RuII Complexes Research Articles

Crystal structure, electrochemical and spectroscopic investigation of mer-tris-[2-(1H-imidazol-2-yl-κN3)pyrimidine-κN1]ruthenium(II) bis-(hexa-fluorido-phosphate) trihydrate.

The crystal structure of the title compound, [Ru(C7H6N4)3](PF6)2·3H2O, a novel RuII complex with the bidentate ligand 2-(1H-imidazol-2-yl)pyrimidine, comprises a complex cation in the meridional form exclusively, with a distorted octa-hedral geometry about the ruthenium(II) cation. The Ru-N bonds involving imidazole N atoms are comparatively shorter than the Ru-N bonds from pyrimidine because of the stronger basicity of the imidazole moiety. The three-dimensional hydrogen-bonded network involves all species in the lattice with water mol-ecules inter-acting with both counter-ions and NH hydrogen atoms from the complex. The supra-molecular structure of the crystal also shows that two units of the complex bind strongly through a mutual N-H⋯N bond. The electronic absorption spectrum of the complex displays an asymmetric band at 421 nm, which might point to the presence of two metal-to-ligand charge-transfer (MLCT) bands. Electrochemical measurements show a quasi-reversible peak referring to the RuIII/RuII reduction at 0.87 V versus Ag/AgCl.

Ruthenium(II) Complexes Having a Pincer‐Type Ligand with Two N‐Heterocyclic Carbene Moieties

Two novel RuII complexes, having 2,2′‐bipyridyl and a pincer‐type methylene‐bridged N‐heterocyclic carbene (NHC) ligand, were synthesized and characterized to evaluate the effects of structural features of the complexes on their redox and photochemical properties. The methylene‐bridged NHC ligand coordinated in a meridional manner and the isopropyl groups on the NHC rings exhibited intramolecular CH/π interaction with the 2,2′‐bipyridyl ligand, which played a role to strongly maintain the distorted ligand structure. In addition, the two Ru complexes exhibited reversible redox waves in the cyclic voltammograms and they were oxidized by an electron‐transfer oxidant to afford RuIII complexes, which were characterized by EPR spectroscopy and theoretical analyses.

Sterically Demanding Phosphines with 2,6-Dibenzhydryl-4-methylphenyl Core: Synthesis of RuII, PdII, and PtII Complexes, and Structural and Catalytic Studies.

The synthesis of sterically demanding aminophosphine and phosphinite ligands Ar*NHPPh2 (1) and Ar*OPPh2 (2), based on 2,6-dibenzhydryl-4-methylphenyl core having bulky benzhydryl groups, and their RuII, PdII and PtII complexes is described. The reactions of 1 and 2 with [Ru(η6- p-cymene)Cl2]2 in 2:1 molar ratios produced mononuclear complexes [RuCl2{(η6- p-cymene)PPh2-EAr*}-κ1-P] (E = NH (3) and O (4)). Interestingly, complexes 3 and 4, upon refluxing in chlorobenzene, displace the p-cymene ring by one of the phenyl rings of side arms, forming rare η6-arene coordinated tethered complexes [RuCl2{(PPh2-EAr*)-κ1-P-η6-arene}] (E = NH (5) and O (6)). Treatment of 1 and 2 with [M(COD)Cl2] [M = Pd, Pt] in 2:1 ratios afforded mononuclear complexes [MCl2{(PPh2EAr*)-κ1-P}2] (E = NH, M= Pd (7), Pt (8); E = O, M= Pd (9), Pt (10)). Similarly, 1:1 reactions of 1 and 2 with [Pd(COD)Cl2] produced chloro-bridged dinuclear complexes [PdCl2{(PPh2EAr*)-κ1-P}]2 (E = NH (11) and O (12)), whereas [Pt(COD)Cl2] yielded only the mononuclear complexes 8 and 10. The reactions of 1 and 2 with [Pd(η3-C3H5)Cl]2 in 2:1 molar ratios produced the mononuclear complexes [PdCl{(η3-C3H5)(PPh2EAr*)-κ1-P}] (E = NH (13) and O (14)). Many of these complexes have been structurally characterized, which show C-H···π interactions between the methine hydrogen of the benzhydryl and with one of the carbon atoms of the phenyl ring attached to the phosphorus center. The complex [RuCl2{(η6- p-cymene)PPh2-NHAr*}-κ1-P] (3) shows very short C-H···π interactions of 2.36 Å; in addition, C-H···M interactions were observed between the methine hydrogen of one of the benzhydryl groups and palladium centers in 11 and 13. The tethered ruthenium complex 5 is found to be an excellent catalyst for the catalytic oxidation of various styrene derivatives.

Undoped Layered Perovskite Oxynitride Li2 LaTa2 O6 N for Photocatalytic CO2 Reduction with Visible Light.

Oxynitrides are promising visible‐light‐responsive photocatalysts, but their structures are almost confined with three‐dimensional (3D) structures such as perovskites. A phase‐pure Li2LaTa2O6N with a layered perovskite structure was successfully prepared by thermal ammonolysis of a lithium‐rich oxide precursor. Li2LaTa2O6N exhibited high crystallinity and visible‐light absorption up to 500 nm. As opposed to well‐known 3D oxynitride perovskites, Li2LaTa2O6N supported by a binuclear RuII complex was capable of stably and selectively converting CO2 into formate under visible light (λ>400 nm). Transient absorption spectroscopy indicated that, as compared to 3D oxynitrides, Li2LaTa2O6N possesses a lower density of mid‐gap states that work as recombination centers of photogenerated electron/hole pairs, but a higher density of reactive electrons, which is responsible for the higher photocatalytic performance of this layered oxynitride.

Undoped Layered Perovskite Oxynitride Li2LaTa2O6N for Photocatalytic CO2 Reduction with Visible Light

AbstractOxynitrides are promising visible‐light‐responsive photocatalysts, but their structures are almost confined with three‐dimensional (3D) structures such as perovskites. A phase‐pure Li2LaTa2O6N with a layered perovskite structure was successfully prepared by thermal ammonolysis of a lithium‐rich oxide precursor. Li2LaTa2O6N exhibited high crystallinity and visible‐light absorption up to 500 nm. As opposed to well‐known 3D oxynitride perovskites, Li2LaTa2O6N supported by a binuclear RuII complex was capable of stably and selectively converting CO2 into formate under visible light (λ>400 nm). Transient absorption spectroscopy indicated that, as compared to 3D oxynitrides, Li2LaTa2O6N possesses a lower density of mid‐gap states that work as recombination centers of photogenerated electron/hole pairs, but a higher density of reactive electrons, which is responsible for the higher photocatalytic performance of this layered oxynitride.

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.

A Readily Accessible Class of Chiral Cp Ligands and their Application in RuII -Catalyzed Enantioselective Syntheses of Dihydrobenzoindoles.

Chiral cyclopentadienyl (Cpx ) ligands have a large application potential in enantioselective transition-metal catalysis. However, the development of concise and practical routes to such ligands remains in its infancy. We present a convenient and efficient two-step synthesis of a novel class of chiral Cpx ligands with tunable steric properties that can be readily used for complexation, giving Cpx RhI , Cpx IrI , and Cpx RuII complexes. The potential of this ligand class is demonstrated with the latter in the enantioselective cyclization of azabenzonorbornadienes with alkynes, affording dihydrobenzoindoles in up to 98:2 e.r., significantly outperforming existing binaphthyl-derived Cpx ligands.

Anti-tumor activity of Organometallic Compounds

Modern medicine has been focusing on proving new and alternative chemotherapeutic compounds with high tumor cytotoxicity and reduced side effects to combat drug resistance and improve drug efficacy in cancer treatment. Organometallic compounds have unique physio-chemical properties like structural diversity, ligand exchange, redox and catalytic properties which are now being used to develop potential candidates for cancer therapy. The impressive clinical effectiveness of cisplatin is limited by the significant side effects and emergence of drug resistance. One of the metals showing promise is ruthenium. Ruthenium compounds often have lower cytotoxicity compared to cisplatin and are better tolerated in vivo. RuIII complexes maintain their metallic oxidation state till they reach the tumor, wherein a hypoxic condition is reduced to RuII. Moreover, in many cancer types, iron uptake is upregulated. Ruthenium, being in the same group as iron is transported into the cells by the transferrin receptor which is overexpressed in many tumors. Therefore, the properties of tumors enhance both Ru uptake and toxicity relative to normal tissues. DNA cleavage will lead to cell cycle arrest until the damage is repaired, or if it is too extensive to repair, it will undergo senescence and death that may be either dependent or independent of p53 tumor suppressor gene function. This project is focused on the synthesis, purification, and characterization of monometallic and bimetallic ruthenium compounds and evaluate its effects on glioblastoma, meningioma and pancreatic cell lines to analyze their effect on the proliferation of the tumor cells and their capacity to induce apoptosis.This project was supported by NIH Grants 5P20RR016477 and P20GM103434 to the West Virginia IDeA Network for BioMedical Research Funding.

A Neutral RuII Hydride Complex for the Regio- and Chemoselective Reduction of N-Silylpyridinium Ions.

A detailed experimental analysis of the 1,4-selective reduction of pyridine with hydrosilanes catalyzed by a coordinatively unsaturated RuII thiolate complex is reported. The previously suggested intermediates, N-silylpyridinium ions and a neutral RuII hydride, have been independently synthesized and do indeed participate in the catalytic cycle. The resting state is not the cationic RuII complex initially used as the catalyst but its pyridine-coordinated congener. All RuII complexes, including the one resulting from hydrosilane activation, are in equilibrium with each other. The N-silylated 1,4-dihydropyridine together with the cationic RuII complex convert back into the corresponding N-silylpyridinium ion and the neutral RuII hydride (retro-hydrosilylation), followed by further backward reaction into the hydrosilane and the pyridine adduct of the cationic complex. These steps prove the overall reversibility of the transformation.

Analysis of ruthenium anticancer agents by MEEKC-UV and MEEKC-ICP-MS: Impact of structural motifs on lipophilicity and biological activity.

We present here the first comprehensive study on the lipophilicity of ruthenium anticancer agents encompassing compounds with broad structural diversity, ranging from octahedral RuIII (azole) through to RuII (arene) complexes. MEEKC was used to determine the capacity factors of the Ru complexes, and after a complex peak was unambiguously assigned using MEEKC-ICP-MS, the results were validated through comparison with the log P determined by octanol/water partitioning experiments. Correlation of the two data sets demonstrated a close relationship despite the limited structural overlap of the compounds studied. The capacity factors found by MEEKC allowed for the clustering of complexes based on their structure and this could be used to rationalize the observed cytotoxicity in the human colon carcinoma HCT116 cell line. It was demonstrated that rather than modification of the mono- or bidentate coordinated ligands much tighter control over a complexes lipophilic properties could be achieved through modification of the Ru(arene) ligand, with minimal detriment to cytotoxicity. This demonstrates the flexibility and potential of the Ru piano-stool scaffold. MEEKC proved to be a highly efficient means of screening the anticancer potential of preclinical ruthenium complex candidates for their lipophilic properties and correlate them with their biological activity and structural properties.

Bioorthogonal Catalytic Activation of Platinum and Ruthenium Anticancer Complexes by FAD and Flavoproteins.

Recent advances in bioorthogonal catalysis promise to deliver new chemical tools for performing chemoselective transformations in complex biological environments. Herein, we report how FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), and four flavoproteins act as unconventional photocatalysts capable of converting PtIV and RuII complexes into potentially toxic PtII or RuII−OH2 species. In the presence of electron donors and low doses of visible light, the flavoproteins mini singlet oxygen generator (miniSOG) and NADH oxidase (NOX) catalytically activate PtIV prodrugs with bioorthogonal selectivity. In the presence of NADH, NOX catalyzes PtIV activation in the dark as well, indicating for the first time that flavoenzymes may contribute to initiating the activity of PtIV chemotherapeutic agents.

Bioorthogonal Catalytic Activation of Platinum and Ruthenium Anticancer Complexes by FAD and Flavoproteins

AbstractRecent advances in bioorthogonal catalysis promise to deliver new chemical tools for performing chemoselective transformations in complex biological environments. Herein, we report how FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), and four flavoproteins act as unconventional photocatalysts capable of converting PtIV and RuII complexes into potentially toxic PtII or RuII−OH2 species. In the presence of electron donors and low doses of visible light, the flavoproteins mini singlet oxygen generator (miniSOG) and NADH oxidase (NOX) catalytically activate PtIV prodrugs with bioorthogonal selectivity. In the presence of NADH, NOX catalyzes PtIV activation in the dark as well, indicating for the first time that flavoenzymes may contribute to initiating the activity of PtIV chemotherapeutic agents.

Performance improvement of Ru II complexes pyridinyl backbone on dye-sensitized solar cells (DSSC)

Two new series of RuII complexes (6–10 bearing an imine bond and 16–20 bearing a sulfonamidate fragment) based 8-aminoquinoline backbone were prepared and characterized by NMR, FT-IR, elemental analysis, UV–vis, CV etc. and tested as a photoactive dye for dye-sensitized solar cells (DSSC). The performance of the RuII-arene containing imine bond complex types (6–10) as a dye on DSSCs produced cells with power conversion efficiencies (PCEs) of around 0.03–0.10%. The [(N-Quinoline-8-yl-benzenesulfonamido)(p-cymene)chlororuthenium(II)] (SD-E1311) complex, which we previously produced was tested instead of the complexes bearing the imine bond (6–10) and its PCE for SD-E1311 was found as 0.12%. Herein, the increase of the Voc is quite interesting and, for this reason, the sulfonamidate based complexes were selected for the backbone structure. To enhance immobilization to the titanium oxide layer and solubility and electron injection of the corresponding excited dye on the DSSC process, 2,2′-bipyridine-4,4′-dicarboxylic acid as the anchor group and thiocyanate ligands were selected instead of p-cymene and chloro ligands over the sulfonamidate complex. Then, the photoactive dye properties of the new RuII complexes (16–20) were investigated and the results showed that the 16–20 dyes bearing sulfonamidate, carboxylic anchoring and thiocyanate fragments benefited the short-circuit current and the open-circuit voltage, and had PCEs of 1.26%, 1.08%, 1.58%, 0.90% and 1.36% under AM1.5G irradiation, respectively. The working devices, results also show that the 16–20 dyes demonstrated average performances with a PCEmax. of 1.58% which was occurred with 18 complex.

N‐Confused Porphyrin Metal Complexes with an Axial Pyridine Directly Tethered from an Inner Carbon: A Bioinspired Ligand as a Versatile Platform for Catalysis

Bioinspired pentadentate ligand N‐confused porphyrin (NCP) bearing a 2‐mercaptopyridine group and its RuII and CoIII complexes were synthesized. Their structures were revealed by single‐crystal X‐ray crystallographic analysis. Installation of an axial thiopyridine ligand shifts the redox potentials negatively and enhances the catalytic activity largely, which was demonstrated in the cyclopropanation reaction using the Co complex.

Enhancing photovoltaic performance of DSSCs sensitized with Ru-II complexes by D–π–A configured carbazole based co-sensitizers

Simple D–π–A architectured carbazole based dyes, P1–4, were employed as co-sensitizers in DSSCs sensitized with Ru-II complexes, viz.NCSU-10 and N3. The results revealed that, the NCSU-10 sensitized devices displayed improved photovoltaic performance when co-sensitized with P1 and P3.

Reversible disassembly of metallasupramolecular structures mediated by a metastable-state photoacid.

The addition of a metastable-state photoacid to solutions containing metal-ligand assemblies renders the systems light responsive. Upon irradiation, proton transfer from the photoacid to the ligand is observed, resulting in disassembly of the metallasupramolecular structure. In the dark, the process is fully reversed. Light-induced switching was demonstrated for six different metal-ligand assemblies containing PdII, PtII or RuII complexes and bridging polypyridyl ligands. The methodology allows liberating guest molecules with light.

Turning intercalators into groove binders: synthesis, photophysics and DNA binding properties of tetracationic mononuclear ruthenium(ii)-based chromophore-quencher complexes.

The synthesis of two new tetracationic mononuclear RuII complexes containing the tetrapyridyl [3,2-a:2',3'-c:3'',2''-h:2''',3'''-j] phenazine ligand in which the uncoordinated site has been converted into a dicationic ethylene-bipyridyldiylium unit is reported. The structure of the complexes is fully assigned through detailed NMR studies and, in one case, through an X-ray crystallography study. Voltammetry, optical spectroscopy and computational studies confirm that the bipyridyldiylium moiety has a low-lying reduction that quenches the 3MLCT-based emission usually observed in such systems. The new complexes interact with DNA in a quite different manner to their dicationic analogues: they both bind to duplex DNA with micromolar affinity through groove binding. These observations are rationalized through a consideration of their structural and electronic properties.

Chemoselectivity Control in the Asymmetric Hydrogenation of γ‐ and δ‐Keto Esters into Hydroxy Esters or Diols

AbstractThe asymmetric hydrogenation of aromatic γ‐ and δ‐keto esters into optically active hydroxy esters or diols under the catalysis of a novel DIPSkewphos/3‐AMIQ–RuII complex was studied. Under the optimized conditions (8 atm H2 , Ru complex/t‐C4H9OK=1:3.5, 25 °C) the γ‐ and δ‐hydroxy esters (including γ‐lactones) were obtained quantitatively with 97–99 % ee. When the reaction was conducted under somewhat harsh conditions (20 atm H2 , [t‐C4H9OK]=50 mm, 40 °C), the 1,4‐ and 1,5‐diols were obtained predominantly with 95–99 % ee. The reactivity of the ester group was notably dependent on the length of the carbon spacer between the two carbonyl moieties of the substrate. The reaction of β‐ and ϵ‐keto esters selectively afforded the hydroxy esters regardless of the reaction conditions. This catalyst system was applied to the enantioselective and regioselective (for one of the two ester groups) hydrogenation of a γ‐ϵ‐diketo diester into a trihydroxy ester.

Organoruthenium Complexes with C^N Ligands are Highly Potent Cytotoxic Agents that Act by a New Mechanism of Action.

Our study demonstrates that four novel kinetically inert C,N-cyclometalated RuII complexes of the type [Ru(C^N)(N^N)2 ][PF6 ] containing a handle for functionalization on the C^N ligand are very potent cytotoxic agents against several different human cancer cell lines and are up to 400-fold more potent than clinically used cisplatin. In addition, the investigated ruthenium complexes are less cytotoxic in noncancerous cells, and exhibit higher selectivity for cancer cells than conventional platinum anticancer drugs. The high potency of the investigated ruthenium compounds can be attributed to several factors, including enhanced internalization and their capability to change mitochondrial transmembrane potential in cells. The new ruthenium complexes also interfere with protein synthesis with a markedly higher potency than conventional inhibitors of DNA translation. Notably, the latter mechanism has not been hitherto described for other cytotoxic Ru compounds and cisplatin.

Spectroscopic Study of the Interactions of Ruthenium-Ketoconazole Complexes of Known Antiparasitic Activity with Human Serum Albumin and Apotransferrin

The pharmacological properties of any drug are related to their ability to interact with macromolecular blood components. The interaction of human serum albumin (HSA) and apotransferrin (ATf) with six RuII complexes containing ketoconazole (KTZ), which we have previously reported to be active against Leishmania major and Trypanosoma cruzi, has been investigated by monitoring the tryptophan fluorescence intensity of each protein upon incremental addition of the complexes. All the Ru-KTZ derivatives, namely cis-fac-[RuIICl2(DMSO)3(KTZ)] (1), cis-[RuIICl2(bipy)(DMSO)(KTZ)] (2), [RuII(η6-p-cymene)Cl2(KTZ)] (3), [RuII(η6-p-cymene)(en)(KTZ)][BF4]2 (4), [RuII(η6-p-cymene)(bipy)(KTZ)][BF4]2 (5), and [RuII(η6-p-cymene)(acac)(KTZ)][BF4] (6) are able to quench the intrinsic fluorescence of HSA and ATf at 27 °C. Analysis of the spectroscopic data using Stern-Volmer plots indicates that in both cases the quenching takes place principally through a static mechanism involving the formation of Ru complex-protein adducts; further analysis of the fluorescence data allowed the estimation of apparent association constants and the number of binding sites for each protein and each compound. The results indicate that both HSA and ATf are possible effective transporters for Ru-KTZ antiparasitic drugs.