Asymmetrically Coordinated Heterodimetallic Ir-Ru System: Synthesis, Computational, and Anticancer Aspects.

Herein, we present an unprecedented formation of a heterodinuclear complex [{(ppy)2IrIII}(µ-phpy){RuII(tpy)}](ClO4)2 {[1](ClO4)2} using terpyridyl/phenylpyridine as ancillary ligands and asymmetric phpy as a bridging ligand. The asymmetric binding mode (N∧N-∩-N∧N∧C-) of the phpy ligand in {[1](ClO4)2} is confirmed by 1H, 13C, 1H-1H correlated spectroscopy (COSY), high-resolution mass spectrum (HRMS), single-crystal X-ray crystallography techniques, and solution conductivity measurements. Theoretical investigation suggests that the highest occupied molecular orbital (HOMO) and the least unoccupied molecular orbital (LUMO) of [1]2+ are located on iridium/ppy and phpy, respectively. The complex displays a broad low energy charge transfer (CT) band within 450-575 nm. The time-dependent density functional theory (TDDFT) analysis suggests this as a mixture of metal-to-ligand charge transfer (MLCT) and ligand-to-ligand charge transfer (LLCT), where both ruthenium, iridium, and ligands are involved. Complex {[1](ClO4)2} exhibits RuIIIrIII/RuIIIIrIII- and RuIIIIrIII/RuIIIIrIV-based oxidative couples at 0.83 and 1.39 V, respectively. The complex shows anticancer activity and selectivity toward human breast cancer cells (IC50; MCF-7: 9.3 ± 1.2 µM, and MDA-MB-231: 8.6 ± 1.2 µM) over normal breast cells (MCF 10A: IC50 ≈ 21 ± 1.3 µM). The Western blot analysis and fluorescence microscopy images suggest that combined apoptosis and autophagy are responsible for cancer cell death.

Cyclometallated iridium complexes inducing paraptotic cell death like natural products: synthesis, structure and mechanistic aspects.

Six mononuclear Ir complexes (1-6) using polypyridyl-pyrazine based ligands (L1 and L2) and {[cp*IrCl(µ-Cl)]2 and [(ppy)2Ir(µ-Cl)]2} precursors have been synthesised and characterised. Complexes 1-5 have shown potent anticancer activity against various human cancer cell lines (MCF-7, LNCap, Ishikawa, DU145, PC3 and SKOV3) while complex 6 is found to be inactive. Flow cytometry studies have established that cellular accumulation of the complexes lies in the order 2 > 1 > 5 > 4 > 3 > 6 which is in accordance with their observed cytotoxicity. No changes in the expression of the proteins like PARP, caspase 9 and beclin-1, Atg12 discard apoptosis and autophagy, respectively. Overexpression of CHOP, activation of MAPKs (P38, JNK, and ERK) and massive cytoplasmic vacuolisation collectively suggest a paraptotic mode of cell death induced by proteasomal dysfunction as well as endoplasmic reticulum and mitochondrial stress. An intimate relationship between p53, ROS production and extent of cell death has also been established using p53 wild, null and mutant type cancer cells.

A dinuclear [{(p-cym)Ru(II)Cl}2(µ-bpytz˙(-))](+) complex bridged by a radical anion: synthesis, spectroelectrochemical, EPR and theoretical investigation (bpytz = 3,6-bis(3,5-dimethylpyrazolyl)1,2,4,5-tetrazine; p-cym = p-cymene).

The reaction of the chloro-bridged dimeric precursor [{(p-cym)Ru(II)Cl}(µ-Cl)]2 (p-cym = p-cymene) with the bridging ligand 3,6-bis(3,5-dimethylpyrazolyl)-1,2,4,5-tetrazine (bpytz) in ethanol results in the formation of the dinuclear complex [{(p-cym)Ru(II)Cl}2(µ-bpytz˙(-))](+), [1](+). The bridging tetrazine ligand is reduced to the anion radical (bpytz˙(-)) which connects the two Ru(II) centres. Compound [1](PF6) has been characterised by an array of spectroscopic and electrochemical techniques. The radical anion character has been confirmed by magnetic moment (corresponding to one electron paramagnetism) measurement, EPR spectroscopic investigation (tetrazine radical anion based EPR spectrum) as well as density functional theory based calculations. Complex [1](+) displays two successive one electron oxidation processes at 0.66 and 1.56 V versus Ag/AgCl which can be attributed to [{(p-cym)Ru(II)C}2(µ-bpytz˙(-))](+)/[{(p-cym)Ru(II)Cl}2(µ-bpytz)](2+) and [{(p-cym)Ru(II)Cl}2(µ-bpytz)](+)/[{(p-cym)Ru(III)Cl}2(µ-bpytz)](2+) processes (couples I and II), respectively. The reduction processes (couple III-couple V), which are irreversible, likely involve the successive reduction of the bridging ligand and the metal centres together with loss of the coordinated chloride ligands. UV-Vis-NIR spectroelectrochemical investigation reveals typical tetrazine radical anion containing bands for [1](+) and a strong absorption in the visible region for the oxidized form [1](2+), which can be assigned to a Ru(II) → π* (tetrazine) MLCT transition. The assignment of spectroscopic bands was confirmed by theoretical calculations.

Synthesis, characterisation and antibacterial activity of [(p-cym)RuX(L)](+/2+) (X = Cl, H2O; L = bpmo, bpms) complexes.

Mononuclear half-sandwiched complexes [(p-cym)RuCl(bpmo)](ClO4) {[1](ClO4)} and [(p-cym)RuCl(bpms)](PF6) {[2](PF6)} have been prepared by reacting heteroscorpionate ligands bpmo = 2-methoxyphenyl-bis(3,5-dimethylpyrazol-1-yl)methane and bpms = 2-methylthiophenyl-bis(3,5-dimethylpyrazol-1-yl)methane, respectively, with a dimeric precursor complex [(p-cym)RuCl(µ-Cl)]2 (p-cym = 1-isopropyl-4-methylbenzene) in methanol. The corresponding aqua derivatives [(p-cym)Ru(H2O)(bpmo)](ClO4)2 {[3](ClO4)2} and [(p-cym)Ru(H2O)(bpms)](PF6)2 {[4](PF6)2} are obtained from {[1](ClO4)} and {[2](PF6)}, respectively, via Cl(-)/H2O exchange process in the presence of appropriate equivalents of AgClO4/AgNO3 + KPF6 in a methanol-water mixture. The molecular structures of the complexes {[1]Cl, [3](ClO4)2 and [4](PF6)(NO3)} are authenticated by their single crystal X-ray structures. The complexes show the expected piano-stool geometry with p-cym in the η(6) binding mode. The aqua complexes [3](ClO4)2 and [4](PF6)2 show significantly good antibacterial activity towards E. coli (gram negative) and B. subtilis (gram positive) strains, while chloro derivatives ({[1](ClO4)} and {[2](PF6)} are found to be virtually inactive. The order of antibacterial activity of the complexes according to their MIC values is [1](ClO4) (both 1000 µg mL(-1)) < [2](PF6) (580 µg mL(-1) and 750 µg mL(-1)) < [3](ClO4)2 (both 100 µg mL(-1)) < [4](PF6)2 (30 µg mL(-1) and 60 µg mL(-1)) for E. coli and B. subtilis strains, respectively. Further, the aqua complexes [3](ClO4)2 and [4](PF6)2 show clear zones of inhibition against kanamycin, ampicillin and chloramphenicol resistant E. coli strains. The detailed mechanistic aspects of the aforesaid active aqua complexes [3](ClO4)2 and [4](PF6)2 have been explored, and it reveals that both the complexes inhibit the number of nucleoids per cell in vivo and bind to DNA in vitro. The results indeed demonstrate that both [3](ClO4)2 and [4](PF6)2 facilitate the inhibition of bacterial growth by binding to DNA.

Facile tandem Suzuki coupling/transfer hydrogenation reaction with a bis-heteroscorpionate Pd-Ru complex.

Design and synthesis of the bis(pyrazol-1-yl)methane based bis-heteroscorpionate Pd-Ru complex results in efficient tandem Suzuki coupling/transfer hydrogenation reaction with a broad range of substrate reactivity.

Dinuclear [{(p-cym)RuCl}2(µ-phpy)](PF6)2 and heterodinuclear [(ppy)2Ir(µ-phpy)Ru(p-cym)Cl](PF6)2 complexes: synthesis, structure and anticancer activity.

Phpy bridged homodinuclear Ru-Ru () and heterodinuclear Ir-Ru complexes () have been developed. Complex induces autophagy towards the cisplatin resistant human breast cancer (MCF7) cell line, whereas is inactive.

Synthesis, characterisation and biological activities of [(p-cym)RuX(pz4lut)]n+ and [{(p-cym)RuX}2(µ-pz4lut)]n+ (X = Cl, H2O and pz4lut = α,α,α',α'-tetra(pyrazol-1-yl)-2,6-lutidine).

Mononuclear [(p-cym)RuCl(pz4lut)]Cl (1) and dinuclear [{(p-cym)RuCl}2(µ-pz4lut)]Cl2 (2) complexes (p-cym = 1-isopropyl-4-methylbenzene) comprising of bis(pyrazol-1-yl)methane based heteroscorpionate ligand α,α,α',α'-tetra(pyrazol-1-yl)-2,6-lutidine (pz4lut) have been synthesised from pz4lut ligand and dimeric precursor complex [(p-cym)RuCl(µ-Cl)]2 in methanol. The aqua derivatives [(p-cym)Ru(H2O)(pz4lut)](ClO4)2 (3) and [{(p-cym)Ru(H2O)}2(µ-pz4lut)](ClO4)4 (4) are obtained from 1 and 2, respectively, via Cl/H2O exchange process in presence of appropriate equivalents of AgClO4 in methanol­water mixture. The molecular structures of dinuclear complexes, 2 and 4 are authenticated by their single crystal X-ray structures. Cyclic voltammetry reveals negligible electronic communication between the metal centres in the ligand bridged complex 2. All four complexes have been tested for their anticancer activities in human breast (MCF7), lung (A549) and colon (HCT116) cancer cell lines. The complexes show dose dependent suppression of cell viability with moderately good IC50 values ranging from 3.5­92 µM. Experimental results have revealed that the aqua derivatives, 3 and 4 exhibit better cytotoxic effect against all those cell lines as compared to the precursor chlorido complexes, 1 and 2. Results also demonstrate that the complexes are more potent against HCT116 cells as compared to other cell lines.