Arene Ruthenium Complexes Research Articles

Synthesis and molecular structure of arene ruthenium(ii) benzhydrazone complexes: impact of substitution at the chelating ligand and arene moiety on antiproliferative activity

A series of ruthenium(ii) arene complexes have been synthesized and evaluated for their in vitro anticancer activities. The complexes exhibit promising anticancer activities in human cancer cells.

Fine tuning through valence bond tautomerization of ancillary ligands in ruthenium(ii) arene complexes for better anticancer activity and enzyme inhibition properties.

Four new ruthenium arene PTA type complexes have been synthesized using substituted picolinamide derivatives as ancillary ligands and characterized by spectroscopic methods. In one of the complexes, the ancillary ligand has shown an unprecedented valence-bond tautomerization in the presence of an ammonium salt to act as a polar neutral donor ligand making the ligand more prone towards substitution. The same compound has shown remarkable antiproliferative activity against three cancer cell lines with GI50 values comparable to Adriamycin, a known therapeutic drug. Along with this it also strongly inhibits the action of thioredoxin reductase, which might be a probable reason for the enhanced proliferative action of the valence-bond tautomerized compound.

Ruthenium(ii) arene complexes containing benzhydrazone ligands: synthesis, structure and antiproliferative activity

Six new Ru(ii) arene anthracene benzhydrazone complexes have been synthesized and show excellent cytotoxicity against human cancer cell lines. The results of apoptosis assays demonstrated that complexes4and6are able to induce apoptosis in human cancer cells.

Antiproliferative activity of ruthenium(ii) arene complexes with mono- and bidentate pyridine-based ligands.

A series of Ru(II) arene complexes of mono- and bidentate N-donor ligands with carboxyl or ester groups and chlorido ancillary ligands were synthesised and structurally characterised. The complexes have a distorted tetrahedral piano-stool geometry. The binding interaction was studied with calf thymus DNA (CT-DNA) by absorption titration, viscosity measurement, thermal melting, circular dichroism, ethidium bromide displacement assay and DNA cleavage of plasmid DNA (pBR322), investigated by gel electrophoresis. The dichlorido complexes bind covalently to DNA in the dark, similar to cisplatin, while the monochlorido complexes bind covalently on irradiation, similar to cisplatin analogues. The compounds are selectively cytotoxic against several tumour cell lines and show specific nonlinear correlation between dose and activity. This phenomenon is closely related to their potential to act preferentially as inhibitors of cell division.

Synthesis and anticancer activity of carbosilane metallodendrimers based on arene ruthenium(ii) complexes.

A series of new organometallic carbosilane dendrimers (first and second generation) and the corresponding non-dendritic mononuclear based on ruthenium arene fragments are described. The metallodendrimers were prepared by reactions of the precursor [Ru(η(6)-p-cymene)Cl2]2 with carbosilane dendrimers functionalized with N-donor monodentate ligands such as NH2- and pyridine, or with N,O-, N,N-chelating imine ligands. While the dendrimer precursors are insoluble in DMSO or water, novel metallodendrimers are soluble in DMSO and some of them are even highly soluble in water. The molecular structure of the "Ru-NH2" mononuclear compound (zero generation) was determined by single-crystal X-ray crystallography. The cytotoxicity activity of these dendritic structures was evaluated in several human cancer cell lines and compared with that of the corresponding mononuclear ruthenium complexes. Most compounds display significant cytotoxic activities in the low micromolar range with the first generation ruthenium dendrimers being the most active compounds. The cell death type for selected compounds has been studied as well as their reactivity towards relevant biomolecules such as DNA, Human Serum Albumin (HSA) and Cathepsin-B. All the data point to a mode of action different from that of cisplatin for most complexes. First generation ruthenium dendrimers inhibit Cathepsin-B, which may suggest potential antimetastatic properties of these compounds.

Structural analysis of ruthenium-arene complexes using ion mobility mass spectrometry, collision-induced dissociation, and DFT.

Ion mobility mass spectrometry (IM-MS) and collision-induced dissociation (CID) techniques were used to investigate the influence of the phosphine ligand on the physicochemical properties of [RuCl2(p-cymene)(PCy3)] (), [RuCl2(p-cymene)(PPh3)] (), and [RuCl2(p-cymene)(PTA)] () in the gas phase (PTA is 1,3,5-triaza-7-phosphaadamantane). Electrospray ionization of complexes and led to the corresponding [RuCl(p-cymene)(PR3)](+) ions via the dissociation of a chlorido ligand, whereas RAPTA-C () afforded two molecular ions by in-source oxidation ([Ru(III)Cl2(p-cymene)(PTA)](+)) or protonation ([RuCl2(p-cymene)(PTA+H)](+)). Control experiments showed that the balance between these two ionization paths was strongly influenced by the nature of the solvent used for infusion. Collision cross sections (CCSs) of the four molecular ions accurately reflected the variations of steric bulk inferred from the Tolman steric parameters (θ) of the phosphine ligands. Moreover, DFT calculations combined with a model based on the kinetic theory of gases (the trajectory method of the IMoS software) afforded reliable CCS predictions. The almost two times higher dipole moment of [RuCl2(p-cymene)(PTA+H)](+) (μ = 13.75 D) compared to [Ru(III)Cl2(p-cymene)(PTA)](+) (μ = 7.18 D) was held responsible for increased ion-induced dipole interactions with a polarizable drift gas such as N2. Further experiments with He and CO2 confirmed that increasing the polarizability of the buffer gas improved the separation between the two molecular ions derived from complex . The fragmentation patterns of complexes were determined by CID. The sequence of collision voltages at which 50% of a precursor ion dissociates (V50) recorded for the molecular ions derived from compounds was in good agreement with simple electronic considerations based on the donor strength of the phosphine ligand. Thus, the CCS and V50 parameters used to determine the shape and stability of ionic species in the gas phase are complementary to the Tolman steric and electronic parameters (θ and TEP) commonly used by organometallic chemists in condensed phases.

Hydrolytic behaviour of mono- and dithiolato-bridged dinuclear arene ruthenium complexes and their interactions with biological ligands

Compared to the inert and highly cytotoxic dinuclearp-cymene ruthenium trithiolato complexes, the less cytotoxic mono- and dithiolato complexes readily hydrolyse in aqueous solution and form adducts with cysteine, but do not interact with DNA.

Synthesis, structures, and DNA and protein binding of ruthenium(ii)-p-cymene complexes of substituted pyridylimidazo[1,5-a]pyridine: enhanced cytotoxicity of complexes of ligands appended with a carbazole moiety

The cytotoxicity of ruthenium-arene complexes appended with carbazole moiety correlates with their DNA binding ability.

Photoswitchable Arene Ruthenium Complexes Containing o-Sulfonamide Azobenzene Ligands

A series of arene ruthenium complexes containing o-sulfonamide azobenzene ligands were synthesized and found to exhibit uncommon coordination pattern with an exocyclic N═N bond. Upon irradiation, these complexes cleanly undergo E → Z photoisomerization followed by thermal Z → E isomerization (upon resting in the dark) whose rate is dependent on the solvent, the nature of the arene group, the sulfonamide moiety, and azobenzene substitution, as revealed by structure–property studies.

Synthesis, Anticancer Activity, and Genome Profiling of Thiazolo Arene Ruthenium Complexes.

Sixteen hydrazinyl-thiazolo arene ruthenium complexes of the general formula [(η(6)-p-cymene)Ru(N,N'-hydrazinyl-thiazolo)Cl]Cl were synthesized. All complexes were tested in vitro for their antiproliferative activity on three tumor cell lines (HeLa, A2780, and A2780cisR) and on a noncancerous cell line (HFL-1). A superior cytotoxic activity of the ruthenium complexes as compared to cisplatin and oxaliplatin, on both cisplatin-sensitive and cisplatin resistant ovarian cancer cells, was observed. In addition, the biological activity of two selected derivatives was evaluated using microarray gene expression assay and ingenuity pathway analysis. p53 signaling was identified as an important pathway modulated by both arene ruthenium compounds. New activated molecules such as FAS, ZMAT3, PRMT2, BBC3/PUMA, and PDCD4, whose overexpressions are correlated with overcoming resistance to cisplatin therapy, were also identified as potential targets. Moreover, the arene ruthenium complexes can be used in association with cisplatin to prevent cisplatin resistance development and synergistically to induce cell death in ovarian cancer cells.

Unmasking the Action of Phosphinous Acid Ligands in Nitrile Hydration Reactions Catalyzed by Arene-Ruthenium(II) Complexes.

The catalytic hydration of benzonitrile and acetonitrile has been studied by employing different arene-ruthenium(II) complexes with phosphinous (PR2OH) and phosphorous acid (P(OR)2OH) ligands as catalysts. Marked differences in activity were found, depending on the nature of both the P-donor and η(6)-coordinated arene ligand. Faster transformations were always observed with the phosphinous acids. DFT computations unveiled the intriguing mechanism of acetonitrile hydration catalyzed by these arene-ruthenium(II) complexes. The process starts with attack on the nitrile carbon atom of the hydroxyl group of the P-donor ligand instead of on a solvent water molecule, as previously suggested. The experimental results presented herein for acetonitrile and benzonitrile hydration catalyzed by different arene-ruthenium(II) complexes could be rationalized in terms of such a mechanism.

Crystal structure of (μ-4-hy-droxy-benzene-thiol-ato-κ(2) S:S)bis-(μ-phenyl-methane-thiol-ato-κ(2) S:S)bis-[(η(6)-1-isopropyl-4-methyl-benzene)-ruthenium(II)] tetra-fluorido-borate.

The crystal structure of the dinuclear arene ruthenium title complex, [Ru2(C6H5OS)(C7H7S)2(C10H14)2]BF4, shows the two Ru(II) atoms to be bridged by two benzyl-thio-pheno-late units and one 4-hy-droxy-thio-pheno-late unit, with the remaining three coordination sites of each Ru(II) atom being occupied by p-cymene ligands, completing the typical piano-stool coordination geometry. The BF4 (-) counter-anion is surrounded by four cationic dinuclear complexes, showing an O-H⋯F hydrogen bond and several weak C-H⋯F inter-actions. This is the first example of an X-ray analysis of a mixed dinuclear tri-thiol-ate arene ruthenium(II) complex.

Flexible arene ruthenium metalla-prisms

Cationic arene ruthenium metalla-prisms of the general formula [Ru6(p-cymene)6(tpmtt)2(OO∩OO)3]6+ (tpmtt=1,3,5-tris(pyridin-4-ylmethyl)-1,3,5-triazinane-2,4,6-trione) have been obtained from the corresponding dinuclear arene ruthenium complexes [Ru2(p-cymene)2(OO∩OO)Cl2] (OO∩OO=oxalato (ox), 2,5-dioxido-1,4-benzoquinonato (dobq), 2,5-dichloro-1,4-benzoquinonato (dClbq), 2,5-dioxido-3-undecyl-1,4-benzoquinonato (dubq), 5,8-dioxido-1,4-naphtoquinonato (donq)) by reaction with the tridentate tpmtt ligand and silver trifluoromethanesulfonate. These cationic arene ruthenium metalla-prisms have been isolated and characterized as their triflate salts. Upon formation of the metalla-prisms, the two tpmtt panels are in close proximity and do not allow encapsulation of guest molecules.

Arene ruthenium(II) complexes with 2-acetamidothiazole derived ligands: Synthesis, structural studies, antifouling and antibacterial properties

Four related arene ruthenium(II) complexes with antifouling properties of the general formula [(η6-arene)Ru(L)Cl2] have been prepared by the reaction of [(η6-arene)RuCl2]2 with 2-acetamidothiazole derived ligands at room temperature (η6-arene=p-cymene, C6Me6; L=2-acetamidothiazole or 5-chloro-2-acetamidothiazole) and were characterized by FTIR, 1H, 13C NMR and mass spectral analysis. The antifouling properties of these ruthenium(II) complexes have been investigated against marine fouling bacteria and the antibacterial properties against clinical pathogens. The complexes showed moderate to good antifouling as well as antibacterial activities. The molecular structure of a representative compound has been established by single crystal X-ray diffraction.

ChemInform Abstract: A Combined Experimental and Computational Study on the Cycloisomerization of 2‐Ethynylbiaryls Catalyzed by Dicationic Arene Ruthenium Complexes.

AbstractThe reaction conditions developed for the cycloisomerization of various 2‐ethinylbiaryls to phenanthrenes are also applied in the cycloisomerization of heteroaryl analogues.

Arene and Hydride Complexes of Ruthenium with fac PSiP Pincer Ligands

AbstractSeveral derivatives of the dinuclear complex [Ru(μ‐Cl){κP, P,Si‐Si(Me)(C6H4‐2‐PiPr2)2}]2 (1) are described. The mononuclear cationic arene complex [Ru{κP, P,Si‐Si(Me)(C6H4‐2‐PiPr2)2}(η6‐C6H6)](CF3SO3) (5), the phosphane adduct [Ru{κP, P,Si‐Si(Me)(C6H4‐2‐PiPr2)2}Cl(PPh3)] (2), and the hydride‐bridged dinuclear derivatives [Ru2(μ‐Cl)(μ‐H){κP, P,Si‐Si(Me)(C6H4‐2‐PiPr2)2}2] (6) and [Ru2(μ‐H){κP, P,Si‐Si(Me)(C6H4‐2‐PiPr2)2}]2 (7) retain the fac coordination mode of the κP, P,Si ligand present in the precursor complex. In contrast, the neutral and cationic acetonitrile derivatives [Ru{κP, P,Si‐Si(Me)(C6H4‐2‐PiPr2)2}Cl(NCMe)2] (3) and [Ru{κP, P,Si‐Si(Me)(C6H4‐2‐PiPr2)2}(NCMe)3](CF3SO3) (4), respectively, show the PSiP pincer coordinated in the more usual mer fashion. Crystal structures determined by X‐ray diffraction are shown for complexes 5, 6, and 7. The factors that influence the choice of coordination mode for the PSiP ligand are discussed.

Multispectroscopic Investigation of the Interaction Between two Ruthenium(II) Arene Complexes of Curcumin Analogs and Human Serum Albumin.

The interaction between two ruthenium(II) arene complexes of curcumin analogs and human serum albumin (HSA) was systematically investigated by multispectroscopic techniques. The fluorescence spectral results indicated that two complexes quenched the intrinsic fluorescence of HSA through static quenching mode. The quenching constants and the corresponding thermodynamic parameters at different temperatures were calculated. The binding interactions of two complexes with HSA resulted in the complex formation of complex-HSA, and the van der Waals interactions and hydrogen bond interactions played major roles in the complex stabilization. The distances between HSA and two complexes were obtained according to fluorescence resonance energy transfer theory. The site competitive replacement experiments illustrated that two complexes mainly bounded with HSA on site I. The results of synchronous fluorescence spectra, three-dimensional fluorescence spectra, FT-IR spectra, and circular dichroism spectra indicated that the secondary structure of HSA was changed at the present of two complexes. The results of mass spectrometry further validated the binding interaction and the binding number between two complexes and HSA.

Metal complexes of curcumin for cellular imaging, targeting, and photoinduced anticancer activity.

Curcumin is a polyphenolic species. As an active ingredient of turmeric, it is well-known for its traditional medicinal properties. The therapeutic values include antioxidant, anti-inflammatory, antiseptic, and anticancer activity with the last being primarily due to inhibition of the transcription factor NF-κB besides affecting several biological pathways to arrest tumor growth and its progression. Curcumin with all these positive qualities has only remained a potential candidate for cancer treatment over the years without seeing any proper usage because of its hydrolytic instability involving the diketo moiety in a cellular medium and its poor bioavailability. The situation has changed considerably in recent years with the observation that curcumin in monoanionic form could be stabilized on binding to a metal ion. The reports from our group and other groups have shown that curcumin in the metal-bound form retains its therapeutic potential. This has opened up new avenues to develop curcumin-based metal complexes as anticancer agents. Zinc(II) complexes of curcumin are shown to be stable in a cellular medium. They display moderate cytotoxicity against prostate cancer and neuroblastoma cell lines. A similar stabilization and cytotoxic effect is reported for (arene)ruthenium(II) complexes of curcumin against a variety of cell lines. The half-sandwich 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane (RAPTA)-type ruthenium(II) complexes of curcumin are shown to be promising cytotoxic agents with low micromolar concentrations for a series of cancer cell lines. In a different approach, cobalt(III) complexes of curcumin are used for its cellular delivery in hypoxic tumor cells using intracellular agents that reduce the metal and release curcumin as a cytotoxin. Utilizing the photophysical and photochemical properties of the curcumin dye, we have designed and synthesized photoactive curcumin metal complexes that are used for cellular imaging by fluorescence microscopy and damaging the cancer cells on photoactivation in visible light while being minimally toxic in darkness. In this Account, we have made an attempt to review the current status of the chemistry of metal curcumin complexes and present results from our recent studies on curcumin complexes showing remarkable in vitro photocytotoxicity. The undesirable dark toxicity of the complexes can be reduced with suitable choice of the metal and the ancillary ligands in a ternary structure. The complexes can be directed to specific subcellular organelles. Selectivity by targeting cancer cells over normal cells can be achieved with suitable ligand design. We expect that this methodology is likely to provide an impetus toward developing curcumin-based photochemotherapeutics for anticancer treatment and cure.

Novel N-coordinate half-sandwich ruthenium(II) arene complexes bearing sulfonamide fragments: Catalytic activities in the TH of acetophenone derivatives

The novel cationic N-coordinate ruthenium(II)/arene complexes (6–10) were prepared from the starting complex [RuCl2(p-cymene)]2 dimer. The structures of the [(p-cymene)RuLCl]Cl (L = N-arenesulfonyl-4,5-dimethyl-o-phenylenediamines) complexes were elucidated by FT-IR, 1H-NMR, 13C-NMR, ionic conductivity techniques, and elemental analysis methods. The 6–10 complexes were applied as catalyst in the transfer hydrogenation (TH) of ketones. The catalytic tests showed that all the complexes are moderate catalysis precursors. Especially, {[N-benzenesulfonyl-4,5-dimethyl-o-phenylenediamine]-(p-cymene)-di-chloro-ruthenium(II)} (8) and {[N-4-chlorobenzenesulfonyl-4,5-dimethyl-o-phenylenediamine]-(p-cymene)-di-chloro-ruthenium(II)} (9) compounds were found to be a good catalysts in comparison to the others giving the corresponding alcohols in a good turnover frequency value of 1534 and 1731 h−1, respectively.

ChemInform Abstract: Biologically Relevant Arene Ruthenium Metalla‐Assemblies

AbstractReview: 83 refs.