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

Wissam Iali,Soumya S Roy,Laurynas Dagys,Gamal A I Moustafa

doi:10.1002/mrc.5144

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 1 H spins have been the natural choice of SABRE hyperpolarisation since its inception due to its simplicity and accessibility, limited spin lifetimes of 1 H makes it harder to employ them in a range of time-dependent NMR experiments. Heteronuclear spins, for example, 13 C and 15 N, 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 15 N signal of an antibiotic drug ornidazole by up to 71,000-folds with net 15 N polarisation reaching ~23%. Further, the effect of co-ligand strategy is studied in conjunction with the optimum field transfer protocols and consequently achieving 15 N hyperpolarised spin lifetime of >3min 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 15 N signal detection for an extended duration of time.

Highlights

Nuclear magnetic resonance (NMR) is one of the most versatile analytical techniques in physical science, but it suffers from low sensitivity that is due to a weak net magnetisation dictated by the thermal equilibrium
Hyperpolarisation (HP) techniques have made significant advances circumventing the issue of poor thermal polarisation of nuclear spins and successfully demonstrated that NMR signals of a large class of important molecular targets can be enhanced by several orders of magnitude.[1,2]
The results further indicate that this and other related drugs could be potentially prepared for biomedical use in a cheap and cost-effective way by using para-hydrogen induced polarisation (PHIP) and Signal amplification by reversible exchange (SABRE)

Summary

Introduction

Nuclear magnetic resonance (NMR) is one of the most versatile analytical techniques in physical science, but it suffers from low sensitivity that is due to a weak net magnetisation dictated by the thermal equilibrium. (b) Chemical structure of ornidazole (Odz) whose α-nitrogen site binds to the Iridium metal centre in a reversible fashion and screening their NMR detection and magnetic state lifetimes is an active field of research in itself.[37,38] Scheme 1 depicts the SABRE mechanism where Odz binds to the catalyst through the less sterically hindered nitrogen (α-nitrogen) reversibly to forge a polarisation transfer pathway (based on J-coupling network) with the hydrides when both are bound.

Results

Conclusion