Examining Para-Substituted Derivatives of Pyridine to Improve Catalytic Efficiency and Understanding of the SABRE Hyperpolarisation Process

The insensitivity of magnetic resonance techniques can be overcome through the use of hyperpolarisation methods such as Signal Amplification by Reversible Exchange (SABRE). SABRE utilises an iridium catalyst to transfer the latent magnetisation of parahydrogen to a substrate by reversible binding. In this thesis, we present a comprehensive quantitative study of substrate-iridium ligation effects and evaluate the role of the substrate in SABRE catalysis. A range of para-substituted pyridines were selected to probe the relationship between their electronic properties and SABRE efficiency. These substrates reacted to form [Ir(H)2(SIMes)(substrate)3]Cl as the key SABRE-active species. The lifetimes of these complexes were assessed via exchange spectroscopy and longer catalyst residence times were clearly linked to short substrate T1 times in solution. SABRE efficiency was shown to be optimal where the rate of substrate dissociation was 6.69 s-1 and the T1 was 6.42 s, as an enhancement of 767 ± 8-fold was observed. These data illustrate that SABRE performance is explicitly linked to substrate exchange and relaxation.

The substrates, 4-hydroxypyridine and isoniazid, were also examined and found to form novel bis-substituted iridium complexes. 4-Hydroxypyridine readily tautomerizes to 4-pyridone resulting in the unusual SABRE-active species; [IrCl(H)2(SIMes)(κ-O-4-pyridone)(κ-N-4-hydroxypyridine)]. The 4-pyridone tautomer ligates to iridium via the oxygen atom in the keto group and lies trans to hydride. This ligand undergoes rapid substrate dissociation (18.31 s-1 at 270 K) resulting in low levels of hyperpolarisation (−31±1-fold). Isoniazid was found to form the SABREactive species [Ir(H)2(SIMes)(κ-N-isonicotinylhydrazide(isonicotinyl-κ-O-κ-Nhydrazide]Cl, where the substrate ligand trans to hydride ligates to iridium via the pyridine nitrogen. The second substrate ligand chelates to iridium via the terminal nitrogen and the oxygen in the hydrazide functional group. This complex undergoes slow substrate dissociation (0.04 s-1 at 280 K) and yields high polarisation levels (−696±17-fold). This work could broaden the scope of the SABRE method in the future.