Single-Chain Fluorinated Catalysts for Efficient SABRE Pyruvate Hyperpolarization and <100 ppb Iridium in Aqueous Solutions

Signal Amplification by Reversible Exchange (SABRE) delivers rapid and inexpensive NMR hyperpolarization using iridium-catalyzed transfer from parahydrogen. For biomedical translation, the resulting SABRE-hyperpolarized metabolites must combine high signal enhancement with efficient removal of the toxic iridium catalyst prior to administration. Here we introduce three single-chain fluorinated Ir–NHC catalysts (NHC = IMesF1, SIMesF1, and IPrF1) for the SABRE hyperpolarization of [1-13C]pyruvate. The catalyst Ir-IMesF1 delivers ~4% 13C polarization with 50% parahydrogen in methanol-d4 (~12% extrapolated to 100% parahydrogen), which is comparable to the benchmark Ir-IMes catalyst, and approximately three times higher than delivered by the previously reported perfluorinated Ir-SIMesF2 system under identical conditions. By combining these catalysts with a redissolution (ReD)-SABRE protocol, aqueous extraction, and filtration through fluorinated silica, the residual iridium content is reduced by nearly two orders of magnitude relative to Ir-IMes, and threefold relative to Ir-SIMesF2, thereby yielding improved aqueous solutions containing <100 ppb Ir. These results are used to demonstrate efficient SABRE hyperpolarization, with simultaneous ultra-low residual iridium levels for the real-time monitoring of the in vitro enzymatic conversion of pyruvate to lactate with partial parahydrogen enrichment.