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 [IrIIIShow more
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 [IrIII(ttp)(IMe)2]+ (2a), [IrIII(oep)(BIMe)2]+ (2d), [IrIII(oep)(I i Pr)2]+ (2e) and [IrIII(F20tpp)(IMe)2]+ (2f) display ruffled porphyrin rings with mesocarbon displacements of 0.483-0.594 Å and long Ir-CNHC 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 IrIII(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 IrIII(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 (Φem < 0.01; τ < 4 μs). [IrIII(por)(IMe)2]+ complexes (por = ttp and oep) are efficient photosensitizers for 1O2 generation (Φso = 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 [IrIII(oep)(IMe)2]+ (2c) treated cells indicates that this Ir complex mainly targets the endoplasmic reticulum. [IrIII(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. Show less
Two novel series of (salen)ruthenium(iii) complexes bearing guanidine and amidine axial ligands were synthesized, characterized, and evaluated for anticancer activity. In vitro cytotoxicity tes Show more
Two novel series of (salen)ruthenium(iii) complexes bearing guanidine and amidine axial ligands were synthesized, characterized, and evaluated for anticancer activity. In vitro cytotoxicity tests demonstrate that these complexes are cytotoxic against various cancer cell lines and the leading complexes have remarkable cancer-cell selectivity. A detailed study of the guanidine complex 7 and the amidine complex 13 reveals two distinguished modes of action. Complex 7 weakly binds to DNA and induces DNA damage, cell cycle arrest, and typical apoptosis pathways in MCF-7 cells. In contrast, complex 13 induces paraptosis-like cell death hallmarked by massive vacuole formation, mitochondrial swelling, and ER stress, resulting in significant cytotoxicity against human breast cancer cells. Our results provide an extraordinary example of tuning the mechanism of action of (salen)ruthenium(iii) anticancer complexes by modifying the structure of the axial ligands. Show less
A macrocyclic ruthenium(III) complex [RuIII (N2 O2 )Cl2 ]Cl (Ru-1) is reported as an inhibitor of angiogenesis and an anti-tumor compound. The complex is re Show more
A macrocyclic ruthenium(III) complex [RuIII (N2 O2 )Cl2 ]Cl (Ru-1) is reported as an inhibitor of angiogenesis and an anti-tumor compound. The complex is relatively non-cytotoxic towards endothelial and cancer cell lines in vitro, but specifically inhibited the processes of angiogenic endothelial cell tube formation and cancer cell invasion. Moreover, compared with known anti-cancer ruthenium complexes, Ru-1 is distinct in that it suppressed the expression of vascular endothelial growth factor receptor-2 (VEGFR2), and the associated downstream signaling that is crucial to tumor angiogenesis. In addition, in vivo studies showed that Ru-1 inhibited angiogenesis in a zebrafish model and suppressed tumor growth in nude mice bearing cancer xenografts. Show less
Four luminescent ruthenium(II) polypyridine estradiol complexes [Ru(NwedgeN)2(bpy-estradiol)](PF6)2 (NwedgeN = 2,2'-bipyridine (bpy), 4,7-diphenyl-1,10-phenanthroline (Ph2-phen); bpy-estradiol = 5-(4- Show more
Four luminescent ruthenium(II) polypyridine estradiol complexes [Ru(NwedgeN)2(bpy-estradiol)](PF6)2 (NwedgeN = 2,2'-bipyridine (bpy), 4,7-diphenyl-1,10-phenanthroline (Ph2-phen); bpy-estradiol = 5-(4-(17alpha-ethynylestradiolyl)phenyl)-2,2'-bipyridine (bpy-ph-est), 4-(N-(6-(4-(17alpha-ethynylestradiolyl)benzoylamino)hexyl)aminomethyl)-4'-methyl-2,2'-bipyridine (mbpy-C6-est)) have been designed as new luminescent biological probes. The lipophilicity and photophysical and electrochemical properties of these complexes have been investigated. Upon photoexcitation, all the complexes exhibited intense and long-lived triplet metal-to-ligand charge-transfer (3MLCT) (dpi(Ru) --> pi*(diimine)) emission in fluid solutions at 298 K and in low-temperature glass. The binding of the complexes to estrogen receptor-alpha (ERalpha) has been studied by emission titrations. The Ph2-phen complexes showed emission enhancement and increased lifetimes upon binding to the protein. Additionally, the cytotoxicity of the complexes toward the HeLa cell line has been examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and the IC50 values ranged from 83.1 to 166.6 microM (cisplatin showed an IC50 value of 34.3 microM under the same experimental conditions). Furthermore, the cellular uptake of the complexes has been investigated by flow cytometry and laser-scanning confocal microscopy. Show less