Gradient‐enhanced 1D HMQC‐ and HSQC‐relayed experiments with maximum sensitivity

Abstract

The incorporation of pulsed-field gradients for coherence selection into 1D proton-detected pulse sequences provides clean spectra free of cancellation artifacts but, frequently, at the expense of a sensitivity loss by a theoretical factor of 2 due to the rejection of another contributed pathway. A series of slightly modified gradient-enhanced 1D carbon-selective HMQC-and HSQC-relayed experiments are proposed to obtain maximum signal-to-noise ratios in the same overall acquisition time. In contrast to the implementation of this so-called PEP approach in multi-dimensional experiments, the proposed 1D experiments do not have extra requirements for data acquisition or data processing with respect to the original ones and the excellent spectral quality due to of gradient-selected experiments is preserved. Copyright  2001 John Wiley & Sons, Ltd. KEYWORDS: NMR; selective experiments; pulsed field gradients; sensitivity improvementUndoubtedly, sensitivity is the major handicap of NMR spectroscopy when used as an analytical tool. Hence the design of new NMR experiments or the improvement of the sensitivity and/or the resolution of already existing NMR pulse sequences is a permanent challenge for the spectroscopist in order to have the benefit of the most valuable methodologies.Nowadays, an extended arsenal of modern 1D and 2D NMR methodologies are suitable for the effective, complete and quick structural characterization of small-and mediumsized molecules. Of these, selective 1D experiments offer optimized selectivity, specific information and, most important, better resolution and reduced acquisition times when compared with equivalent multi-dimensional counterparts.

Modern proton‐detected 1D 1H–15N NMR experiments. Application to the measurement of 1H,15N coupling constants at natural abundance

“…For this reason, relatively concentrated samples or some degree of 15 N labeling are highly recommended when possible in order to reduce unavoidable long accumulation times in conventional probes. However, one interesting advantage when choosing 15 N over 13 C is that usually only a few or only a single nitrogen nucleus is contained in the chemical structure. Therefore, all 1D experiments proposed in this work can be successfully run without selective nitrogen excitation in cases where unambiguous resonance assignments are feasible.…”

“…approach, 13,18 from which the sensitivity of the experiment is doubled in the same acquisition time and without further extra requirements for acquisition or processing set-up. This fact is much more important when working on 15 N in order to reduce long accumulation times.…”

“…In principle, any proposed proton-detected NMR experiment applied to the 13 C nucleus can be easily adapted to 15 N. Only characteristic changes in frequencies, pulse durations, power levels and delay settings as a function of J(N,H) are required. The major differences between the two nuclei rely on the inherent low sensitivity of 15 N basically owing to its lower gyromagnetic ratio and its relatively low natural abundance.…”

“…1 slight modifications of the conventional gradient-enhanced 1D HSQC-TOCSY experiment 13,14 in which a two-step propagation is clearly established. First, an out-of-back 1 H-15 N transfer polarization using an HSQC block via 1 J(N,H) is accomplished followed by a conventional TOCSY transfer to other protons belonging to the same spin system.…”

“…For this reason, we have adapted a series of 1D experiments, that have already demonstrated their usefulness when applied to 13 C, for the purpose of quick resonance assignments and also for the precise determination of direct and long-range proton-nitrogen coupling constants for samples at natural abundance. Several approaches are presented, practical details are given and the major inconvenients are discussed.…”