The 2D HMQC-TOCSY experiment is an hybrid inverse experiment consisting of an initial HMQC pulse train followed by a TOCSY mixing sequence. 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, such magnetization is step-wise propagated through the whole coupled homonuclear spin network via J(HH). Similar results are obtained from the analog 2D HSQC-TOCSY experiment.

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

The basic sequence of the 2D HMQC-TOCSY experiment is based on the four-pulse 2D HMQC experiment in which an isotropic mixing sequence (MLEV, WALTZ or DIPSI) 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 ( 86JMR375-69 ). Carbon decoupling is usually applied during proton acquisition. Decoupling duirng acquisition is optional:

Other modified versions:

• Editing of relayed responses can be achieved by incorporating an heteronuclear spin echo prior to acquisition ( 92MRCS71 ).
• Undistortioned cross-peaks can be obtained and easily analyzed using a gradient-based G-BIRD element as a preparation period instead of the classical BIRD cluster ( 96JMRA247-118 ).
• TANGO and spin-lock pulses have been introduced as a preparation period to improve 1H-12C suppression ( 92JMR426-99 ).
• Improved results can be obtained from the gradient enhanced version (see ge-2D HMQC-TOCSY experiment).

Some applications: 90MRC792 and 92JHC1805 .

The 2D HMQC-TOCSY experiment can be recorded in routine/automation modes. The experiment is basically optimized as described for the 2D HMQC experiment. The most important paramter to optimize is the mixing time length. More details on practical implementation of 2D HMQC-TOCSY experiments on AVANCE spectrometers can be found in

Tutorials: 2D inverse experiments

Tutorials: 2D gradient-based inverse experiments

The HMQC-TOCSY 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 connectivites (HMQC cross-peak) and the relayed 1H-X connectivities due to the cumulative transfer ¹J(XH)+J(HH). Alternatively, short distance relay responses can also be detected by a 2D HMQC-COSY experiment.

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

A 3D HMQC-TOCSY experiment is easily designed by incorporating a second variable evolution period between the HMQC and the isotropic mixing period ( 91ANG1329 ). On the other hand, a very similar pulse sequence is used for the w1-X-filtered 2D TOCSY experiment ( 91ANG1329 ) by fixing the variable period in the HMQC block of this 3D HMQC-TOCSY experiment.

Related experiments:

2D Inverse experiments

2D Inverse gradient-enhanced experiments