Ruthenium Complexes Research Articles

Artificial Neural Network-Based Validation, DFT, Thermal and Biological Evaluation of 4-Aminoantipyrine-Derived Ru(III) Complexes.

New methodologies have been evaluated for validating analytical characterization with artificial neural networks (ANNs). Compared to previous machine learning models, these provide more accurate and automated results with high testing accuracy. The Schiff base ruthenium complexes used in the proposed study were synthesized using 4-aminoantipyrine derivatives. 4-Aminoantipyrine is a biologically active pharmacophore. The geometry of the complexes was confirmed by IR, electronic, and magnetic measurements. XRD analysis pointed out the nanocrystalline behavior of the chelates. The molecular structures have been optimized using DFT calculations. The ruthenium complexes are one of the main chemotherapeutic agents in anticancer therapy over platinum drugs due to a wide range of peculiarities. Complexes exhibit octahedral geometry as confirmed by magnetic measurements exhibiting more biological activity. The complexes are redox active depicting high biological potency. The Ru chelates also display high photocatalytic efficiency. The chelates also adhere to Lipinski's rule of five as evidenced from mole inspiration calculations. Among the chelates, RuL3 exhibits high anticancer potency suggesting a valuable candidate for the treatment of cancer. RuL5 has high antibacterial efficiency, and RuL4 complex possesses high antifungal activity. The chelates may serve as potential antimicrobial agents.

Tolane-Based Phosphino- and Arsino-Ruthenium Complexes in Three Different Oxidation States: Ru(I), Ru(II) and Ru(III).

Targeting Ru(III) and Ru(I) η2-alkyne species, 2,2'-(iPr2E)2-substituted diphenylacetylenes (1-E, E = P, As) were em-ployed for the pre-paration of [ECCE]-coordinated ruthenium com-plexes. The re-actions between 1-E and cis-(MeCN)2(COD)RuCl2 led to the required Ru(II) starting materials cis-[ECCE]RuCl2(MeCN) (3-E). Upon oxi-dation of 3-E with PhICl2, the Ru(III) target com-plexes [ECCE]RuCl3 (7-E) were detectable for E = P and E = As, but only the arsa-deriva-tive 7-As was obtained in a pure form, namely via oxi-da-tion of cis-[AsCCAs]RuCl2(THT) (THT = tetrahydrothiophene). Upon re-duction of compounds 3-E, a hitherto unprecedented Ru(I) η2-alkyne complex, [PCCP]RuCl (9), was obtained for E = P. The former square planar Ru(I) complex (9) was characterized com-prehensively and examined in detail by means of DFT and CASSCF calculation. Upon treatment of 9 with TlPF6, a diamagnetic µ-Tl-bridged compound (10) with a nearly linear Ru-Tl-Ru array was formed and isolated in high yields. Careful analysis of the bonding situation suggested that the Ru-Tl-Ru moiety in 10 is best interpreted in terms of a 3c-4e- bond.

Enhanced Electrochemiluminescence from Ruthenium-Tagged Immune Complex at Flexible Chains for Sensitive Analysis of Glutamate Decarboxylase Antibody

Herein, a sensitive electrochemiluminescence (ECL) immunosensor is designed by immobilizing ruthenium-tagged immune complexes at flexible poly-ethylene-glycol (PEG) chains on the electrode surface, which offers more freedom for the collision of the ruthenium complex at the electrode during the initial ECL reaction. The electrochemical characterizations confirm the loose structure of the assembled layer with the immune complex, providing an increase in the current and the resultant enhanced ECL emissions. Comparing the sensors with the rigid structure, a 34-fold increase in the maximal ECL emission is recorded when PEG3400 is used as a linker. Using the optimized protocol, the prepared immunosensor exhibits a wide-ranging linear response to the model antibody (glutamate decarboxylase antibody) ranging from 10 pg/mL to 10 ng/mL. The detection limit is almost two orders lower than the value using the classic enzyme-linked immunosorbent assay, which offers a new design to enhance ECL emissions and the resultant analytical performance.

A Ruthenium(II) Complex With a Two‐Armed Benzimidazole Ligand as the G‐Quadruplex Luminescent Probe

ABSTRACTThe selective detection of G‐quadruplex DNA has the potential to reveal its biological function and provide important information for cancer diagnosis and treatment. Herein, a ruthenium(II) complex containing a two‐armed benzimidazole ligand (bimbpy) (RC1) has been developed as a selective luminescence probe toward G4 DNA. RC1 exhibited distinguishable luminescence response to G4 DNA, such as HTDNA, c‐MYC, and 22AG. Especially, in the presence of HTDNA, the luminescence intensity of RC1 increased to 6.1‐fold. The limit of detection is 30 nM for HTDNA. However, it showed a small change in luminescence intensity against doubled‐strand and single‐strand DNA. The DNA binding experimental results indicated that RC1 effectively stabilized G4 DNA through hydrogen bonds and π‐π stacking. The selectivity of RC1 to G4 DNA might be due to the increase in the rigidity of the two‐armed benzimidazole ligand after binding to G4 DNA. Therefore, the design of ruthenium(II) complexes with a two‐armed ligand will be an effective method to obtain Ru(II)‐based G‐quadruplex luminescent probes by adjusting the degree of rigidity of the two arms.

Synthesis and Evaluation of Cytotoxic Activity of RuCp(II) Complexes Bearing (Iso)nicotinic Acid Based Ligands

Background/Objectives: Cancer remains one of the major challenges of our century. Organometallic ruthenium complexes are gaining recognition as a highly promising group of compounds in the development of cancer treatments. Methods: Building on the auspicious results obtained for [Ru(η5-C5H5)(PPh3)(bipy)][CF3SO3] (TM34), our focus has shifted to examining the effects of incorporating bioactive ligands into the TM34 framework, particularly within the cyclopentadienyl ring. Results: In this study, we report the synthesis and characterization of two new ruthenium(II) complexes with the general formula [Ru(η5-C5H4CCH3=R)(PPh3)(bipy)][CF3SO3], where R represents a nicotinic acid derivative (NNHCO(py-3-yl)) (1) or an isoniazid derivative (NNHCO(py-4-yl)) (2). The complexes were fully characterized using a combination of spectroscopic techniques and computational analysis, revealing the presence of E/Z-hydrazone isomerism. Stability studies confirmed the robustness of both complexes in biological media, with compound 1 maintaining good stability in buffer solutions mimicking physiological (pH 7.4) and tumor-like (pH 6.8) environments. The cytotoxicity of the complexes was evaluated in vitro in several human cancer cell lines, namely melanoma (A375), alveolar adenocarcinoma (A549), epidermoid carcinoma (A431), and breast cancer (MDA-MB 231). Conclusions: Both compounds exhibited moderate to high cytotoxic activity, with complex 1 showing a greater propensity to induce cell death, particularly in the A431 and MDA-MB 231 cell lines.

Advances in the Design of Photoactivatable Metallodrugs: Excited State Metallomics.

Photoactivatable metal complexes offer the prospect of novel drugs with low side effects and new mechanisms of action to combat resistance to current therapy. We highlight recent progress in the design of platinum, ruthenium, iridium, gold and other transition metal complexes, especially for applications as anticancer and anti-infective agents. In particular, understanding excited state chemistry related to identification of the bioactive species (excited state metallomics/pharmacophores) is important. Photoactivatable metallodrugs are classified here as photocatalysts, photorelease agents and ligand-activated agents. Their activation wavelengths, cellular mechanisms of action, experimental and theoretical metallomics of excited states and photoproducts are discussed to explore new strategies for the design and investigation of photoactivatable metallodrugs. These photoactivatable metallodrugs have potential in clinical applications of Photodynamic Therapy (PDT), Photoactivated Chemotherapy (PACT) and Photothermal Therapy (PTT).

Advances in the Design of Photoactivatable Metallodrugs: Excited State Metallomics

AbstractPhotoactivatable metal complexes offer the prospect of novel drugs with low side effects and new mechanisms of action to combat resistance to current therapy. We highlight recent progress in the design of platinum, ruthenium, iridium, gold and other transition metal complexes, especially for applications as anticancer and anti‐infective agents. In particular, understanding excited state chemistry related to identification of the bioactive species (excited state metallomics/pharmacophores) is important. Photoactivatable metallodrugs are classified here as photocatalysts, photorelease agents and ligand‐activated agents. Their activation wavelengths, cellular mechanisms of action, experimental and theoretical metallomics of excited states and photoproducts are discussed to explore new strategies for the design and investigation of photoactivatable metallodrugs. These photoactivatable metallodrugs have potential in clinical applications of Photodynamic Therapy (PDT), Photoactivated Chemotherapy (PACT) and Photothermal Therapy (PTT).

RuIII-Morpholine-Derived Thiosemicarbazone-Based Metallodrugs: Lysosome-Targeted Anticancer Agents.

The idea of coordinating biologically active ligand systems to metal centers to exploit their synergistic effects has gained momentum. Therefore, in this report, three RuIII complexes 1-3 of morpholine-derived thiosemicarbazone ligands have been prepared and characterized by spectroscopy and HRMS along with the structure of 2 through a single-crystal X-ray diffraction study. The solution stability of 1-3 was tested using conventional techniques such as UV-vis and HRMS. Further, the anticancer activity of 1-3 was tested in HT-29 and HeLa cancer cell lines. To gain insight into their mechanism of action, the cytotoxicity, hydrophobicity, and the interaction of 1-3 with DNA and HSA were evaluated by different conventional methods such as absorption, fluorescence, and circular dichroism studies. Along with favorable biomolecule interaction, 1-3 revealed potent selectivity toward cancer cells, which is a prerequisite for the generation of an anticancer drug. According to cell viability results, 1 has the highest cytotoxicity among all in the group, against both cells, respectively. Additionally, the fluorescence-active ruthenium complexes selectively target lysosomes, which is evaluated by live-cell imaging. 1-3 disrupt the lysosome membrane potential by generating an excessive amount of reactive oxygen species, which results in an apoptotic mode of cell death.

Binuclear ruthenium complex linker length tunes DNA threading intercalation kinetics.

Binuclear ruthenium complexes have been investigated for potential DNA-targeted therapeutic and diagnostic applications. Studies of DNA threading intercalation, in which DNA base pairs must be broken for intercalation, have revealed means of optimizing a model binuclear ruthenium complex to obtain reversible DNA-ligand assemblies with the desired properties of high affinity and slow kinetics. Here, we used single-molecule force spectroscopy to study a binuclear ruthenium complex with a longer semi-rigid linker relative to the model complex. Equilibrium results suggest a DNA affinity that is an order of magnitude higher than the parent binuclear ruthenium complex, likely due to a sterically-relieved DNA threading intercalation mechanism. Notably, kinetics analysis shows that less DNA elongation is required for threading intercalation compared to the parent complex, and the association rate is two orders of magnitude faster. The ruthenium complex elongates the DNA duplex by ∼0.3 nm per bound ligand to reach the equilibrium intercalated state, with a significantly different energy landscape relative to the parent complex. Mechanical properties of the ligand-saturated DNA duplex show a higher persistence length, indicating that the longer semi-rigid linker provides enough molecular spacing to allow a single monomer to fully stack with base pairs, comparable to the monomeric parent ruthenium complex. The DNA base pairs in the equilibrium threading intercalated state are likely intact and the ruthenium complex is shielded from the polar solution, providing measurable single-molecule confocal fluorescence signals. The obtained confocal fluorescence imaging of the bound dye confirms mostly uniform intercalation along the tethered DNA, consistent with other intercalators. The results of this study, along with previously examined ruthenium complex variants, illustrate tunable intercalation mechanisms guided by rational design of therapeutic and diagnostic small molecules to target and modify the DNA duplex.

Ruthenium(II) Complex with 8-Hydroxyquinoline Exhibits Antitumor Activity in Breast Cancer Cell Lines

Ruthenium(II) Complex with 8-Hydroxyquinoline Exhibits Antitumor Activity in Breast Cancer Cell Lines

Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma Cells

Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma Cells

Ancillary ligand induced variation in electronic spectral and catalytic properties of heteroleptic ONO-pincer complexes of ruthenium

Abstract: In this paper we report our studies on a group of mixed-ligand complexes of ruthenium(II) bearing a ONO-coordinated dipicolinate (DPA) as the pincer ligand, and some selected ancillary ligands...

Transformable Cis-trans Isomerism of Ruthenium (II) Complexes with Photoactivated Anticancer Activity

Photoactivated chemotherapy (PACT) provides a new alternative cancer treatment strategy compared to conventional therapy. In this study, a series of diisocyano ruthenium (II) complexes Ru(PBO)2(RNC)2 containing 2-benzoxazol-2-ylphenolate (PBO) auxiliary ligand...

Development of chiral ferrocenyl P,P,N,N,O-ligands for ruthenium-catalyzed asymmetric hydrogenation of ketones.

A new type of ferrocenyl P,P,N,N,O-ligand has been developed through a one-step transformation. This represents a rare example of a ligand containing both chiral bisphosphine and diamine groups suitable for ruthenium-catalyzed asymmetric hydrogenation. Its ruthenium complex can be directly prepared by stirring the ligand and [Ru(benzene)Cl2]2 at 90 °C in DMF for 4 hours. The catalyst showed high reactivity and enantioselectivity in the hydrogenation (AH) of simple ketones and α,β-unsaturated ketones, providing the corresponding chiral aryl alkyl alcohols and chiral allyl alcohols with up to 99% yield and 96% ee.

A novel ratiometric luminescent probe based on a ruthenium(II) complex-rhodamine scaffold for ATP detection in cancer cells.

Adenosine 5'-triphosphate (ATP) plays a pivotal role as an essential intermediate in energy metabolism, influencing nearly all biological metabolic processes. Cancer cells predominantly rely on glycolysis for ATP production, differing significantly from normal cells. Real-time in situ monitoring and rapid response to intracellular ATP levels offers more valuable insights into cancer cell physiology. Herein, we report a novel ratiometric luminescent probe, Ru-Rho, comprised of a ruthenium(II)-based complex and rhodamine 6G (Rho 6G) with excellent water solubility and photostability. Notably, Ru-Rho selectively responds to ATP at acidic conditions, matching the need of monitoring ATP under the acidic intracellular environment of cancer cells. Moreover, the fast ratiometric detection and imaging of ATP under single wavelength excitation improve the detection accuracy. Ru-Rho has been effectively utilized not only for ratio imaging ATP in cells and zebrafish, but also for assessing the efficacy of glycolysis-inhibiting anticancer drugs in intracellular levels, which accelerates the screening process for anticancer drugs and supports the development of new therapeutic agents. The design strategy based on transition metal ruthenium(II) complexes opens a new pathway for constructing ATP luminescent probes, allowing for better adaptation to complex detection requirements.

Necrosis inducing tetranuclear Ru(II)-Re(I) metal complex for anticancer therapy.

Chemotherapy is one of the most widely used anticancer treatments worldwide. However, despite its clinical effectiveness, most chemotherapeutic agents are associated with severe side effects. To address this limitation, there is an urgent need for the development of novel anticancer agents. Among the promising alternatives, Ruthenium and Rhenium complexes have garnered significant attention in the scientific literature. This study proposes combining these two metal moieties into a single tetranuclear complex, bridged by a 2,2'-bipyrimidine ligand. Cytotoxicity tests revealed broad activity of the novel metal complex against multiple cancer cell lines. Mechanistic studies suggested that the complex induces cell death by necrosis. Further analyses demonstrated its ability to eradicate colon carcinoma tumor spheroids at micromolar concentrations. To the best of our knowledge, this represents the first example of a Ru(II)-Re(I) tetranuclear metal complex as an anticancer agent.

Light enhanced cytotoxicity and antitumoral effect of a ruthenium-based photosensitizer inspired from natural alkaloids.

In this work, we report on the synthesis and properties of a new sensitizer for photodynamic therapy applications, constituted by a ruthenium(ii) complex (1) featuring a ligand inspired from natural isoquinoline alkaloids. The spectroscopic analysis revealed that 1 is characterized by an intense red emission (λ em = 620 nm, Φ = 0.17) when excited at 550 nm, a low energy radiation warranting for a safe therapeutic approach. The phototoxicity of 1 on human breast cancer (Hs578T) and melanoma (A375) cell lines was assessed after irradiation using a LED lamp (525 nm, total fluence 10 J cm-2). In vitro biological assays indicated that the cytotoxicity of 1 was significantly enhanced by light reaching IC50 values below the micromolar threshold. The cell damage induced by 1 proved to be strictly connected with the overproduction of reactive oxygen species (ROS) responsible for mitochondrial dysfunction leading to the activation of caspases and then to apoptosis, and for DNA photocleavage leading to cell cycle arrest.

Ambient-pressure selective hydrogenation of unsaturated aldehydes and ketones into unsaturated alcohols in the water phase.

A universal and green catalytic system for the hydrogenation of unsaturated aldehydes and ketones into the corresponding alcohols with the CC bonds retained under atmospheric hydrogen pressure in the water phase was realized by N-functionalized amino ligand-stabilized ruthenium complexes (o-PPh2C6H4NHMe)[(CH2NHR)2]RuCl2 (R = H, Me, Et) and (o-PPh2C6H4NMe2)[(CH2NHEt)2]RuCl2 with wide substrate compatibility and excellent functionality tolerance. The structural synergism between o-PPh2C6H4NHMe and (CH2NHEt)2 achieves the enhanced performance, with a positive correlation with the electron density of the amino ligand.

An aromatic ruthenium complex with high antimicrobial efficiency by disrupting biofilms and recruiting M2 macrophages

An aromatic ruthenium complex with high antimicrobial efficiency by disrupting biofilms and recruiting M2 macrophages

Luminescence Lifetime-Based Water Conductivity Sensing Using a Cationic Dextran-Supported Ru(II) Polypyridyl Complex.

Water conductivity sensing relies universally on electrical measurements, which are subject to corrosion of the electrodes and subsequent signal drift in prolonged in situ uses. Furthermore, they cannot provide contactless sensing or remote readout. To this end, a novel device for water conductivity monitoring has been developed by employing a microenvironment-sensitive ruthenium complex, [Ru(2,2'-bipyridine-4,4'-disulfonato)3]4-, embedded into a quaternary ammonium functionalized cross-linked polymer support. The degree of swelling of the latter, which leads to a change in the emission lifetime, depends on the water conductivity. The sensor displays a reversible response (2 min ≤ t90 ≤ 3 min) and has been shown to be stable for >65 h of continuous monitoring of 0.8-12.8 mS cm-1 KCl solutions. Changes to the cation do not affect the sensor response, while changes to the anion type induce small effects. Variations in the dissolved O2 or temperature require corrections of the response. The sensor can be interrogated alongside dissolved O2 and pH luminescent sensors based on the same family of indicator dyes to exploit the definite advantages of luminescence lifetime-based detection.