parahydrogeninducerad

Parahydrogen-induced polarization, also known as PHIP, refers to a set of techniques that create enhanced nuclear spin polarization in molecules by using parahydrogen, the spin isomer of molecular hydrogen with anti-aligned proton spins. The result is signal amplification in NMR and related spectroscopic methods, providing sensitivity beyond the Boltzmann limit.

The core idea is that the unique spin order carried by parahydrogen can be transferred to other nuclei. In standard PHIP, a substrate is hydrogenated in the presence of a suitable transition-metal catalyst so that the two hydrogens from parahydrogen add to the same substrate molecule in a pairwise fashion. The preserved spin correlation then evolves into enhanced NMR signals in the product. This approach typically requires enrichment of hydrogen gas in the parahydrogen form and carefully chosen catalysts and reaction conditions to enable pairwise transfer.

A related approach is SABRE, or Signal Amplification By Reversible Exchange, which transfers parahydrogen spin order to a substrate through transient, reversible binding to a metal complex without chemically altering the substrate. SABRE can operate at room temperature and in solution, offering advantages in ease of use and potential for broad substrate scope. PHIP-SAH and related strategies extend these concepts by routing polarization through temporary chemical handles or through solvent-based pathways.

Applications of parahydrogen-induced polarization include enhanced sensitivity in NMR spectroscopy, faster reaction monitoring, and exploratory efforts in magnetic resonance imaging and metabolic studies. Limitations include a dependence on suitable substrates and catalysts, the need for para-enriched hydrogen, potential catalyst-related toxicity for in vivo use, and relatively short polarization lifetimes that require rapid data acquisition and optimized timing. The concept emerged in the 1980s, with further development culminating in modern SABRE techniques in the late 2000s and beyond.