IrTMes – a stable SABRE catalyst for the hyperpolarization of [1-13C]-pyruvate

Abstract

Signal amplification by reversible exchange (SABRE) can enhance nuclear magnetic resonance (NMR) signals by catalyzing the transfer of spin order from para-hydrogen to a substrate via transient coordination of both to an iridium complex. An important target substrate due to its biomedical relevance is [1-¹³C]-pyruvate. Hyperpolarizing [1-¹³C]-pyruvate in an acetone water mixture (Ace-SABRE) increases the biocompatibility of hyperpolarized [1-¹³C]-pyruvate due to easier solvent removal. However, the Ace-SABRE solvent system causes rapid deactivation of the catalyst, requiring frequent renewal of the sample. Here, we introduce a more resource-efficient Ace-SABRE catalyst IrTMes, where the iridium center is ligated with 1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene. At a para-hydrogen pressure of 5.17 bar, the IrTMes catalyst exhibits 17-times longer-lasting functionality under Ace-SABRE conditions and four times under exposure to the atmosphere compared to IrIMes at room temperature. This increased stability of IrTMes allows for reproducible and repeatable SABRE experiments. IrTMes achieves a signal enhancement of around 5000 at 50% para-hydrogen enrichment at 1.45 T, which corresponds to a polarization level of 0.62% or around 1.9% when extrapolated for 100% para-hydrogen. IrTMes reaches the maximum SABRE enhancement at 20 °C, avoiding the otherwise cumbersome cooling in SABRE hyperpolarization of [1-¹³C]-pyruvate. Under the same conditions, a polarization level of 1.26% (extrapolated to around 3.8% for 100% para-hydrogen) can be achieved with the benchmark catalyst IrIMes.