Cluster-based redox-responsive super-atomic MRI contrast agents

Transition metal molecular clusters hold great promise as magnetic resonance imaging (MRI) probes, where careful chemical design can afford control over the size, shape, and total spin state of the contrast agent (CA). Although such clusters can act as a single entity, exhibiting advanced in situ reactivity to key diagnostic biomolecules, their dissociation/speciation in biological media hinders their potential as MRI CAs. To resolve this, the N-2-pyrimidylimidoyl-2-pyrimidylamidine chelate was employed to selectively bind 3d metal ions, forming highly stable mixed-metal clusters. Through spectroscopic, electrochemical, and magnetic analysis, along with in vitro and in vivo studies, the application of iron and manganese homo- and heterometallic complexes as MRI CAs capable of mapping tumor redox status through a simple T₁w/T₂w ratiometric approach was demonstrated. The use of heteropolynuclear 3d super-atomic complexes suitable for semi-quantitative in vivo MRI of tissue redox status opens new avenues for non-invasive characterization of biochemical microenvironments by MRI.