Interplay between exchange kinetics, molecular dynamics and polarisation transfer in SABRE hyperpolarisation

Signal amplification by reversible exchange (SABRE) is an effective hyperpolarisation technique that enhances nuclear magnetic resonance (NMR) signal by orders of magnitude through transferring spin order from parahydrogen to target nuclei of a substrate without chemically altering the substrates. The efficiency of SABRE hyperpolarisation is influenced by several factors. These include the polarisation transfer rates and mechanisms governed by the nuclear shieldings, as well as the scalar and dipolar couplings between the nuclei. It also depends on the lifetime of the metal complex, where the polarisation transfer occurs, which is determined by the substrate and hydride dissociation rates. In addition, it depends on the nuclear relaxation times defining the lifetime of the polarisation in the free and the complex-bound substrates. In this work, we have used variable-temperature NMR exchange and relaxation experiments, spin dynamics simulations, and quantum-chemical calculations to shed light into the complicated process of SABRE polarisation in four different molecules: pyridine, pyrazine, 3-fluoropyridine, and 3,5-difluoropyridine. With simulations, we have studied the effects of the individual parameters on the polarisation transfer. As a result, we have obtained a better understanding of the effect of longitudinal relaxation times on the polarisation transfer process, along with optimal dissociation rates to maximise the polarisation transfer efficiency for ¹H, ¹⁹F and ¹⁵N nuclei of the substrate. Finally, we predict the temperature ranges to achieve such optimal conditions for the studied systems.