HETCOR

The HETCOR (HETeronuclear CORrelation) experiment produces a two dimensional spectrum that correlates protons and a heteronucleus, typically carbon. It is one of the earliest 2D experiments and is best used with a direct detect probe. Today, the HETCOR experiment has been replaced by the HSQC experiment. This post will discuss why the HETCOR experiment is now little used and under what circumstances you might still want to use it.

The HETCOR experiment produces a 2D spectrum that correlates protons with a heteronucleus over a single bond. It provides the same information as a HSQC. The difference between a HSQC and a HETCOR is that the HETCOR detects magnetisation via heteronuclei instead of via protons. Thus, the HETCOR dimensions are swapped relative to the HSQC.

Originally probes were built with the heteronuclear coil closest to the sample, to maximise signal from the less sensitive nuclei. With this design it makes sense to detect via the heteronucleus, and hence the HETCOR experiment was developed. Once the INEPT technique became available, however, probes were built with the inverse configuration and HMQC or HSQC experiments were used to obtain heteronuclear correlations, as these techniques are more sensitive.

The figure below shows a HETCOR spectrum and a HSQC spectrum both recorded in three hours on the same sample. These spectra were recorded using an inverse configuration probe, which is not ideal for the HETCOR. Still, all the expected peaks are present, the signal to noise is reasonable, and there is no breakthrough water streak. The HSQC shows similar signal to noise, but this spectrum could have been recorded in minutes instead of hours. The increased sensitivity of the HSQC is why the HETCOR is now little used.

One advantage of the HETCOR is that it is easy to obtain high resolution for the heteronuclear dimension. Notice the peaks in the projection across the top of the HETCOR are very sharp and thin. As the heteronuclear dimension of the HETCOR is the detected one, increased resolution can be obtained by increasing the acquisition time, which makes little difference to the length of the experiment. With a HSQC, to increase the resolution of the heteronuclear dimension requires increasing the number of rows collected, which is directly proportional to the length of the experiment.

The HETCOR experiment might still be useful in situations where sensitivity is not so much of an issue, and where a direct detect probe is available. For example, with the Chemistry Department's Xsense cryoprobe that is optimised for ¹³C detection, a HETCOR may be more sensitive than a HSQC. Similarly, Biochemistry's 800 cryoprobe optimised for ¹⁵N detection would be a good choice for acquiring an ¹⁵N HETCOR.

HETCOR experiments can also be recorded using the Hadamard technique, where only the rows that contain ¹H signals are collected. The chemical shifts of all the ¹H signals must be known before hand but this greatly speeds data acquisition.