Achieving High Levels of NMR-Hyperpolarization in Aqueous Media With Minimal Catalyst Contamination Using SABRE

Signal amplification by reversible exchange (SABRE) is shown to allow access to strongly enhanced ¹H NMR signals in a range of substrates in aqueous media. To achieve this outcome, phase-transfer catalysis is exploited, which leads to less than 1.5×10⁻⁶ mol dm⁻³ of the iridium catalyst in the aqueous phase. These observations reflect a compelling route to produce a saline-based hyperpolarized bolus in just a few seconds for subsequent in vivo MRI monitoring. The new process has been called catalyst separated hyperpolarization through signal amplification by reversible exchange or CASH-SABRE. We illustrate this method for the substrates pyrazine, 5-methylpyrimidine, 4,6-d₂-methyl nicotinate, 4,6-d₂-nicotinamide and pyridazine achieving ¹H signal gains of approximately 790-, 340-, 3000-, 260- and 380-fold per proton at 9.4 T at the time point at which phase separation is complete.