Understanding substrate substituent effects to improve catalytic efficiency in the SABRE hyperpolarisation process

Abstract

The use of parahydrogen based hyperpolarisation in NMR is becoming more widespread due to the rapidly expanding range of suitable target molecules and low-cost of parahydrogen production. Hyperpolarisation via SABRE catalysis employs a metal complex to transfer polarisation from parahydrogen into a substrate whilst they are bound. In this paper we present a quantitative study of substrate–iridium ligation effects by reference to the substrates 4-chloropyridine (A), 4-pyridinecarboxaldehyde methyl hemiacetal (B), 4-methylpyridine (C) and 4-methoxypyridine (D), and evaluate the role they play in the SABRE catalysis. Substrates whose substituents enable stronger associations yield slower substrate dissociation rates (k_d). A series of variable temperature studies link these exchange rates to optimal SABRE performance and reveal the critical impact of NMR relaxation times (T₁). Longer catalyst residence times are shown to result in shorter substrate T₁ values in solution as binding to iridium promotes relaxation thereby not only reducing SABRE efficiency but decreasing the overall level of achieved hyperpolarisation. Based on these data, a route to achieve more optimal SABRE performance is defined.