PhIP

PHIP, or para-hydrogen-induced polarization, is a method in nuclear magnetic resonance (NMR) spectroscopy that uses the spin order of parahydrogen to amplify NMR signals. The technique enhances sensitivity by transferring the unique spin alignment of parahydrogen to the nuclei of a substrate during hydrogenation.

In typical PHIP, parahydrogen is added to an unsaturated substrate in the presence of a catalyst, producing a saturated product. Because the two added protons originate from parahydrogen with correlated spins, the product initially exhibits non-equilibrium spin order, which can be converted into enhanced magnetization on certain nuclei (such as 1H, 13C, or 15N) through radiofrequency pulses and spin-order transfer sequences.

PHIP has several variants. PHIP-SAH (side-arm hydrogenation) enables polarization of molecules without permanent incorporation of hydrogen into the final product by separating the polarization transfer from chemical modification. A related approach is SABRE (signal amplification by reversible exchange), where parahydrogen polarizes substrates through reversible binding to a metal complex, without permanent hydrogenation, allowing continuous hyperpolarization for certain compounds.

Applications of PHIP include increasing sensitivity in NMR spectroscopy for chemical analysis, reaction monitoring, and, in some cases, magnetic resonance imaging (MRI) of select metabolites. The technique has spurred ongoing research into expanding the range of usable substrates, improving transfer efficiency, and extending hyperpolarization lifetimes.

Limitations include the need for suitable catalysts and substrates, the often short lifetime of the hyperpolarized state, and the requirement for specialized equipment to handle parahydrogen and optimize transfer conditions.