Ruthenium Complexes Research Articles

Induced of axial chirality in near-infrared-absorbing ball-shaped ruthenium complexes

Ball-shaped metal complexes that absorb in the near-infrared (NIR) region can be synthesized in a single step. Although stereogenic-at-metal complexes have been obtained, the induction of axial chirality has not yet been demonstrated. In this study, NIR-absorbing ball-shaped ruthenium complexes with axial chirality were facilely synthesized using asymmetric diiminoisoindoline derivatives. Despite lacking a discrete point chiral moiety, these complexes exhibited molecular chirality. The incorporation of bulky substituents facilitated enantiomeric differentiation. High-performance liquid chromatography (HPLC) with a chiral column enabled the isolation of the pure enantiomers as stable compounds. The absolute configurations of these isomers were revealed using vibrational circular dichroism (VCD) spectroscopy. The characteristic peaks originating from ligand vibrations exhibited distinct mirror images, and the experimental spectra were well reproduced by theoretical calculations. This methodology has broad applicability for the development of chiral ball-shaped metal complexes as NIR materials.

Application of enaminone ruthenium(II) complexes as catalysts in the transfer hydrogenation of ketones

This study reported the synthesis of two new ligands (1,2) and their Ru(II)-enaminone complexes (3,4). The Ru(II) complexes were obtained from the reaction of the [RuCl2(p-cymene)]2 dimers with the new enaminone derivative ligands (1,2). The use of standard spectroscopy techniques entirely characterized the compounds. Single crystal studies investigated the crystal structure of ligand (1) and complexes (3,4). X-ray diffraction data analysis was used to confirm the enaminone form of 1. Also, 3 and 4 exhibited the classical three-legged piano stool structure with Ru(II) coordinated by the nitrogen and oxygen atoms of 1 and a chloride ligand as the legs and the η6-π-bound p-cymene ligand occupies the seat of the piano stool. The Ru(II) complexes have been studied as catalysts in the transfer hydrogenation of acetophenone and other various ketones in the presence of KOtBu. The catalytic conditions were optimized using different substrate/catalyst and base/catalyst ratios. We found that the complexes show good activities and up to 100 % selectivity. The best turnover frequency (1667 h−1) was found for 3 when using acetophenone as the substrate.

AIE-based ruthenium complexes as photosensitizers for specifically photo-inactivate gram-positive bacteria

The emergence of multidrug-resistant bacterial have caused severe burden for public health. Particularly, Staphylococcus aureus as one of ESKAPE pathogens have induced various infectious diseases and resulted in increasing deaths. Developing new antibacterial agents is still urgent and challenging. Fortunately, in this study, based on aggregation-induced emission (AIE) ruthenium complexes were designed and synthesized, which realized the high efficiency of reactive oxygen species generation and remarkably killed S. aureus unlike conventional antibiotics action. Significantly, owing to good singlet oxygen production ability, Ru1 at only 4 μg/mL of concentration displayed good antibacterial photodynamic therapy effect upon white light irradiation and could deplete essential coenzyme NADH to disrupt intracellular redox balance. Also, the electrostatic interaction between Ru1 and bacteria enhanced the possibility of antibacterial. Under light irradiation, Ru1 could efficiently inhibit the biofilm growth and avoid the development of drug-resistant. Furthermore, Ru1 possessed excellent biocompatibility and displayed remarkable therapy effect in treating mice-wound infections in vivo. These findings indicated that AIE-based ruthenium complexes as new antibacterial agent had great potential in photodynamic therapy of bacteria and addressing the drug-resistance crisis.

Ruthenium complexes with abiraterone acetate as antiproliferative agents

This study is dedicated to the development of multimodal anticancer agents. We have obtained ruthenium complexes conjugated with the steroid-type antitumor drug abiraterone acetate in order to take advantage of the dual antitumor properties of both ruthenium and abiraterone. The compounds exhibit good antiproliferative activity against cancer cells, with selectivity over primary fibroblasts. Real-time cell analysis revealed that compound dichlorido(η6-p-cymene)(abiraterone acetate)ruthenium(II) had pronounced antiproliferation activity compared to abiraterone acetate. Flow cytometric studies on the mechanism of cell death have revealed that the most active compound induces apoptosis more effectively than abiraterone acetate. Our findings demonstrate the potential of this novel dual-action compound as promising candidates for further development as anticancer agents.

Asymmetric Transfer Hydrogenation of gem-Difluorocyclopropenyl Ketones: The Synthesis and Functionalization of Enantioenriched cis gem-Difluorocyclopropyl Ketones.

The asymmetric transfer hydrogenation of gem-difluorocyclopropenyl ketones, catalyzed by a Noyori-Ikariya ruthenium complex, was developed to access substituted optically enriched cis-disubstituted gem-difluorocyclopropyl ketones, and the value of these latter building blocks was illustrated by the synthesis of heterocycles fused to the difluorocyclopropyl moiety.

Functionalization of ionic liquids for heterogeneous catalysis in CO2 conversion: Cycloaddition of epoxides and hydrogenation

The mitigation of environmental impacts caused by greenhouse gas emissions has become increasingly urgent, and the use of CO2 as a primary carbon source is an alternative in chemical transformations, including the synthesis of organic carbonates, formic acid, or methanol. This work aims to synthesize ionic liquids from the imidazolium cation family to be used in the cycloaddition of CO2 with ILs anchored in SiO2-clay heterostructure, MCM-41 and KIT-6 mesoporous materials, as well as the hydrogenation of CO2 with ILs added to ruthenium complexes, i.e., two catalytic systems. The most satisfactory result for CO2 cycloaddition (TON PC = 226) was obtained using the IL (MeO)3Sipmim.Cl anchored in SiO2-clay heterostructure (0.16 mol%) as the catalyst and ZnBr2 (0.04 mol%) as the co-catalyst. The hydrogenation was conducted with the IL (edaO)3Sipmim.Cl and the ruthenium complex Ru-PNN were not successful, but with co-catalyst PEHA, formic acid/formamide was produced (TON Form = 552). The unique catalytic system that showed activity for forming methanol was the commercial Ru-MACHO, Ru-C29H30ClNOP2, (TON MeOH = 3.3). These results highlight the potential of ruthenium-based complexes and supported ionic liquids as active systems in CO2 conversion.

Stereoselective Synthesis of Chiral C2-Symmetric 1,3- and 1,5-Bis-Sulfoxides Guided by the Horeau Principle: Understanding the Influence of the Carbon Chain Nature in Its Ability for Metal Coordination.

The stereoselective synthesis of two distinct types of C2-symmetric chiral bis-sulfoxides, 1,3- and 1,5-bis(sulfinyl) derivatives, has been achieved based on the DAG methodology. The 1,5-bis(sulfinyl) derivatives constitute a new family of tridentate chiral ligands thanks to the presence of an additional sulfenyl or sulfinyl group in the carbon chain acting as a bridge. A systematic development and optimization of two synthetic routes, one for each ligand family, have been undertaken, highlighting the strategic utilization of Horeau's law to enhance enantioselectivity. Additionally, palladium (Pd) and ruthenium (Ru) complexes derived from the synthesized bis-sulfoxides were prepared, and their structures were elucidated through spectroscopic analysis. Isolation of Pd(II) complexes involving 1,3-bis-sulfoxides was exclusively achieved using trifluoroacetates as coligands. In the case of Ru(II) complexes, the trans geometry could be determined for 1,3-bis-sulfoxides. The introduction of a third sulfur atom as a coordinating element in the 1,5-bis(sulfinyl) derivatives facilitates the formation of two distinct tricoordinated Ru(II) complexes. The structure of these complexes is intricately influenced by the oxidation state adopted by the central sulfur on the chain, whether as a thioether or as a sulfoxide.

A New N‐functionalized Pyrrole Derivative Bearing Ruthenium Tris(2,2’‐bipyridine) Subunit

AbstractIn recent years, nitrogen‐based ruthenium complexes have become an important material for dye‐sensitized solar cells and photo‐catalytic H2O and CO2 reduction research and applications, thanks to their charge transfer feature from the metal to the ligand. The electronic and spectral properties of such materials can be easily modified by changing the substituents and ligands. In this study, a new ruthenium (II) complex with N‐functionalized pyrrole derivative ([Ru(bpy)2(bpyCONHArPy)]+2 complex) was successfully synthesized and characterized. Its optical and electrochemical properties were studied by means of fluorescence, UV‐vis spectrometry, FTIR spectroscopy and cyclic voltammetry. These results were compared with that of its components (4‐(1H‐pyrrol‐1‐yl) aniline, N4,N4′‐bis(4‐(1H‐pyrrol‐1‐yl)phenyl)‐[2,2′‐bipyridine]‐4,4′‐dicarboxamide and ligand [Ru(bpy)3]+2). Related theoretical studies were also studied to find energy levels of complex. The present work is carried out to understand what chemical changes bring when combination of all the pieces of the puzzle into a chemical structure step by step.

RUTHENIUM ORGANOMETALLIC COMPOUNDS IN CANCER TREATMENT

Organometallic complexes with ruthenium have shown promise as potential anticancer agents. These complexes represent a class of compounds that can exhibit unique mechanisms of action, and they may offer advantages or overcome some limitations associated with platinum-based drugs, such as cisplatin. Ruthenium-based complexes can have diverse mechanisms of action. They may interact with DNA, proteins, or other cellular components, leading to cytotoxic effects on cancer cells. The versatility of ruthenium coordination chemistry allows for the design of complexes with specific properties. Some cancers that become resistant to platinum-based drugs may still respond to ruthenium-based compounds. This reduced cross-resistance is attributed to differences in the mechanisms of action between platinum and ruthenium complexes. Researchers can design ruthenium complexes to target specific cellular pathways or processes associated with cancer. This targeted approach aims to enhance the selectivity of the treatment for cancer cells while minimizing the impact on normal cells. Ruthenium complexes often have unique structural features that contribute to their stability and reactivity. These features can be tailored to optimize the pharmacological properties of the compounds. Ruthenium-based complexes may be explored in combination with other anticancer agents to achieve synergistic effects and enhance overall treatment efficacy. Ongoing research continues to explore the potential of ruthenium-based organometallic complexes, and preclinical studies have demonstrated promising results. As with any emerging field, further investigations and clinical trials are needed to fully understand the therapeutic potential and safety profiles of these compounds for various types of cancers.

Hydrogen Production from Aqueous Formic Acid through the Ligand Design Strategy in Half-Sandwich Ruthenium Complexes

Hydrogen Production from Aqueous Formic Acid through the Ligand Design Strategy in Half-Sandwich Ruthenium Complexes

New Organoruthenium(II) Complexes Containing Andrographolide‐Appended Hydrazide Derivatives: Synthesis, Spectral Characterization, Anticancer Evaluation

ABSTRACTA new set of andrographolide‐appended hydrazide derivatives (AFC, AGC, and ATC) were prepared from the reaction of andrographolide with furan‐2‐carboxylic acid hydrazide (AFC), pyridine‐3‐carboxylic acid hydrazide (AGC), and thiophene 2‐carboxylic acid hydrazide (ATC), and their corresponding ruthenium(II) complexes (Ru‐AFC, Ru‐AGC, and Ru‐ATC) were synthesized by the direct reaction of [RuCl2(η6‐p‐cymene)]2 with ligands in dichloromethane under stirring condition. The compounds were analyzed by elemental analysis, IR, UV‐Vis, 1H NMR, and ESI‐MS spectrometric techniques, and the obtained spectral data revealed that the ligands coordinated to Ru(II) ion through their enone oxygen and amine nitrogen. Antioxidant activities of the ligands and complexes were calculated against DPPH•, ABTS•+, O2−, and NO• free radicals and their results were compared with standard antioxidants. The cytotoxic activity of the synthesized ligands and complexes toward A549 and HeLa cell lines was evaluated using MTT method (MTT = 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide). Among the compounds, the complex Ru‐AGC showed better cytotoxic effect against A549 and HeLa cancer cells with IC50 values of 4.75 ± 0.17 and 6.32 ± 0.26 μM, respectively. Further, the nontoxic nature of the compounds was confirmed by using human umbilical vein endothelial (HUVEC) cells. The apoptosis was inspected with AO/EB and DAPI staining methods; further, the percentages of the apoptotic and necrotic cells were determined by flow cytometry. Overall, the biological activities of our ruthenium(II)‐arene complexes were found to be more potent than their parent ligands due to chelation, and among the complexes, Ru‐AGC showed better activity due to the presence of pyridine ring in the N‐terminal position of the ligand. The obtained results highlighted the strong possibility to develop highly active ruthenium complexes as anticancer agents.

Ruthenium Catalyzed Formation of Fused Pyridine Derivatives or Substituted Indoles from Hydrazine‐Derived Enamines and Propargyl Alcohols

New ruthenium‐catalyzed transformations of secondary propargyl alcohols with hydrazine‐derived enamines are presented, affording fused pyridines or substituted indoles depending on the hydrazine derivative used. The cascade reactions are catalyzed by an air‐ and moisture‐stable bifunctional ruthenium complex and proceed via redox‐isomerization of the propargyl alcohol, subsequent Michael addition and cyclocondensation. In case of phenylhydrazine a Fischer‐indole synthesis also takes place, prior to the final release of the products. The produced heterocyclic motifs are important scaffolds in medicinal and agricultural chemistry.

Effect of solution environment on the binding properties of ruthenium(II) complexes [Ru(bim)2(7-CH3-dppz)]2+ and [Ru(bim)2(dppx)]2+ with double-stranded RNA poly(A)·poly(U)

Two new ruthenium(Ⅱ) complexes containing the same ancillary ligands and different intercalating ligands, [Ru(bim)2(7-CH3-dppz)]2+ (Ru1, bim = 2,2′-biimidazole, 7-CH3-dppz = 7-methyl-dipyrido-[3,2-a,2′,3′-c]-phenazine) and [Ru(bim)2(dppx)]2+ (Ru2, dppx = 7,8-dimethyldipyridophenazine), have been synthesized and characterized in this work, and the interactions of Ru1 and Ru2 with double-stranded RNA poly(A)·poly(U) have been comparatively studied under both dilute and molecular crowding conditions. Analysis of spectral titrations and viscosity experiments as well as thermal denaturation experiments suggests that although complexes Ru1 and Ru2 in both dilute and molecular crowding solutions bind to poly(A)·poly(U) via intercalation, while the binding and stabilizing effects of the two complexes toward poly(A)·poly(U) under molecular crowding conditions significantly decreases in comparision with those in dilute solutions, suggesting that molecular crowding has a significant weakening effect on the interaction of the two complexes with poly(A)-poly(U). The results obtained will contribute to the understanding of the effects of molecular crowding conditions on the binding and stabilization of double-stranded RNA by metal complexes, in particular Ru(II) complexes.

4+2]‐Cycloaddition Reactions to Corannulene Accelerated by η6‐Coordination of Ruthenium Complexes

AbstractThe influence of different (LRu)nII (L=Cp– (n=1, 2); C6H6) moieties η6‐coordinated to corannulene ((CpRu)+, (Benzene)Ru2+ and (CpRu)22+) has been explored by using the Activation Strain Model (ASM) of reactivity together with the Energy Decomposition Analysis (EDA) scheme. The results obtained have been compared with those obtained for the non‐coordinated corannulene counterpart. It has been observed that the presence of the ruthenium moiety favors both kinetically and thermodynamically the [4+2]‐cycloaddition reaction with cyclopentadiene. The factors governing these differences depend on the nature of the [Ru] complex. Whereas the interaction energy is solely responsible for the lower activation energy for the monocationic system (CpRu)+, not only the higher interaction but also the lower strain energy explain the much higher reactivity observed for the dicationic systems ((C6H6)Ru2+ and (CpRu)22+). In this latter case, the Pauli repulsion energy term is the factor controlling the differences in the interaction energies, following the so‐called Pauli repulsion‐lowering concept. Finally, when η6‐coordinating mono‐ or dicationic ruthenium complexes, although the [4+2]‐cycloaddition reaction in the external rim bonds remains the thermodynamically and kinetically more favourable, the cycloaddition becomes also thermodynamically feasible in some internal bonds.

Synthesis and reactivity of isomeric Ru complexes with hydroxypyridyl fragment: Active catalysts for β‑alkylation of secondary alcohols with primary alcohols

When the ligand LOH, containing a 2-hydroxy pyridine group, reacts with an equimolar amount of the precursor Ru(DMSO)4Cl2, two isomeric ruthenium complexes are formed. These isomers are termed cis-1 and trans-1, based on the relative positions of the N atom in N-(2-(6-hydroxy pyridin-2-yl)phenyl)acetamide and the pyridine groups of bis((1,4-pyridin-2-yl)methyl)amine. Treatment of these isomers with equimolar amounts of NaH results in deprotonation of the uncoordinated hydroxy pyridine groups, leading to the formation of complex 2 with newly coordinated pyridine groups. The catalytic activity of these three ruthenium complexes in the β-alkylation reaction of primary alcohols and secondary alcohols was evaluated, with complex 2 displaying the highest activity and selectivity. Complex 2 may be seen as an intermediate in the catalysis of the β-alkylation reaction by the isomers (cis-1 and trans-1). These findings are valuable for the development of more effective bifunctional catalysts.

Synthesis, structural characterization and computational studies of half- sandwich Ru(II) (η6-p–cymene) TPA appended benzhydrazone complex

A ruthenium complex of the type Ru[η6(p–cymene)Cl(L)] where L = Triphenylamine (TPA) appended O^N bidendate benzhydrazone ligand was synthesized and characterized by various analytical and spectral [UV, FT-IR, NMR (1H and 13C) and HRMS] methods. The solid state molecular structure of the ruthenium complex was investigated with the aid of X-ray crystallography results with pseudo-octahedral geometry around the metal centre. FT-IR spectroscopy confirms the coordination via the azomethine nitrogen and imidolate oxygen. Density Functional theory (DFT) calculations have been used to analyse the composition of frontiers orbitals. The bonding interactions between the ligand and ruthenium complex fragments have been examined by EDA. The spin-allowed singlet transitions were calculated with the TD-DFT method. NBO analysis shows that the donation from ligand to metal has value of 136.64 kcal/mol and the back donation is equal to 109.61 kcal/mol. Hence the ligand is a σ-donor with weak π-acceptor properties. The DOS spectrum of both ligand and complex were plotted in terms of Mullikan population analysis were calculated using the GassSum program. Further, the relative contributions to the Hirshfeld surface area for the various close intermolecular contacts of ruthenium complex are investigated and H…H interactions plays an important role for the construction of the crystal structure of the ruthenium complex.

Synthesis, Characterization, and Catalytic Evaluation of Ruthenium Complexes Bearing Xanthinium-8-dithiocarboxylate Ligands Derived from Caffeine and Theophylline

Synthesis, Characterization, and Catalytic Evaluation of Ruthenium Complexes Bearing Xanthinium-8-dithiocarboxylate Ligands Derived from Caffeine and Theophylline

New ruthenium(II) isocyanide catalysts for the transfer hydrogenation of ethyl levulinate to γ-valerolactone in C2-C6 alcohols

Transfer hydrogenation (TH) processes are receiving great attention for biomass valorization and ruthenium(II) complexes are renowned TH catalysts both on laboratory and industrial scale. Only a few homogeneous catalytic precursors are available in the literature for the TH of ethyl levulinate (EL) to γ-valerolactone (GVL). Herein, starting from simple, commercially available isocyanides, two classes of air-stable ruthenium(II) complexes were synthesized and tested as catalytic precursors. First, an optimized preparation of Ru(II) p-cymene isocyanide complexes was developed. Then, the thermally induced p-cymene/DMSO substitution gave access to unprecedented ruthenium isocyanide-DMSO complexes. All the complexes were characterized and tested in TH of EL to GVL showing promising performances, adopting 2-propanol as hydrogen donor, a low catalyst (Ru) and co-catalyst (KOH) amount, working under microwave heating for 1 h at 150 °C. The most selective systems were also successfully tested with different biomass-derived alcohols, including 2-butanol. Finally, the recycling of the best catalyst was also investigated, thus improving the efficiency of the entire process.

Preparation and application of multiple particle binding-liposomes for electrochemiluminescent signal amplification in bioassays.

In this study, multiple particle binding-liposomes (MPB-Lips), encapsulating the luminophore tris(2',2-bipyridyl)ruthenium (II) complex ([Ru(bpy)3]2+), were developed as an electrochemiluminescence (ECL) signal amplifier and were applied to detect the model analyte streptavidin (SA) using the indirect competitive ECL method. The MPB-Lips were prepared by mixing various ratios of two different liposomes-one containing a phospholipid with a primary amine group and a biotinyl group (BIO/NH2-Lip) and one containing a phospholipid with an N-hydroxysuccinimide group (NHS-Lip) to allow binding between particles via amide bonds. Quartz crystal microbalance analysis using SA-modified gold-coated quartz crystals showed that the frequency shift values of MPB-Lips gradually decreased in the order BIO/NH2-Lip:NHS-Lip = 1:0 < 1:1 < 1:3 < 1:5. This indicated that MPB-Lips were successfully formed. The indirect competitive ECL method using SA-modified gold electrodes showed that the 1:5-Lip system had greater sensitivity than the 1:0-Lip system-the limit of detection and quantification values for the systems were 1.84 and 6.30μgmL-1 for 1:0-Lip, and 1.20 and 1.74μgmL-1 for 1:5-Lip. Finally, the recovery of SA spiked in fetal bovine serum samples using the 1:5-Lip system showed good accuracy and precision with a recovery rate of 83-106% and relative standard deviation of 4-14%. Our study demonstrated that the MPB-Lips system was an effective and useful ECL amplifier and the ECL method using MPB-Lips could be applied to detect an analyte in a real sample.

Exploring the DNA-binding and anticancer potential of polypyridyl ruthenium(II) complexes

Organometallic medicines based on ruthenium (Ru) have attracted interest as chemotherapeutic and bioimaging agents due to their low toxicity and superior physical optical characteristics. However, there are still no ideal candidates in clinical trials due to the lack of understanding of the structure-activity relationships (SARs) of polypyrodyl Ru(II) complexes. Though increasing the electron-donating ability of the ligands has been proven to benefit bioactivity due to the fast hydroxylation rate between chlorine and DNA, the total electronic effects are much more important, especially for the binding modes between Ru(II)-polypyridyl complexes and DNA. By evaluating the electron-donating ability of the ligand complexes 1 - 4 through density functional theory (DFT) calculations, bioactivities tests, and docking studies, we investigated the relationship between the structures of Ru(II) complexes and cytotoxicity. Our findings showed that it was insufficient to merely consider the impact of electron-donating effects on biological activities in place of interaction modes. Furthermore, the cellular imaging study investigated the complex with phenyl substituents (1) and confirmed that the main target was DNA. Besides, the “off-on” emission phenomena of complex 1 indicated that there is also covalent interaction with DNA. These findings offer valuable insight into the development of SARs of polypyrodyl Ru(II) complexes.