IrIII−Pyridoannelated N‐Heterocyclic Carbene Complexes: Potent Theranostic Agents via Mitochondria Targeting

A novel family of Ir-III complexes bearing a pyridoannelated N-heterocyclic carbene is herein described. The target compounds 1-5 are straightforwardly prepared and fully characterized. Comprehensive investigation of their optical properties reveals a rare case of dual emission ascribed to two excited states localized onto different portions of the molecule, as confirmed by both optical spectroscopy and time-dependent density functional calculations including spin-orbit coupling. The cytotoxicity against cancer cell lines is investigated as well. Remarkably, 2-5 show up to 50-fold higher anticancer activity in vitro compared to oxaliplatin market drug with concentration values required to reduce by 50 % the cell viability (IC50) in the low mu M range. Finally, in-depth biological investigation on the most cytotoxic compound 4 reveals its powerful mitochondrial dysfunctioning activity and efficient reactive oxygen species production, associated with apoptosis as the mechanism of cell death.