Magnetic resonance with para-hydrogen induced polarisation of x-nuclei

Hyperpolarisation is a deviation away from the Boltzmann distribution in Nuclear Magnetic Resonance (NMR). The hyperpolarisation technique, Signal Amplification By Reversible Exchange (SABRE), is explored in this work with biologically relevant pyrimidines which reflect nucleobases and drugs including anticancer and antifungal agents. Methods to increase the 1H NMR sensitivity of pyrimidine are explored and optimised by examining the various factors that influence the efficiency of polarisation transfer. This led to a 1H NMR signal enhancement of −382 ± 14-fold on the H-2 of pyrimidine being recorded at 9.4 T.
Studies on 5-fluorouracil, one of the most common anticancer agents, are also described. In addition to 1H hyperpolarisation, hyperpolarisation of its 19F nuclei is evaluated under SABRE. Polarisation levels of −106-fold and 0.85 ± 0.53-fold for 5-fluorouracil were achieved for 1H and 19F, respectively. This work was expanded to include other fluorinated N-heterocyclic compounds including, 3-fluoropyridine which gave the greatest 1H and 19F signal enhancement of −1287 ± 65-fold and 62 ± 6-fold respectively. After structural characterisation, it was found that two complexes form in these experiments, [Ir(H)2(IMes)(sub)3]Cl (A) and [IrCl(H)2(IMes)(sub)2] (B). H2 loss was found to proceed via B at between 0.4 and 0.2 s−1 which is comparable to that of A with 5-fluoropyridine-3-carboxylic acid in the presence of Cs2CO3. 19F MRI images were also recorded for these molecules.
The final chapters expand the range of substrates available to the SABRE technique and considers 13C, 15N and 31P hyperpolarisation through oxalate, adenosine triphosphate, urea, uracil and 5-fluorouracil. It was postulated that sodium oxalate could create a long-lived single spin order in its 13C2 form. The most effective approach involved utilisation of the co-ligand, DMSO but unfortunately the dimeric species, [Ir(H)2(DMSO)(IMes)]2(µ-oxalate), forms readily (as demonstrated by NMR and X-ray diffraction) and limits SABRE performance.