A novel phenotype-based approach for systematically screening antiproliferation metallodrugs

Ruthenium (Ru) derivatives have less toxicity and higher water-solubility than cisplatin, giving them great potential as antitumor metallodrugs. In this study, zebrafish were employed as a whole-organism model to screen new Ru compounds for anti-cell proliferation activity. After soaking fish embryos in cisplatin and five Ru derivatives, [Ru(terpy)(bpy)Cl]Cl, [Ru(terpy)(dppz)OH₂](ClO₄)₂, [Ru(terpy)(tMen)OH₂](ClO₄)₂, [Ru(terpy)(Me₄Phen)OH₂](ClO₄)₂, and Ru(bpy)₂Cl₂, only cisplatin and [Ru(terpy)(bpy)Cl]Cl-treated embryos displayed obvious phenotypic effects, such as fin-reduction. After further modification of [Ru(terpy)(bpy)Cl]Cl's main structure and the synthesis of two structurally related compounds, [Ru(terpy)(dcbpyH₂)Cl]Cl and [Ru(terpy)(dmbpy)Cl]Cl, only [Ru(terpy)(dmbpy)Cl]Cl exhibited fin-reduction phenotypes. TUNEL assays combined with immunostaining techniques revealed that treatment with cisplatin, [Ru(terpy)(bpy)Cl]Cl, and [Ru(terpy)(dmbpy)Cl]Cl led proliferating fin mesenchymal cells to undergo apoptosis and consequently caused fin-reduction phenotypes. Furthermore, [Ru(terpy)(bpy)Cl]Cl was able to activate the P53-dependent and independent pathways, and induced human hepatoma cells to undergo apoptosis. In summary, it was concluded that the zebrafish model was effective for the screening of phenotype-based antiproliferation metallodrugs.     

Five- and six-coordinate ruthenium(II) porphyrin tetiaryphosphine complexes,and their reactions with dioxygen via inner- and outer-sphere mechanisms

The 5-coordinate ruthenium(II) octaethylporphyrin complex Ru(OEP)(PPh₃) has been prepared by reduction of Ru(OEP)(PPh₃)Br using zinc amalgam. Both the Ru(OEP)(PPh₃)₃ complexes (n = 1,2) undergo reaction in toluene with O₂ to generate OPPh₃, RuO₂, and the parent porphyrin H₂(OEP); trace water and the μ-oxo dimer [Ru(OEP)(OH)]₂O are implicated in the oxidation reaction, which is considered to be initiated by coordination of O₂ to Ru(OEP)(PPh₃). In contrast, a catalytic O₂-oxidation of excess PPh₃ to the oxide probably goes via an initial outer-sphere reaction with Ru(OEP)(PPh₃)₂, that generates superoxides and Ru(III), both detectable by ESR; the superoxide is believed to be stabilized via portion addition as HO₂· that subsequently disproportionates to O₂ and H₂O₂. PPh₃ is oxidized by the peroxide, and during a reduction step that regenerates the Ru(II) catalyst from Ru(III).     

Interactions of bis-[μ-chloro-chlorotricarbonylruthenium(II)] and poly-[μ-dichloro-dicarbonylruthenium(II)] with nucleosides

The interactions of dimeric complex bis-[μ-chloro-chlorotricarbonylruthenium(II)], [Ru(CO)₃Cl₂]₂, and the polymeric complex poly-[μ-dichlorodicarbonylruthenium(II)], [Ru(CO)₂Cl₂]_x, with nucleosides (Nucl) in a 1:1 Ru:Nucl molar ratio for the dimer and 1:2 Ru:Nucl for the polymer, resulted in formation of the monomeric mononucleoside [Ru(CO)₃(Nucl)Cl₂] and bis-nucleoside [Ru(CO)₂(Nucl)₂Cl₂] complexes, respectively. The dimer [Ru(CO)₃Cl₂]₂ also gave the ionic bis-nucleoside complexes [Ru(CO)₃(Nucl)₂Cl]Cl in the molar ratio 1:2 Ru:Nucl. The mononucleoside complexes are stable in solution while the bis-nucleoside complexes tend to lose one nucleoside in strong complexing solvents, probably by solvent substitution. The complexes [Ru(CO)₃(Nucl)Cl₂] and [Ru(CO)₂(Nucl)₂Cl₂] with one N(1)H ionizable imino proton undergo ionization in alkaline solution and the complexes [Ru(CO)₃(NuclH⁺)Cl] and [Ru(CO)₂(NuclH⁺)₂], respectively, were isolated. In these deprotonated complexes the nucleosides behave as bidentate ligands, while in the protonated ones they act as monodentate. All Complexes were characterized by elemental analyses and various spectroscopic methods.     

Ruthenium(II) complexes of tetra-2-pyridyl-1,4-diazine

Tetra-2-pyridyl-1,4-diazine (TPD) reacts with one equivalent of Ru(tpy)Cl₃ to provide (tpy)Ru(TPD)²⁺ which when treated with a second equivalent of Ru(tpy)Cl₃ under more forcing conditions provides the TPD bridged binuclear complex, (tpy)Ru(TPD)Ru(tpy)⁴⁺. The structure of both complexes, particularly with regard to planarity of the pendant pyridine rings is analyzed by high field NMR. The electronic spectrum of the binuclear complex shows pronounced bathochromic shift, while the redox potentials for (tpy)Ru(TPD)²⁺. indicate a diminished HOMO-LUMO energy gap.     

Photoproducts from the photolysis of tris(bipyridine)ruthenium(II) chloride in dimethylformamide

Six photoproducts were observed in the photolysis of [Ru(bpy)₃]²⁺ in N,N-dimethylformamide (DMF) in the presence of chloride ions. The primary products were cis-[Ru(bpy)₂Cl₂] and cis-[Ru(bpy)₂-(DMF)Cl]⁺. The remaining ruthenium products, which were thermally unstable to varying degrees, were cis-[Ru(bpy)₂Cl₂]⁺, [Ru(bpy)₃]⁺, and a binuclear species we have tentatively identified as [Ru(bpy)₂Cl]₂ⁿ⁺ (n = 3 or 4).     

Ligand reactivity in polypyridine complexes; [Ru(bipy)3]n+ analogs incorporating pendant polyamine substituents

The complex cation [Ru(bipy)₂L]²⁺ (bipy = 2,2′- bipyridine, L = 4,4′-dichloro-2,2′-bipyridine) is activated towards nucleophilic substitution of chloride. Reactions of [Ru(bipy)₂L]²⁺ with potentially polydentate amines give rise to novel derivatives [Ru(bipy)₂L′]²⁺ which possess a central redox and photochemically active ‘Ru(bipy)3’ core, and a potentially multidentate periphery for coordination to other metal centres.     

Ruthenium(II/III) mediated transformation of 1,2-bis(2′-pyridylmethyleneimino)benzene (L) to 2-(2′-benzimidazolyl)pyridine (L′H) and its in situ formed complexes with Ru(II): X-ray structure of trans-[Ru(PPh3)2(L′H)2](ClO4)2

A series of ruthenium (II) complexes of formulae trans-[Ru(PPh₃)₂(L′H)₂](ClO₄)₂ (1), [Ru(bpy)(L′H)₂](ClO₄)₂ (2), [Ru(bpy)₂(L′H)](ClO₄)₂ (3), cis-[Ru(DMSO)₂(L′H)₂]Cl₂ (4), and [Ru(L′H)₃](PF₆)₂ (5) (where L′H = 2-(2′-benzimidazolyl)pyridine) have been synthesized by reaction of the appropriate ruthenium precursor with 1,2-bis(2′-pyridylmethyleneimino)benzene (L). The complexes were characterized by elemental analyses, spectroscopic and electrochemical data. All the complexes were found to be diamagnetic and hence metal is in +2 oxidation state. The molecular structure of trans-[Ru(PPh₃)₂(L′H)₂](ClO₄)₂ has been determined by the single crystal X-ray diffraction studies. The molecular structure shows that Ru(II) is at the center of inversion of an octahedron with N₄P₂ coordination sphere. The ligand acts as a bidentate N,N′donor. The electronic spectra of the complexes display intense MLCT bands in the visible region.Cyclic voltammetric studies show quasi-reversible oxidative response at 0.99-1.32 V (vs Ag/AgCl reference electrode) due to Ru(III)/Ru(II) couple.     

High‐Performance Hydrogen Evolution by Ru Single Atoms and Nitrided‐Ru Nanoparticles Implanted on N‐Doped Graphitic Sheet

The most efficient electrocatalyst for the hydrogen evolution reaction (HER) is a Pt‐based catalyst, but its high cost and nonperfect efficiency hinder wide‐ranging industrial/technological applications. Here, an electrocatalyst of both ruthenium (Ru) single atoms (SAs) and N‐doped‐graphitic(G_N)‐shell‐covered nitrided‐Ru nanoparticles (NPs) (having a Ru‐N_x shell) embedded on melamine‐derived G_N matrix { 1 : [Ru(SA)+Ru(NP)@RuN_x@G_N]/G_N}, which exhibits superior HER activity in both acidic and basic media, is presented. In 0.5 m H₂SO₄/1 m KOH solutions, 1 shows diminutive “negative overpotentials” (?η = |η| = 10/7 mV at 10 mA cm^?2, lowest ever) and high exchange current densities (4.70/1.96 mA cm^?2). The remarkable HER performance is attributed to the near‐zero free energies for hydrogen adsorption/desorption on Ru(SAs) and the increased conductivity of melamine‐derived G_N sheets by the presence of nitrided‐Ru(NPs). The nitridation process forming nitrided‐Ru(NPs), which are imperfectly covered by a G_N shell, allows superb long‐term operation durability. The catalyst splits water into molecular oxygen and hydrogen at 1.50/1.40 V (in 0.1 m HClO₄/1 m KOH), demonstrating its potential as a ready‐to‐use, highly effective energy device for industrial applications.     

Photoinduced oxidation of a tris(2,2'‐bipyridyl)ruthenium(II)–peroxodisulfate chemiluminescence system for the analysis of mebeverine HCl pharmaceutical formulations and biological fluids using a two‐chip device

A new method for the analysis of mebeverine hydrochloride (MEB) has been developed using a two‐chip device. The method is highly selective, sensitive, rapid and consumes minute amount of reagents. The developed method is free of interference from the degradation products of MEB and from common ingredients present in pharmaceutical formulations. The limit of detection was 0.043 µg/mL, and the limit of quantification was 0.138 µg/mL. The short analysis time per sample (20 s) allowed a large number of analyses to be performed within a very short time. Various samples were analyzed, including two different pharmaceutical formulations and a uniformity of content analysis for 20 tablets from a known batch and two biological samples at different concentrations. In addition, the method was compared with a validated high‐performance liquid chromatography (HPLC) method and the results clearly indicated the suitability of the developed method for routine analyses. A new mechanism for the tris(2,2'‐bipyridyl)ruthenium(II) (Ru(bpy)₃²⁺)‐peroxodisulfate (S₂O₈^2?) chemiluminescence (CL) system has also been proposed. The mechanism is based on photoinduced oxidation of Ru(bpy)₃²⁺ to Ru(bpy)₃³⁺ via the formation of Ru(bpy)₃²⁺* upon irradiation with visible light. S₂O₈^2? then oxidizes Ru(bpy)₃²⁺* to Ru(bpy)₃³⁺ and the analyte subsequently reduces the resultant Ru(bpy)₃³⁺ to Ru(bpy)₃²⁺*, which then produces the CL signal. Copyright © 2013 John Wiley & Sons, Ltd.     

A theoretical study of Ru(II) polypyridyl DNA intercalators: Structure and electronic absorption spectroscopy of [Ru(phen)2(dppz)] and [Ru(tap)2(dppz)] complexes intercalated in guanine-cytosine base pairs

The structural and spectroscopic properties of [Ru(phen)₂(dppz)]²⁺ and [Ru(tap)₂(dppz)]²⁺ (phen = 1,10-phenanthroline; tap = 1,4,5,8-tetraazaphenanthrene; dppz = dipyridophenazine ) have been investigated by means of density functional theory (DFT), time-dependent DFT (TD-DFT) within the polarized continuum model (IEF-PCM) and quantum mechanics/molecular mechanics (QM/MM) calculations. The model of the Δ and Λ enantiomers of Ru(II) intercalated in DNA in the minor and major grooves is limited to the metal complexes intercalated in two guanine-cytosine base pairs. The main experimental spectral features of these complexes reported in DNA or synthetic polynucleotides are better reproduced by the theoretical absorption spectra of the Δ enantiomers regardless of intercalation mode (major or minor groove). This is especially true for [Ru(phen)₂(dppz)]²⁺. The visible absorption of [Ru(tap)₂(dppz)]²⁺ is governed by the MLCT_tap transitions regardless of the environment (water, acetonitrile or bases pair), the visible absorption of [Ru(phen)₂(dppz)]²⁺ is characterized by transitions to metal-to-ligand-charge-transfer MLCT_dppz in water and acetonitrile and to MLCT_phen when intercalated in DNA. The response of the IL_dppz state to the environment is very sensitive. In vacuum, water and acetonitrile these transitions are characterized by significant oscillator strengths and their positions depend significantly on the medium with blue shifts of about 80 nm when going from vacuum to solvent. When the complex is intercalated in the guanine-cytosine base pairs the ¹IL_dppz transition contributes mainly to the band at 370 nm observed in the spectrum of [Ru(phen)₂(dppz)]²⁺ and to the band at 362 nm observed in the spectrum of [Ru(tap)₂(dppz)]²⁺.     

Self‐quenching in the electrochemiluminescence of Ru(bpy)32+ using ascorbic acid as co‐reactant

In this study, electrochemiluminescence (ECL) of Ru(bpy)₃²⁺ (bpy = 2,2′‐bipyridyl) using ascorbic acid (H₂A) as co‐reactant was investigated in an aqueous solution. When H₂A was co‐existent in a Ru(bpy)₃²⁺‐containing buffer solution, ECL peaks were observed at a potential corresponding to the oxidation of Ru(bpy)₃²⁺, and the intensity was proportional to H₂A concentration at lower concentration levels. The formation of the excited state *Ru(bpy)₃²⁺ was confirmed to result from the co‐reaction between Ru(bpy)₃³⁺and the intermediate of ascorbate anion radical (A⁻•), which showed the maximum ECL at pH = 8.8. It is our first finding that the ECL intensity would be quenched significantly when the concentration of H₂A was relatively higher, or upon ultrasonic irradiation. In most instances, quenching is observed with four‐fold excess of H₂A over Ru(bpy)₃²⁺. The diffusional self‐quenching scheme as well as the possible reaction pathways involved in the Ru(bpy)₃²⁺–H₂A ECL system are discussed in this study. Copyright © 2008 John Wiley & Sons, Ltd.     

Halogenation of Ru(COD)(8-quinolinolate)2 and Ru(COD)(5-formyl-8-quinolinolate)2

An improved synthesis of Ru(COD)(8-quinolinolate)₂ (COD = 1,5-cyclooctadiene) and the synthesis of Ru(COD)(5-formyl-8-quinolinolate)₂ is reported. Electrophilic halogenation of these complexes with N-halosuccinimides proceeded smoothly resulting in 5,7-dihalogenation of the quinolinolate ligands in Ru(COD)(8-quinolinolate)₂ and in 7-halogenation of Ru(COD)(5-formyl-8-quinolinolate)₂. All compounds exhibit strong absorbance in the visible up to 500 nm, resulting in an intensively yellow colour. With all complexes no luminescence was observed.     

Inorganic models of photosystem II of plant photosynthesis. Catalytic and photocatalytic oxidation of water with participation of manganese compounds

Manganese dioxide is shown to be the catalyst of oxygen evolution at the oxidation of water by the one-electron oxidant Ru(bpy)₃³⁺ in neutral and slightly acidic media. Catalytic activity of MnO₂ depends on the method of preparation, the most active samples being those consisting of the smallest particles, i.e., having the largest surface-to-volume ratio. Ru(bpy)₃³⁺ was found to be formed at the irradiation of Ru(bpy)₃²⁺ solutions by visible light (λ = 436 nm) in the presence of such acceptors as Ce(IV), Hg(II), and Mn(IV) pyrophosphate. Continuous O₂ evolution from water is observed when the system Mn(IV) pyrophosphate plus Ru(bpy)₃²⁺ plus MnO₂ is irradiated by visible light. The system is discussed in connection with the active center of photosystem II of plant photosynthesis.     

The relationship between the structures of periphery ligands and the DNA binding mode of [Ru(II)(1,10-phenanthroline)(L1L2)dipyrido[3,2-a:2',3'-c]phenazine](n+) (L1=Cl or pyridine and L2=pyridine, n=1,2)

The binding modes of the [Ru(II)(1,10-phenanthroline)(L₁L₂) dipyrido[3,2-a:2′,3′-c]phenazine]²⁺ {[Ru(phen)(py) Cl dppz]⁺ (L₁ = Cl, L₂ = pyridine) and ([Ru(phen)(py)₂dppz]²⁺ (L₁ = L₂ = pyridine)} to native DNA is compared to that of the [Ru(II)(1,10-phenanthroline)₂dipyrido[3,2-a:2′,3′-c]phenazine]²⁺ complex ([Ru(phen)₂dppz]²⁺) by various spectroscopic and hydrodynamic methods including electric absorption, linear dichroism (LD), fluorescence spectroscopy, and viscometric titration. All measured properties, including red-shift and hypochromism in the dppz absorption band, nearly perpendicular molecular plane of the dppz ligand with respect to the local DNA helix axis, prohibition of the ethidium binding, the light switch effect and binding stoichiometry, increase in the viscosity upon binding to DNA, increase in the melting temperature are in agreement with classical intercalation of dppz ligand of the [Ru(phen)₂dppz]²⁺ complex, in which both phenanthroline ligand anchored to the DNA phosphate groups by electrostatic interaction. [Ru(phen)(py)₂ dppz]²⁺ and [Ru(phen)(py) Cl dppz]⁺ complexes had one of the phenanthroline ligand replaced by either two pyridine ligands or one pyridine plus a chlorine ion. They exhibited similar protection from water molecules, interaction with DNA bases, and occupying site that is common with ethidium. The dppz ligand of these two Ru(II) complex were greatly tilted relative to the DNA helix axis, suggesting that the dppz ligand resides inside the DNA and is not perpendicular relative to the DNA helix axis. These observation suggest that anchoring the [Ru(phen)₂dppz]²⁺complex by both phenanthroline is essential for the dppz ligand to be classically intercalated between DNA base-pairs.     

Reactions of pentaammineruthenium complexes with 1,2- and 1,4-dicyanobenzene and cyanobenzamides: evidences of neighboring group participation

The spectral (UV-Vis and IR) and electrochemical behavior of the nitrile bonded complexes [Ru(NH₃)₅L]²⁺ (L = 1,4-dicyanobenzene (1,4-dcb), 1,2-dicyanobenzene (1,2-dcb)), [Ru(NH₃)₅(NHC(OH)-bz-4-CN)]³⁺, [Ru(NH₃)₅(NHC(O)-bz-2-CN)]²⁺ and [Ru(NH₃)₅(NH(C)NHC(O)bz)]³⁺ (NH(C)NHC(O)-bz = 3-imino-1-oxo-isoindoline) are described. Oxidation of [Ru(NH₃)₅L]²⁺, at 0 ? pH ? 6, is followed by hydrolysis of the coordinated nitrile to give amide complexes in which the amide is through the nitrogen, with pH-dependent rate constants. The estimated values of the rate constant of hydrolysis (k_obs) at 25 °C are 2.9 × 10⁻³ s⁻¹ for [Ru(NH₃)₅(1,4-dcb)]³⁺ and 5.6 × 10⁻³ s⁻¹ for [Ru(NH₃)₅(1,2-dcb)]³⁺ at pH 4.65. Reduction of [Ru(NH₃)₅(NHC(O)-bz-4-CN)]²⁺ and [Ru(NH₃)₅(NHC(O)-bz-2-CN)]²⁺ is followed by two reactions, one is an aquation forming [Ru(NH₃)₅(OH₂)]²⁺ and free ligand, and the other an intramolecular linkage isomerization forming [Ru(NH₃)₅(NC-bz-4-NH₂C(O))]²⁺ and [Ru(NH₃)₅(NC-bz-2-NH₂C(O))]²⁺. The oxidized1,2-cyanobenzamide complex [Ru(NH₃)₅(NHC(OH)-bz-2-CN)]³⁺ undergoes an amide to nitrile intramolecular linkage isomerization, followed by a cyclization reaction resulting in [Ru(NH₃)₅(NH-(C)(HN-C(O)-2-bz))]³⁺ ((NH-(C)(HN-C(O)-2-bz)) = 3-imino-1-oxo-isoindoline bonded through the exocyclic nitrogen) (pK_a = 4.3). The rates of these reactions, which occur with neighboring group participation, increase with acidity. The reduced form, [Ru(NH₃)₅(NH-(C)(HN-C(O)-2-bz))]²⁺, is relatively substitution inert.     

Photo-oxidation of water sensitised by ruthenium(II) tris(bipyrazine)

The excited state of ruthenium(II) tris(bipyrazine) (Ru(bipyz)₃^2+*) is quenched by the sacrificial electron acceptors, S₂O₈²⁻ and Co(NH₃)₅Cl²⁺. Under acidic solutions (pH 0), Ru(bipyz)₃^2+* is quenched by protons and therefore quite short-lived (τ = 50 ns). At pH 0, steady-state irradiation of the Ru(bipyz)₃²⁺ in the presence or absence of either S₂O₈²⁻ or Co(NH₃)₅Cl²⁺ did not produce any permanent products. In addition, no O₂ evolution was observed when an O₂ catalyst was added. At pH 6, Ru(bipyz)₃²⁺¹ is much longer-lived (τ = 1.04 μs) and steady-state irradiation of a Ru(bipyz)₃²⁺ solution containing S₂O₈²⁻, rather than Co(NH₃)₅Cl²⁺, did produce changes in absorbance, emission and pH, due to the oxidative degradation of the sensitiser. Microsecond flash photolysis work indicated that Ru(bipyz)₃^2+* is oxidatively quenched by the S₂O₈⁻ ions leading to the generation of Ru(bipyz)₃³⁺, a very strong and unstable oxidant. Steady-state irradiations carried out on the Ru(bipyz)₃²⁺/S₂O₈⁻ photochemical system at pH 6, in the presence of an O₂ catalyst, resulted in O₂ generation (φ(O₂) = 0.0025), however photodegradation of the Ru(bipyz)₃²⁺ sensitiser still took place, albeit at a reduced rate.     

Potential‐resolved electrochemiluminescence of Ru(bpy)32+/C2O42− system on gold electrode

The electrogenerated chemiluminescence of Ru(bpy)₃²⁺/C₂O₄^2? system on a pre‐polarized Au electrode was studied using a potential‐resolved electrochemiluminescence (PRECL) method. Two anodic ECL peaks were observed at 1.22 V (vs. SCE) (EP1), 1.41 V (vs. SCE) (EP2), respectively. The effects of the concentration of oxalate and Ru(bpy)₃²⁺, adsorbed sulphur, CO₂, O₂, pH of the solution and pretreatment of the Au electrode on the two PRECL peaks were examined. The surface state of the pre‐oxidized gold electrode was also studied using the X‐ray photoelectron spectroscopy (XPS) technique. Moreover, comparative studies on i–E and I–E curves were carried out and a possible mechanism involving both the catalytic and the direct electro‐oxidation pathways was proposed for the ECL of Ru(bpy)₃²⁺/C₂O₄^2? system. EP1 is attributed to the Ru(bpy)₃^2/3+ reaction catalysed by C₂O₄^2? to generate Ru(bpy)₃^2+*. EP2 is likely because C₂O₄^2? was oxidized at the electrode to form CO₂^?·, followed by reaction with Ru(bpy)₃³⁺ to generate Ru(bpy)₃^2+*. Copyright © 2002 John Wiley & Sons, Ltd.     

Reactions of ketones with coordinated nitriles on β-diketonato ruthenium complexes leading to formation of compounds with new carbon-carbon bonds

The reactions of [Ru(acac)₂(CH₃CN)₂] with four ketones (acetone, ethyl methyl ketone, acetylacetone and monochloroacetone), and the reactions of [Ru(acac)₂(C₆H₅CN)₂] with two ketones (acetone and ethyl methyl ketone) yielded six novel compounds of β-ketiminato ruthenium complexes: [Ru(acac)₂(mhmk)], [Ru(acac)₂(ehmk)], [Ru(acac)₂(mAmk)], [Ru(acac)₂(mClmk)], Ru(acac)₂(mhbk)], and [Ru(acac)₂(ehbk)] (mhmk = 4-iminopentane-2-one mono anion, ehmk = 5-iminohexane-3-one mono anion, mAmk = 3-(1-iminoethyl)-2,4-pentanedione mono anion, mClmk = 3-chloro-4-imino-pentane-2-one mono anion, mhbk = 1-phenyl-1-iminobutane-3-one mono anion, ehbk = 1-phenyl-1-iminopentane-3-one mono anion). All the new complexes have been characterized by elemental analyses, ¹H NMR, MS and electronic spectral data. Crystal and molecular structures for the six β-ketimine complexes have been solved by single crystal X-ray diffraction studies. A mechanism involving the attack of ketones on the coordinated nitrile has been proposed. The electrochemical redox behavior of the β-ketimine complexes has been elucidated.     

Ruthenium(II) thiacrown complexes: Synthetic, spectroscopic, electrochemical, DFT, and single crystal X-ray structural studies of [Ru([15]aneS5)Cl](PF6)

We wish to report the synthesis of the Ru(II) crown thioether complex, (1,4,7,10,13-pentathiacyclopentadecane)chlororuthenium(II) hexafluorophosphate, [Ru([15]aneS₅)Cl](PF₆), and a study of its properties utilizing single crystal X-ray diffraction, electronic spectroscopy, NMR spectroscopy, density functional theory calculations and cyclic voltammetry. The crystal structure shows a single [15]aneS₅ macrocycle and a chloro ligand coordinated in a distorted octahedral fashion around the ruthenium(II) center. A significant shortening (0.15 Å) of the trans Ru-S bond length occurs in this complex compared to the related PPh₃ complex (2.4458(10) to 2.283(1) Å) due to the differences in the trans influence of the two ligands. ¹³C NMR spectroscopy demonstrates that the structure of [Ru([15]aneS₅)Cl]⁺ is retained in solution. As expected for a Ru(II) complex, the electronic absorption spectrum shows two d-d transitions at 402 and 331 nm. These are red-shifted compared to hexakis(thioether)ruthenium(II) complexes and consistent with the weaker ligand field effect of the chloro ligand. The electrochemical behavior of the complex in acetonitrile shows a single one-electron reversible oxidation-reduction at +0.722 V versus Fc/Fc⁺ which is assigned as the Ru(II)/Ru(III) couple. DFT calculations for [Ru([15]aneS₅)Cl]⁺ show a HOMO with orbital contributions from a t_2g type orbital of the Ru ion, a π component from a p orbital of the axial S atom of [15]aneS₅, and a p orbital of the chloro ligand while the LUMO consists of orbital contributions of d_x²-y² orbital of the Ru center and p orbitals of the four equatorial S donors.     

Binding to DNA purine bases and amino acid residues of a ruthenium(II) antitumor complex: A density functional study

The hydrolyzed α-[Ru(azpy)₂Cl₂] (azpy is 2-(phenylazo)pyridine; α indicates that the isomer in which the coordinating pairs Cl, N(py), and N(azo) are cis, trans, and cis, respectively) binding to guanine (G), adenine (A), methionine (Met), and histidine (His) residues were investigated by using density functional theory. Reactant complexes (RC), product complexes (PC), and transition states (TS) involved were fully characterized. The calculated energy profiles showed that the activation free energies for the substitutions of hydrolyzed α-[Ru(azpy)₂Cl₂] with Met was apparently lower than those of guanine and adenine. This indicate that the hydrolyzed α-[Ru(azpy)₂Cl₂] compounds may preferentially bind to the sulfur-containing amino acids residues in vivo. Moreover, the natural orbital population analysis (NPA) showed that the Ru atom gained the greatest negative charges in the reactions of hydrolyzed α-[Ru(azpy)₂Cl₂] with Met, which may contribute to their remarkably low activation free energies partially.