15N hyperpolarisation of the antiprotozoal drug ornidazole by Signal Amplification By Reversible Exchange in aqueous medium

Abstract

Signal amplification by reversible exchange (SABRE) offers a cost-effective route to boost nuclear magnetic resonance (NMR) signal by several orders of magnitude by employing readily available para-hydrogen as a source of hyperpolarisation. Although 1H spins have been the natural choice of SABRE hyperpolarisation since its inception due to its simplicity and accessibility, limited spin lifetimes of 1H makes it harder to employ them in a range of time-dependent NMR experiments. Heteronuclear spins, for example, 13C and 15N, in general have much longer T1 lifetimes and thereby are found to be more suitable for hyperpolarised biological applications as demonstrated previously by para-hydrogen induced polarisation (PHIP) and dynamic nuclear polarisation (DNP). In this study we demonstrate a simple procedure to enhance 15N signal of an antibiotic drug ornidazole by up to 71,000-folds with net 15N polarisation reaching ~23%. Further, the effect of co-ligand strategy is studied in conjunction with the optimum field transfer protocols and consequently achieving 15N hyperpolarised spin lifetime of >3 min at low field. Finally, we present a convenient route to harness the hyperpolarised solution in aqueous medium free from catalyst contamination leading to a strong 15N signal detection for an extended duration of time.