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The synthesis of a new heterodinuclear Re I Ru II metallointercalator containing Ru II (dppz) and Re I (dppn) moieties is reported. Cell-free studies reveal that the complex has similar photophysical properties to its homoleptic M(dppz) analogue and it also binds to DNA with a similar affinity. However, the newly reported complex has very different in-cell properties to its parent. In complete contrast to the homoleptic system, the Ru II (dppz)/Re I (dppn) complex is not intrinsically cytotoxic but displays appreciable phototoxic, despite both complexes displaying very similar quantum yields for singlet oxygen sensitization. Optical microscopy suggests that the reason for these contrasting biological effects is that whereas the homoleptic complex localises in the nuclei of cells, the Ru II (dppz)/Re I (dppn) complex preferentially accumulates in mitochondria. These observations illustrate how even small structural changes in metal based therapeutic leads can modulate their mechanism of action., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Using a new mononuclear "building block," for the first time, a dinuclear Ru II (dppn) complex and a heteroleptic system containing both Ru II (dppz) and Ru II (dppn) moieties are reported. The complexes, including the mixed dppz/dppn system, are 1 O 2 sensitizers. However, unlike the homoleptic dppn systems, the mixed dppz/dppn complex also displays a luminescence "switch on" DNA light-switch effect. In both cisplatin sensitive and resistant human ovarian carcinoma lines the dinuclear complexes show enhanced uptake compared to their mononuclear analogue. Thanks to a favorable combination of singlet oxygen generation and cellular uptake properties all three of the new complexes are phototoxic and display potent activity against chemotherapeutically resistant cells., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)