The 2D HSQC (Heteronuclear Single-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 HMQC experiment.

Easy implementation on any AVANCE spectrometer equipped with an inverse probehead

The basic 2D HSQC pulse sequence consists of four independent parts ( 80CPL185 and 86JMR546-69 ):

1. An initial INEPT pulse train transfers polarization from 1H to X via 1J(XH) (see INEPT block).
2. The antiphase 13C magnetization evolves during the variable evolution t1 period under the effect of X chemical shift. Heteronuclear 1H-X couplings are refocused by applying a 180º 1H pulse at the middle of this period (see 1H-decoupled X evolution block).
3. A retro-INEPT pulse train converts X magnetization to in-phase 1H magnetization (see reverse-INEPT block).
4.  Proton acquisition is performed with X decoupling (see 1H-acquisition with X-decoupling).

A number of alternatives have been proposed:
 
• Use of spin-lock pulses for purging undesired coherences ( 88JMR569-76 and 89JMR608-85 and 91JMR394-94 ).
• Improved sensitivity can be obtained using the PEP methodology ( 91JMR151-93 and 93AR1 ). A second retro-INEPT pulse train is inserted prior to acquisition in order to select orthogonal components evolving during the t1 period.
• Multiplicity-editing by inserting an heteronuclear spin-echo during the t1 period ( 90JMR589-90 and 91JMR665-91 ).
• The decoupled HSQC (or Double INEPT) experiment in which the initial INEPT and the last retro-INEPT pulse trains are replaced by refocused INEPT pulse trains in order to achieve in-phase carbon magnetization during the t1 period ( 90JMR304-86 and 90JMR488-87 ).
• Constant-Time HSQC experiment to remove 13C-13C scalar coupling during the t1 period.
• Gradient-enhanced versions (see ge-2D HSQC experiment).
• Removing axial peaks artifacts by modified phase cycling ( 94JMRA246-109 and 96JMRB91-110 ).
• Semi-selective versions to achieve better resolution in the indirect dimension (see Semi-selective HSQC experiment)

The 2D HSQC experiment can be recorded in routine/automation modes. Minor changes are required if a predefined parameter set is available.The interpulse d2 delay is optimized to 1/2*JCH (3.3-3.8 ms).
 
More details on practical implementation of ge-2D HSQC experiments on AVANCE spectrometers can be found in the corresponding tutorials:

• 2D HSQC experiment (phase-sensitive)
• 2D HSQC experiment (phase-sensitive with presaturation)

The HSQC 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.

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

Related sequences:

• 2D HSMQC experiment ( 90JMR346-86 ).
• 2D Double DEPT sequence ( 89METH134 and 91JMR151-93 ).
• 2D Inverse experiments
• 2D Inverse gradient-enhanced experiments