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

Abstract

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)(IⁱPr)₂]⁺ (2e) and [Ir^III(F₂₀tpp)(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 ¹H 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 ¹MLCT 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 ¹O₂ 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 IC₅₀ values at submicromolar levels. The cytotoxicity of these complexes could be further enhanced upon light irradiation with IC₅₀ 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.