Half-sandwich Ru Research Articles

Facile Method to Obtain Functionalised η6-Bound Arenes in Ru(II) and Os(II) Half-Sandwich Complexes.

Half-sandwich Ru(II)- and Os(II)-arene complexes have great potential for catalytic and biological applications. The possibility of fine-tuning their chemical reactivity by including modifications in the ligands around the metal adds to their many advantages. However, structural modifications at the η6-bound arene have had significant synthetic limitations, particularly in the design of Os(II)-tethered complexes. For the first time, we have employed a practical C(sp3)-C(sp2) coupling to obtain 28 new Ru(II) and Os(II) η6-arene half-sandwich complexes with a wide variety of arene functionalities, including those that enable the formation of tether rings, such as quinoline, and coumarin. The introduction of novel functional groups at the arene in Ru(II)- and Os(II) half-sandwich complexes can broaden the synthetic scope of this type of organometallic complexes, and help to take full advantage of their structural diversity, for example, in intracellular catalysis.

Synthesis, electrochemical, biological and catalytical studies of half-sandwich Ru(II)-NSHC complexes bearing benzothiazol-2-ylidene

The half-sandwich ruthenium(II)-NSHC complexes (2a-l) bearing benzothiazol-2-ylidene were synthesized by in situ deprotonation of N-substituted benzothiazolium salts (1a-l) with Ag2O and of [(p-cymene)Cl2Ru]2, in dichloromethane under mild conditions. However, 1m and 1n under the same conditions gave N-coordinated Ru(II) complex (3). The structures of the compounds were elucidated by NMR, FT-IR, UV–Vis, HR-MS spectroscopic methods and elemental analysis. In addition, the structures of 2k and 3 were studied by X-ray crystallography. The electrochemical properties of the complexes were investigated. Ru(II)-NSHC complexes have been used as catalysts in the transfer hydrogenation of carbonyls to secondary alcohols in the presence i-PrOH/KOH. Additionally, the effects of structural differences arising from different alkyl groups on the nitrogen atom in the benzothiazole skeleton in Ru(II)-NSHC complexes on anticancer, antifungal and antimicrobial activity were also examined.

Coumarin-modified ruthenium complexes: Synthesis, characterization, and antiproliferative activity against human cancer cells.

Among ruthenium complexes studied as anticancer metallodrugs, NKP-1339, NAMI-A, RM175, and RAPTA-C have already entered clinical trials due to their potent antitumor activity demonstrated in preclinical studies and reduced toxicity in comparison with platinum drugs. Considering the advantages of ruthenium-based anticancer drugs and the cytostatic activity of organometallic complexes with triazole- and coumarin-derived ligands, we set out to synthesize Ru(II) complexes of coumarin-1,2,3,-triazole hybrids (L) with the general formula [Ru(L)(p-cymene)(Cl)]ClO4. The molecular structure of the complex [Ru(2a)(p-cymene)(Cl)]ClO4 (2aRu) was determined by single-crystal X-ray diffraction, which confirmed the coordination of the ligand to the central ruthenium(II) cation by bidentate mode of coordination. Coordination with Ru(II) resulted in the enhancement of cytostatic activity in HepG2 hepatocellular carcinoma cells and PANC-1 pancreatic cancer cells. Coumarin derivative 2a positively regulated the expression and activity of c-Myc and NPM1 in RKO colon carcinoma cells, while the Ru(II) half-sandwich complex 2cRu induced downregulation of AKT and ERK signaling in PANC-1 cells concomitant with reduced intracellular levels of reactive oxygen species. Altogether, our findings indicated that coumarin-modified half-sandwich Ru(II) complexes held potential as anticancer agents against gastrointestinal malignancies.

Preparation, thermal properties, and structures of ionic plastic crystals with sandwich and half-sandwich Ru complexes

We have recently been investigating the phase behavior of salts of cationic sandwich complexes in pursuit of novel ionic plastic crystals (IPCs). In this study, we synthesized salts containing sandwich complexes [Ru(Cp)(C6H6)]X ([1]X; X = CPFSA− (1,1,2,2,3,3-hexafluoropropane-1,3-disulfonimide), SbCl6−) and half-sandwich complexes [Ru(Cp)(DMSO)3]X ([2]X; X = CPFSA−, FSA− ((FSO2)2N−), PF6−). In addition, we examined their thermal properties and crystal structures. Among them, [1]CPFSA exhibited an IPC phase between 365 and 630 K, whereas the others did not undergo phase transitions at 123–403 K. The cations and anions were alternately arranged in the crystals of [1]X, whereas [2]X did not exhibit the alternating arrangement except for [2]PF6. The results showed that alternating molecular arrangements are crucial for the IPC formation, although low symmetry of the ion environment and intermolecular steric hindrance may inhibit it.

Development of Half-Sandwich Ru, Os, Rh, and Ir Complexes Bearing the Pyridine-2-ylmethanimine Bidentate Ligand Derived from 7-Chloroquinazolin-4(3H)-one with Enhanced Antiproliferative Activity.

Kinesin spindle protein (KSP) inhibitors are one of the most promising anticancer agents developed in recent years. Herein, we report the synthesis of ispinesib-core pyridine derivative conjugates, which are potent KSP inhibitors, with half-sandwich complexes of ruthenium, osmium, rhodium, and iridium. Conjugation of 7-chloroquinazolin-4(3H)-one with the pyridine-2-ylmethylimine group and the organometallic moiety resulted in up to a 36-fold increased cytotoxicity with IC50 values in the micromolar and nanomolar range also toward drug-resistant cells. All studied conjugates increased the percentage of cells in the G2/M phase, simultaneously decreasing the number of cells in the G1/G0 phase, suggesting mitotic arrest. Additionally, ruthenium derivatives were able to generate reactive oxygen species (ROS); however, no significant influence of the organometallic moiety on KSP inhibition was observed, which suggests that conjugation of a KSP inhibitor with the organometallic moiety modulates its mechanism of action.

Synthesis and antimicrobial activity of new pyridine-based half-sandwich Ru(II) complexes

Eight new ruthenium complexes (C1, C2 (Ru-benzene or Ru-toluene complexes with L1, 3-amino-2-chloropyridine); C3, C4 (Ru-benzene or Ru-toluene complexes with L2, 2-amino-5-chloropyridine); C5, C6 (Ru-benzene or Ru-toluene complexes with L3, 3-acetylpyridine); and C7, C8 (Ru-benzene or Ru-toluene complexes with L4, 4-acetylpyridine) were synthesized. The chemical structures and purity of the compounds were confirmed using standard analytical methods such as 1H,13C NMR and IR spectroscopy, mass spectrometry, and elemental analysis, and their electrochemical behavior was evaluated using cyclic voltammetry experiments. The stability of the compounds in dimethyl sulfoxide solution was confirmed using 1H NMR spectroscopy. Finally, the antimicrobial potential of two complex precursors (CP1, [Ru(η6-benzene)Cl(μ-Cl)]2 and CP2, [Ru(η6-toluene)Cl(μ-Cl)]2), four ligands (L1–L4), and eight corresponding complexes (C1–C8) was screened against nine pathogenic microorganisms and two reference bacterial strains using the micro-well dilution method. The highest antibacterial activity (0.63 mg/mL) was for C5 against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Salmonella enteritidis, while C8 displayed more pronounced antimicrobial activity against Candida albicans (MIC/MMC = 0.31 mg/mL). Subsequently, the studied complexes underwent a detailed examination utilizing the DFT methodology, acquiring important quantum-chemical descriptors. Notably, the HOMO-LUMO gap was established as a significant correlate with the antimicrobial activity of synthesized compounds.

Design, synthesis and anticancer evaluation of novel half-sandwich Ru(II) complexes bearing pyrazalone moiety: Apoptosis inducers based on mitochondrial dysfunction and G0/G1 arrest

Six half-sandwich Ru(II) complexes (Ru1-Ru6), integrated with 5-phenyl-2-(pyridin-2-yl)-2,4-dihydro-3H-pyrazol-3-one (PDPO1-PDPO6) ligands, were synthesized and spectroscopically characterized. The structure of Ru3 that crystallized as a monoclinic crystal with P21/c space group was further confirmed by X-ray single crystal diffraction. Prototropic tautomerism within the complexes transformed OH-form ligands to NH-form, forming a hydrogen bond (Cl1---H-N3). The complexes and ligands' cytotoxicity was assessed against several cancerous (HepG2, A549, MCF-7) and normal Vero cell lines. Relative to the ligands and Cisplatin, complexes (Ru2, Ru3, Ru5, Ru6) exhibited potent cytotoxicity against cancer cells, with IC50 values from 2.05 to 15.69 μM/L, excluding Ru1 and Ru4. Specifically, Ru2, Ru3, and Ru5 demonstrated superior anti-HepG2 properties. Compared to Cisplatin, Ru2 and Ru5 were less toxic to Vero cells, highlighting their enhanced selectivity in toxicity. Structure-activity relationship (SAR) studies indicated that t-butyl substitution (in Ru2) or -Cl (in Ru5) on the benzene ring significantly improved the selective toxicity. These complexes manifested substantial lipophilicity, cellular uptake, and were quickly hydrolyzed to Ru-H2O species. Roughly positive correlations were observed between hydrolysis rate, lipophilicity, cellular uptake, and anticancer activities. Ru2, investigated specifically, induced apoptosis in HepG2 cells at concentrations of 10 and 20 μM/L through ROS-mediated mitochondrial dysfunction and G0/G1phase arrest, associated with altered P21, cyclin D, and CDK4 expression levels.

Naphthalene Diimide-Functionalized Half-Sandwich Ru(II) Complexes as Mitochondria-Targeted Anticancer and Antimetastatic Agents.

In this work, four naphthalene diimide (NDI)-functionalized half-sandwich Ru(II) complexes Ru1-Ru4 bearing the general formula [(η6-arene)RuII(N^N)Cl]PF6, where arene = benzene (bn), p-cymene (p-cym), 1,3,5-trimethylbenzene (tmb), and hexamethylbenzene (hmb), have been synthesized and characterized. By introducing the NDI unit into the N,N-chelating ligand of these half-sandwich complexes, the poor luminescent half-sandwich complexes are endowed with excellent emission performance. Besides, modification on the arene ligand of arene-Ru(II) complexes can influence the electron density of the metal center, resulting in great changes in the kinetic properties, catalytic activities in the oxidative conversion of NADH to NAD+, and biological activities of these compounds. Particularly, Ru4 exhibits the highest reactivity and the strongest inhibitory activity against the growth of three tested cancer cell lines. Further study revealed that Ru4 can enter cells quickly in an energy-dependent manner and preferentially accumulate in the mitochondria of MDA-MB-231 cells, inducing cell apoptosis via reactive oxygen species overproduction and mitochondrial dysfunction. Significantly, Ru4 can effectively inhibit the cell migration and invasion. Overall, the complexation with NDI and modification on the arene ligand endowed the half-sandwich Ru(II) complexes with improved spectroscopic properties and anticancer activities, highlighting their potential applications for cancer treatment.

Coordination of Ru(II)-Arene Fragments to Dipyridophenazine Ligands Leads to the Modulation of Their In Vitro and In Vivo Anticancer Activity

Despite extensive research on the anticancer properties of Ru complexes with dipyrido[3,2-a:2',3'-c]phenazine (dppz) ligands, their in vivo efficacy is rarely investigated. Aiming to understand whether the coordination of certain half-sandwich Ru(II)-arene fragments might improve the therapeutic potential of dppz ligands, we prepared a series of Ru(II)-arene complexes with the general formula [(η6-arene)Ru(dppz-R)Cl]PF6, where the arene fragment was benzene, toluene, or p-cymene and R was -NO2, -Me, or -COOMe. All compounds were fully characterized by 1H and 13C NMR spectroscopy and high-resolution ESI mass-spectrometry, and their purity was verified by elemental analysis. The electrochemical activity was investigated using cyclic voltammetry. The anticancer activity of dppz ligands and their respective Ru complexes was assessed against several cancer cell lines, and their selectivity toward cancer cells was assessed using healthy MRC5 lung fibroblasts. The substitution of benzene with a p-cymene fragment resulted in a more than 17-fold increase of anticancer activity and selectivity of Ru complexes and significantly enhanced DNA degradation in HCT116 cells. All Ru complexes were electrochemically active in the biologically accessible redox window and were shown to markedly induce the production of ROS in mitochondria. The lead Ru-dppz complex significantly reduced tumor burden in mice with colorectal cancers without inducing liver and kidney toxicity.

Synthesis, chemical characterization, and antimicrobial potency of picolinate-based half-sandwich Ru(II) complexes

Eleven new and three reported half-sandwich Ru(II) arene complexes were synthesized using [Ru(η6-benzene)Cl(μ-Cl)]2 and [Ru(η6-toluene)Cl(μ-Cl)]2 and four pyridine carboxylic acid-based ligands (dicarboxylic acids and halogen derivatives). The structures and purity of synthesized compounds were confirmed using 1H and 13C NMR spectroscopy, infrared spectroscopy, mass spectrometry, and elemental analysis. The stability of synthesized compounds in dimethyl sulfoxide solution was confirmed using 1H NMR spectroscopy. The seven ligands, two complex precursors (CP1 and CP2), and 14 half-sandwich Ru(II) picolinate complexes (C1–C14) were evaluated for in vitro antibacterial and antifungal activity against pathogens, such as Staphylococcus aureus, Bacillus cereus, Proteus mirabilis, Klebsiella pneumoniae, Ecsherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Enterobacter aerogenes, and yeast Candida albicans, using the microwell-dilution method. Among the tested samples, the ligands showed better inhibitory effect against Gram-positive bacteria when compared to the metal complexes. The most susceptible Gram-negative bacteria was Ecsherichia coli, with a MIC value of 1.25 mg/mL, for C3, C6, and C10. All synthesized complexes showed similar, slightly better activity against Candida albicans.

Half-Sandwich Ruthenium Arene Complexes Bearing Clinically Approved Drugs as Ligands: The Importance of Metal-Drug Synergism in Metallodrug Design.

A novel strategy in metallodrug discovery today is incorporating clinically approved drugs into metal complexes as coordinating ligands. Using this strategy, various drugs have been repurposed to prepare organometallic complexes to overcome the resistance of drugs and to design promising alternatives to currently available metal-based drugs. Notably, the combination of organoruthenium moiety and clinical drug in a single molecule has been shown, in some instances, to enhance pharmacological activity and reduce toxicity in comparison to the parent drug. Thus, for the past two decades, there has been increasing interest in exploiting metal-drug synergism to develop multifunctional organoruthenium drug candidates. Herein, we summarized the recent reports of rationally designed half-sandwich Ru(arene) complexes containing different FDA-approved drugs. This review also focuses on the mode of coordination of drugs, ligand-exchange kinetics, mechanism of action, and structure-activity relationship of organoruthenated complexes containing drugs. We hope this discussion may serve to shed light on future developments in ruthenium-based metallopharmaceuticals.

Impact of the central atom and halido ligand on the structure, antiproliferative activity and selectivity of half-sandwich Ru(II) and Ir(III) complexes with a 1,3,4-thiadiazole-based ligand.

Half-sandwich complexes [Ru(η6-pcym)(L1)X]PF6 (1, 3) and [Ir(η5-Cp*)(L1)X]PF6 (2, 4) featuring a thiadiazole-based ligand L1 (2-(furan-2-yl)-5-(pyridin-2-yl)-1,3,4-thiadiazole) were synthesized and characterized by varied analytical methods, including single-crystal X-ray diffraction (X = Cl or I, pcym = p-cymene, Cp* = pentamethylcyclopentadienyl). The structures of the molecules were analysed and interpreted using computational methods such as Density Functional Theory (DFT) and Quantum Theory of Atoms in Molecules (QT-AIM). A 1H NMR spectroscopy study showed that complexes 1-3 exhibited hydrolytic stability while 4 underwent partial iodido/chlorido ligand exchange in phosphate-buffered saline. Moreover, 1-4 demonstrated the ability to oxidize NADH (reduced nicotinamide adenine dinucleotide) to NAD+ with Ir(III) complexes 2 and 4 displaying higher catalytic activity compared to their Ru(II) analogues. None of the complexes interacted with reduced glutathione (GSH). Additionally, 1-4 exhibited greater lipophilicity than cisplatin. In vitro biological analyses were performed in healthy cell lines (CCD-18Co colon and CCD-1072Sk foreskin fibroblasts) as well as in cisplatin-sensitive (A2780) and -resistant (A2780cis) ovarian cancer cell lines. The results indicated that Ir(III) complexes 2 and 4 had no effect on human fibroblasts, demonstrating their selectivity. In contrast, complexes 1 and 4 exhibited moderate inhibitory effects on the metabolic and proliferation activities of the cancer cells tested (selectivity index SI > 3.4 for 4 and 2.6 for cisplatin; SI = IC50(A2780)/IC50(CCD-18Co)), including the cisplatin-resistant cancer cell line. Based on these findings, it is possible to emphasize that mainly complex 4 could represent a further step in the development of selective and highly effective anticancer agents, particularly against resistant tumour types.

Synthesis, Characterization and Biological Investigations of Half-Sandwich Ruthenium(II) Complexes Containing Benzimidazole Moiety.

Half-sandwich Ru(II) complexes belong to group of biologically active metallo-compounds with promising antimicrobial and anticancer activity. Herein, we report the synthesis and characterization of arene ruthenium complexes containing benzimidazole moiety, namely, [(η6-p-cymene)RuCl(bimCOO)] (1) and [(η6-p-cymene)RuCl2(bim)] (2) (where bimCOO = benzimidazole-2-carboxylate and bim = 1-H-benzimidazole). The compounds were characterized by 1H NMR, 13C NMR, IR, UV-vis and CV. Molecular structures of the complexes were determined by SC-XRD analysis, and the results indicated the presence of a pseudo-tetrahedral (piano stool) geometry. Interactions in the crystals of the Ru complexes using the Hirshfeld surface analysis were also examined. In addition, the biological studies of the complexes, such as antimicrobial assays (against planktonic and adherent microbes), cytotoxicity and lipophilicity, were performed. Antibacterial activity of the complexes was evaluated against S. aureus, E. coli, P. aeruginosa PAO1 and LES B58. Cytotoxic activity was tested against primary human fibroblasts and adenocarcinoma human alveolar basal epithelial cells. Obtained biological results show that the ruthenium compounds have bacteriostatic activity toward Pseudomonas aeruginosa PAO1 strain and are not toxic to normal cells. A molecular docking study was applied as a predictive source of information about the plausibility of examined structures binding with HSA as a transporting system.

Syntheses and Applications of Symmetrical Dinuclear Half-Sandwich Ruthenium(II)–Dipicolinamide Complexes as Catalysts in the Transfer Hydrogenation of Ketones

The treatment of [Ru(η6-p-cymene)Cl2]2 with N,N’-(1,2-phenylene)dipicolinamide (H2L1) afforded the double salt complex [{Ru(η6-p-cymene)2-µ-Cl}L1][Ru(η6-p-cymene)Cl3], (Ru1) in moderate yields. Separately, the reactions of ligands (H2L1), N,N’-(4,5 dimethyl-1,2-phenylene)dipicolinamide (H2L2), and N,N’-(4-methoxy-1,2-phenylene)dipicolinamide (H2L3) with the [Ru(η6-p-cymene)Cl2]2 in the presence of KPF6 afforded the respective dinuclear half-sandwich Ru(II) complexes [{(Ru(η6-p-cymene)2--µ-Cl}L1][PF6] (Ru2), [{(Ru(η6-p-cymene)2-µ-Cl}L2][PF6] (Ru3), and [{(Ru(η6-p-cymene)2-µ-Cl}L3][PF6] (Ru4). NMR and FT-IR spectroscopies, ESI-MS spectrometry, and elemental analyses were used to establish the molecular structures of the new dinuclear ruthenium(II) complexes. Single crystal X-ray crystallography was used to confirm the piano-stool geometry of the dinuclear complexes Ru1 and Ru4, as containing N^N chelated ligand and bridging chlorido ligands in each Ru(II) atom. The complexes (Ru1-Ru4) showed good catalytic activities at low catalyst concentrations of 0.005 mol% in the transfer hydrogenation of a wide range of ketone substrates.

Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes.

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η6-arene)Ru(N,N′)L][PF6]2 containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λmax = 418 nm) compared with C1 and C2 (λmax = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC50 = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT).

Half-sandwich Ru(II)-thioamide complexes as catalysts for one pot synthesis of aromatic 1,5-diketones

Four Ru(II)-arene thioamide complexes of the type [(η6-cymene)Ru(PPh3)(L)]+ (L = bidentate monoanionic thioamide ligand) have been synthesized and isolated as their hexafluorophosphate salts. All these complexes are fully characterized by spectroscopic methods. Molecular structures of the ligands (HL2 and HL3) and complex (3) were determined by single crystal X-ray crystallography. The ligands coordinated to Ru center through phenolic O and thioamide S atoms. All the four complexes were tested as catalysts in the one pot synthesis of 1,5-diketones from aromatic ketones and alcohols in the presence of KOtBu, and the products were analyzed by GC/GC–MS/1H NMR. Complexes 1 and 2 behaved as catalysts to produce 1,5-diketones while complexes 3 and 4 catalyzed the reactions to form alkylated ketones. Scope of the reaction was extended to various substituted alcohols and ketones to prepare 1,5-diketones with catalyst 1.

Density functional theory investigation of Ru(II) and Os(II) asymmetric transfer hydrogenation catalysts.

Transition metal ions have a unique ability to organise and control the steric and electronic effects around a substrate in the active site of a catalyst. We consider half-sandwich Ru(II) (Noyori-type) and Os(II) sulfonyldiamine 16-electron active catalysts [Ru/Os(η6-p-cymene)(TsDPEN-H2)], where TsDPEN is N-tosyl-1,2-diphenylethylenediamine containing S,S or R,R chiral centres, which catalyse the highly efficient asymmetric transfer hydrogenation of aromatic ketones to chiral alcohols using formic acid as a hydride source. We discuss the recognition of the prochiral ketone acetophenone by the catalyst, the protonation of a ligand NH and transfer of hydride from formate to the metal, subsequent transfer of hydride to one enantiotopic face of the ketone, followed by proton transfer from metal-bound NH2, and regeneration of the catalyst. Our DFT calculations illustrate the role of the two chiral carbons on the N,N-chelated sulfonyldiamine ligand, the axial chirality of the π-bonded p-cymene arene, and the chirality of the metal centre. We discuss new features of the mechanism, including how a change in metal chirality of the hydride intermediate dramatically switches p-cymene coordination from η6 to η2. Moreover, the calculations suggest a step-wise mechanism involving substrate docking to the bound amine NH2 followed by hydride transfer prior to protonation of the O-atom of acetophenone and release of the enantio-pure alcohol. This implies that formation and stability of the M-H hydride intermediate is highly dependent on the presence of the protonated amine ligand. The Os(II) catalyst is more stable than the Ru(II) analogue, and these studies illustrate the subtle differences in mechanistic behaviour between these 4d6 and 5d6 second-row and third-row transition metal congeners in group 8 of the periodic table.

Ru(ii)arene(N^N bpy/phen)-based RAPTA complexes for in vitro anti-tumour activity in human glioblastoma cancer cell lines and in vivo toxicity studies in a zebrafish model.

Herein, we have introduced a series of half-sandwich Ru(ii)arene(N^N bpy/phen)-based RAPTA complexes for brain cancer therapy. Among all the synthesized complexes, [(η6-p-cymene)RuII(κ2-N,N-4,7dimethyl phenanthroline)(PTA)]·2PF6 (4c) and [(η6-p-cymene)RuII(κ2-N,N-4,7diphenyl phenanthroline)(PTA)]·2PF6 (4d) showed outstanding potency against the T98G, LN229 and U87MG cancer cells. The antiproliferative activity of these complexes was reinforced by neurosphere, DNA intercalation, agarose gel electrophoresis, cell cycle analysis and time-dependent ROS detection assays. The real-time reverse transcription (RT)-polymerase chain reaction (PCR) study showed that complex 4c inhibited the TNF-α-induced NF-κB phosphorylation in glioma cells. Moreover, the in vivo biodistribution of complex 4c in different organs and the morphological patterns of widely used zebrafish embryos due to toxic effects have been evaluated.

One pot three component synthesis of DNA targeting phototoxic Ru(II)-p-cymene dipyrido[3,2-a:2',3'-c]phenazine analogues.

We have developed a one pot three component synthetic protocol for half-sandwich Ru(II)-p-cymene dipyrido[3,2-a:2',3'-c]phenazine analogues for selective cancer therapy under light irradiation. On average, the cytotoxicity of all the complexes is indeed doubled upon light irradiation and also exhibited significant photo and dark selectivity against cancer cells with respect to normal cells. Out of five Ru(II) complexes (RuL1-RuL5), [(η6-p-cymene)RuIICl(K2-N,N-11-nitrodipyrido[3,2-a:2',3'-c]phenazine]PF6 (RuL4) exhibited the best phototoxicity (lowest IC50 under light irradiation). Intracellular ROS generation was studied by the 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay. Moreover, these complexes exhibited a strong serum albumin and DNA binding capacity. These complexes also exhibited good stability in 10% DMSO-buffer and under 1 mM GSH conditions. Overall, the remarkable photocytotoxic efficacy of new Ru(II)-p-cymene dipyrido[3,2-a:2',3'-c]phenazine analogues (RuL1-RuL5) makes them potential photochemotherapeutics as an alternative of current PDT agents.

Synthesis and Catalytic Properties of a Carbometalated Half-Sandwich Ru(II) Complex Bearing a Rigid Polyaromatic Tether

Synthesis and Catalytic Properties of a Carbometalated Half-Sandwich Ru(II) Complex Bearing a Rigid Polyaromatic Tether