NMR Diffusion Measurements in Complex Mixtures Using Constant-Time-HSQC-IDOSY and Computer-Optimized Spectral Aliasing for High Resolution in the Carbon Dimension

Abstract

A new 3D pulse sequence for NMR diffusion measurements in complex mixtures is presented. It is based on the constant-time (CT) HSQC experiment and combines diffusion delay with the carbon evolution time. This combination has great potential to obtain high resolution in the carbon dimension. When using classical sampling of the carbon dimension, maximal resolution would require a large number of time increments, leading to unrealistically long acquisition times. The application of computer-optimized spectral aliasing allows one to reduce the number of time increments and the total acquisition time by 1-2 orders of magnitude by taking advantage of the information content of 1D carbon spectra, HSQC experiments, or both. With the new CT-HSQC-IDOSY experiment, the diffusion rates of the six anomers present in a 0.1 M D2O solution of glucose, maltose, and maltotriose could be obtained at natural abundance in 8 h with standard deviations below 5%.

The DOSY Toolbox: A new tool for processing PFG NMR diffusion data

“…When signal overlap is severe in the 1 H spectrum, one of the many more sophisticated 2D [13,24,[38][39][40][41][42][43] or 3D [39,[44][45][46][47][48][49][50][51][52][53][54][55] DOSY experiments available will often allow individual peaks to be resolved, allowing the HR-DOSY approach to be used. It is however not always desirable or even possible (e.g., due to restrictions in time, signal-to-noise ratio etc.)…”

Computer optimized spectral aliasing in the indirect dimension of 1H–13C heteronuclear 2D NMR experiments. A new algorithm and examples of applications to small molecules

“…3. This is very useful when one needs to acquire series of heteronuclear experiments, for example for relaxation measurements, 2D diffusion measurements [8][9][10], or in higher-dimensionality experiments.…”

“…We have developed a CT-HSQC-IDOSY sequence where the diffusion and t 1 -evolution times are combined [10]. For these applications, acquisition times are reduced from many days, a duration which is unacceptable in most NMR laboratories, to a few hours.…”

“…In such a case, the optimized conditions can be used directly keeping in mind the above-mentioned problem of signal damping in t 1 . A resolution enhancement factor of two has been obtained in aliased CT-HSQC-IDOSY experiments [10]. The third possibility consists of changing the signal-width scaling factor of the optimization program and using k = 0.5/p [see Annex 1].…”

Stable isotope-enhanced two- and three-dimensional diffusion ordered 13C NMR spectroscopy (SIE-DOSY 13C NMR)

“…First, the addition of a third dimension necessitates excessively long experimental times to give usable resolution. To some extent this can be mitigated by the spectral aliasing technique of Vitorge and Jeannerat [15]. Second, for sensitivity reasons, DOSY NMR methods based on proton nuclei have been generally preferable, limiting these methods to 1 H-detected spectra.…”