Luminescent ruffled iridium(iii) porphyrin complexes containing N-heterocyclic carbene ligands: structures, spectroscopies and potent antitumor activities under dark and light irradiation conditions

A panel of iridium(iii) porphyrin complexes containing axial N-heterocyclic carbene (NHC) ligand(s) were synthesized and characterized. X-ray crystal structures of the bis-NHC complexes [Ir(III)(ttp)(IMe)(2)](+) (2a), [Ir(III)(oep)(BIMe)(2)](+) (2d), [Ir(III)(oep)(I(i)Pr)(2)](+) (2e) and [Ir(III)(F(20)tpp)(IMe)(2)](+) (2f) display ruffled porphyrin rings with mesocarbon displacements of 0.483–0.594 Å and long Ir–C(NHC) bonds of 2.100–2.152 Å. Variable-temperature (1)H NMR analysis of 2a reveals that the macrocycle porphyrin ring inversion takes place in solution with an activation barrier of 40 ± 1 kJ mol(–1). The UV-vis absorption spectra of Ir(III)(por)–NHC complexes display split Soret bands. TD-DFT calculations and resonance Raman experiments show that the higher-energy Soret band is derived from the (1)MLCT dπ(Ir) → π*(por) transition. The near-infrared phosphorescence of Ir(III)(por)–NHC complexes from the porphyrin-based (3)(π, π*) state features broad emission bands at 701–754 nm with low emission quantum yields and short lifetimes (Φ(em) < 0.01; τ < 4 μs). [Ir(III)(por)(IMe)(2)](+) complexes (por = ttp and oep) are efficient photosensitizers for (1)O(2) generation (Φ(so) = 0.64 and 0.88) and are catalytically active in the light-induced aerobic oxidation of secondary amines and arylboronic acid. The bis-NHC complexes exhibit potent dark cytotoxicity towards a panel of cancer cells with IC(50) values at submicromolar levels. The cytotoxicity of these complexes could be further enhanced upon light irradiation with IC(50) values as low as nanomolar levels in association with the light-induced generation of reactive oxygen species (ROS). Bioimaging of [Ir(III)(oep)(IMe)(2)](+) (2c) treated cells indicates that this Ir complex mainly targets the endoplasmic reticulum. [Ir(III)(oep)(IMe)(2)](+) catalyzes the photoinduced generation of singlet oxygen and triggers protein oxidation, cell cycle arrest, apoptosis and the inhibition of angiogenesis. It also causes pronounced photoinduced inhibition of tumor growth in a mouse model of human cancer.