Luminescent Ruthenium Complexes Research Articles

Luminescent Ruthenium(II) Complexes Used for the Detection of 8-Oxoguanine in the Human Telomeric Sequence.

Detecting cancer at the early stage of the disease is crucial to keep the best chance for successful treatment. The recent development of genomic screening, a methodology that is addressed to asymptomatic patients presumably at risk of carcinogenesis, has stimulated the quest for new tools able to signal the level of risk. Carcinogenesis has been associated to chronic oxidative stress exceeding the antioxidant defenses and leading to critical genome alteration levels. The telomeric regions are presumably the most exposed to oxidative stress due to their high concentration of guanine (i.e., the easiest oxidizable nucleic base). Accumulation of 8-oxoguanine in telomeres, thus oxidative lesions, was reportedly associated with telomeric crisis and carcinogenesis. In this study, we report on the capacity of Ru(II) polyazaaromatic complexes to photoprobe 8-oxoguanine into the human telomeric sequence with the view of developing new tools for cancer risk screening.

A Photostable 1D Ruthenium−Zinc Coordination Polymer as a Multimetallic Building Block for Light Harvesting Systems

AbstractA luminescent ruthenium complex bearing two 2,6‐di(quinolin‐8‐yl)‐pyridine carboxylic acid (dqpCOOH) ligands has been successfully synthesised and fully characterised. The new metalloligand has been coordinated to zinc ions through the terminal carboxylate groups using a one‐step solvothermal method, to give a multimetallic photoactive 1D coordination polymer, Ru−(dqpCOO)−Zn−(OOCH)2. Through use of X‐ray crystallography, advanced microscopy techniques as well as photophysical studies, we have extensively characterised the coordination polymer. The optical properties of the ruthenium complex and corresponding coordination polymer show that the material experiences a dramatic increase in photostability compared to the free parent metalloligand, in solution. Electrochemical measurements of the coordination polymer also confirm the RuII/RuIII redox couple is maintained in the polymeric network. The development of this material gives a new strategy in the design of novel photoactive materials as multimetallic building blocks for their use in light‐based applications.

Mitochondria-Targeting Click-Derived Pyridinyltriazolylmethylquinoxaline-Based Y-Shaped Binuclear Luminescent Ruthenium(II) and Iridium(III) Complexes as Cancer Theranostic Agents.

Due to several negative issues, market available drugs have been gradually losing their importance in the treatment of cancer. With a view to discover suitable drugs capable of diagnosing as well as inhibiting the growth of cancer cells, we have aspired to develop a group of theranostic metal complexes which will be (i) target specific, (ii) cytoselective, thus rendering the normal cell unaffected, (iii) water-soluble, (iv) cancer cell permeable, and (v) luminescent, being beneficial for healing the cancer eternally. Therefore, to reach our goal, we have prepared novel Ru(II)- and Ir(III)-based bimetallic and hetero bimetallic scaffolds using click-derived pyridinyltriazolylmethylquinoxaline ligands followed by metal coordination. Most of the compounds have displayed significant cytoselectivity against colorectal adenocarcinoma (Caco-2) and epithiloid cervical carcinoma (HeLa) cells with respect to normal human embryonic kidney cells (HEK-293) compared to cisplatin [cis-diamminedichloroplatinum(II)] along with excellent binding efficacy with DNA as well as serum albumin. Complex [(η6-p-cymene)(η5-Cp*)RuIIIrIIICl2(K2-N,N-L)](PF6)2 [RuIrL] exhibited the best cytoselectivity against all the human cancer cells and was identified as the most significant cancer theranostic agent in terms of potency, selectivity, and fluorescence quantum yield. Investigation of the localization of complex [Ir2L] and [RuIrL] in the more aggressive colorectal adenocarcinoma cell HT-29 indicates that mitochondria are the key cellular target for destroying cancer cells. Mitochondrial dysfunction and G2/M phase cell cycle arrest in HT-29 cell were found to be involved in the apoptotic cell death pathway induced by the test complexes [Ir2L] and [RuIrL]. These results validate the concept that these types of complexes will be reasonably able to exert great potential for tumor diagnosis as well as therapy in the near future.

Latent fingermark detection using functionalised silicon oxide nanoparticles: Optimisation and comparison with cyanoacrylate fuming

Among the different types of nanoparticles (NPs) proposed for fingermark detection, silicon oxide nanoparticles (SiO2 NPs) are arguably the most promising due to their unique characteristics. In this study, carboxyl-functionalised SiO2 NPs doped with luminescent ruthenium complex—RuBpy-doped CES-SiO2 NPs—were further studied to investigate their effectiveness for latent fingermark detection. A modified version of the functionalised SiO2 NPs with a lower amount of surface functionalisation is proposed for improved fingermark detection effectiveness. A shaking incubator was also incorporated into the fingermark detection process to offer a more viable treatment approach in comparison to the previously published method. The shaking incubator offered a more robust application approach, as well as improved fingermark detection quality. To gain an insight into fingermark detection effectiveness relative to benchmark techniques, the performance of the optimised RuBpy-doped CES-SiO2 NPs was compared to that of a benchmark fingermark detection method—cyanoacrylate fuming (CAF) followed by luminescent dye staining. Relative fingermark detection effectiveness across the two techniques was evaluated via the treatment of 1724 fingermark specimens. It was concluded that, in general, the benchmark method provided superior detection results. It was evident that the SiO2 NPs are less affected by donor variability but are more dependent on substrate types. Such characteristics are encouraging as they could be favourable to practitioners in casework scenarios where the substrate is known but donor variability is obscure prior to fingermark processing. It should be noted that the overall effectiveness of the proposed NP-based technique will need to be improved before it could be considered for operational implementation.

Latent fingermark detection using functionalised silicon oxide nanoparticles: Method optimisation and evaluation

The application of nanoparticles for latent fingermark detection has been reported in the literature over the past two decades. One of the nanoparticles that shows promise to become a routine technique is functionalised silicon oxide nanoparticles (SiO2 NPs). In a recent optimisation of the technique, the use of carboxyl-functionalised SiO2 NPs doped with luminescent ruthenium complex was proposed as a breakthrough for latent fingermark detection.In this study, the aforementioned functionalised SiO2 NPs were extensively evaluated. Modification and optimisation of the original detection parameters were performed to enhance detection quality and improve applicability. Various detection parameters were evaluated and assessed. A lower concentration of the functionalised nanoparticles used in the colloidal dispersion was determined to offer improved detection effectiveness. A combination of increased bath temperature and reduced immersion time was found to produce good overall results. A set of modified detection parameters was suggested for the use of the functionalised SiO2 NPs to detect latent fingermarks. Performance of the modified detection parameters was compared against that of the published detection method. Comparison experiments were carried out on fingermark specimens deposited on aluminium foil, transparent polypropylene plastic and green polyethylene plastic. Three donors (weak, average and strong) and two age intervals (ten days and three months) were considered in the comparison study. Evaluation of the results suggested that the overall performance of the modified method for latent fingermark detection was superior to that obtained using the previously published detection parameters.

A fluorometric turn-on aptasensor for mucin 1 based on signal amplification via a hybridization chain reaction and the interaction between a luminescent ruthenium(II) complex and CdZnTeS quantum dots

A fluorometric method is described for the determination of the tumor biomarker mucin 1 (MUC1). It is based on signal amplification of the hybridization chain reaction (HCR), and the interaction between a luminescent ruthenium(II) complex and CdZnTeS quantum dots (QDs). If MUC1 bind to the biotin-labeled aptamer, it will initiate HCR with hairpins H1 and H2 to form a long-range dsDNA. The long nucleic acid chains are then linked on the surface of streptavidin-modified magnetic microparticles (MMPs) through streptavidin-biotin interaction. The luminescent ruthenium(II) complex is then embedded in the long dsDNA linked to the MMPs. Hence, there is little Ru complex in the supernatant after magnetic separation, and the fluorescence of the CdZnTeS QDs (best measured at excitation/emission wavelengths of 350/530nm) is only slightly quenched. In the absence of target, the fluorescence of the CdZnTeS QDs is strongly quenched. Fluorescence increases linearly in the 0.2-100ng·mL-1 MUC1 concentration range, and the LOD is 0.13ng·mL-1 (at S/N= 3). The method was applied to the determination of MUC1 in spiked human serum samples. Graphical abstract A fluorometric turn-on aptasensor for mucin 1 is described that is based on theinteraction between aRu(II) complex and quantum dots (QDs). The detection system includes biotin-labeled aptamer-H0, hairpins H1 and H2, streptavidin-modified magnetic microparticles (MMPs), Ru(bpy)2(dppx)2+ and CdZnTeS QDs.

Luminescent Ruthenium(II) Polypyridine Complexes for a Wide Variety of Biomolecular and Cellular Applications.

Ruthenium(II) polypyridine complexes are one of the most extensively studied and developed systems in the family of luminescent transition-metal complexes. Notably, there has been a large amount of interest in the biological applications of these luminescent ruthenium(II) complexes because of their rich photophysical and photochemical properties. In this Viewpoint, we explore past and recent works on the possible biological and cellular applications of these promising complexes, with a focus on their use as bioimaging reagents, biomolecular probes, and phototherapeutic agents.

Luminescent ruthenium(II) polypyridyl complexes acted as radiosensitizer for pancreatic cancer by enhancing radiation-induced DNA damage.

Background: Pancreatic cancer is a highly lethal malignancy which ranks 4th most common cause of cancer death in US and 6th in China. Novel drugs are required to improve the survival and prognosis of patients.Methods: Ruthenium(II) complexes with variation number of DIP ligand were synthesized and further adopted as radiosensitizer for pancreatic cancer. The influence of ruthenium(II) complexes on cell behaviors and tumor growth were investigated. The DNA binding affinity of ruthenium(II) complexes and plasmid was measured by using agarose gel electrophoresis.Results: Luminescent ruthenium(II) complex can rapidly enter into cell nuclei and consequently combine with DNA, resulting in the enhanced DNA damage induced by X-ray irradiation. Upon intratumoral injection of ruthenium(II) complex, excellent tumor growth inhibition was accomplished under ionizing radiation of human pancreatic cancer xenograft nude mice.Conclusions: Taken together, our study suggest that the ruthenium(II) polypyridyl complexes can effectively enhance radiation-induced DNA damage, which is likely to benefit the imaging-guided cancer radio-chemotherapy.

Mesoporous silica coating NaYF4:Yb,Er@NaYF4 upconversion nanoparticles loaded with ruthenium(II) complex nanoparticles: Fluorometric sensing and cellular imaging of temperature by upconversionand ofoxygenby downconversion.

Accurate detection of temperature and oxygen concentration at the cellular level is important in tumor diagnosis. Multifunctional nanocomposites are described that consist of upconversion luminescent nanoparticles capped with mesoporous silica and loaded with an oxygen-sensitive luminescent ruthenium complex. The nanocomposites of type NaYF4:Yb,Er@NaYF4@mSiO2-Ru have two modes of operation: Its red downconversion luminescence (at excitation/emission peaks of 455/606nm) is quenched by oxygen (O2), and this is used to sense and image O2. The green upconversion luminescence (typically acquired at excitation/emission wavelengths of 980/525 and 544nm), in turn, is used to measure temperature. The nanocomposites were then applied to dual mode in-vitro imaging of temperature and O2 in hepatocellular carcinoma cells (HepG-2). Graphical abstract A new multifunctional nanocomposite of mesoporous silica coating NaYF4:Yb,Er@NaYF4 upconversion nanopaticless loaded with ruthenium (II) complex has been designed with both green upconversion and red downconversion luminescence for temperature detection, oxygen sensing and dual mode cell imaging.

Highly Stable and NIR Luminescent Ru-LPMSN Hybrid Materials for Sensitive Detection of Cu2+ in Vivo.

Herein, new near-infrared (NIR) luminescent ruthenium complexes were prepared for detecting Cu2+ ions. Then, ruthenium complex hybrid nanomaterials (Ru-LPMSNs) were fabricated successfully by imbedding the ruthenium complex into mesoporous silica nanoparticles. Benefiting from the novel large-pore mesoporous structure and good adsorbility of LPMSNs, Ru-LPMSN hybrid materials showed a significantly enhanced fluorescence intensity and stability. NIR fluorescence of Ru-LPMSNs was rapidly quenched by Cu2+ ions. Ru-LPMSNs also showed high Cu2+ ion selectivity and sensitivity as a sensor. The detection limit of Cu2+ ions was 10 nM with a wide linear relationship between the fluorescence intensity of Ru-LPMSNs and the concentration of Cu2+ ions. The mechanism of fluorescence quenching might be that the combination of the ruthenium complex and Cu2+ ions constrained the photoinduced electron-transfer process. Furthermore, Ru-LPMSNs dramatically increased the fluorescence signals in cells and achieved Cu2+-ion detection. Ru-LPMSNs had different tissue affinities and could monitor distribution of exogenous Cu2+ ions in vivo. Moreover, Ru-LPMSNs realized direct and rapid detection of Cu2+-ion content in serum. These results indicated the potential applications of the prepared nanomaterials as Cu2+ detection agents.

Controlling Second Coordination Sphere Effects in Luminescent Ruthenium Complexes by Means of External Pressure.

Two luminescent heteroleptic RuII complexes with a 2,2'-biimidazole (biimH2 ) ligand form doubly hydrogen-bonded salt bridges to 4-sulfobenzoate anions in single crystals. The structure of one of these cation-anion adducts shows that the biimH2 ligand is deprotonated. Its 3 MLCT luminescence band does not shift significantly under the influence of an external hydrostatic pressure, a behavior typical for these electronic transitions. In contrast, hydrostatic pressure on the other crystalline cation-anion adduct induces a shift of proton density from the peripheral N-H groups of biimH2 towards benzoate, leading to a pronounced redshift of the 3 MLCT luminescence band. Such a significant and pressure-tunable influence from an interaction in the second coordination sphere is unprecedented in artificial small-molecule-based systems.

Synthesis, characterisation, cellular uptake and cytotoxicity of functionalised magnetic ruthenium (II) polypyridine complex core-shell nanocomposite

The development of multifunctional nanoparticles comprising of a magnetic core in conjunction with appropriate molecules with capabilities to impart functionalities like luminescent, specific binding sites to facilitate attachment of moieties. This has attracted increasing attention and enables identification of promising candidates using for applications such as diagnostics and cure through early detection and localized delivery. Many studies have been performed on the synthesis and cellular interactions of core–shell nanoparticles, in which a functional inorganic core is coated with a biocompatible polymer layer that should reduce nonspecific uptake and cytotoxicity Here we report the synthesis and characterisation of multifunctional core-shell magnetic, luminescent nanocomposite (Fe3O4@SiO2@[Ru(Phen)3]2+@SiO2@NH2). Fe3O4 as core and a luminescent ruthenium (II) complex encapsulated with silica shell, and then it is functionalized by an amine group by APTMS. The magnetic, luminescent, and biological activity of this multifunctional nanocomposite have also been studied to prove the nanocomposite is biocompatible, cellular uptake. The synthesized nanocomposite was completely characterized by X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), and emission spectroscopy. MTT assay and cellular uptake by flow cytometry results proved that magnetic ruthenium (II) polypyridine complex – core shell nanocomposite has biocompatibility, minimum cytotoxicity and internalized inside B16F10 cells and confirms the potential biomedical applications.

Luminescent Ruthenium Complex Labels for Correlative Microscopy.

Luminescent Ruthenium Complex Labels for Correlative Microscopy.

CuAAC click reactions for the design of multifunctional luminescent ruthenium complexes

CuAAC (Cu(i) catalyzed azide-alkyne cycloaddition) click chemistry has emerged as a versatile tool in the development of photoactive ruthenium complexes with multilateral potential applicability. In this contribution we discuss possible synthetic approaches towards CuAAC reactions with ruthenium(ii) polypyridine complexes and their differences with respect to possible applications. We focus on two main application possibilities of the click-coupled ruthenium assemblies. New results within the development of ruthenium based photosensitizers for the field of renewable energy supply, i.e. DSSCs (dye-sensitized solar cells) and artificial photocatalysis for the production of hydrogen, or for anticancer photodynamic therapeutic applications are reviewed.

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.

Improving the Anticancer Efficacy of Laminin Receptor-Specific Therapeutic Ruthenium Nanoparticles (RuBB-Loaded EGCG-RuNPs) via ROS-Dependent Apoptosis in SMMC-7721 Cells.

Functionalization can promote the uptake of nanoparticles into cancer cells via receptor-mediated endocytosis, enabling them to exert their therapeutic effects. In this paper, epigallocatechin gallate (EGCG), which has a high binding affinity to 67 kDa laminin receptor (67LR) overexpressed in HCC cells, was employed in the present study to functionalized ruthenium nanoparticles (RuNPs) loaded with luminescent ruthenium complexes to achieve antiliver cancer efficacy. [Ru(bpy)2(4-B)] (ClO4)2·2H2O (RuBB)-loaded EGCG-RuNPs (bpy = 2,2'-bipyridine) showed small particle size with narrow distribution, better stability, and high selectivity between liver cancer and normal cells. The internalization of RuBB-loaded EGCG-RuNPs was inhibited by 67LR-blocking antibody or laminin, suggesting that 67LR-mediated endocytosis played an important role in the uptake into HCC cells. Moreover, transmission electron microscopy and confocal microscopic images showed that RuBB-loaded EGCG-RuNPs accumulated in the cytoplasm of SMMC-7721 cells. Furthermore, our results indicated that the EGCG-functionalized nanoparticles displayed enhanced anticancer effects in a target-specific manner. Concentrations of RuBB-loaded EGCG-RuNPs, nontoxic in normal L-02 cells, showed direct reactive oxygen species-dependent cytotoxic, pro-apoptotic, and anti-invasive effects in SMMC-7721 cells. Furthermore, in vivo animal study demonstrated that RuBB-loaded EGCG-RuNPs possessed high antitumor efficacy on tumor-bearing nude mice. It is encouraging to conclude that the multifunctional RuNPs may form the basis of new strategies on the treatment of liver cancer and other malignancies.

Luminescent ruthenium(II) complex bearing bipyridine and N-heterocyclic carbene-based C∧N∧C pincer ligand for live-cell imaging of endocytosis.

Luminescent ruthenium(II)-cyanide complex with N-heterocyclic carbene pincer ligand C∧N∧C = 2,6-bis(1-butylimidazol-2-ylidene)pyridine and 2,2′-bipyridine (bpy) shows minimal cytotoxicity to both human breast carcinoma cell (MCF-7) and human retinal pigmented epithelium cell (RPE) in a wide range of concentration (0.1–500 μM), and can be used for the luminescent imaging of endocytosis of the complex in these cells.

A luminescent ruthenium(II) complex for light-triggered drug release and live cell imaging.

We report a novel ruthenium(II) complex for selective release of the imidazole-based drug econazole. While the complex is highly stable and luminescent in the dark, irradiation with green light induces release of one of the econazole ligands, which is accompanied by a turn-off luminescence response and up to a 34-fold increase in cytotoxicity towards tumour cells.

In cellulo protein labelling with Ru-conjugate for luminescence imaging and bioorthogonal photocatalysis.

Labelling of proteins with a luminescent ruthenium complex enables the direct visualization and photocatalytic reduction of aryl azide in live cells. The confinement of catalysis to the labeled proteins was visualized using an azide-based immolative linker releasing a precipitating dye.

Luminescent azide and thiocyanate phosphine complexes of ruthenium(II) with acetonitrile as co-ligand

Four novel luminescent ruthenium(II) complexes of general formulas [RuH(X)(MeCN)(CO)(PPh3)2] and [Ru(X)2(MeCN)(PPh3)2] (where X=N3−, NCS−) were synthesized and characterized by IR, NMR, UV–Vis spectroscopy, X-ray crystallography and electrochemical studies. The emission properties of the complexes were studied at ambient and low temperatures. The quantum yields of fluorescence, lifetimes and nature of the excited states were discussed based on molecular properties. To elucidate the structural, spectroscopic and bonding properties of obtained complexes, calculations at the DFT level were undertaken. The received azide and thiocyanate analogs of precursor complexes, [RuHCl(CO)(PPh3)3] and [RuCl2(PPh3)3], exhibit luminescence properties at ambient temperature as well as at the temperature of liquid nitrogen (77K). The carefully studies of the emissive excited states nature, play an important role in understanding the luminescent properties of phosphine ruthenium(II) complexes, which are poorly characterized in that field. The emission spectra, the decay times, the quantum yields of luminescence in correlation with electrochemistry and quantum–mechanical calculations indicate that, in the creation of excited states of the complexes engaged are both the metal d orbitals and pseudohalide ligands orbitals.