Transfer of Parahydrogen-Induced Hyperpolarization to Heteronuclei

Abstract

Homogeneously catalyzed hydrogenation reactions of unsaturated substrates with H ₂ gas mixtures enriched in parahydrogen yield strong NMR signal enhancements of the transferred ¹H nuclei if the symmetry of H₂ is broken in the resulting hydrogenated products. This chemically induced hyperpolarization phenomenon known as parahydrogen-induced polarization (PHIP) is a well-established polarization technique in NMR spectroscopy. Ever since its theoretical prediction and subsequent experimental verification the method has been used to increase signal intensity in ¹H-NMR spectroscopy for the elucidation of catalytic pathways of hydrogenation reactions and their kinetic behavior. Furthermore, PHIP is not confined to the attached protons and ¹H nuclei which are close to the hydrogenation site but it can also be transferred spontaneously to heteronuclei, which are present in the hydrogenation product. In this review we give an overview of the different experiments that have been performed in recent years in order to efficiently transfer PHIP-derived polarization to insensitive magnetically active nuclei following the catalyzed parahydrogenation of their unsaturated precursor molecules. A detailed description of the experiments dealing with every individual heteronucleus in particular is followed by a discussion of the mechanisms leading to PHIP transfer. Subsequently, we describe the existing set of pulse sequences that have been designed and successfully employed in order to induce an exchange of increased magnetization originating from PHIP between protons and heteronuclei using conventional coherence transfer schemes. Finally, possible applications of non-proton PHIP spectroscopy in medicine and clinical research are outlined.