How to face the low intrinsic sensitivity of 2D heteronuclear NMR with fast repetition techniques: go faster to go higher!

Abstract

Nuclear magnetic resonance (NMR) is one of the most widely used analytical techniques in numerous domains where molecules are objects of investigation. However, major limitations of multidimensional NMR experiments come from their low sensitivity and from the long times needed for their acquisition. In order to overcome such limitations, fast repetition NMR techniques allowed for the reduction of 2D experimental time and for the conversion of the gained time into a higher number of scans leading to a better sensitivity. Thus, fast repetition 2D heteronuclear NMR techniques have allowed new advances in NMR, especially to access infomation on low abundant nuclei, to enhance the detection of low concentrated compounds and to probe weak interactions like hydrogen bonds at natural abundance. Copyright © 2017 John Wiley & Sons, Ltd.

Measurement of long‐range heteronuclear coupling constants using the peak intensity in classical 1D HMBC spectra

“…To cope with the overall‐sensitivity problem (if many long‐range coupling constants have to be determined) and the problem with overlapping resonances, series of 2D HMBC maps (in form of a pseudo‐3D spectrum) could be recorded in which in contrast to the constant time approach, the long‐range coupling evolution delay Δ is varied systematically from 0 to Δ max . When combined with novel fast acquisition methods like the Acceleration by Sharing Adjacent Polarization (ASAP) scheme and nonuniform sampling (NUS), well‐resolved HMBC data with high signal‐to‐noise ratios can be obtained in a few minutes . A simple superposition of all data allows the user to easily determine the delay Δ for which each individual cross‐peak vanish and thus allows for a fast, quite accurate measurement of the individual coupling value.…”

“…When combined with novel fast acquisition methods like the Acceleration by Sharing Adjacent Polarization (ASAP) scheme [57] and nonuniform sampling (NUS), [58] well-resolved HMBC data with high signal-to-noise ratios can be obtained in a few minutes. [59,60] A simple superposition of all data allows the user to easily determine the delay Δ for which each individual cross-peak vanish and thus allows for a fast, quite accurate measurement of the individual coupling value. This parallels the prerequisite of recording and superposing several individual selHSQMBC-TOCSY spectra for obtaining a full 2D map.…”

NMR-based metabolomics and fluxomics: developments and future prospects

“…Fortunately, the NMR community has developed a great variety of methods to accelerate multi-dimensional experiments. 28 These methods include fast repetition techniques, 29 spectral aliasing, 30 non-uniform sampling (NUS) 31 of the indirect dimension(s) or less conventional methods such as Hadamard 32 or Ultrafast (UF) 33 spectroscopies. It is only recently that some of these approaches have reached a sufficient level of maturity to be applied to metabolomics studies.…”

“…69 Recent examples in the literature highlight the complementarity of those methods in a variety of situations. 29,70 Concerning the diffusion-edited experiment, it is worth highlighting the 2D DOSY (diffusion-ordered spectroscopy) experiment, which has the potential to virtually separate signals from mixture components based on their diffusion coefficients. 71 However, this method has been little applied in metabolomics studies, apart from examples where it was used for the identification of metabolites with overlapping signals.…”

Merging Gradient‐Based Methods to Improve Benchtop NMR Spectroscopy: A New Tool for Flow Reaction Optimization

“…Here, the total time for each experiment was between 7 to 14 min due to the pseudo 2D mode of the TSE PSYCHE scheme. Efforts to reduce the overall time is under progress with fast repetition techniques and Non Uniform Sampling or NUS in order to further accelerate the NMR measurement time and to make it compatible with the monitoring of faster chemical events. Thus, combining resolution‐enhanced schemes could open new horizons for emerging applications of benchtop NMR on concentrated samples such as edible oils or biolfuids like urine.…”