A new family of trinuclear Ru(II) polypyridyl complexes acting as pH-induced fluorescence switch

Tripodal ligands 1,3,5-tris{4-((1,10-phenanthroline-[5,6-d]imidazol-2-yl)phenoxy)methyl}-2,4,6-trimethylbenzene (L¹), 1,1,1-tris{4-((1,10-phenanthroline-[5,6-d]imidazol-2-yl)phenoxy)methyl}propane (L²), 2,2′,2′′-tris{4-((1,10-phenanthroline-[5,6-d]imidazol-2-yl)phenoxy)ethyl}amine (L³), and corresponding Ru(II) complexes [(bpy)₆L^1–3(Ru^II)₃](PF₆)₆, shortly called (Ru–L^1–3), have been synthesized. UV–vis absorption and fluorescence spectra of these complexes are both strongly dependent on the pH of the buffer solution. These complexes act as pH-induced off–on–off fluorescence switch through protonation and deprotonation of the imidazole-containing ligands.     

Preparation,spectroscopic, and electrochemical properties of four novel trinuclear Ru(II) polypyridyl complexes containing diazafluorene

Four tripodal ligands 2,2′,2″-tris[4-(4,5-diazafluoren-9-ylhydrazinyl)methylenephenoxyethyl]amine (L¹), 1,1,1-tris[4-(4,5-diazafluoren-9-ylhydrazinyl)methylenephenoxymethyl]propane (L²), 1,3,5-tris[4-(4,5-diazafluoren-9-ylhydrazinyl)methylenephenoxymethyl]-2,4,6-trimethylbenzene (L³), 1,3,5-tris[4-(4,5-diazafluoren-9-ylhydrazinyl)methylenephenoxymethyl]benzene (L⁴), and corresponding Ru(II) complexes [(bpy)₆L^1–4(Ru^II)₃](PF₆)₆ (Ru-L^1–4) have been synthesized. Cyclic voltammetry of these complexes comprise one Ru(II)-centered reversible oxidation and three ligand-centered reductions. Photophysical behaviors are investigated by UV–Vis absorption and luminescence spectrometry. These complexes display metal-to-ligand charge transfer absorption at around 410 nm and emission at around 582 nm.     

Preparation,photophysical, and electrochemical properties of three novel trinuclear Ru(II) polypyridyl complexes based on diazafluorenes

Three tripodal ligands 2,2′,2″-tris[(4,5-diazafluoren-9-ylimino)phenoxyethyl]amine (L¹), 1,3,5-tris[(4,5-diazafluoren-9-ylimino)phenoxymethyl]-2,4,6-trimethylbenzene (L²), 1,1′,1″-tris[(4,5-diazafluoren-9-ylimino)phenoxymethyl]-1″′-(p-tosyloxymethyl)-methane (L³), and corresponding Ru(II) complexes [(bpy)₆L^1–3(Ru^II)₃](PF₆)₆ (Ru-L^1–3) have been prepared. Cyclic voltammetry of the three complexes are consistent with one Ru(II)-centered quasi-reversible oxidation and three ligand-centered reductions. Photophysical behaviors are investigated by UV–Vis absorption and fluorescence spectrometry. The three complexes display metal-to-ligand charge transfer absorption at 445 nm and emission at 578 nm.     

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 interaction of Cr(III) polypyridyl complexes with DNA

Two chromium(III) complexes containing derivatives of 1,10-phenanthroline were synthesized and characterized using different spectroscopic methods. The interaction of the synthesized complexes with DNA was performed. From the absorption titration data, the binding constant for the complexes [Cr(imiphen)₂Cl₂]⁺ (1) and [Cr(furphen)₂Cl₂]⁺ (2) with DNA were found to be 5.69 ± 0.3 × 10⁴ M^− 1 for 1 and 3.7 ± 0.2 × 10⁴ M^− 1 for 2, respectively. The viscosity studies show that both the complexes bind to DNA in a partial intercalative mode. The results of competitive binding assay reveal that both complexes displace EB from DNA marginally. Gel electrophoresis data show that both the complexes 1 and 2 requires co-reagent to induce DNA cleavage but complex 2 exhibit better nuclease activity compared to complex 1. The results from this study describe the role of ligand structure in the binding and cleavage of DNA as furan based ligand exhibit better cleaving ability compared to imidazole moiety.     

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.     

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.     

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.     

Ru(II) and Zn(II) complexes of multicomponent ligands incorporating triazine-based tridentate ligands

Ru(II) and Zn(II) complexes of multicomponent ligands have been synthesised and characterised incorporating triazine-based coordinating motifs with pendant phenanthryl and phenyl–phenanthryl groups. At room temperature the ligands emit from intra-ligand charge-transfer (ILCT) states, the energy of which may be lowered significantly by metal–ion coordination (e.g. Zn(II)). The ILCT state is efficiently quenched in the Ru(II) complexes by energy transfer to a low-lying metal–ligand charge-transfer ³MLCT state.     

Zeolite encapsulated Ru(III), Cu(II) and Zn(II) complexes as effective catalysts for the oxidation of ethylbenzene

Ru(III), Cu(II) and Zn(II) complexes of imidazole (ImzlH) have been synthesized in the supercages of zeolite-Y by flexible ligand method and characterized by spectroscopic (IR and UV?CVis) studies, XRD and thermogravimetric analysis, surface area, and pore volume measurements. These complexes were screened for their catalytic study towards the oxidation of ethylbenzene to a mixture of acetophenone, benzaldehyde and styrene using tert-butylhydroperoxide (TBHP) as an oxidant. A best-suited reaction condition has been optimized for these catalysts by varying the amount of the oxidant and catalyst, reaction time and volume of solvent for maximum transformation of ethylbenzene. Under the optimized reaction conditions, [Cu(ImzlH)]-Y gave 79.3% conversion after 1?h of reaction time. All these catalysts were more selective towards acetophenone formation. Among the prepared catalysts, zeolite encapsulated Cu(II) complex was found to be more active than the corresponding Ru(III) and Zn(II) complexes and all the complexes were stable enough to be reused. The catalytic activities of the neat complexes and metal exchanged zeolites were also compared with the zeolite encapsulated metal complexes.     

Reversible electrochemical and chemical addressing of optical properties of ternary Os(II) polypyridyl complexes

Electrochemical- and chemical-induced variation of the metal oxidation state of ternary Os(II) polypyridyl complexes triggers reversible changes in optical properties. This read/write process can be carried out conveniently and monitored with optical (UV/Vis or luminescence) spectrophotometers. An excellent sensitivity and reversibility may make it a suitable candidate for integration of molecular sensors and logic gate system.     

Synthesis and characterization of partially crosslinked poly(N-vinylcarbazole-vinylalcohol) copolymers with polypyridyl Ru(II) luminophores: Potential materials for electroluminescence

Summary A novel difunctionalized 5,5'-dibromomethylene-2,2' bipyridine ligand was prepared and covalently bound with concurrent crosslinking by a post-polymer modification method to (N-vinylcarbazole-vinylalcohol) copolymer. The electrochemistry and UV-vis spectroscopy results both confirm the covalent attachment of ruthenium transition metal complex to the polymer backbone. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) indicate high thermal stability of the copolymer. The copolymer is also highly phosphorescent making it a potential polymeric material for transition metal based electroluminescent devices. Received: 1 November 1998/Revised version: 18 August 1999/Accepted: 18 August 1999     

Zeolite encapsulated Ru(III), Cu(II) and Zn(II) complexes of benzimidazole as reusable catalysts for the oxidation of organic substrates

Ru(III), Cu(II) and Zn(II) complexes of benzimidazole (BzlH) have been synthesized in the supercages of zeolite-Y by the flexible ligand method and were characterized by spectroscopic (IR, UV–Vis and ESR) studies, XRD and thermogravimetric analysis, surface area, and pore volume measurements. The zeolite encapsulated complexes catalyzed the oxidation of ethylbenzene, benzoin, and cyclohexanol. Various parameters, such as concentration of oxidant and catalyst, reaction time, temperature of the reaction and type of solvents have been optimized to obtain the maximum transformation of ethylbenzene to a mixture of acetophenone, benzaldehyde and styrene. Under the optimized reaction conditions, [Ru(BzlH)]-Y gave 80.4 % conversion of ethylbenzene in 1 h. All these zeolite encapsulated complexes were more selective towards acetophenone formation. Oxidation of benzoin catalyzed by [Cu(BzlH)]-Y, [Ru(BzlH)]-Y and [Zn(BzlH)]-Y encapsulated complexes resulted in 75.5, 78.7 and 59.9 % conversion respectively to give benzaldehyde as exclusive product. A maximum conversion of 39.1 % cyclohexanol with [Cu(BzlH)]-Y was achieved to give cyclohexanone. The activity of neat complexes towards these reactions was also carried out. The encapsulated catalysts were significantly more active than neat complexes and recyclable without much loss in catalytic activity.     

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.     

Novel Chiral Ru(II) Complexes as Potential c-myc G-quadruplex DNA Stabilizers Inducing DNA Damage to Suppress Triple-Negative Breast Cancer Progression

Currently, effective drugs for triple-negative breast cancer (TNBC) are lacking in clinics. c-myc is one of the core members during TNBC tumorigenesis, and G-rich sequences in the promoter region can form a G-quadruplex conformation, indicating that the c-myc inhibitor is a possible strategy to fight cancer. Herein, a series of chiral ruthenium(II) complexes ([Ru(bpy)₂(DPPZ-R)](ClO₄)₂, Λ/Δ−1: R = -H, Λ/Δ−2: R = -Br, Λ/Δ−3: R = -C≡C(C₆H₄)NH₂) were researched based on their interaction with c-myc G-quadruplex DNA. Λ−3 and Δ−3 show high affinity and stability to decrease their replication. Additional studies showed that Λ−3 and Δ−3 exhibit higher inhibition against different tumor cells than other molecules. Δ−3 decreases the viability of MDA-MB-231 cells with an IC₅₀ of 25.51 μM, which is comparable with that of cisplatin, with an IC₅₀ of 25.9 μM. Moreover, Δ−3 exhibits acceptable cytotoxic activity against MDA-MB-231 cells in a zebrafish xenograft breast cancer model. Further studies suggested that Δ−3 decreases the viability of MDA-MB-231 cells predominantly through DNA-damage-mediated apoptosis, which may be because Δ−3 can induce DNA damage. In summary, the results indicate that Ru(II) complexes containing alkinyl groups can be developed as c-myc G-quadruplex DNA binders to block TNBC progression.     

Platinum(II) phenanthroimidazoles for targeting telomeric G-quadruplexes

A rationally designed progression of phenanthroimidazole platinum(II) complexes were examined for their ability to target telomere-derived intramolecular G-quadruplex DNA. Through the use of circular dichroism, fluorescence displacement assays, and molecular modeling we show that these complexes template and stabilize G-quadruplexes from sequences based on the human telomeric repeat (TTAGGG)(n). The greatest stabilization was observed for the p-chlorophenyl derivative 6((G4)DC(50) =0.31 μM). We also show that the G-quadruplex binding complexes are able to inhibit telomerase activity through a modified telomerase repeat amplification protocol (TRAP-LIG assay). Preliminary cell studies show that complex 6 is preferentially cytotoxic toward cancer over normal cell lines, indicating its potential use in cancer therapy.     

[Ru(L)2(3-tppp)]2 + (L = bpy,phen) stabilizes two different forms of the human telomeric G-quadruplex DNA

The binding properties of new complexes [Ru(L)₂(3-tppp)]^2 + (L = bpy, phen) towards two different forms of the human telomeric G-quadruplexes DNA have been investigated by UV–Vis spectroscopy, fluorescent indicator displacement (FID) assays, fluorescence resonance energy transfer (FRET) melting assays and molecular docking studies. The molecular docking studies indicated that both complexes interacted with 22AG with the stoichiometric ratio of 1:1, but the two complexes showed different G-quadruplexed DNA binding affinity. Complex 2 bound to the G-quadruplexes DNA more tightly than complex 1 did. Moreover, the FRET melting assay revealed that both complexes could be potential stabilizers for G-quadruplex architectures. These studies are useful not only for better understanding of the interaction between the target G-quadruplexes DNA and metal complexes but also valuable in defining the best strategy to prepare metal complexes as potential anticancer drugs.     

Interactions of polypyridyl cobalt complexes with DNA studied by rotating electrode methods

The interaction of transition metal complexes Co(phen)₂TATP^3ë+, Co(phen)₃^3ë+ and Co(bpy)₃^3ë+ (where TATP = 1,4,8,9-tetra-aza-trisphenylene, phen = 1,10-phenanthroline, and bpy=2,2-bipyridine) with calf thymus DNA was investigated using the rotating ring-disk electrode technique. The values of the apparent diffusion coefficient and rate constant at the formal potential for reduction of these three polypyridyl cobalt complexes were found to decrease significantly in the presence of DNA as compared with that in the absence of DNA. The formal potentials at which the redox reaction takes place in the absence or presence of DNA were in the order of Co(phen)₂TATP^3ë+/2ë+ > Co(phen)₃^3ë+/2ë+ > Co(bpy)₃^3ë+/2ë+. The interaction between the complexes and DNA varied significantly, depending on the nature of ligands. The binding strength of these complexes to DNA was found in the order of Co(phen)₂TATP^3ë+ > Co(phen)₃^3ë+ > Co(bpy)₃^3ë+. The interaction modes of the polypyridyl cobalt complexes with DNA were discussed in line of electrochemical observations.     

Novel Unsymmetrical Ru(III) and Mixed-valence Ru(III)/Ru(II) Dinuclear Compounds Related to the Antimetastatic Ru(III) Drug NAMI-A

In this paper we report the stepwise preparation and the characterization of new unsymmetrical monoanionic Ru(III) dinuclear compounds, [NH(4)][{trans-RuCl(4)(Me(2)SO-S)}(mu-L){mer-RuCl(3)(Me(2)SO-S)(Me(2)SO-O)}] (L = pyz (1), pym (2)). By a similar synthetic approach we also prepared new mixed-valence Ru(III)/Ru(II) dinuclear compounds of formula [NH(4)][{trans-RuCl(4)(Me(2)SO-S)}(mu-pyz){cis,cis,cis-RuCl(2)(Me(2)SO-S)(2)(CO)}] (L = pyrazine (pyz, 3), pyrimidine (pym, 4)). Moreover, we describe the chemical behavior of compounds 1-4 in physiological solution, also after complete reduction (with ascorbic acid) to the corresponding Ru(II)/Ru(II) species. Overall, the chemical behavior of 1 and 2 after reduction resembles that of the corresponding dianionic and neutral dinuclear species, [{trans-RuCl(3)(Me(2)SO-S)}(2)(mu-L)](2-)and [{mer-RuCl(3)(Me(2)SO-S)(Me(2)SO-O)}(2) (mu-L)]. On the other hand, the mixed-valence dinuclear compounds 3 and 4, owing to the great inertness of the cis,cis,cis-RuCl(2)(Me(2)SO-S)(2)(CO)(1/2mu-L) fragment, behave substantially like the mononuclear species [trans-RuCl(4)(Me(2)SO-S)(L)](-) in which the terminally bonded L ligand can be considered as bearing a bulky substituent on the other N atom.