Exploring the hyperpolarisation of EGTA-based ligands using SABRE

The design of molecules whose magnetic resonance (MR) signals report on their biological environment is receiving attention as a route to non-invasive functional MR. Hyperpolarisation techniques improve the sensitivity of MR and enable real time low concentration MR imaging, allowing for the development of novel functional imaging methodologies. In this work, we report on the synthesis of a series of EGTA-derived molecules (EGTA - ethylene glycol-bis(2-aminoethylether)-N,N,N ',N '-tetraacetic acid), whose core structures are known to bind biologically relevant metal ions in vivo, in addition to pyridyl rings that allow reversible ligation to an iridium dihydride complex. Consequently, they are amenable to hyperpolarisation through the parahydrogen-based signal amplification by reversible exchange (SABRE) process. We investigate how the proximity of EGTA and pyridine units, and the identity of the linker group, affect the SABRE hyperpolarisation attained for each agent. We also describe the effect of catalyst identity and co-ligand presence on these measurements and can achieve H-1 NMR signal enhancements of up to 160-fold. We rationalise these results to suggest the design elements needed for probes amenable to SABRE hyperpolarisation whose MR signals might in the future report on the presence of metal ions.

Automated summary

This study focuses on the design of molecules that can report on their biological environment through their magnetic resonance signals, with a specific interest in hyperpolarization techniques for enhanced sensitivity. The synthesized EGTA-derived molecules, containing pyridyl rings for reversible ligation to an iridium dihydride complex, are investigated for their hyperpolarization potential through the SABRE process. The results show the importance of the proximity of EGTA and pyridine units, as well as the identity of the linker group, in achieving optimal hyperpolarization for MR imaging.