Ru Polypyridyl Complexes Research Articles

Aquation Is a Crucial Activation Step for Anticancer Action of Ruthenium(II) Polypyridyl Complexes to Trigger Cancer Cell Apoptosis.

Aquation has been proposed as crucial chemical action step for ruthenium (Ru) complexes, but its effects on the action mechanisms remain elusive. Herein, we have demonstrated the aquation process of a potent Ru polypyridyl complex (RuBmp=[Ru(II) (bmbp)(phen)Cl]ClO4 , bmbp=2,6-bis(6-methylbenzimidazol-2-yl) pyridine, phen=phenanthroline) with a chloride ligand, and revealed that aquation of RuBmp effectively enhanced its hydrophilicity and cellular uptake, thus significantly increasing its anticancer efficacy. The aquation products (H-RuBmp=[Ru(II) (bmbp)(phen)Cl]ClO4 , [Ru(II) (bmbp)(phen)(H2 O)]ClO4 , bmbp) exhibited a much higher apoptosis-inducing ability than the intact complex, with involvement of caspase activation, mitochondria dysfunction, and interaction with cell membrane death receptors. H-RuBmp demonstrated a higher interaction potency with the cell membrane and induced higher levels of ROS overproduction in cancer cells to regulate the AKT, MAPK, and p53 signaling pathways. Taken together, this study could provide useful information for fine-tuning the rational design of next-generation metal medicines.

Biological evaluation of nitrile containing Ru(II) polypyridyl complexes as potential photodynamic therapy agents

The use of Ru complexes in light-mediated treatment of cancer (i.e. Photodynamic Therapy – PDT) has recently become extremely relevant with the entry into clinical trials of the first complex of this class against bladder cancer in the very near future. Herein, we report on the potential application as PDT agents of two inert Ru(II) polypyridyl complexes bearing a nitrile containing dppz ligand and two bipy or phen ancillary ligands for 1 and 2, respectively (dppz=dipyrido[3,2-a:2′,3′-c]phenazine, bipy=2,2′-bipyridine, phen=1,10-phenathroline). More specifically, a full characterization of the novel compound 2 was first performed. The distribution coefficients (log D) and 1O2 quantum yields in two solvent systems and at two irradiation wavelengths were then determined for both compounds. The phototoxicity of complexes 1 and 2 was evaluated on cervical cancer HeLa cells and on non tumorigenic retinal pigment epithelial (RPE1-hTERT) cells. None of the complexes was found to be phototoxic. In vitro fluorescence microscopy indicated a scarce cellular uptake for 2. The lack of biological activity for complexes 1 and 2 highlights that more investigations are required in order to understand the relationship between structure and biological activity for this class of compounds.

Unexpected high photothemal conversion efficiency of gold nanospheres upon grafting with two-photon luminescent ruthenium(II) complexes: A way towards cancer therapy?

The design and development of functional hybrid nanomaterials is currently a topic of great interest in biomedicine. Herein we investigated the grafting of Ru(II) polypyridyl complexes onto gold nanospheres (Ru@AuNPs) to improve the particles' near infrared (NIR) absorption, and ultimately allow for application in photothermal cancer therapy. As demonstrated in this article, these ruthenium(II) complexes could indeed significantly enhance gold nanospheres' two-photon luminescence (PTL) intensity and photothermal therapy (PTT) efficiency. The best dual functional nanoparticles of this study were successfully used for real-time luminescent imaging-guided PTT in live cancer cells. Furthermore, in vivo tumor ablation was achieved with excellent treatment efficacy under a diode laser (808 nm) irradiation at the power density of 0.8 W/cm2 for 5 min. This study demonstrates that the coupling of inert Ru(II) polypyridyl complexes to gold nanospheres allows for the enhancement of two-photon luminescence and for efficient photothermal effect.

Design, synthesis, DNA-binding affinity, cytotoxicity, apoptosis, and cell cycle arrest of Ru(II) polypyridyl complexes

A novel polypyridyl ligand CNPFIP (CNPFIP=2-(5(4-chloro-2-nitrophenyl)furan-2-yl)-1H-imidazo[4,5f][1,10]phenanthroline) and its mononuclear Ru(II) polypyridyl complexes of [Ru(phen)2CNPFIP]2+(1) (phen=1,10-phenanthroline), [Ru(bpy)2CNPFIP]2+(2) (bpy=2,2′-bipyridine), and [Ru(dmb)2CNPFIP]2+(3) (dmb=4,4′-dimethyl-2,2′-bipyridine) have been synthesized successfully and characterized thoroughly by elemental analysis, UV/Vis, IR, NMR, and ESI-MS. The interaction of the Ru(II) complexes with calf thymus DNA (CT-DNA) was investigated by absorption titration, fluorescence, viscosity measurements. The experimental results suggest that three complexes bind to CT-DNA through an intercalative mode and the DNA-binding affinity of complex 1 is greater than that of complexes 2 and 3. The photocleavage of plasmid pBR322 DNA by ruthenium complexes 1, 2, and 3 was investigated. We have also tested three complexes for their antimicrobial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria. The in vitro cytotoxicity of these complexes was evaluated by MTT assay, and complex 1 shows higher cytotoxicity than 2 and 3 on HeLa cells. The induced apoptosis and cell cycle arrest of HeLa cells were investigated by flow cytometry for 24h. The molecular docking of ruthenium complexes 1, 2, and 3 with the active site pocket residues of human DNA TOP1 was performed using LibDock.

Anticancer activity studies of a ruthenium(II) polypyridyl complex against human hepatocellular (BEL-7402) cells

A Ru(II) polypyridyl complex [Ru(bpy)2(HMSPIP)](ClO4)2 (1) (bpy=2,2′-bipyridine, HMSPIP=2-(4-methylsulfonyl)phenyl-1H-imidazo[4,5-f][1,10] phenanthroline) was synthesized. The IC50 value of the complex against human hepatocellular cell BEL-7402 is 21.6±2.7μM. The complex shows no cytotoxic activity toward human lung adenocarcinoma cell A549, human osteosarcoma cell MG-63 and human breast cancer cell SK-BR-3 cells. It is easily for complex 1 to be taken up by BEL-7402 cells. The complex can enhance the reactive oxygen species (ROS) levels and induce the decrease in the mitochondrial membrane potential. The complex inhibits the cell growth in BEL-7402 cells at G2/M phase. Complex 1 can regulate the expression of Bcl-2 family proteins. The results show that the complex induces apoptosis of BEL-7402 cells through a ROS-mediated mitochondrial dysfunction pathway.

Theoretical studies on interaction properties of chiral Ru(II) polypyridyl complexes with DNA

Theoretical studies on DNA-photocleavage mechanisms and abilities of chiral Ru(II) polypyridyl complexes have been carried out using the density functional theory (DFT) method. The stable DNA-docking models of chiral Ru(II) polypyridyl complexes were obtained using the docking and DFT methods. Based on the obtained DNA-docking models, the DNA-binding energies of chiral Ru(II) complexes were computed using UB3LYP and UB3LYP-D3 methods, and the trend in DNA-binding affinities of chiral Ru(II) polypyridyl complexes were reasonably explained. According to the distances between complexes and DNA, the reason of DNA-binding abilities of Δ-complexes stronger than those of Λ-complexes was also explained. In addition, the excited-state reduction potentials, electrons-transfer (ET) activation energies and intramolecular reorganization energies of chiral Ru(II) polypyridyl complexes were calculated and the DNA-photocleavage abilities were reasonably explained.

Lightening up Ruthenium Complexes to Fight Cancer?

In medicine, light is used in a medical treatment called photodynamic therapy (PDT) to treat some types of cancer and skin diseases. This technique generally allows for reduced side effects compared to traditional chemotherapy. However, PDT is not fully effective on hypoxic tumors (i.e. lacking oxygen). To overcome this important drawback, photoactivated chemotherapy (PACT) agents have been designed to obtain light-mediated cancer cell death via an oxygen-independent mechanism. Ruthenium complexes have already been and are currently deeply explored as traditional anticancer agents. However, as reported in this short review article, such compounds can also bring novel opportunities in the field of light-mediated cancer treatment. Herein, we report on our findings in the optimization of Ru(II) polypyridyl complexes as PDT and PACT agents for the potential treatment of cancer and, interestingly, also of bacterial infections.

ChemInform Abstract: Towards the Development of Functionalized Polypyridine Ligands for Ru(II) Complexes as Photosensitizers in Dye‐sensitized Solar Cells (DSSCs)

AbstractReview: 148 refs.

Benzimidazole-functionalized ancillary ligands for heteroleptic Ru(II) complexes: synthesis, characterization and dye-sensitized solar cell applications.

We have designed and synthesized heteroleptic Ru(ii) complexes with a pyridine-benzimidazole ligand (PYBI) for dye-sensitized solar cell (DSSC) applications. The PYBI ligand has major advantages by having the flexibility to introduce appropriate substituents at the four readily available positions through molecular engineering () compared to other ancillary bipyridyl-based ligands. We have substituted position A of the PYBI ligand with either electron-releasing triphenylamine () or pyrene (). We have also introduced 2-hexylthiophene at position A and 3,5-di tert-butyl phenyl group at position B of the PYBI ligand (). All three heteroleptic Ru(ii) complexes have been characterized by mass spectrometry, (1)H NMR, and absorption and emission spectroscopies as well as electrochemical methods. The absorption spectrum of complex is red-shifted and the emission spectrum is blue-shifted, when compared to the standard sensitizer. Testing of these newly designed heteroleptic Ru(ii) sensitizers has revealed that complex exhibits an efficiency of 7.88% using an I(-)/I3(-) redox electrolyte. Experimental observations corroborated by computational calculations have elucidated the high efficiency of complex , primarily due to the fact that the substituents at position A are more influential than those at position of B of the PYBI ligand.

Interactions of Ru(II) polypyridyl complexes with DNA mismatches and abasic sites.

Polypyridyl based ruthenium(II) complexes, [Ru(bpy)2(furphen)](PF6)2 (1) and [Ru(bpy)2(imiphen)](PF6)2 (2) {furphen: 2-(furan-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline and imiphen: 2-(1H-imidazol-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline} were synthesized and characterized by ESI-MS, NMR, UV-Visible and fluorescence spectroscopic techniques. The interaction of Ru(II) complexes with calf-thymus DNA (CT DNA) as well as oligonucleotides containing mismatches and abasic sites was studied along with unmodified control DNA. Based on absorption titration studies, binding constants (Kb) for the interaction of complexes 1 and 2 with DNA were found to be 6.7 ± 0.2 × 10(3) and 4.9 ± 0.2 × 10(4) M(-1), respectively. Hydrodynamic studies revealed weak interactions between the two complexes and CT-DNA. Luminescence studies revealed that both the complexes exhibit a five-fold increase in emission upon addition of CT-DNA. The integrated emission intensity of complexes 1 and 2 with CC mismatch oligonucleotides was 1.5 and 1.2 fold higher than that of control GC match oligonucleotides, respectively. Both the complexes did not show any specificity towards abasic or other mismatch sites except for CC mismatch. The results from this study provide an insight into the requirements of ligand shape in recognising DNA mutations such as mismatch and selectivity between DNA mismatches.

Synthesis and strong photooxidation power of a supramolecular hybrid comprising a polyoxometalate and Ru(ii) polypyridyl complex with zinc(ii)

A novel method for constructing supramolecular hybrids composed of polyoxometalates and photofunctional metal complexes was developed. A Ru(II) complex with phosphonate groups (RuP) strongly interacted with Zn(II) to afford a 2 : 1 trinuclear metal complex ([(RuP)2Zn](3+)). In dimethylsulfoxide, [(RuP)2Zn](3+) strongly interacted with a Keggin-type heteropolyoxometalate (Si-WPOM) to form a 1 : 1 hybrid ([(RuP)2Zn]-POM). Irradiation of [(RuP)2Zn]-POM in the presence of diethanolamine caused rapid accumulation of the one-electron reduced hybrid with a quantum yield of 0.99.

Emission spectroscopy of a ruthenium(ii) polypyridyl complex adsorbed on calcium niobate lamellar solids and nanosheets.

Ru(ii) tris-diimine complexes are known to exhibit emission at around 630 nm as a result of (1)MLCT photoexcitation. The emission is quenched in the presence of a suitable semiconductor solid due to electron injection from the excited state of a Ru(ii) complex to the conduction band of the adjacent semiconductor. Here we investigated emission quenching behaviour of Ru(II){(4,4'-(CH3)2-bpy)2(4,4'-(CH2PO3H2)2-bpy)} (bpy = 2,2'-bipryridine) adsorbed on HCa2Nb3O10 solids having an ordered lamellar structure or a disordered nanostructure. Even though electron injection from the excited state of the Ru complex to the conduction band of nanostructured HCa2Nb3O10 is thermodynamically less favorable than that of layered HCa2Nb3O10, faster electron injection was observed using nanostructured HCa2Nb3O10. Experimental results highlighted that electron injection from the excited Ru complex takes place not only in the conduction band of HCa2Nb3O10 but also mid-gap states whose density is strongly dependent on both the morphological feature and the preparation method of HCa2Nb3O10.

The biological effect of the nitroimidazole derivative of a polypyridyl ruthenium complex on cancer and endothelial cells.

The ruthenium polypyridyl complexes [Ru(dip)2(bpy/bpy-2-nitroIm)](2+) (dip = 4,7-diphenyl-1,10-phenanthroline, bpy = 2,2'-bipyridine, bpy-2-nitroIm = 4-[3-(2-nitro-1H-imidazol-1-yl)propyl]) were found to be ca. ten times more cytotoxic against breast cancer (4T1) and human lung adenocarcinoma epithelial cells (A549) than a well-known anticancer drug, cisplatin. Even though the Ru complexes were quite cytotoxic towards FVB mouse lung microvascular endothelial cells (MLuMEC FVB) their efflux from these non transformed cells was much more efficient than from cancer ones. Both Ru complexes accumulated in cells. The cellular uptake of both Ru complexes occurs through passive diffusion while the nitroimidazole derivative is also endocytosed. They arrest cell growth in the S-phase and induce apoptosis. Such cell response can result from activation of oxidative stress by Ru complexes. The modulation of the mRNA expression profile for genes which might be involved in metastasis and angiogenesis processes by Ru complexes was analyzed for both cancer (4T1) and endothelial (MLuMEC FVB) cells. Ru complexes appeared to have a distinct impact on cell adhesion and migration as well as they affect endothelial cell vasculature. They are not only cytotoxic but are also potentially invasive and anti-metastatic agents. This work illustrates the putative future development of polypyridyl ruthenium.

Varying the electronic structure of surface-bound ruthenium(II) polypyridyl complexes.

In the design of light-harvesting chromophores for use in dye-sensitized photoelectrosynthesis cells (DSPECs), surface binding to metal oxides in aqueous solutions is often inhibited by synthetic difficulties. We report here a systematic synthesis approach for preparing a family of Ru(II) polypyridyl complexes of the type [Ru(4,4'-R2-bpy)2(4,4'-(PO3H2)2-bpy)](2+) (4,4'(PO3H2)2-bpy = [2,2'-bipyridine]-4,4'-diylbis(phosphonic acid); 4,4'-R2-bpy = 4,4'-R2-2,2'-bipyridine; and R = OCH3, CH3, H, or Br). In this series, the nature of the 4,4'-R2-bpy ligand is modified through the incorporation of electron-donating (R = OCH3 or CH3) or electron-withdrawing (R = Br) functionalities to tune redox potentials and excited-state energies. Electrochemical measurements show that the ground-state potentials, E(o')(Ru(3+/2+)), vary from 1.08 to 1.45 V (vs NHE) when the complexes are immobilized on TiO2 electrodes in aqueous HClO4 (0.1 M) as a result of increased Ru dπ-π* back-bonding caused by the lowering of the π* orbitals on the 4,4'-R2-bpy ligand. The same ligand variations cause a negligible shift in the metal-to-ligand charge-transfer absorption energies. Emission energies decrease from λmax = 644 to 708 nm across the series. Excited-state redox potentials are derived from single-mode Franck-Condon analyses of room-temperature emission spectra and are discussed in the context of DSPEC applications.

New photosensitizers containing the dipyridoquinoxaline moiety and their use in dye-sensitized solar cells

New Ru(II) polypyridyl complexes containing two N, N bidentate ligands, [Ru(phendione)2dpq(COOH)2](BF4)2 (L101), {Ru(phendione)[dpq(COOH)2]2}(BF4)2 (L102) and [Ru(phendione)dpq(COOH)2 (SCN)2](L103), (phendione=5,6 dione-1,10-phenanthroline and dpq(COOH)2=6,7-dicarboxylicdipyrido[2,2-d:2′,3′f]quinoxaline) have been synthesized and characterized, and attached to a TiO2 substrate to be tested as solar cell sensitizers. We found that the solar to electricity conversion efficiency of cell is strongly affected by the type of ancillary ligand, the efficiency of L102 (with one phendione moiety) adsorbed on TiO2 nanocrystalline films being 2.5 times as large as that of L101 (with two phendione moieties) adsorbed on the same films. The effect of ancillary ligand on the photovoltaic performance of the complexes was compared to results of computational methods by ab initio DFT molecular dynamics simulations and quantum dynamics calculations of electronic relaxation to investigate the interfacial electron transfer in L101–103/TiO2-anatase nanostructures. It is found that the primary process in the interfacial electron-transfer dynamics involves an ultrafast (τ1=6fs) electron-injection. The concepts of attribute ancillary ligand substitution and HOMO–LUMO alignment of dye with conduction band of semiconductor and electrolyte redox state are shown very helpful for tuning the photovoltaic properties and the rational architecture of polypyridyl photosensitizer with anticipated good properties.

Ruthenium(II) polypyridyl complexes: synthesis, cytotoxicity in vitro, reactive oxygen species, mitochondrial membrane potential and cell cycle arrest studies

Two Ru(II) polypyridyl complexes [Ru(dmb)2(idpq)](ClO4)2 (1) (idpq = indeno[1,2-b]dipyrido[3,2-f:2′,3′-h]-quinoxaline-6-one, dmb = 4,4′-dimethyl-2,2′-bipyridine) and [Ru(bpy)2(idpq)](ClO4)2 (2) (bpy = 2,2′-bipyridine) have been synthesized and characterized. Their in vitro cytotoxicities, apoptosis, cellular uptake, production of reactive oxygen species (ROS), mitochondrial membrane potential assays and effects on cell cycle distribution were studied. The IC50 values range from 13.1 ± 1.1 to 30.9 ± 3.1 μM. Complex 1 is toxic to HeLa cells with an IC50 value of 13.1 ± 1.1 μM, while complex 2 shows relatively high cytotoxicity against HepG-2 cells. However, both complexes exhibit lower cytotoxicity than cisplatin toward selected cell lines under identical conditions. Both complexes can induce apoptosis and cell cycle arrest at the S and G0/G1 phases in HeLa cells, respectively. In addition, both Ru(II) complexes, which can be effectively taken up by HeLa cells, induced generation of intracellular ROS in a concentration-dependent manner and produced a decrease in mitochondrial membrane potential. The results show that these complexes induce apoptosis in HeLa cells through a ROS-mediated mitochondrial dysfunction pathway.

Light Harvesting and Charge Separation in a π-Conjugated Antenna Polymer Bound to TiO2

This paper describes the photophysical and photoelectrochemical characterization of a light harvesting polychromophore array featuring a polyfluorene backbone with covalently attached Ru(II) polypyridyl complexes (PF-Ru-A), adsorbed on the surface of mesostructured TiO2 (PF-Ru-A//TiO2). The surface adsorbed polymer is characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, providing evidence for the morphology of the surface adsorbed polymer and the mode of binding. Photoexcitation of the Ru(II) complexes bound to the metal oxide surface (proximal) results in electron injection into the conduction band of TiO2, which is then followed by ultrafast hole transfer to the polymer to form oxidized polyfluorene (PF+). More interestingly, chromophores that are not directly bound to the TiO2 interface (distal) that are excited participate in site-to-site energy transfer processes that transport...

Electrocatalytic Reduction of Carbon Dioxide: Let the Molecules Do the Work

This review summarizes the development of electrochemical CO2 reduction catalysts in the UNC Energy Frontier Research Center for Solar Fuels. Two strategies for converting CO2 to CO or formate have been explored. In one, polypyridyl complexes of Ru(II) have been used to reduce CO2 to CO in acetonitrile and in acetonitrile/water mixtures. In the absence of CO2 water is reduced to H2 by these complexes. With added weak acids in acetonitrile with added water and CO2, reduction to syngas mixtures of CO and H2 is observed. A single polypyridyl complex of Ru(II) has been shown to be both a catalyst for water oxidation and CO2 reduction in an electrochemical cell for CO2 splitting into CO and O2. In parallel, Ir pincer catalysts have been shown to act as selective electrocatalysts for reducing CO2 to formate in acetonitrile with added water and in pure water without competition from electrocatalytic H2 production. Details of the catalytic mechanisms of each have also been investigated.

Targeting nucleus DNA with a cyclometalated dipyridophenazineruthenium(II) complex.

Recently, coordinatively saturated and substitutionally inert Ru(II) complexes have been investigated as anticancer agents. Herein a cyclometalated Ru(II) complex, [Ru(bpy)(phpy)(dppz)](+), was found to be rapidly taken up by cancer cells, and nearly 90% of the complex accumulated in the nuclei of cancer cells after a 2 h incubation. The anticancer activity of this complex was screened against a panel of cancer cell lines. Remarkably, it exhibited IC50 values that were an order of magnitude lower than those of cisplatin. This complex also displayed potencies superior to those of cisplatin against 3D tumor spheroids. Further studies revealed that the high DNA binding affinity of [Ru(bpy)(phpy)(dppz)](+) resulted in effective disruption of the binding of transcription factor NF-κB to DNA sequences, thereby inhibiting cellular transcription and leading to irreversible cancer cell apoptosis. Our work provides new insights into understanding the biological interactions and anticancer molecular mechanisms of DNA-specific Ru(II) polypyridyl complexes.

Rolling cycle amplification based single-color quantum dots–ruthenium complex assembling dyads for homogeneous and highly selective detection of DNA

In this work, a new, label-free, homogeneous, highly sensitive, and selective fluorescent biosensor for DNA detection is developed by using rolling-circle amplification (RCA) based single-color quantum dots–ruthenium complex (QDs–Ru) assembling dyads. This strategy includes three steps: (1) the target DNA initiates RCA reaction and generates linear RCA products; (2) the complementary DNA hybridizes with the RCA products to form long double-strand DNA (dsDNA); (3) [Ru(phen)2(dppx)]2+ (dppx=7,8-dimethyldipyrido [3,2-a:2′,3′-c] phenanthroline) intercalates into the long dsDNA with strong fluorescence emission. Due to its strong binding propensity with the long dsDNA, [Ru(phen)2(dppx)]2+ is removed from the surface of the QDs, resulting in restoring the fluorescence of the QDs, which has been quenched by [Ru(phen)2(dppx)]2+ through a photoinduced electron transfer process and is overlaid with the fluorescence of dsDNA bonded Ru(II) polypyridyl complex (Ru-dsDNA). Thus, high fluorescence intensity is observed, and is related to the concentration of target. This sensor exhibits not only high sensitivity for hepatitis B virus (HBV) ssDNA with a low detection limit (0.5pM), but also excellent selectivity in the complex matrix. Moreover, this strategy applies QDs–Ru assembling dyads to the detection of single-strand DNA (ssDNA) without any functionalization and separation techniques.