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Parahydrogen and NMR

When hydrogen reacts, and its symmetry is broken in an oxidative addition reaction to a metal centre, novel NMR effects can be seen provided the reaction proceeds in a spin correlated manner. This can be readily achieved when an MH2 containing product is formed and the two protons are magnetically inequivalent. The four spin combinations that are present in dihydrogen are conserved in the new MH2 group. The NMR signals that are normally seen in a 1D NMR spectrum for such a species would be two doublets. Because hydrogen naturally contains approximately equal numbers of molecules in each of its four spin configurations, the four possible configurations in the product are also populated approximately equally. Since the intensity of an NMR signal is proportional to the population difference between the energy levels, i.e., the number of nuclei capable of undergoing the transition normally very low intensity signals are detected. This situation is illustrated below, where approximately 1 in 30,000 nuclei are capable of undergoing a detectable transition at a field of 9.4 T.

A normal NMR experiment

Fig 1: A normal NMR experiment on a MH2 moiety without hyperpolarisation.

In this case, hydrogen molecules in the αα and ββ configurations generate αα and ββ configurations in the product. Furthermore, the linear combinations αβ+βα and αβ-βα contribute equally to the αβ and βα configurations in the product.

Parahydrogen and NMR

If we were to use only one of the spin configurations of hydrogen, the αβ-βα, we would selectively populate only one of the spin states in the product. Because of the resultant hyperpolarisation, a term used to indicate the populations of each energy level are greatly different to the usual Boltzmann distribution, the NMR signals of the product are greatly increased. It is easy to see if the enhancement has worked, since the resultant signals are now antiphase, one set in absorption and the other in emission.

A parahydrogen enhanced NMR experiment

Fig 2: An NMR experiment on a MH2 moiety formed after reacting with the parahydrogen.
The selective spin state produces an enhanced NMR signal.

Conditions

Once the enhancement has been observed by NMR, the sample relaxes back to equilibrium. As a result, it is often necessary to have the chemical system "refresh" itself by reaction with more p-H2 throughout the experiment. This can be achieved by raising the temperature of the sample to promote exchange between molecules that have already relaxed and hydrogen in solution, which will still be predominantly in the para state. Although this maintains the enhancement, it increases the speed at which the hydrogen in the sample is consumed, reducing its duration.

Another important factor is the concentration of the sample. Conventional thinking states that when a sample is present in high concentration, the signals are greater. However, a high concentration of reactant can very quickly consume all the parahydrogen in solution, reducing the time that the enhancement lasts, meaning that very few scans can be made (possibly even quenching the enhancement before a scan can be made). Therefore, in PHIP-NMR experiments signal intensity is at its maximum at lower concentrations.

Pulse Programs

In order to observe the polarisation of protons resulting from parahydrogen, all pulse programs need to be modified to have a 45 pulse angle. A 90 pulse will tilt the spins in such a way that they cancel, and the signals will completely disappear. This simple change can be made to any pulse program and as a result, PHIP can be performed on a multitude of experiments, including 2D experiments. Using an HMQC sequence, it is possible to sensitise heteronuclei in a molecule, an essential technique for identified the species detected with PHIP.