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

Multimodal probes : superresolution and transmission electron microscopy imaging of mitochondria, and oxygen mapping of cells, using small-molecule Ir(III) luminescent complexes

We describe an Ir(III)-based small-molecule, multimodal probe for use in both light and electron microscopy. The direct correlation of data between light- and electron-microscopy-based imaging to investigate cellular processes at the ultrastructure level is a current challenge, requiring both dyes that must be brightly emissive for luminescence imaging and scatter electrons to give contrast for electron microscopy, at a single working concentration suitable for both methods. Here we describe the use of Ir(III) complexes as probes that provide excellent image contrast and quality for both luminescence and electron microscopy imaging, at the same working concentration. Significant contrast enhancement of cellular mitochondria was observed in transmission electron microscopy imaging, with and without the use of typical contrast agents. The specificity for cellular mitochondria was also confirmed with MitoTracker using confocal and 3D-structured illumination microscopy. These phosphorescent dyes are part of a very exclusive group of transition-metal complexes that enable imaging beyond the diffraction limit. Triplet excited-state phosphorescence was also utilized to probe the O2 concentration at the mitochondria in vitro, using lifetime mapping techniques

Heteronuclear Ir(III)–Ln(III) Luminescent Complexes: Small-Molecule Probes for Dual Modal Imaging and Oxygen Sensing

Luminescent, mixed metal d–f complexes have the potential to be used for dual (magnetic resonance imaging (MRI) and luminescence) in vivo imaging. Here, we present dinuclear and trinuclear d–f complexes, comprising a rigid framework linking a luminescent Ir center to one (Ir·Ln) or two (Ir·Ln2) lanthanide metal centers (where Ln = Eu(III) and Gd(III), respectively). A range of physical, spectroscopic, and imaging-based properties including relaxivity arising from the Gd(III) units and the occurrence of Ir(III) → Eu(III) photoinduced energy-transfer are presented. The rigidity imposed by the ligand facilitates high relaxivities for the Gd(III) complexes, while the luminescence from the Ir(III) and Eu(III) centers provide luminescence imaging capabilities. Dinuclear (Ir·Ln) complexes performed best in cellular studies, exhibiting good solubility in aqueous solutions, low toxicity after 4 and 18 h, respectively, and punctate lysosomal staining. We also demonstrate the first example of oxygen sensing in fixed cells using the dyad Ir·Gd, via two-photon phosphorescence lifetime imaging (PLIM)