Homogeneous Catalysts for Hydrogenative PHIP Used in Biomedical Applications

Abstract At present, two competing hyperpolarization (HP) techniques, dissolution dynamic nuclear polarization (DNP) and parahydrogen (para‐H 2 ) induced polarization (PHIP), can generate sufficiently high liquid state 13 C signal enhancement for in vivo studies. PHIP utilizes the singlet spin state of para‐H 2 to create non‐equilibrium spin populations. In hydrogenative PHIP, para‐H 2 is irreversibly added to unsaturated precursors, typically in the presence of a homogeneous catalyst. The hydrogenation catalyst plays a crucial role in converting the singlet spin order of para‐H 2 into detectable nuclear polarization. Currently, rhodium(I) bisphosphine complexes are the most widely employed catalysts for PHIP, capable of catalyzing the addition of para‐H 2 to unsaturated precursors in organic solvents or aqueous media, depending on the ligand. Chiral catalysts enable the stereoselective production of hyperpolarized substrates. Ruthenium(II) piano stool complexes are capable of trans addition and are used to generate hyperpolarized fumarate. However, these catalysts systems are not optimal, and the greatest source of nuclear spin polarization loss is attributed to the mixing of singlet and triplet states of the protons derived from the para‐H 2 during the hydrogenation process. Hence, future efforts should focus on enhancing the efficiency and kinetics of these catalysts.