Investigation of inducing apoptosis in human lung cancer A549 cells and related mechanism of a ruthenium(II) polypyridyl complex

Two Ru(II) polypyridyl complexes [Ru(bpy)₂(pztp)]^2 + (Ru1) and [Ru(bpy)₂(pytp)]^2 + (Ru2) were synthesized and characterized. Our data demonstrated that Ru2 displayed relatively higher cytotoxic activity against lung cancer A549 cells and had higher selectivity between tumor and normal cells in comparison with cisplatin. Studies on the molecular mechanism revealed that Ru2 caused cell cycle arrest at G2/M in A549 cells and induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway. The further studies by comet assay at single cell level indicated that DNA damage in A549 cells was triggered by Ru2, following with the up-regulation of phosphorylated ATM (Ser1984), Histone H2A.X (Ser139) and p53 (Ser15). Western blot analysis suggested that MAPKs signaling pathways, especially ERK, were involved in Ru2-induced apoptosis. Moreover, both DNA damage and MAPKs signaling pathways were regulated by the level of ROS. To our knowledge, this is the first report of the ruthenium (II) polypyridyl complex which induces apoptosis partly through the activation of ERK.     

Antimicrobial and nuclease activity of mixed polypyridyl ruthenium(II) complexes

The ruthenium(II) complexes with 2,9-dimethyl-1,10-phenanthroline (dmphen) and terpyridine derivatives have been synthesized and screened for their antimicrobial potency. The interaction of these complexes with Herring Sperm DNA was investigated by thermal denaturation, viscosity measurements, gel electrophoresis and spectrophotometric methods. The results indicate that the complexes bound to DNA via partial intercalative mode. The salt-dependent binding of these complexes has been determined by UV–Vis spectrophotometric titration. The contribution of the non-electrostatic binding free energy (ΔG_t^o) to the total binding free energy change (ΔG^o) is found to be ~ 88% at [Na⁺] = 0.075 M. The large value suggests that the stabilization of the DNA binding is mostly due to the contribution of non-electrostatic process.     

Studies on thermodynamic nature of steroselectivity for ruthenium(II) polypyridyl complex binding to DNA

A pair of ruthenium(II) complex isomers, Δ- and Λ-[Ru(bpy)₂(p-mpip)]²⁺ {bpy = 2,2′-bipyridine, p-mpip = 2-(4-methylphenyl)imidazo[4,5-f]1,10-phenanthroline} have been synthesized and characterized. Thermodyanmics of binding of the two isomers to calf thymus DNA (CT DNA) has been investigated by isothermal titration calorimetry (ITC). It is rare that the Λ isomer binds to DNA more strongly than the Δ isomer, which has been verified by viscosity measurements, and can be explained by their different thermodynamic driving forces of DNA binding for the first time. This suggests that the dominant factor governing the stereoselectivity of DNA binding of metal complex may be the different thermodynamic driving forces between interactions of its different isomer with DNA. This new finding may be very helpful to understand the nature of steroselective DNA binding of small chiral molecules, and be useful to the development of DNA molecular probes and new DNA targeting therapeutic drugs.     

Aggregation-induced emission of ruthenium(II) polypyridyl complex [Ru(bpy)2(pzta)]2+

A new ruthenium(II) complex [Ru(bpy)₂(pzta)]²⁺ (1) [bpy = 2,2′-bipyridine; pzta = 6-(pyrzin2-yl)-1,3,5-triazine-2,4-diamine] has been synthesized and characterized. This complex exhibits a typical aggregation-induced emission (AIE) behavior that it is faint in solution but intense in the aggregate state.     

Anticancer activity studies of ruthenium(II) polypyridyl complexes against human gastric carcinoma SGC-7901 cell

A new ligand TCPI and its three ruthenium(II) polypyridyl complexes [Ru(N-N)₂(TCPI)](PF₆)₂ (N-N = bpy: 2,2′-bipyridine 1; phen: phenanthroline 2; dmp: 2,9-dimethyl-1,10-phenanthroline 3) were synthesized and characterized by elemental analysis, ESI-MS, ¹H NMR, IR, absorption and emission spectra. The cytotoxic activity in vitro of the ligand and complexes against cancer cells SGC-7901, PC-12, HepG-2, SiHa, Eca-109, HeLa and normal cell LO2 was evaluated by MTT method. Complex 3 shows the highest cytotoxic activity toward SGC-7901 cell among the complexes. Interestingly, the complexes show low or no cytotoxic activity against normal cell LO2. The apoptosis in SGC-7901 cell was investigated with AO/EB staining method. The ROS levels and the changes of mitochondrial membrane potential were studied under fluorescent microscope and flow cytometry. The cell invasion, cell cycle arrest and the expression of Bcl-2 family proteins were studied in detail. The results demonstrate that the complexes induce apoptosis in SGC-7901 cell through a ROS-mediated mitochondrial dysfunction pathway, which was accompanied by the regulation of Bcl-2 family proteins.     

(Terpyridine)(acetylacetonate)ruthenium(II) complex with a zwitterionic form of phosphoniophenylcyanamide ligand

The complex [Ru(tpy)(acac)(PPh₄cyd)][PF₆] (where tpy: 2,2^′:6^′,2″-terpyridine, acac: acetylacetone and PPh₄cyd: 4-triphenylphosphoniophenylcyanamide) has been synthesized. It contains the zwitterionic form of the phosphoniophenylcyanamide ligand. Characterizations were carried out using IR, ES-MS, UV–Vis, electrochemistry and ¹H, ¹³C and ³¹P NMR spectroscopy.     

Synthesis and catalytic activity of a novel ruthenium(III) complex containing a sugar-based ligand

The novel mixed-ligand complex [Ru^III(TDL)(bipy)(H₂O)]⁺ (1) (TDL = N-3,5-ditertiarybutylsalicylidine-d-glucosamine; bipy = 2,2′-bipyridine) has been synthesized and characterized. Complex 1 found to catalyze the epoxidation of styrene and oxidize 1-indanol to 1-indanone in dichloromethane using t-BuOOH as a terminal oxidant. Enanantiomeric induction was observed in case of styrene epoxidation. Formation of a high valent Ru(V)-oxo species is proposed to be the catalytic oxidative species.     

Synthesis, spectroscopic, and electrochemical properties of one novel hexanuclear Ru(II) polypyridyl complex

One novel hexapodal ligand 1,2,3,4,5,6-hexakis[(4,5-diazafluoren-9-yliminoxy)methyl]benzene (L) and corresponding Ru(II) polypyridyl complex [(bpy)₁₂(Ru^II)₆L](PF₆)₁₂ have been synthesized. Spectroscopic properties of the complex are investigated by UV–Vis absorption and fluorescence spectrometry. The complex shows metal-to-ligand charge transfer absorption at 438 nm and emission at 579 nm. Cyclic voltammetry of the complex comprises one Ru(II)-centered quasi-reversible oxidation at 1.31 V and three ligand-centered reductions.     

Synthesis, characterization and crystal structure of a novel thiocyanate–ruthenium(II) complex

The cis-[Ru(dppb)(Me-bipy)(NCS)₂], dppb = 1,4-bis (diphenylphosphino)butane, Me-bipy = 4,4′-dimethyl-2,2′-bipyridine, and NCS = thiocyanate, was synthesized and characterized by spectroscopic and electrochemical techniques and its structure was determined by crystal X-ray analysis. The crystal structure reveals that the coordination geometry around the Ru(II) center is distorted octahedron where two molecules of thiocyanate are bonded to the ruthenium through nitrogen atom in cis orientation. The half-wave formal potential value E_1/2 = 0.8 V (versus Ag/AgCl) observed is considerable higher than that for the cis-[RuCl₂(dppb)(Me-bipy)] complex, E_1/2 = 0.6 V (versus Ag/AgCl), well illustrating the strong π-acceptor effect the NCS ligand toward the backbonding interaction with the Ru(II) metal center. The MLCT absorption bands of the thiocyanate complex present a higher molar absorptivity (about 12%) compared with the cis-[RuCl₂(dppb)(Me-bipy)] complex, in the same experimental conditions. These properties make the complex potentially promising for the photosensitization process.     

Arene ruthenium(II) p-chloroacetophenone phenylthiosemicarbazone complex mediated transfer hydrogenation of ketones

A series of cationic half-sandwich arene ruthenium(II) complexes of general formula [Ru(η⁶-p-cymene)Cl(L)]Cl have been synthesized from the reaction of [Ru(η⁶-p-cymene)Cl₂]₂ with thiosemicarbazone derivatives (L). Characterization of the complexes were accomplished by analytical and spectral (FT-IR, UV–Vis, ¹H NMR) methods. Single crystal structure determination reveals the presence of a pseudooctahedral three-legged piano stool conformation. All the complexes exhibit a quasi-reversible one electron reduction in the range from ?0.75 to ?0.85 V. Further, the catalytic activity of the titled complex has been investigated in the transfer hydrogenation of ketones in the presence of isopropanol/NaOH.     

Electropolymerization and characterization of terpyridinyl iron (II) and ruthenium (II) complexes

Electroactive 2,2′: 6,2″-terpyridinyl ligands ( 3, 5, 6 ) and their iron(II) ( 7a–9a ) and ruthenium(II) complexes ( 7b–9b ) were synthesized. Bis[3-(aminophenyl)-2,2′ :6,2″-terpyridinyl]metal(II) complexes ( 7a, 7b ) and bis[2-(hydroxyphenyl)-2,2′ :6,2″-terpyridinyl]metal(II) complexes ( 8a, 8b ) were electropolymerized on to the surface of Pt or In-SnO₂ (ITO) electrodes in acetonitrile containing Bu₄NCIO₄ by scanning the potential between O and + 1.6V (for 7a and 7b ), and ?0.8 and +1.6V (for 8a and 8b ) versus saturated calomel electrode. The electrodes obtained by electropolymerization exhibited reversible electrochromism based on Fe(II)/Fe(III) or Ru(II)/Ru(III) redox couple. Photoresponses to visible light were found in the modified electrode obtained by electropolymerization of ruthenium complex 7b in an aqueous LiClO₄ solution containing methylviologen (cation MV²⁺) under an O₂ atmosphere. The mechanism for the photoresponded cathodic current was explained in terms of an excitation of bis(terpyridinyl)ruthenium(II) complex [Ru(terpy)²₂⁺] by visible light, an electron transfer from the excited state [Ru(terpy)^2+*₂] to MV²⁺, reduction of Ru(terpy)³⁺₂ at an electrode, and oxidation of MV^+* with O₂.     

Electrogenerated chemiluminescence of ruthenium (II) bipyridyl complex directly immobilized on glassy carbon electrodes

Ru(bpy)₃Cl₂ was used to modify the glass carbon electrodes (GCE) by oxidation and co-deposition on the electrode surface. The modified electrodes were characterized by atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). About 2.2 × 10⁻⁹ mol Ru(bpy)₃ ²⁺ was immobilized on the GCE surface (ϕ = 4 mm). The modified GC electrodes showed stable electrochemiluminescence with tripropylamine (TPrA) as the co-reactant with a linear range from 10 to 500 μM (R ² = 0.999). Among the 10 amino acids tested, the modified electrode system showed selective response to arginine and lysine, indicating that the molecular structure played an important role as co-reactant. This simple and sensitive electrode modifying method when combined with flow-injection or liquid chromatography systems has the potential for amino acid analyses.     

Synthesis of electrochemiluminescent graphene oxide functionalized with a ruthenium(II) complex and its use in the detection of tripropylamine

We report an approach for the preparation of graphene oxide covalently functionalized with a Ru(II) complex (Ru–GO). A ruthenium(II) complex designed with a long alkyl amino functional group on one of its diimine ligands, bis(2,2′-bipyridine) (N-(2-aminoethyl)-4-(4′-methyl-2,2′-bipyridine-4-yl)butanamide) ruthenium(II), was covalently grafted onto GO by the amide reaction between the amino group of the Ru(II) complex and the carboxyl group of the GO. The as-prepared Ru–GO showed excellent electrochemiluminescence (ECL) activity, good solubility and good stability. Using this hybrid material, a reagent-free ECL method was developed for the detection of tripropylamine to demonstrate the applicability of this new functionalized material. This approach is reliable and highly efficient, and might be extended to other chemiluminescent molecules containing an amino group such as luminol and its analogues to functionalize GO with ECL activity.     

Pentamethylcyclopentadienyl ruthenium(III) vs hexamethylbenzene ruthenium(II) in sulfur-centered reactivity of their thioether-thiolate and allied complexes

The reactivity features of [Cp*Ru(III){eta(3)-tpdt)}] (7) and [(HMB)Ru(II)(eta(3)-tpdt)] (10) {Cp* = eta(5)-C(5)Me(5); HMB = eta(6)-C(6)Me(6); tpdt = 3-thiapentane-1,5-dithiolate, S(CH(2)CH(2)S(-))(2)} are presented, together with selected aspects of their (eta(3)-apdt) analogues 8 and 11 {apdt = 3-azapentane-1,5-dithiolate, HN(CH(2)CH(2)S(-))(2)}. This account will highlight the differences observed in their reactions with metal fragments of compounds of Ru and groups 10 and 11 in various coordination environments and with alkylating agents, including alpha,omega-dibromoalkanes. The mechanistic pathway of the alkylation of 7 will be discussed in some detail.     

A ruthenium(II) complex with bis(3,5-dimethylpyrazol-1-yl)dithioacetate built layer-by-layer on silver and gold surfaces

A ruthenium(II) complex with bis(3,5-dimethylpyrazol-1-yl)dithioacetate was self-assembled layer-by-layer on silver and gold surfaces. The two-step process and the ability of the complex to scavenge nitric oxide were studied by cyclic voltammetry.     

Trinuclear Ru(II) polypyridyl complexes as human telomeric quadruplex DNA stabilizers

Two new trinuclear ruthenium(II) complexes [(bpy)₆Ru₃(tpbip)]⁶⁺ (1) and [(bpy)₆Ru₃(tptaip)]⁶⁺ (2) (bpy = 2,2′-bipyridine, tpbip = 1,3,5-tris(1,10-phenanthroline-[5,6-d]imidazol-2-yl)-benzene, tptaip = 2,4,6-tri(1,10-phenanthroline-[5,6-d]imidazol-2-yl)-1,3,5-triazine) have been synthesized and characterized. The interaction of human telomeric DNA with Ru(II) complexes was explored by means of CD spectroscopy, fluorescence titration, ITC and FRET melting. Results indicated that two complexes not only induce a remarkable conformational change of human telomeric DNA, but also have the ability to stabilize the G-quadruplex.     

Synthesis,structure and norbornene polymerization activity of a bulky β-diketiminato palladium(II) complex

A new bulky β-diketiminato palladium(II) complex was synthesized by direct reaction of (ⁱPr₂Ph)₂nacnacH ((ⁱPr₂Ph)₂nacnac = CH{C(Me)N(C₆H₃-2,6-ⁱPr₂)}₂) with Pd(OAc)₂ which yielded [(ⁱPr₂Ph)₂nacnac]Pd(OAc) as a mononuclear species with chelating nacnac and acetato ligands. Preliminary investigations into the polymerization of norbornene in the presence of BF₃OEt₂ were performed.     

Electrochemiluminescent determination of nicotine based on tri(2,2′-bipyridyl) ruthenium (II) complex through flow injection analysis

This paper describes the electrogenerated chemiluminescence (ECL) processes of Ru(bpy)₃²⁺/nicotine system at ITO working electrode. An ECL-based method for rapid and sensitive detection of nicotine in phosphate buffer solution at pH 8.0 is established. Strong ECL emission was observed at a positive potential of 1.4 V vs. Ag/AgCl. A possible ECL mechanism is proposed for the Ru(bpy)₃²⁺/nicotine system, the oxidation product of nicotine at the electrode surface reacts with the 3+ state of ruthenium bipyridyl (2+) complex and form ruthenium complex exited state ions and thus releases photons. Effect of pH (medium/electrolyte), working potential, buffer composition, buffer concentration, reactant and co-reactant (nicotine) concentration, flow rate and loop size on the ECL spectrum of the Ru(bpy)₃²⁺/nicotine were studied. At the optimized experimental conditions, lower detection limit for nicotine was observed as 1.2 nmol L⁻¹ (S/N = 3). Linear relationship between ECL current and concentration of nicotine was observed (up to 100 μmol L⁻¹) with R-value of 0.997. The relative standard deviation with 5 μmol L⁻¹ concentration of nicotine for 20 analyses was only 1.4%. A 94% recovery rate was observed in a real sample analysis without any complications/disturbance in measurement. Interferences of humid acid, camphor and SDS were not observed in their presence in the sample solution. The established procedure for nicotine quantification manifests fascinating results and can be suggested for further applications.