSQMBC versions [23][24][25][26].…”

Assignment of oxime and hydrazone configuration using 1H‐15N and 13C‐15N coupling measurements at natural abundance

“…We have found that the PIP‐HSQMBC 13 and IPAP‐HSQMBC 14 pulse sequences permit facile determination of 1 H‐ 15 N coupling constants of a variety of oximes, hydrazones and thio derivatives of oximes. The advantages of the two pulse sequences have been detailed in the relevant publications . It is sufficient to note that in systems where the protons of interest are singlets or the 1 H‐ 1 H coupling is less than the 1 H‐ 15 N coupling to be measured, the coupling constant can be measured directly from the PIP‐HSQMBC .…”

“…Advances in spectrometer and probe technology now allow routine measurement of 1 H‐ 15 N coupling to be accomplished using a variety of techniques . Specifically, variants of the HSQMBC pulse sequence have been proven to be especially useful . In addition, we recently introduced a new pulse sequence for measurement of 13 C‐ 15 N coupling at natural abundance, the HCNMBC experiment .…”

Perspectives in the application of residual dipolar couplings in the structure elucidation of weakly aligned small molecules

“…Examples include a variant of the F1‐coupled J ‐scaled HSQC with insertion of a HMQC‐like evolution block, the P.E. HSQC – both relying on the well known E.COSY experiment, which may also applied to measure n T HH – and the PIP–HSQC . Reliable coupling extraction from general COSY‐type spectra is often impossible because of broad lines, large couplings and signal overlap.…”