Macrocyclic transition-metal parashift complexes for MRI at clinical and pre-clinical magnetic fields†

A series of macrocyclic transition-metal complexes, including Fe(II), Co(II), Ni(II), and Cu(II) complexes, have been evaluated for parashift MRI imaging applications, by assessing their paramagnetic NMR properties, including proton chemical shifts, nuclear relaxation rates, and any exchange dynamics in solution, at magnetic fields strengths relevant to clinical and pre-clinical imaging. Among the complexes studied, Fe(II) and Co(II) systems demonstrated significant paramagnetic shifts with desirable relaxation properties, making them potential candidates for lanthanide-free parashift molecular probes for MRI. Field-dependent nuclear relaxation rate analyses provided insights into electronic relaxation times, confirming the suitability of certain complexes for parashift imaging at lower magnetic fields. Phantom imaging experiments at 9.4 T further validated the feasibility of molecular imaging using a cyclen-based macrocyclic Fe(II) complex, making a significant advance toward developing transition metal-based MRI probes using biogenic metal ions, and offer promise for future responsive imaging due to the direct signal detection.