From chemotherapy to phototherapy ‐ changing the therapeutic action of a metallo‐intercalating RuII‐ReI luminescent system by switching its sub‐cellular location.
The synthesis of a new heterodinuclear ReIRuII metallointercalator containing RuII(dppz) and ReI(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 RuII(dppz)/ReI(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 RuII(dppz)/ReI(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.Zum Volltext
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