Mixed-ligand Ruthenium Research Articles

Development of mixed-ligand ruthenium complexes bearing phosphine and imine ligands for utilisation as catalysts in Suzuki-type C–C cross-coupling reactions

ABSTRACT Herein we report the development of two mixed-ligand ruthenium (II) complexes bearing phosphine and imine ligands, their thorough characterisation and their utilisation as homogeneous catalysts in Suzuki-type C–C cross-coupling reactions. Reactions of two tetradentate Schiff base ligands, derived from imidazole-2-carboxaldehyde and ethylenediamine (H2L1 ) or propylenediamine (H2L2 ), with [Ru(PPh3)3Cl2] in refluxing ethanol in the presence of NEt3 afforded two complexes of type [Ru(L1)(PPh3)2] and [Ru(L2)(PPh3)2], respectively. The solid-state structure of [Ru(L2)(PPh3)2] was determined by single crystal X-ray diffraction analysis. The molecular structure of [Ru(L1)(PPh3)2] was optimised by the DFT method. Electronic spectra of the complexes showed intense absorptions spanning over the visible and ultra-violet regions, the origin of which was probed with TDDFT calculations. Redox properties of the complexes were studied by cyclic voltammetry. These mixed-ligand ruthenium(II) complexes serve as efficient catalyst-precursors for Suzuki-type C–C cross-coupling reactions.

Phenalenyl-ruthenium synergism for effectual catalytic transformations of primary amines to amides.

The synthesis of amides holds great promise owing to their impeccable contributions as building blocks for highly valued functional derivatives. Herein, we disclose the design, synthesis and crystal structure of a mixed-ligand ruthenium(II) complex, [Ru(η6-Cym)(O,O-PLY)Cl], (1) where Cym = 1-isopropyl-4-methyl-benzene and O,O-PLY = deprotonated form of 9-hydroxy phenalenone (HO,O-PLY). The complex catalyzes the aerobic oxidation of various primary amines (RCH2NH2) to value-added amides (RCONH2) with excellent selectivity and efficiency under relatively mild conditions with common organic functional group tolerance. Structural, electrochemical, spectroscopic, and computational studies substantiate that the synergism between the redox-active ruthenium and π-Lewis acidic PLY moieties facilitate the catalytic oxidation of amines to amides. Additionally, the isolation and characterization of key intermediates during catalysis confirm two successive dehydrogenation steps leading to nitrile, which subsequently transform to the desired amide through hydration. The present synthetic approach is also extended to substitution-dependent tuning at PLY to tune the electronic nature of 1 and to assess substituent-mediated catalytic performance. The effect of substitution at the PLY moiety (5th position) leads to structural isomers, which were further evaluated for the catalytic transformations of amine to amides under similar reaction conditions.

Photocatalytic Activity of Ruthenium(II) Complex with 1,10-Phenanthroline-3,8-dicarboxylic Acid in Aerobic Oxidation Reactions

Mixed-ligand ruthenium(II) complex with 2,2′-bipyridine and 1,10-phenanthroline-3,8-dicarboxylic acid with the composition [Ru(phen-C)(bpy)2]Cl2·5H2O (bpy = 2,2′-bipyridine, phen-C = 1,10-phenantroline-3,8-dicarboxylic acid) has been synthesized and characterized by spectral data. The complex has been tested as photocatalyst in aerobic oxidation reactions, including transformation of arylboronic acids to phenols, primary amines to imines, and sulfides to sulfoxides in aqueous medium. The possibility of regeneration of the catalyst in the oxidation of sulfides has been demonstrated.

Improving Cytotoxicity against Breast Cancer Cells by Using Mixed-Ligand Ruthenium(II) Complexes of 2,2'-Bipyridine, Amino Acid, and Nitric Oxide Derivatives as Potential Anticancer Agents.

Several metal-based molecules that display cytotoxicity against multiple cell lines have been pursued in an attempt to fight against cancer and to overcome the typical side effects of drugs like cisplatin. In this scenario, ruthenium complexes have been extensively studied due to their activity in both in vitro and in vivo biological systems, including various cancer cell strains. We aimed to develop a method to synthesize novel [Ru(NO)(bpy)2L2]2+ complexes containing amino acid ligands by using an alternative Click Chemistry approach, namely the copper azide-alkyne cycloaddition reaction (CuAAC reaction), to construct nitrosyl/nitrite complexes bearing a modified lysine residue. We synthesized a new ligand by Click Chemistry approach and new compounds bearing the unprecedented ligand. Cytotoxicity was assessed by the classical MTT colorimetric assay. MCF-7 and MDAMB- 231 cells were used as breast cancer cell models. MCF-10 was used as a model of healthy cells. Amino acid ligands related to N3-Lys(Fmoc) and the new pyLys were successfully synthesized by the diazotransfer reaction and the CuAAC reaction, respectively. The latter reaction involves coupling between N3-Lys(Fmoc) and 3ethynylpyridine. Both N3-Lys(Fmoc) and the new pyLys were introduced into the ruthenium bipyridine complex I, or cis-[RuII(NO)(NO2)(bpy)2]2+, to generate the common nitro-based complex III, which was further converted to the final complex IV. Results of the MTT assay proved the cytotoxic effect of cis- [RuII(NO)(pyLysO-)(bpy)2](PF6)2 against the mammalian breast cancer cells MCF-7 and MDA-MB231. The viability assays revealed that complex IV, bearing a NO group and a modified lysine residue, was able to release NO and cross tumor cell membranes. In this work, Complex IV was observed to be the most active ruthenium bipyridine complex against the mammalian breast cancer cells MCF-7 and MDA-MB231: it was approximately twice as active as cisplatin, whilst complexes I-III proved to be less cytotoxic than complex IV. Additional tests using healthy MCF 10A cells showed that complexes II-IV were three- to sixfold less toxic than cisplatin, which suggested that complex IV was selective against cancer cells.

Ruthenium-Benzimidazole complex: Structural, optical and solvent-free catalytic studies

Two different applications namely catalytic oxidation under solvent free conditions and optical power limiting studies were done on a mixed ligand ruthenium complex containing benzimidazole moiety and Triphenylphosphine. The complex was evaluated for its potential catalytic activity on the alcohol oxidation reaction in presence of hydrogen peroxide (30% aqueous solution) as oxidant to synthesize the corresponding carbonyls and the highlight of the process was that the reaction proceeded without the presence of any solvent. Excellent selectivity was achieved by the Ruthenium catalyst Ru(L)PPh3Cl2 for conversion of aromatic alcohols to aldehydes under milder conditions. One another application namely the non-linear optical activity was also studied. This activity of the complex was extracted at 532 nm wavelength, by the Z-scan method. The experimental result displays strong nonlinear absorption in the ruthenium complex and found to be 15.55 cm/W concluding that the complex displays superior optical limitation.

Design, synthesis and nonlinear optical characterization of novel mixed ligand ruthenium metal-organic complex

In the present study, novel mixed ligand ruthenium metal-organic complex (RuThAP) was designed and synthesized. The chemical structural analysis was performed using NMR, UV–Vis and FTIR spectroscopy. RuThAP/Poly(methylmethacrylate) (PMMA) films were successfully fabricated by homogeneously embedding RuThAP in optically inactive PMMA using spin-coating. Third-order nonlinear optical coefficients of RuThAP in liquid and solid phase were determined by Z-scan technique with nanosecond laser beam. RuThAP molecule exhibited strong reverse saturable absorptive (βeff = 8.81 ± 0.88 x10−9 m/W) and negative refractive (n2 = −5.47 ± 0.55 x10−9 esu) optical nonlinearity at 532 nm. The RuThAP molecule also demonstrated strong optical limitation with optical limiting clamping level as low as 38 μJ due to large absorptive optical nonlinearity. These results pave the platform for high efficient metal-organic/PMMA films based solid-state optical limiters with low cost, flexible, dependable and low optical loss.

Synthesis of Mixed Ligand Ruthenium (II/III) Complexes and Their Antibacterial Evaluation on Drug-Resistant Bacterial Organisms

The potential antimicrobial properties of a tridentate polypyridyl ligand 4-butoxy-N,N-bis(pyridin-2-ylmethyl)aniline (BUT) 1 and its corresponding mixed ligand ruthenium complexes were investigated on drug-resistant and non-drug-resistant bacterial species. The ligand and its complexes were synthesized and successfully characterized by1H NMR, UV/Vis, and FTIR spectra; ESI-MS; and magnetic susceptibility. Electronic spectra and magnetic susceptibility of these Ru(II)/(III) complexes suggest that they are of a low spin crystal field split, where the Ru(III) is ad5and Ru(II)d6low spin. These compounds were tested for antibacterial activity on two bacterial species:Staphylococcus aureus(S. aureus) andKlebsiella pneumoniae(K. pneumoniae), as well as their drug-resistant strains methicillin-resistantStaphylococcus aureus(MRSA) and multidrug resistantKlebsiella pneumoniae(MDRK. pneumoniae). All the compounds inhibited growth of the two non-drug-resistant bacteria and only one drug-resistant strain MRSA. However, only the ligands BUT and 2,2-dipyridylamine showed activity against MRSA, while all complexes did not show any antibacterial activity on MRSA. We observed large zones of inhibition for the Gram-positiveS. aureusand MRSA bacteria, compared to the Gram-negativeK. pneumoniaebacteria. DNA cleavage studies with gel electrophoresis showed denatured bacterial DNA on the gel from all the complexes, with the exception of the ligand, suggesting DNA nuclease activity of the complexes in the bacterial DNA.

Unusual Photooxidation of S-Bonded Mercaptopyridine in a Mixed Ligand Ruthenium(II) Complex with Terpyridine and Bipyridine Ligands.

An unusual photooxidation of a coordinated 4-mercaptopyridine ( SpyH) ligand in the [Ru(Hmctpy)(dmbpy)(κ S-SpyH)]2+complex (Hmctpy = 4'-carboxy-2,2';6',2″-terpyridine, dmbpy = 4,4'-dimethyl-2,2'-bipyridine) takes place under visible and UV irradiation, in aerated acetonitrile. The [Ru(mctpy)(dmbpy)(κ S-SO2py)] sulfinato product has been characterized by a variety of methods, including X-ray diffraction which supports the presence of the Ru-κ S-SpyH isomer in the starting complex. The photooxidation of the 4-mercaptopyridine ligand enhances the back-bonding interactions in the complex by means of the strongly acceptor 4-pyridinesulfinato-SO2py species, increasing the redox potential of the Ru(III)/Ru(II) couple significantly from 1.23 to 1.62 V. It also led to pronounced changes in the electronic and NMR spectra of the complexes, corroborated by DFT and ZINDO-S calculations. A possible mechanism based on referenced data of photooxidation has been proposed, which involves the formation of a reactive oxygen species and intermediate endoperoxide species, yielding a very stable Ru-sulfinato product. This novel species exhibits stronger luminescence (Φ f = 0.004) than the starting complex under UV excitation.

Mixed-ligand (triphenylphosphine)ruthenium complexes of diphenylcarborane by ligand manipulation and an asymmetric, bimolecular “symbiotic” cluster

Deprotonation of [exo-5,6,10-{RuCl(PPh3)2}-5,6,10-(μ-H)3-nido-7,8-C2B9H9] (1a) and its C,C-diphenyl analogue (1b) affords the anions [3,3-(PPh3)2-3-Cl-closo-3,1,2-RuC2B9H11]− (2a) and [1,2-Ph2-3,3-(PPh3)2-3-Cl-closo-3,1,2-RuC2B9H9]− (2b), respectively. Dehalogenation of 2b in the presence of one equivalent of tBuNC yields [1,2-Ph2-3,3-(tBuNC)2-3-PPh3-pseudocloso-3,1,2-RuC2B9H9] (3), and if 2b is dehalogenated in the presence of CO a very similar compound, [1,2-Ph2-3,3-(CO)2-3-PPh3-pseudocloso-3,1,2-RuC2B9H9] (4), is formed. Treatment of 2b with Ag+ in the absence of a donor ligand affords, amongst a number of products, the compound [{1,2-Ph2-pseudocloso-3,1,2-RuC2B9H9}{1′,8′-Ph2-closo-2′,1′,8′-RuC2B9H9}] (5) in which two different {RuPh2C2B9H9} units both achieve electronic and coordinative saturation at their Ru centres by η6-coordination of a Ph ring on the other cluster in a symbiotic manner. Compounds 1b, 3, 4 and 5 were fully characterised, including by crystallographic studies.

Synthesis, structure, DNA binding and anticancer activity of mixed ligand ruthenium(II) complex

In order to obtain a potential chemotherapeutic which is not affected on the normal BALB/3T3 cell line, a new arene ruthenium(II) complex {[RuCl(L1)(η6-p-cymene)]PF6}2 · H2O has been synthesized by a direct reaction of precursor, [{(η6-p-cymene)Ru(μ-Cl)}2Cl2], with N,N-chelating ligand (L1 - 2,2′-bis(4,5-dimethylimidazole). The compound has been fully characterized by elemental analysis, X-ray diffraction, IR, UV–Vis and 1H, 13C NMR spectroscopies. X-ray analysis have confirmed that the compound crystallized in the monoclinic group Cc as an inversion twin. The asymmetric unit contains two symmetrically independent cationic complexes [RuCl(L1)(η6-p-cymene)]+ whose charge is balanced by two PF6− counterions. The shape of each cationic coordination polyhedral can be described as a distorted dodecahedron and shows a typical piano-stool geometry. In addition, an analysis of the crystal structure and the Hirshfeld surface analysis were used to detect and visualize important hydrogen bonds and intermolecular interaction. Moreover, the antiproliferative behavior of the obtained complex was assayed against three human cells: MV-4-11, LoVo, MCF-7 and BALB/3T3 - normal mice fibroblast cells. To predict a binding mode, a potential interaction of ruthenium complex with calf thymus DNA (CT-DNA) has been explored using UV absorption and circular dichroism (CD).

Mixed-ligand ruthenium(II) complexes capable of hydrogen-bonding interactions with DNA: DNA binding, nuclease activity, cytotoxicity, and topoisomerase inhibition

Two novel mixed-ligand ruthenium(II) complexes cis-[RuClL(PP)2]+ and cis-[RuL2(PP)2]2+ (L=1,6-diaminohexane (1,6-dahx), 1-aminohexane (1-ahx); PP=2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), 4,7-diphenyl-1,10-phenanthroline (Ph2phen)) were synthesized and characterized. The apparent DNA-binding constants (Kapp) of cis-[RuCl(1,6-dahx)(bpy)2]+ (1) and cis-[Ru(1,6-dahx)2(bpy)2]2+ (3) for H-bonding to DNA were larger than those of cis-[RuCl(1,6-ahx)(bpy)2]+ (2) and cis-[Ru(1,6-ahx)2(bpy)2]2+ (4) with no H-bonding. Furthermore, the Kapp value of 3 was larger than that of 1 possessing two binding modes: covalent bonding and H-bonding with DNA. The Kapp values of cis-[RuCl(1,6-dahx)(phen)2]+ (5) and cis-[Ru(1,6-dahx)2(phen)2]2+ (6) with partial intercalation in DNA were 3–5 times larger than those of 1 and 3. Although the chemical nuclease activity of 1–6 was observed in the presence of H2O2, these complexes showed no cytotoxic activity against HeLa and cisplatin-sensitive L1210 cell lines because of the negative log Po/w values. However, it is noteworthy that 1–4 were 1.5–17 times more active than cisplatin in the cisplatin-resistant L1210/cisR cell line. cis-[RuCl(1-dahx)(Ph2phen)2]+ (7) and cis-[Ru(1-dahx)2(Ph2phen)2]2+ (8) had the positive log Po/w values with favorable cytotoxic activity against the HeLa cell line and inhibited the activity of both Topo I and II.

Mixed ligand ruthenium arene complexes containing N-ferrocenyl amino acids: Biomolecular interactions and cytotoxicity against MCF7 cell line

Synthesis, characterization, DNA and protein binding as well as anticancer activity of the organometallic complexes [Ru(η6-p-cym)(L)Cl] (where, p-cym = p-cymene MeC6H4Pri, L = N-ferrocenyl amino acid conjugates) RAFcA 1–4 have been described. The complexes 1–4 exhibited strong DNA/BSA binding and anticancer activity against breast cancer MCF7 cell line. Their binding with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) have been examined by absorption and emission spectral studies. Strong interactions between complexes and CT-DNA have been affirmed by absorption spectral and EB displacement studies, while interaction with BSA via static quenching was explored by fluorescence titration. Cytotoxicity, apoptosis and in vitro anticancer activity of 1–4 toward MCF7 cell line have been investigated by MTT assay. The IC50 values (37.1 μM - 86.6 μM) were found to be distinctly lower than those of NAMI-A and RAPTA complexes for MCF7 cell line which was followed by gene expression studies to confirm apoptosis as the mode of cell death.

Synthesis, characterization and biological evaluation of mixed-ligand ruthenium(II) complexes for photodynamic therapy.

This study investigated the photodynamic therapy (PDT) and anticancer activity of mixed ligand Ru(ii) terpyridyl complexes (Ru1-Ru3). The photophysical and photochemical properties, hydrophobic properties, DNA binding and DNA transcription inhibition abilities, cell uptake efficiency, cellular localization and photo-cytotoxicity were investigated. Ru1-Ru3 exhibited red luminescence between 670-710 nm and functioned as photo-sensitizers (PSs) by generating both singlet oxygen and radical ions. Without light activation, Ru1-Ru3 were located at the cytoplasm and were nontoxic to cells. However, upon light activation, Ru1-Ru3 exhibited significant photocytotoxicity. After PDT treatment, mitochondria alteration and nuclear membrane disruption occurred, which resulted in relocalization of the complexes from the cytoplasm to the nucleus. Moreover, high cellular oxidative stress caused cell necrocytosis after PDT treatment.

Kinetic Aspects for the Reduction of CO2and CS2with Mixed-Ligand Ruthenium(II) Hydride Complexes Containing Phosphine and Bipyridine

A new water-soluble ruthenium hydride complex [Ru(H)(bpy)2(PTA)]PF6 (bpy = 2,2'-bipyridine, PTA = 1,3,5-triaza-7-phosphaadamantane) (1a) was prepared. 1a reacted with CO2 and CS2 to give the corresponding formate and dithioformate complexes, respectively. Both the insertions of CO2 and CS2 into the Ru-H bond of 1a followed second-order kinetics. The second-order rate constant (k2) of CO2 insertion reaction varied from (9.40 ± 0.41) × 10(-4) M(-1) s(-1) in acetone to (1.13 ± 0.08) × 10(-1) M(-1) s(-1) in methanol; moreover, the ln(k2) is in good linear relationship with the acceptor number (AN) of the solvent used. Although, the k2 of CS2 insertion reaction ranged from (3.43 ± 0.10) M(-1) s(-1) in methanol to (24.0 ± 0.5) M(-1) s(-1) in N,N-dimethylformamide, which is 1000 times faster than CO2 insertion. Generally, the k2 of CS2 insertion increased with the static dielectric constant (D(s)) of the reaction medium investigated. For comparison purposes, we further investigated the reactivity of [Ru(H)(bpy)2(PPh3)]PF6 (PPh3 = triphenylphosphine) (1b) with CO2 and CS2. 1b reacted with CO2 slowly in the methanol with a k2 of (1.46 ± 0.09) × 10(-3) M(-1) s(-1), yielding a formate complex [Ru(η(1)-OC(H)═O)(bpy)2(PPh3)]PF6 (2b). The reaction of 1b with CS2 is 1000 times faster than that of CO2. The structures of 1a, 1b, and 2b were determined by X-ray crystallographic analysis.

Ruthenium(II) bipyridine complexes bearing new keto–enol azoimine ligands: Synthesis, structure, electrochemistry and DFT calculations

The novel azoimine ligand, PhNHNC(COCH3)NHPh(CCH) (H2L), was synthesized and its molecular structure was determined by X-ray crystallography. Catalytic hydration of the terminal acetylene of H2L in the presence of RuCl3·3H2O in ethanol at reflux temperature yielded a ketone (L1=PhNNC(COCH3)NPh(COCH3) and an enol (L2=PhNNC(COCH3)NPhC(OH)CH2) by Markovnikov addition of water. Two mixed-ligand ruthenium complexes having general formula, trans-[Ru(bpy)(Y)Cl2] (1–2) (where Y=L1 (1) and Y=L2 (2), bpy is 2.2′-bipyrdine) were achieved by the stepwise addition of equimolar amounts of (H2L) and bpy ligands to RuCl3·3H2O in absolute ethanol. Theses complexes were characterized by elemental analyses and spectroscopic (IR, UV–Vis, and NMR (1D 1H NMR, 13C NMR, (DEPT-135), (DEPT-90), 2D 1H–1H and 13C–1H correlation (HMQC) spectroscopy)). The two complexes exhibit a quasi-reversible one electron Ru(II)/Ru(III) oxidation couple at 604mV vs. ferrocene/ferrocenium (Cp2Fe0/+) couple along with one electron ligand reduction at −1010mV. The crystal structure of complex 1 showed that the bidentate ligand L1 coordinates to Ru(II) by the azo- and imine-nitrogen donor atoms. The complex adopts a distorted trans octahedral coordination geometry of chloride ligands. The electronic spectra of 1 and 1+ in dichloromethane have been modeled by time-dependent density functional theory (TD-DFT).

DNA binding behaviors and nuclease activities of novel mixed-ligand ruthenium(II) complexes

Two types of ruthenium(II) complexes cis-[Ru(bpy)2ClL]+ and cis-[Ru(bpy)2L2]2+ (L=1,6-diaminohexane (1,6-dahx), 1-aminohexane (1-ahx)) were synthesized, and the interactions of these complexes with DNA were investigated. Importantly, cis-[Ru(bpy)2(1,6-dahx)2]2+ possessed hydrogen-bonding to DNA, preferentially binds at adenine and/or thymine residues, and exhibits more efficient nuclease activity.

Mixed-ligand ruthenium polypyridyl complexes as apoptosis inducers in cancer cells, the cellular translocation and the important role of ROS-mediated signaling.

Ruthenium (Ru) polypyridyl complexes have emerged as leading players among the potential metal-based candidates for cancer treatment. However, the roles of cellular translocation in their action mechanisms remain elusive. Herein we present the synthesis and characterization of a series of ruthenium (Ru) complexes containing phenanthroline derivatives with varying lipophilicities, and examine their mechanism of anticancer action. Results showed that increasing the lipophilicity of complexes can enhance the rates of cellular uptake. The in vitro anticancer efficacy of these complexes depended on the levels of ROS overproduction, rather than on cellular Ru uptake levels. The introduction of a phenolic group on the ligand effectively enhanced their intracellular ROS generation and anticancer activities. In particular, complex 4, with an ortho-phenolic group on the ligand, exhibited better selectivity between cancer and normal cells in comparison with cisplatin. Notably, complex 4 entered the cancer cells partially through transferrin receptor-mediated endocytosis, and then it translocated from lysosomes to the mitochondria, where it activated mitochondrial dysfunction by regulation of Bcl-2 family proteins, thus leading to intracellular ROS overproduction. Excess ROS amplified apoptotic signals by activating many downstream pathways such as p53 and MAPK pathways to promote cell apoptosis. Overall, this study provides a drug design strategy for discovery of Ru-based apoptosis inducers, and elucidates the intracellular translocation of these complexes.

Mixed ligand ruthenium(III) complexes of benzaldehyde 4-methyl-3-thiosemicarbazones with triphenylphosphine/triphenylarsine co-ligands: Synthesis, DNA binding, DNA cleavage, antioxidative and cytotoxic activity

The new ruthenium(III) complexes with 4-methyl-3-thiosemicarbazone ligands, (E)-2-(2-chlorobenzylidene)-N-methylhydrazinecarbothioamide (HL1) and (E)-2-(2-nitrobenzylidene)-N-methylhydrazinecarbothioamide (HL2), were prepared and characterized by various physico-chemical and spectroscopic methods. The title compounds act as bidentate, monobasic chelating ligands with S and N as the donor sites and are preferably found in the thiol form in all the complexes studied. The molecular structure of HL1 and HL2 were determined by single crystal X-ray diffraction method. DNA binding of the ligands and complexes were investigated by absorption spectroscopy and IR spectroscopy. It reveals that the compounds bind to nitrogenous bases of DNA via intercalation. The oxidative cleavage of the complexes with CT-DNA inferred that the effects of cleavage are dose dependent. Antioxidant study of the ligands and complexes showed the significant antioxidant activity against DPPH radical. In addition, the in vitro cytotoxicity of the ligands and complexes against MCF-7 cell line was assayed which showed higher cytotoxic activity with the lower IC50 values indicating their efficiency in killing the cancer cells even at low concentrations.

Synthesis and Characterisation of RuII Polypyridyl Complexes: DNA-Binding, Photocleavage, and Topoisomerase I and II Inhibitory Activity

Two mixed-ligand ruthenium(ii) complexes [Ru(phen)2(cptcp)]2+ (Ru1; phen = 1,10-phenanthroline, cptcp = 2-(4-carbazol-9-yl-phenyl)-1H-1,3,7,8-tetraaza-cyclopenta-[l]-phenanthrene) and [Ru(phen)2(btcpc)]2+ (Ru2; btcpc = 9-butyl-6-(1H-1,3,7,8-tetraaza-cyclo-cyclopenta-[l]-phenanthren-2-yl)-9H-carbazole-3-carbaldehyde) have been synthesised and characterised. The DNA-binding behaviours of the two complexes have been investigated by using spectroscopic and viscosity measurements. Results suggest that the two complexes bind to DNA by intercalation. The photocleavage of plasmid pBR322 DNA indicates that Ru1 exhibits more effective DNA cleavage activity in comparison to that exhibited by Ru2 under the same conditions, and different cleavage mechanisms are determined. Topoisomerase inhibition and DNA strand passage assay confirm that Ru1 may act as an efficient dual inhibitor of topoisomerases I and II, whereas Ru2 may only act as a single inhibitor of topoisomerases II.

Oxidative Cleavage of DNA by Ruthenium(II) Complexes Containing a Ferrocene/Non-Ferrocene Conjugated Imidazole Phenol Ligand

Three mixed-ligand ruthenium(II) complexes with general formula [Ru(bpy)2L](PF6) (1–3), where L = 2-{4,5-bis[(E)-2-ferrocenylvinyl]-1H-imidazol-2-yl}phenol (1), 2-{4,5-bis[(E)-2-ferrocenylvinyl]-1H-imidazol-2-yl)-4,6-dichlorophenol (2), 2-{4,5-bis[(E)-2-(4-chlorophenyl)ethenyl]-1H-imidazol-2-yl}phenol (3), have been synthesized and characterized. All the three complexes bring about DNA cleavage in the presence of H2O2. Due to the presence of three redox-active metal centers in complexes 1 and 2 these two complexes show enhanced DNA cleaving activity in comparison to that exhibited by complex 3, which contains only one redox-active metal center.