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

Abstract

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. In order to achieve this outcome phase-transfer-catalysis is exploited which leads to less than less than 1.5 x 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 via 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 signals gains of approximately 790-, 340-, 3000-, 260- and 380-fold per proton at 9.4 T at the time point where phase separation is complete