The 2D HMQC (Heteronuclear Multiple-Quantum Correlation) experiment permits to obtain a 2D heteronuclear chemical shift correlation map between directly-bonded 1H and X-heteronuclei (commonly, 13C and 15N) . It is widely used because it is based on proton-detection, offering high sensitivity when compared with the conventional carbon-detected 2D HETCOR experiment. Similar results are obtained using the 2D HSQC experiment.

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

The basic 2D HMQC pulse sequence is a four-pulse experiment ( 83JMR301-55 and 88JMR356-77 ):
• A 90º 1H pulse creates transverse magnetization that evolves during a d2 period under the effect of heteronuclear coupling. A 90º X pulse creates heteronuclear multiple-quantum coherences that evolve during the variable evolution period. A 180º 1H pulse inserted at the middle of this period removes the evolution of heteronuclear couplings and proton chemical shifts (see 1H-decoupled X evolution block).
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• After this period, a second 90º X pulse creates antiphase SQC proton magnetization which is refocused after a second d2 delay (see SQC from heteronuclear MQC).
• Proton acquisition is performed with X decoupling (see 1H-acquisition with X-decoupling).
A BIRD-recovery cluster is usually incorporated as a preparation period in order to reduce the large unwanted 1H-X (typically, 12C or 14N) magnetization ( 86JMR565-67 ). A number of other modifications have been proposed:
 
• A TANGO purging sequence as a preparation period ( 92JMR426-99 ).
• A combination of BIRD cluster and spin-lock purging sequence ( 93JMRA83-104 ).
• Folding in the heterodimension ( 83JMR301-55 ).
• Water suppression using jump-and-return ( 84BIO4395 ) or other methods.
• Multiplicity selection incorporating a DEPT pulse sequence as a preparation period (2D DEPT-HMQC experiment ( 89JMR400-85 , 91JMR625-94 , and 91JMR430-93 ) or by inserting an heteronuclear echo prior to acquisition ( 89JMR640-82 , and 89JMR598-84 ).
• Improved sensitivity using the PEP methodology ( 91JMR151-93 , and 93AR1 ).
• 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 ).
• Gradient-enhanced versions (see ge-2D HMQC experiment).
• Semi-selective versions to achieve better resolution in the indirect dimension (see Semi-selective HMQC experiment)

The 2D HMQC experiment can be recorded in routine/automation modes. A detailed description of experimental parameter set-up is found in 88MRC867 . The interpulse d2 delay is optimized to 1/2*JCH (3.3-3.8 ms). The recovery period after the BIRD cluster must be optimized for each sample (typically 300-500 ms for medium-size molecules).
 
More details on practical implementation of ge-2D HMQC experiments on AVANCE spectrometers can be found in the corresponding tutorials:

Tutorials: 2D inverse experiments

Tutorials: 2D gradient-based inverse experiments

The HMQC spectrum correlates chemical shifts of heteronucleus X (F1 dimension) and protons (F2 dimension) via the direct heteronuclear coupling 1J(XH). Carbon decoupling is usually performed during proton acquisition and the corresponding satellites colapse to a single resonance showing all proton-proton couplings. Since JHH evolution occurs during t1 and t2, the 1H multiplets appear with a 45º tilt in the F1 dimension.

Comparison of different 2D inverse correlations have been carried out ( 90JMR304-86 and 90JMR488-87 ).

Related experiments:

2D Inverse experiments

2D Inverse gradient-enhanced experiments