The 2D HMQC-NOESY experiment is an hybrid inverse experiment consisting of an initial HMQC pulse train followed by a NOESY building block. In the first step, magnetization is transferred from the X nucleus (13C or 15N) to the directly-bonded proton nuclei via ¹J(CH). In the second step, polarization transfer is achieved via dipolar coupling (NOE). Similar results are obtained from the analog 2D HSQC-NOESY experiment.

Easy implementation on any AVANCE spectrometer equipped with an inverse probehead.

The basic sequence of the 2D HMQC-NOESY experiment is based on the four-pulse 2D HMQC experiment in which a NOESY mixing sequence (consisting of 90º(1H)-delay-90º(1H)) is inserted prior to acquisition. A BIRD-recovery cluster is used as a preparation period in order to reduce the large unwanted 1H-X (typically, 12C or 14N) magnetization ( 89JMR193-82 ). Carbon decoupling is optionally applied during proton acquisition.

Improved results can be obtained from the gradient enhanced version (see ge-2D HMQC-NOESY experiment).

Some published applications:

Study of polynuclear aromatic systems ( 90MRC774 )

NOEs measurements in overlapped systems ( 90MRC792 )

NOEs in pseudo-equivalent systems ( 92JHC1869 )

Backbone amide resonance assignments in a membrane protein ( 03JB327-26 )

The 2D HSQC-NOESY experiment can be recorded in routine/automation modes. The experiment is basically optimized as described for the 2D HMQC experiment. The most important parameter to optimize is the NOESY mixing time length.

More details on practical implementation of 2D HMQC-NOESY experiments on AVANCE spectrometers can be found in

Tutorials: 2D inverse experiments

Tutorials: 2D gradient-based inverse experiments

The HMQC-NOESY spectrum correlates chemical shifts of heteronucleus X (F1 dimension) and protons (F2 dimension) via the direct heteronuclear coupling ¹J(XH). Two different cross-peaks are present for each X resonance: The direct 1H-X NOE connectivites and the NOE 1H-X connectivities due to the cumulative transfer ¹J(XH) + 1H-1H NOE. The same NOE effects could also be detected by a 2D HMQC-ROESY, 2D HSQC-ROESY and 2D HSQC-NOESY experiments.

Comparison of different 2D inverse correlations have been carried out ( 90JMR488-87 ).

A 3D HMQC-NOESY experiment is easily designed by incorporating a second variable evolution period between the HMQC and the NOESY mixing period. On the other hand, a very similar pulse sequence is used for the w1-X-filtered 2D NOESY experiment by fixing the variable period in the HMQC block of this 3D HMQC-NOESY experiment.

Related experiments:

2D Inverse experiments

2D Inverse gradient-enhanced experiments