Heteronuclear single quantum coherence spectroscopy

The Heteronuclear Single Quantum Coherence (HSQC) or Heteronuclear Single Quantum Correlation experiment is used frequently in NMR spectroscopy of organic molecules and is of particular significance in the field of protein NMR. The experiment was first described by Geoffrey Bodenhausen and D. J. Ruben in 1980. The resulting spectrum is two-dimensional (2D) with one axis for proton (¹H) and the other for a heteronucleus (an atomic nucleus other than a proton), which is usually ¹³C or ¹⁵N. The spectrum contains a peak for each unique proton attached to the heteronucleus being considered. The 2D HSQC can also be combined with other experiments in higher-dimensional NMR experiments, such as NOESY-HSQC or TOCSY-HSQC.

General scheme

The HSQC experiment is a highly sensitive 2D-NMR experiment and was first described in a ¹H—¹⁵N system, but is also applicable to other nuclei such as ¹H—¹³C system. The basic scheme of this experiment involves the transfer of magnetization on the proton to the second nucleus, which may be ¹⁵N or ¹³C, via an INEPT (Insensitive nuclei enhanced by polarization transfer) step. After a time delay (t₁), the magnetization is transferred back to the proton via a retro-INEPT step and the signal is then recorded. In HSQC, a series of experiments is recorded where the time delay t₁ is incremented. The ¹H signal is detected in the directly measured dimension in each experiment, while the chemical shift of ¹⁵N or ¹³C is recorded in the indirect dimension which is formed from the series of experiments.