Ditopic tris(2-mercaptoimidazol-1-yl)borate ligands and their coordination behavior toward [Ru(p-cymene)]

The ditopic tris(2-mercaptoimidazol-1-yl)borate ligand K₂[(mt^Et)₃B-B(mt^Et)₃] cannot be prepared from B₂(NMe₂)₄/4 Hmt^Et/2 Kmt^Et, because the stable intramolecular diadduct (mt^Et)B(μ-mt^Et)₂B(mt^Et) is generated instead (Hmt^Et = 2-mercapto-1-ethylimidazole). Introduction of a meta- or para-phenylene spacer between the two boron atoms precludes the 2-mercaptoimidazol-1-yl groups from adopting a bridging position so that the potassium salts K₂[(mt^Et)₃B-(m-C₆H₄)-B(mt^Et)₃] and K₂[(mt^Et)₃B-(p-C₆H₄)-B(mt^Et)₃] become readily accessible. These ligands react with [(p-cym)RuCl₂]₂ to give the dinuclear Ru^II complexes [(p-cym)Ru(mt^Et)₃B-(m-C₆H₄)-B(mt^Et)₃Ru(p-cym)]Cl₂ and [(p-cym)Ru(mt^Et)₃B-(p-C₆H₄)-B(mt^Et)₃Ru(p-cym)]Cl₂ (p-cym = p-cymene). After the exchange of the Cl⁻ counterions for [PF₆]⁻, both complexes have been crystallized and structurally characterized by X-ray diffraction.     

Highly and Broad-Spectrum In Vitro Antitumor Active cis-Dichloridoplatinum(II) Complexes with 7-Azaindoles

The cis-[PtCl₂(naza)₂] complexes (1–3) containing monosubstituted 7-azaindole halogeno-derivatives (naza), showed significantly higher activity than cisplatin towards ovarian carcinoma A2780, its cisplatin-resistant variant A2780R, osteosarcoma HOS, breast carcinoma MCF7 and cervix carcinoma HeLa cell lines, with the IC₅₀ values of 3.8, 3.5, 4.5, 2.7, and 9.2 μM, respectively, obtained for the most active complex 3. As for 4 and 5 having disubstituted 7-azaindoles in their molecule, the significant cytotoxicity was detected only for 4 against A2780 (IC₅₀ = 4.8 μM), A2780R (IC₅₀ = 3.8 μM) and HOS (IC₅₀ = 4.3 μM), while 5 was evaluated as having only moderate antiproliferative effect against the mentioned cancer cell lines with IC₅₀ = 33.4, 24.7 and 46.7 μM, respectively. All the studied complexes 1–5 effectively avoided the acquired resistance of ovarian carcinoma cell line. On the other hand, the complexes did not reveal any inhibition activity on the purified 20S proteasome from the A2780 cells. The representative complexes 3 and 5 showed low ability to be hydrolysed, but their stability was markedly lowered in the presence of physiological sulphur-containing biomolecule glutathione (GSH), as proved by the ¹H NMR spectroscopy and mass spectrometry studies. A rate of interaction of the studied complexes with GSH was affected by an addition of another mechanistically relevant biomolecule guanosine monophosphate. The differences in interactions of 3 and 5 with GSH correlate well with their different cytotoxicity profiles.     

Arene-Ru(II)-chloroquine complexes interact with DNA, induce apoptosis on human lymphoid cell lines and display low toxicity to normal mammalian cells

The complexes [Ru(η⁶-p-cymene)(CQ)Cl₂] (1), [Ru(η⁶-benzene)(CQ)Cl₂] (2), [Ru(η⁶-p-cymene)(CQ)(H₂O)₂][BF₄]₂ (3), [Ru(η⁶-p-cymene)(en)(CQ)][PF₆]₂ (4), [Ru(η⁶-p-cymene)(η⁶-CQDP)][BF₄]₂ (5) (CQ = chloroquine base; CQDP = chloroquine diphosphate; en = ethylenediamine) interact with DNA to a comparable extent to that of CQ and in analogous intercalative manner with no evidence for any direct contribution of the metal, as shown by spectrophotometric and fluorimetric titrations, thermal denaturation measurements, circular dichroism spectroscopy and electrophoresis mobility shift assays. Complexes 1-5 induced cytotoxicity in Jurkat and SUP-T1 cancer cells primarily via apoptosis. Despite the similarities in the DNA binding behavior of complexes 1-5 with those of CQ the antitumor properties of the metal drugs do not correlate with those of CQ, indicating that DNA is not the principal target in the mechanism of cytotoxicity of these compounds. Importantly, the Ru-CQ complexes are generally less toxic toward normal mouse splenocytes and human foreskin fibroblast cells than the standard antimalarial drug CQDP and therefore this type of compound shows promise for drug development.     

Novel [Ru(polypyridine)(CO)2Cl2] and [Ru(polypyridine)2(CO)Cl]-type complexes: Characterizing the effects of introducing azopyridyl ligands by electrochemical, spectroscopic and crystallographic measurements

The reaction of ruthenium carbonyl polymer ([Ru(CO)₂Cl₂]_n) with azopyridyl compounds (2,2′-azobispyridine; apy or 2-phenylazopyridine; pap) generated new complexes, [Ru(azo)(CO)₂Cl₂] (azo = apy, pap). [Ru(apy)(CO)₂Cl₂] underwent photodecarbonylation to give a chloro-bridged dimer complex, whereas the corresponding pap complex ([Ru(pap)(CO)₂Cl₂]) was not converted to a dimer. The reactions of the chloro-bridged dimer containing the bpy ligand (bpy = 2,2′-bipyridine) with either apy or pap resulted in the formation of mixed polypyridyl complexes, [Ru(azo)(bpy)(CO)Cl]⁺. The novel complexes containing azo ligands were characterized by various spectroscopic measurements including the determination of X-ray crystallographic structures. Both [Ru(azo)(CO)₂Cl₂] complexes have two CO groups in a cis position to each other and two chlorides in a trans position. The azo groups are situated cis to the CO ligand in [Ru(azo)(bpy)(CO)Cl]⁺. All complexes have azo N-N bond lengths of 1.26-1.29 Å. The complexes exhibited azo-based two-electron reduction processes in electrochemical measurements. The effects of introducing azopyridyl ligands to the ruthenium carbonyl complexes were examined by ligand-based redox potentials, stretching frequencies and force constants of CO groups and bond parameters around Ru-CO moieties.     

Hydrolysis study of the bifunctional antitumour compound RAPTA-C, [Ru(eta6-p-cymene)Cl2(pta)

The hydrolysis of [Ru(η⁶-p-cymene)Cl₂(PTA)] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decanephosphine; RAPTA-C) was studied using UV-visible (UV-vis) spectrophotometry and NMR spectroscopy. In analogy to in silico studies, [Ru(η⁶-p-cymene)Cl(H₂O)(PTA)]⁺ was found to be the most abundant hydrolysis product, although the dihydrolysed species [Ru(η⁶-p-cymene)(OH)(H₂O)(PTA)]⁺ and the dichloro compound are present. Rate constants for the different aquation and anation steps and the equilibrium constants were determined. Hydrolysis is suppressed at high chloride concentrations. These results have important implications on the mode of action of the RAPTA drug candidates.     

Reactivity study of arene(azido)ruthenium N∩O-base complexes with activated alkynes

Substitution reaction of chloro η⁶-arene ruthenium N∩O-base complexes [(η⁶-arene)Ru(N∩O)Cl] [N∩O = pyrazine-2-carboxylic acid (pca-H), 8-hydroxyquinoline (hq-H); arene = p-ⁱPrC₆H₄Me, N∩O = hq (1); arene = C₆Me₆, N∩O = hq (2)] with NaN₃ yield the neutral arene ruthenium azido complexes of the general formula [(η⁶-arene)Ru(N∩O)N₃] [N∩O = pca, arene = p-ⁱPrC₆H₄Me (3), arene = C₆Me₆ (4); N∩O = hq, arene = p-ⁱPrC₆H₄Me (5), arene = C₆Me₆ (6)]. These complexes undergo [3 + 2] dipolar cycloaddition reaction with activated alkynes dimethyl and diethyl acetylenedicarboxylates to yield the arene triazole complexes [(η⁶-arene)Ru(N∩O){N₃C₂(CO₂R)₂}] [N∩O = pca, R = Me, arene = p-ⁱPrC₆H₄Me (7), C₆Me₆ (8); R = Et, arene = p-ⁱPrC₆H₄Me (9), C₆Me₆ (10); N∩O = hq, R = Me, arene = p-ⁱPrC₆H₄Me (11) C₆Me₆ (12); R = Et, arene = p-ⁱPrC₆H₄Me (13), C₆Me₆ (14)]. On the bases of proton NMR study, in the above triazole complexes N(2) isomers are assigned with dimethylacetylenedicarboxylate whereas N(1) isomers with diethylacetylenedicarboxylate. All complexes have been characterized by IR and NMR spectroscopy as well as by elemental analysis. The molecular structures of the azido complexes [(η⁶-p-ⁱPrC₆H₄Me)Ru(pca)N₃] (3), [(η⁶-p-ⁱPrC₆H₄Me)Ru(hq)N₃] (5) and [(η⁶-C₆Me₆)Ru(hq)N₃] (6) have been established by single crystal X-ray diffraction studies.     

Diiron and diruthenium aminocarbyne complexes containing pseudohalides: stereochemistry and reactivity

Acetonitrile is easily displaced from [Fe₂{μ-CN(Me)(R)}(μ-CO)(CO)(MeCN)(Cp)₂][SO₃CF₃] (R = 2,6-Me₂C₆H₃ (Xyl) (1a); Me (1b)) upon stirring in THF at room temperature in the presence of [NBu₄][SCN]. The resulting complexes trans-[Fe₂{μ-CN(Me)(R)}(μ-CO)(CO)(NCS)(Cp)₂] (R = Xyl (trans-2a); Me (trans-2b)) are completely isomerised to cis-[Fe₂{μ-CN(Me)(R)}(μ-CO)(CO)(NCS)(Cp)₂] (R = Xyl (cis-2a); Me (cis-2b)) when heated at reflux temperature. Similarly, the complexes cis-[M₂{μ-CN(Me)(R)}(μ-CO)(CO)(NCO)(Cp)₂] (M = Fe, R = Me (4a); M = Ru, R = Xyl (4b); M = Ru, R = Me (4c)) and cis-[M₂{μ-CN(Me)(R)}(μ-CO)(CO)(N₃)(Cp)₂] (M = Fe, R = Xyl (5a); M = Fe, R = Me (5b); M = Ru, R = Xyl (5c)) can be obtained by heating at reflux temperature a THF solution of [M₂{μ-CN(Me)(R)}(μ-CO)(CO)(MeCN)(Cp)₂][SO₃CF₃] (M = Fe, R = Xyl (1a); M = Fe, Me (1b); M = Ru, R = Xyl (1c); M = Ru, R = Me (1d)) in the presence of NaNCO and NaN₃, respectively. The reactions of 5 with MeO₂CCCCO₂Me, HCCCO₂Me and (NC)(H)CC(H)(CN) afford the triazolato complexes [M₂{μ-CN(Me)(R)}(μ-CO)(CO){N₃C₂(CO₂Me)₂}(Cp)₂] (M = Fe, R = Xyl (6a); M = Fe, R = Me (6b); M = Ru, R = Xyl (6c)), [M₂{μ-CN(Me)(R)}(μ- CO)(CO){N₃C₂(H)(CO₂Me)}(Cp)₂] (M = Fe, R = Me (7a); M = Ru, R = Xyl (7b)) and [Fe₂{μ-CN(Me)(Xyl)}(μ-CO)(CO){N₃C₂(H)(CN)}(Cp)₂] (8), respectively. The asymmetrically substituted triazolato complexes 7-8 are obtained as mixtures of N(1) and N(2) bonded isomers, whereas 6 exists only in the N(2) form. Methylation of 6-8 results in the formation of the triazole complexes [Fe₂{μ-CN(Me)(Xyl)}(μ-CO)(CO){N₃(Me)C₂(CO₂Me)₂}(Cp)₂][CF₃SO₃] (9), [M₂{μ-CN(Me)(R)}(μ-CO)(CO){N₃(Me)C₂(H)(CO₂Me)}(Cp)₂][CF₃SO₃] (M = Fe, R = Me (10a); M = Ru, R = Xyl (10b)) and [Fe₂{μ-CN(Me)(Xyl)}(μ-CO)(CO){N₃(Me)C₂(H)(CN)}(Cp)₂][CF₃SO₃], 11. The crystal structures of trans-2b, 4b · CH₂Cl₂, 5a, 6b · 0.5CH₂Cl₂ and 8 · CH₂Cl₂ have been determined.     

Unexpected differences in reactivity between tin and lead organyl chlorides - crystal structures of their organylphosphonium salts

Pentacoordinated tin is known since the late 1950s but little is known about the ability of lead to form similar structures. Originally we investigated the reaction between a number of tetraorganylphosphonium chlorides [PR₄]⁺Cl⁻ (R=Me, Buⁿ, and Ph) and several diorganyltin dichlorides SnR^′₂Cl₂ (R^′=Me, Et, Prⁿ, Buⁿ, Ph, o-, m-, p-Tol) between 100 and 240 °C. Novel pentacoordinated tin complexes, tetraorganylphosphonium diorganyltrichlorostannates [PR₄][SnR^′₂Cl₃] (1-19), were formed in good to excellent yields. In a second step, this synthetic approach was extended to include the reaction of diphenyllead dichloride Ph₂PbCl₂ with [PR₄]⁺Cl⁻ (R=Buⁿ, Ph). Surprisingly, a two chloride transfer was observed to form the hexacoordinated lead species [PBuⁿ₄]₂[PbPh₂Cl₄] (20). Under similar conditions, the pentacoordinated [PPh₄][PbPh₃Cl₂] (21) was obtained by a phenyl transfer. Complexes 20 and 21 were characterised by NMR (¹H, ¹³C, ³¹P, and ²⁰⁷Pb), IR, MS, and X-ray crystallography. The anion of 20 assumes a lightly distorted octahedral geometry with the phenyl substituents in trans-positions. In the anion of 21 the phenyl substituents occupy the equatorial positions of a lightly distorted trigonal bipyramid. A thorough spectroscopical investigation of the tin complexes 1-19, including X-ray structural studies, which were possible for complexes with R^′=aryl, revealed that these complexes are monomeric with a distorted trigonal bipyramidal [SnR^′₂Cl₃]⁻ anion. Both aryl groups occupy equatorial positions.     

Efficient synthesis of ruthenium complexes of the type (R-bpy)2RuCl2 and [(R-bpy)2Ru(L-L)]Cl2 by microwave-activated reactions (R: H, Me, tert-But) (L-L: substituted bibenzimidazoles, bipyrimidine, and phenanthroline)

Complexes of the type (R-bpy)₂RuCl₂ (R: H, Me, tert-but) were synthesised by microwave-activated reactions of [Ru(cod)Cl₂]_n with substituted 2,2′-bipyridines in dimethylformamide as the solvent. The complexes were isolated in high yields and high purity from the reaction mixture. Microwave-assisted or thermal reaction of the (R-bpy)₂RuCl₂ solutions with substituted bibenzimidazoles, 1,10 phenanthroline or bipyrimidine in dmf/water mixtures resulted in the formation of mixed ligand complexes of the type [(R-bpy)₂Ru(L-L)]Cl₂. The complexes were characterised by NMR spectroscopy and MS. Furthermore, their photochemical and electrochemical properties were investigated and the solid state structure of (4-tert-butyl-bpy)₂RuCl₂ (3), [(4-tert-butyl-bpy)₂Ru(tetramethylbibenzimidazole)](PF₆)₂ (4), and [(4-tert-butyl-bpy)₂Ru(bipyrimidine] (PF₆)₂ (5) was determined by X-ray diffraction analysis of single crystals.     

Interactions of arene-Ru(II)-chloroquine complexes of known antimalarial and antitumor activity with human serum albumin (HSA) and transferrin

The interactions of π-arene-Ru(II)-chloroquine complexes with human serum albumin (HSA), apotransferrin and holotransferrin have been studied by circular dichroism (CD) and UV-Visible spectroscopies, together with isothermal titration calorimetry (ITC). The data for [Ru(η⁶-p-cymene)(CQ)(H₂O)Cl]PF₆ (1), [Ru(η⁶-benzene)(CQ)(H₂O)Cl]PF₆ (2), [Ru(η⁶-p-cymene)(CQ)(H₂O)₂][PF₆]₂ (3), [Ru(η⁶-p-cymene)(CQ)(en)][PF₆]₂ (4), [Ru(η⁶-p-cymene)(η⁶-CQDP)][BF₄]₂ (5) (CQ: chloroquine; DP: diphosphate; en: ethylenediamine), in comparison with CQDP and [Ru(η⁶-p-cymene)(en)Cl][PF₆] (6) as controls demonstrate that 1, 2, 3, and 5, which contain exchangeable ligands, bind to HSA and to apotransferrin in a covalent manner. The interaction did not affect the α-helical content in apotransferrin but resulted in a loss of this type of structure in HSA. The binding was reversed in both cases by a decrease in pH and in the case of the Ru-HSA adducts, also by addition of chelating agents. A weaker interaction between complexes 4 and 6 and HSA was measured by ITC but was not detectable spectroscopically. No interactions were observed for complexes 4 and 6 with apotransferrin or for CQDP with either protein. The combined results suggest that the arene-Ru(II)-chloroquine complexes, known to be active against resistant malaria and several lines of cancer cells, also display a good transport behavior that makes them good candidates for drug development.     

In vitro and in vivo biological activity screening of Ru(III) complexes involving 6-benzylaminopurine derivatives with higher pro-apoptotic activity than NAMI-A

A series of novel octahedral ruthenium(III) complexes involving 6-benzylaminopurine (L) derivatives as N-donor ligands has been prepared by the reaction of [(DMSO)₂H][trans-RuCl₄(DMSO)₂] with the corresponding L derivative. The complexes 1-12 have the general compositions trans-[RuCl₄(DMSO)(n-Cl-LH)] ⋅ xSol (1-3), trans-[RuCl₄(DMSO)(n-Br-LH)] · xSol (4-6), trans-[RuCl₄(DMSO)(n-OMe-LH)] · xSol (7-9) and trans-[RuCl₄(DMSO)(n-OH-LH)] · xSol (10-12); n = 2, 3, and 4, x = 0-1.5; and Sol = H₂O, DMSO, EtOH and/or (Me)₂CO. The complexes have been thoroughly characterized by elemental analysis, UV-visible, FTIR, Raman, and EPR spectroscopy, ES + (positive ionization electrospray) mass spectrometry, thermal analysis, cyclic voltammetry, magnetic and conductivity measurements. The X-ray molecular structure of trans-[RuCl₄(DMSO)(3-Br-LH)] ⋅ (Me)₂CO (5) revealed the distorted octahedral coordination in the vicinity of the central atom, and also confirmed that the 3-Br-L ligand is present as the N3-protonated N7-H tautomer and is coordinated to Ru(III) through the N9 atom of the purine moiety. The tested complexes have been found to be in vitro non-cytotoxic against K562, G361, HOS and MCF7 human cancer cell lines with IC₅₀ > 100 μM in contrast to the moderate results regarding the antiradical activity with IC₅₀ ≈ 10^− 3 M. On the contrary, in vivo antitumor activity screening showed that the prepared Ru(III) complexes possess higher pro-apoptotic activity than NAMI-A. The reduction of Ru(III) to Ru(II) and Ru(II)-species formation in tumor tissues was confirmed by means of a simple method of detection and visualization of intracellular Ru(II) by fluorescence microscopy. The originality of this method is based on the preparation of a Ru(II)-bipyridine complex in situ.     

Syntheses and properties of new metal-carbon bonded heteroleptic complexes of ruthenium(II) containing terpyridine coligand

Reactions of 2-(arylazo)aniline, HL [H represents the dissociable protons upon orthometallation and HL is p-RC₆H₄N = NC₆H₄-NH₂; R = H for HL¹; CH₃ for HL² and Cl for HL³] with Ru(R₁-tpy)Cl₃ (where R₁-tpy is 4′-(R₁)-2,2′,6′′,2′′-terpyridine and R₁ = H or 4-N,N-dimethylaminophenyl or 4-methylphenyl) afford a group of complexes of type [Ru(L)(R₁-tpy)]·ClO₄ each of which contains C,N,N coordinated L⁻ as a tridentate ligand along with a terpyridine. Structure of one such complex has been determined by X-ray crystallography. All the Ru(II) complexes are diamagnetic, display characteristic ¹H NMR signals and intense dπ(Ru^II) → π∗(tpy) MLCT transitions in the visible region. Cyclic voltammetric studies on [Ru(L)(R₁-tpy)]·ClO₄ complexes show Ru(II)-Ru(III) oxidation within 0.63-0.67 V versus SCE.     

Reactions of the cationic monobut-2-yne complex [WI(CO)(NCMe)(dppm)(η2-MeC2Me)][BF4] {dppm = Ph2P(CH2)PPh2} with carbon monoxide and tButylisonitrile

The compound [WI(CO)(NCMe)(dppm)(η²-MeC₂Me)][BF₄] reacts with carbon monoxide and ^tbutylisonitrile in CH₂Cl₂ at room temperature to give the substituted products [WI(CO)₂(dppm)(η²-MeC₂Me)][BF₄] (1) and [WI(CO)(CN^tBu)(dppm)(η²-MeC₂Me)][BF₄] (2) in good yield. The new complexes were fully characterised by elemental analysis, infrared, ¹H and ¹³C NMR spectroscopy. ¹³C NMR spectroscopy suggests that the but-2-yne ligand is donating four electrons to the tungsten in these complexes.     

Ruthenium(II) arene complexes containing four- and five-membered monoanionic O,O-chelate rings

Optimization of the design of half-sandwich organometallic Ru^II arene complexes as anticancer agents depends on control of ligand exchange reactions. We have studied the aqueous chemistry of complexes containing O,O-chelate rings. The presence of the four-membered O,O-chelate ring from acetate (AcO) in [η⁶-p-cymene)Ru(AcO)Cl] was confirmed by X-ray crystallography, but in solution the acetate ligand was labile and the hydroxo-bridged dimer [((η⁶-p-cymene)Ru)₂(μ-OH)₃]⁺ readily formed. The dimer was relatively unreactive towards 9-ethyl guanine. The tropolonato (trop) complex [(η⁶-p-cymene)Ru(trop)Cl] was stable in aqueous media and the X-ray crystal structure of the aqua adduct [(η⁶-p-cymene)Ru(trop)(H₂O)]CF₃SO₃, containing a five-membered O,O-chelate ring from trop, was determined. [(η⁶-p-cymene)Ru(trop)Cl] reacted with guanosine to form N7 adducts and with adenosine to form both N7 and N1 adducts. Competitive reactions with guanosine and adenosine gave rise to guanosine:adenosine adducts in a ca. 1.3:1 mol ratio.     

Formation of novel ene-yne substituted β-diketonato ruthenium(III) complexes by the Heck-like reactions on coordinated ligand

Two new ene-yne substituted 2,4-pentanedionatoruthenium(III) complexes formed by the Heck-like reactions in the course of the Sonogashira reactions. The two complexes are structural isomers; one is [Ru(E-1,4-mBSima)(dpm)₂] and another is [Ru(E-2,4-mBSima)(dpm)₂], where E-1,4-mBSima is E-3-(1,4-bis(trimethylsilyl)-1-butene-3-ynyl)-2,4-pentanedionate, E-2,4-mBSima is E-3-(2,4-bis(trimethylsilyl)-1-butene-3-ynyl)-2,4-pentanedionate, and dpm is dipivaloylmethanate (2,2,6,6-tetramethylheptan-3,5-dionate). Both of complexes have been characterized by ¹H NMR and infrared spectroscopies, mass spectrometry, and electrochemistry. [Ru(E-1,4-mBSima)(dpm)₂] has also been characterized by X-ray crystallography. The ruthenium(III) is coordinated in an octahedral arrangement by the oxygen atoms of three β-diketonate ligands. The dihedral angle between the 2,4-pentanedionato chelate ring and the ene-yne plane on the E-1,4-mBSima ligand is 91°. The ene-yne group in [Ru(E-1,4-mBSima)(dpm)₂] is fixed either in the solution state suggested by the ¹H NMR spectrum with no symmetry.     

Synthesis and characterization of mixed-ligand ruthenium(III) complexes with oxalate and acetylacetonate ions

Two mononuclear mixed-ligand ruthenium(III) complexes with oxalate dianion (ox²⁻) and acetylacetonate ion (2,4-pentanedionate, acac⁻), K₂[Ru(ox)₂(acac)] (1) and K[Ru(ox)(acac)₂] (2), were prepared as a candidate for a building block. In fact, reaction of complex 2 with manganese(II) sulfate gave a heterometallic tetranuclear complex, TBA[Mn^II{(μ-ox)Ru^III(acac)₂}₃] (5) in the presence of tetrabutylammonium (TBA) bromide. The ¹H NMR, UV-Vis, selected IR and FAB mass spectral data of these complexes are presented. Both mixed-ligand ruthenium(III) complexes gave a Nernstian one-electron reduction step in 0.1 mol dm⁻³ Na₂SO₄ aqueous solution on a mercury electrode at 25 °C. Comparison of observed reversible half-wave potentials with calculated values for a series of [Ru(ox)_n(acac)_3 − n]ⁿ⁻ (n=0-3) complexes by using Lever’s ligand electrochemical parameters is presented.     

The interesting DNA-binding properties of three novel dinuclear Ru(II) complexes with varied lengths of flexible bridges

Three binuclear Ru(II) complexes with two [Ru(bpy)₂(pip)]²⁺-based subunits {where bpy = 2,2′-bipyridine and pip = 2-phenylimidazo[4,5-f][1,10]phenanthroline} being linked by varied lengths of flexible bridges, were synthesized and characterized by ¹H NMR, elemental analysis, UV-visible (UV-vis) and photoluminescence spectroscopy. The structures of the three complexes were optimized by density functional theory calculations. The interaction of the complexes with calf thymus DNA was investigated by UV-vis and luminescence titrations, steady-state emission quenching by [Fe(CN)₆]⁴⁻, DNA competitive binding with ethidium bromide, DNA melting experiments, and viscosity measurements. The experimental results indicated that the three complexes bound to the DNA most probably in a threading intercalation binding mode with high DNA binding constant values three orders of magnitude greater than the DNA binding constant value reported for proven DNA intercalator, mononuclear counterpart [Ru(bpy)₂(p-mopip)]²⁺ {p-mopip = 2-(4-methoxylphenyl)imidazo[4,5-f][1,10]phenanthroline}.     

Synthesis and NMR characterization of the novel mixed-ligands Pt(II) complexes Pt(amine)(pyrimidine)X2 and trans,trans-X2(amine)Pt(μ-pyrimidine)Pt(amine)X2 (X = I and Cl)

Mixed-ligand complexes of the type Pt(amine)(pm)I₂, (pm = pyrimidine) were synthesized and characterized by IR spectroscopy and by multinuclear (¹⁹⁵Pt, ¹H and ¹³C) magnetic resonance spectroscopy. The cis compounds were prepared from the reaction of I(amine)Pt(μ-I)₂Pt(amine)I with pyrimidine (1:2 proportion) in water, while the trans isomers were synthesized from the isomerization of the cis complexes in acetone. The cis isomers could not be isolated with several amines, especially the more bulky ones. In ¹H NMR, the pyrimidine protons of the cis compounds were found at lower fields than those of the trans analogs and the J(¹⁹⁵Pt-¹H) coupling constants are slightly larger in the cis geometry. For n-butylamine, the reaction produced also I₂(n-butylamine)Pt(μ-pm)Pt(n-butylamine)I₂. No such dimer could be isolated with the other amines. The compounds Pt(amine)(pm)Cl₂ were also prepared (amine = methylamine and t-butylamine) from the ionic complex K[Pt(amine)Cl₃] using an excess of pyrimidine. The IR and NMR characterization showed that the methylamine compound was a cis-trans mixture, while only the trans isomer was isolated with t-butylamine. When the same reaction was performed using a Pt:pm ratio of 2:1, Cl₂(amine)Pt(μ-pm)Pt(amine)Cl₂ was isolated. The pyrimidine-bridged dimers were identified by IR and multinuclear magnetic resonance spectroscopies as the trans-trans isomers. The trans monomers and dimers showed only one ν(Pt-Cl) band. The ¹⁹⁵Pt NMR signals of the dimers were found close to those of the monomer trans-Pt(amine)(pm)Cl₂.     

Stability of an organometallic ruthenium-ubiquitin adduct in the presence of glutathione: relevance to antitumour activity

The interactions of the ruthenium(II) complex Ru(η⁶-p-cymene)(pta)Cl₂ (RAPTA-C), an effective anticancer and antimetastatic agent, with biological nucleophiles are important with respect to its mechanism of action, for example, the reaction with glutathione (GSH) potentially plays an important role in detoxification. RAPTA-C reacts rapidly with glutathione forming a series of adducts including Ru(η⁶-p-cymene)(pta)(GS), Ru(η⁶-p-cymene)(GS) and bis-GSH conjugates, which were characterised by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). In addition, the ability of glutathione to cleave ruthenium-ubiquitin bonds was assayed and it was shown that GSH is capable of removing the Ru moiety from the protein, although no ternary adducts were identified.