Combined homogeneous and heterogeneous hydrogenation to yield catalyst-free solutions of parahydrogen-hyperpolarized [1-¹³C]succinate

We show that catalyst-free aqueous solutions of hyperpolarized [1-¹³C]succinate can be produced using parahydrogen-induced polarization (PHIP) and a combination of homogeneous and heterogeneous catalytic hydrogenation reactions. We generate hyperpolarized [1-¹³C]fumarate via PHIP using para-enriched hydrogen gas with a homogeneous ruthenium catalyst, and subsequently remove the toxic catalyst and reaction side products via a purification procedure. Following this, we perform a second hydrogenation reaction using normal hydrogen gas to convert the fumarate into succinate using a solid Pd/Al₂O₃ catalyst. This inexpensive polarization protocol has a turnover time of a few minutes, and represents a major advance for in vivo applications of [1-¹³C]succinate as a hyperpolarized contrast agent.