Hyperpolarizing Small Molecules using Parahydrogen and Solid-State Spin Diffusion

Parahydrogen-induced polarization (PHIP) is an inexpensive way to produce hyperpolarized molecules with polarization levels of >10 % in the solution-state, but is strongly limited in generality since it requires chemical reactions/ interactions with H₂. Here we report a new method to widen the scope of PHIP hyperpolarization: a source molecule is produced via PHIP with high ¹³C polarization, and precipitated out of solution together with a target species. Spin diffusion within the solid carries the polarization onto ¹³C spins of the target, which can then be dissolved for solution-state applications. We name this method PHIP-SSD (PHIP with solid-state spin diffusion) and demonstrate it using PHIP-polarized [1-¹³C]-fumarate as the source molecule, to polarize different ¹³C-labelled target molecules. ¹³C polarizations of between 0.01 and 3 % were measured on [1-¹³C]-benzoic acid, depending on the molar ratio of fumarate:benzoate in the solid state. We also show that PHIP-SSD does not require specific co-crystallization conditions by grinding dry powders of target molecules together with solid fumarate crystals, and obtain ¹³C signal enhancements of between 100 and 200 on [¹³C,¹⁵N₂]-urea, [1-¹³C]-pyruvate, and [1-¹³C]-benzoic acid. This approach appears to be a promising new strategy for facile hyperpolarization based on PHIP.