Novel magnetisation transfer catalysts and their applications in hyperpolarised magnetic resonance

Signal Amplification By Reversible Exchange (SABRE) is a hyperpolarisation technique that uses iridium catalysts to transfer magnetisation from parahydrogen (p-H2) to target substrates. Relayed polarisation via 1H exchange involving [Ir(H)2(IMes)(NH3)3]Cl achieves 1400-fold 13C and 700-fold 1H NMR signal enhancements at 9.4 T for non-ligating alcohols such as 3-methyl-1-butanol. This is extended to natural products, lactate esters and pyruvate. Sodium pyruvate 13C NMR signal enhancements of just 65-fold are only visible <15 minutes after pyruvate addition to [Ir(H)2(IMes)(NH2R)3]Cl due to formation of [Ir(H)2(κ2-OOCC(CH3)NR)(IMes)(NH2R)]. Hyperpolarised 13C sites of these bound imine ligands exist as singlet states with NMR signal enhancements and lifetimes of 750-fold and 20 s respectively. The chemical shift of the hydride ligands vary by 15.5 ppm allowing ligand sensing applications. The hyperpolarisation of α-keto acids via [Ir(H)2(IMes)(κ2-O-substrate)(sulfoxide)] achieves 13C NMR signal enhancements of 2135-fold for sodium pyruvate-1,2-[13C2] and 985-fold for sodium ketoisokaproate-[1-13C] in methanol-d4 at 9.4 T. EXSY and DFT studies reveal that [IrCl(H)2(IMes)(sulfoxide)2] plays an important role by refreshing p-H2. SABRE hyperpolarised 13C NMR was used to monitor the reaction between pyruvate and H2O2. Kinetic fitting at 298 K yields a rate constant (0.056 ± 0.003 dm3 mol-1 s-1) consistent with values obtained from thermal 1H NMR and UV spectroscopy. Interestingly, a short lived 2-hydroxy-2-propanoate intermediate can be detected in a single scan 13C NMR spectrum at 273 K. The polarisation transfer catalysts presented expand the scope of SABRE and allow MR applications such as chemosensing, reaction monitoring, and intermediate detection. Hyperpolarisation of molecules such as pyruvate is now achieved using a readily accessible and simple approach that does not involve chemical modification.