Synthesis, Characterization, and Biological Evaluation\nof Novel [M(η<sup>6</sup>‑arene)<sub>2</sub>]<sup>+</sup> (M = Re, <sup>99m</sup>Tc) Hosted Terpyridines and Copper Complexes\nThereof

We report the synthesis,\ncharacterization, and in vitro biological\nactivities of [Re(η<sup>6</sup>-arene)<sub>2</sub>]<sup>+</sup>-terpyridine conjugates and their Cu<sup>II</sup> complexes. The\nterpyridine (terpy) chelators were attached to the [Re(η<sup>6</sup>-arene)<sub>2</sub>]<sup>+</sup> scaffold via secondary amine\nlinkers allowing for heteroleptic mono- and homoleptic bis-terpyridine-substituted\nchelators. Complexation with CuCl<sub>2</sub> afforded the respective\nsquare pyramidal [Cu(terpy)Cl<sub>2</sub>] complexes hosted on the\n[Re(η<sup>6</sup>-arene)<sub>2</sub>]<sup>+</sup> scaffold.\nThe chelator conjugates and their respective complexes were found\nto be remarkably cytotoxic against malignant HT29 and A549 human cancer\ncell lines in vitro with IC<sub>50</sub> values in the low micromolar\nrange. Mitochondrial respiration disruption was identified as a possible\nmode of action of these novel drug candidates. Crucially, the [Re(η<sup>6</sup>-arene)<sub>2</sub>]<sup>+</sup> hosts delivered water solubility\nof the otherwise insoluble [Cu(terpy)Cl<sub>2</sub>] motif. Importantly, the homoleptic [<sup>99m</sup>Tc(η<sup>6</sup>-arene)<sub>2</sub>]<sup>+</sup>-terpyridine\nconjugate is available in a single step, which enables the presented\nsystem to be used as a theranostic approach to modern medicinal inorganic\nchemistry.