Parahydrogen
The limits of NMR spectroscopy
Unlike some other methods of analysis, NMR is an incredibly insensitive technique. When compared to methods like mass spectrometry, which can effectively operate with as little as a microgram of a sample, NMR requires that a species must be present in high concentration. This means that unstable reaction products which do not accumulate and reaction intermediates which are present only for a short period of time are not normally detected by NMR spectroscopy. Often, the insensitivity of the experiment can be increased by scanning the sample several, often hundreds or thousands, of times and combining the data until a signal becomes observable. However, this does not solve the problem of intermediates and unstable products that may not be around long enough to complete 10 scans, yet alone the 10,000 that would be needed to detect species in such low concentrations.
Hyperpolarisation
The insensitivity of NMR is due to the fact that the signal intensity is related to the relative populations of the magnetic energy levels being probed (the polarisation). At thermal equilibirum, these energy levels are extremely close together, requiring very little energy for the nuclei to be promoted from one to the other just by normal thermal conditions. In the simple case of a single spin-½ nucleus with two magnetic energy levels, the Boltzmann distribution predicts that an almost equal number of nuclei will be in the higher energy level and lower energy level. This is the case even in the highest magnetic fields that are available for use in modern NMR instruments. If this can altered so that many more nuclei inhabit one state over the another, a massive increase in the intensity of NMR signals can occur because more nuclei will be free to move from one level to another. This is known as hyperpolarisation and is an extremely successfully method whereby NMR signals can be enhanced several thousand times over their normal levels.
Parahydrogen Induced Polarisation, PHIP
The effect of parahydrogen on NMR spectra was first predicted and successfully tested by Bowers and Weitkamp in the late 1980s and the technique has since been refined and applied to many different chemical systems. The polarisation created by using parahydrogen results from its existence in a pure singlet state. As a result, PHIP is also of interest to scientists working in the field of quantum computing.