Assigning stereochemistry with NOEs

Relative stereochemistry can often be determined by analysis of nuclear Overhauser effects or NOEs. I have seen many papers where the stereochemistry was defined based on the observation of one particular peak, but this may not be sufficient and some care must be taken when interpreting NOEs. Here I offer a few pointers on how best to interpret the crosspeaks in NOESY and ROESY spectra.

GEMSTONE-NOESY

GEMSTONE is a new highly selective NMR technique. Combining it with traditional homonuclear 2D experiments creates exceptionally selective 1D versions of these experiments, which can be useful when trying to characterize highly overlapped spectra. In this post I compare the GEMSTONE-NOESY experiment with the standard 1D selective NOESY.

The sign of NOESY peaks

Occasionally NOESY spectra of small molecules show a mixture of positive and negative peaks. The negative peaks are often due to exchange between different magnetic environments. I recently came across a good example of this in the NOESY spectrum of 2,3-dihydroxybenzamide.

Suppressing zero quantum artifacts

In the previous post zero quantum artifacts in NOESY spectra were described. Misintrepretation of these artifacts can lead to errors in structure elucidation. A method for suppressing zero quantum artifacts has been developed¹ and it is quite effective.

Zero quantum artifacts in NOESY spectra

Unlike most other NMR experiments that correlate resonances via J-coupling through bonds, the NOESY experiment correlates resonances via cross-relaxation through space. Since the intensity of the correlation is strongly dependent on the distance between the interacting nuclei, the intensity of the NOE peak is related to the distance between the atoms. This makes the NOESY experiment very useful for determining three dimensional structures and assigning stereochemistry. However, interpreting NOESY spectra has to be done carefully, as artifacts due to zero-quantum transitions are often observed.

NOESY and ROESY

Unlike nearly all other NMR experiments, NOESY and ROESY record correlations transferred through space via the nuclear Overhauser effect (noe) instead of using through-bond scalar coupling. This makes NOESY and ROESY experiments useful for determining stereochemistry and is the basis for the solution structure determination of biomolecules.