Heteronuclear Metal Complexes Based on Compartmental Bridging Ligands for Dual-Modal Imaging

The design of dual- or multi-modal probes, in which two or more independent reporters are integrated into one unit, is an area of immense interest, as visualisation of biological matter can be enhanced enormously by sequentially exploiting the advantages of each detection mode. In particular, dual optical/MRI contrast agents are appealing, as the combination of a luminescent dye with an MRI-active unit within a single entity, produces a superior probe capable of imaging both the ‘bigger picture’ and the intricate detail within a cell. By combining the synergistic signals arising from both imaging modalities, images can be developed to reveal exquisite detail. To this end, a series of water-soluble, heterometallic ruthenium(II)-based complexes based on compartmental bridging ligands have been synthesised for exploitation as dual-modal contrast agents. Incorporation of the commonly used MRI-active metal, Gd(III), into the probe design to produce multimetallic Ru(II)-Gd(III) hybrids has been investigated, as well as the relatively unexploited paramagnetic properties of Mn(II) in Ru(II)-Mn(II) hybrids. Assessment of the concentration-normalised longitudinal relaxivity values (r1) for each of the complexes has been undertaken, and the Ru(II)-Gd(III) hybrids have been evaluated as probes for cellular imaging. Incorporation of the NIR-luminescent Ln(III) ions, Yb(III) and Nd(III), in place of the MRI-active metals Gd(III) and Mn(II), has also provided a route to dual-modal optical/NIR imaging probes. Photoinduced energy-transfer from the photoactivated Ru(II) centre has been shown to sensitise emission from the Ln(III) ion, producing a dual-luminescent probe that has distinguishable emission, owing to the luminescent lifetimes of the two different metal centres being orders-of-magnitude apart.