Fine-tuning the efficiency of para-hydrogen-induced hyperpolarization by rational N-heterocyclic carbene design

Iridium N-heterocyclic carbene (NHC) complexes catalyse the para-hydrogen-induced hyperpolarization process, Signal Amplification by Reversible Exchange (SABRE). This process transfers the latent magnetism of para-hydrogen into a substrate, without changing its chemical identity, to dramatically improve its nuclear magnetic resonance (NMR) detectability. By synthesizing and examining over 30 NHC containing complexes, here we rationalize the key characteristics of efficient SABRE catalysis prior to using appropriate catalyst-substrate combinations to quantify the substrate's NMR detectability. These optimizations deliver polarizations of 63% for ¹H nuclei in methyl 4,6-d₂-nicotinate, 25% for ¹³C nuclei in a ¹³C₂-diphenylpyridazine and 43% for the ¹⁵N nucleus of pyridine-¹⁵N. These high detectability levels compare favourably with the 0.0005% ¹H value harnessed by a routine 1.5 T clinical MRI system. As signal strength scales with the square of the number of observations, these low cost innovations offer remarkable improvements in detectability threshold that offer routes to significantly reduce measurement time.