Trinuclear Ru Research Articles

Confined Trinuclear Ru Sites in Phosphine-Incorporated Porous Organic Polymers for the Direct Synthesis of Alcohols from Reductive Hydroformylation of Alkenes

Confined Trinuclear Ru Sites in Phosphine-Incorporated Porous Organic Polymers for the Direct Synthesis of Alcohols from Reductive Hydroformylation of Alkenes

Chemical Structure Elucidation in the Development of Inorganic Drugs: Evidence from Ru‐, Au‐, As‐, and Sb‐based Medicines

AbstractStructure elucidation plays a critical role across the landscape of medicinal chemistry, including medicinal inorganic chemistry. Herein, we discuss the importance of structure elucidation in drug development and then provide three vignettes that capture key instances of its relevance in the development of biologically active inorganic compounds. In the first, we describe the exploration of the biological activity of the trinuclear Ru compound called ruthenium red and the realization that this activity derived from a dinuclear impurity. We next explore the development of Au‐based antitubercular and antiarthritic drugs, which features a key step whereby ligands were discovered to bind to Au through S atoms. The third exposition traces the development of As‐based antiparasitic drugs, a key step of which was the realization that the reaction of arsenic acid and aniline does not produce an anilide of arsenic acid, as originally thought, but rather an amino arsonic acid. These case studies provide the motivation for an outlook in which the development of Sb‐based antiparasitic drugs is described. Although antileishmanial pentavalent antimonial drugs remain in widespread use to this day, their chemical structures remain unknown.

Synthesis, characterization, photophysical, lipophilicity, and in vitro fluorescence studies of mono-, di-, and trinuclear Ru(II) polypyridyl complexes of pyridinyl benzimidazole derivatives.

The synthesis, characterization, and photophysical properties of mononuclear ruthenium(II) complexes [Ru(bpy)2(py-BIm-Bz)](ClO4)2 (1) and [Ru(phen)2(py-BIm-Bz)](ClO4)2 (2), dinuclear complexes [(bpy)2Ru-μ2-(py-BIm-Xy)-Ru(bpy)2](ClO4)4 (3) and [(phen)2Ru-μ2-(py-BIm-Xy)-Ru(phen)2](ClO4)4 (4), and trinuclear complexes [((bpy)2Ru)3-μ3-(py-BIm-Ms)](ClO4)6 (5) and [((phen)2Ru)3-μ3-(py-BIm-Ms)](ClO4)6 (6) of pyridinyl benzimidazole ligands with 2,2'-bipyridine or 1,10-phenanthroline ancillary ligands as fluorescent imaging probes are reported. The ligand py-BIm-Bz crystallizes with inherent disorder due to the competing π-π interactions between two (2-pyridinyl)benzimidazole moieties aligned in parallel and in the opposite direction. The complex 2 forms non-merohedrally twinned crystal with the twin law matrix [0.259 -0.776 0.741, 0.000 -1.000 0.000, 1.259 -0.776 -0.259] and a batch scale factor (BASF) of 0.05. The electronic absorption spectra of the complexes 1-6 differ typically in the π-π* transitions of the ancillary ligands. The complexes exhibit orange-red fluorescence at 624-634nm at room temperature with quantum yield (0.096 - 0.117) higher than that of [Ru(bpy)3]2+ and a hypsochromic shift of the emission maxima in frozen acetonitrile (λem = 613-628nm) due to the rigidochromic effect. The excited state lifetime of these complexes are in the range 72-194ns with the mononuclear complexes exhibiting the highest values. The complexes 1-6 are nontoxic (IC50 > 275μM) toward both HeLa and Vero cell lines. They are hydrophilic and the logPo/w values are in the -0.53 to -1.46 range. The confocal microscopic study of cellular localization of the complexes on the HeLa cells co-stained with the nuclear staining DAPI dye shows their localization in the cytoplasm and the nuclear membrane penetration increases with nuclearity.

Effects of Photosensitizers and Reaction Media on Light‐Driven Water Oxidation with Trinuclear Ruthenium Macrocycles

AbstractPhotocatalytic water oxidation is a promising process for the production of solar fuels and the elucidation of factors that influence this process is of high significance. Thus, we have studied in detail light‐driven water oxidation with a trinuclear Ru(bda) (bda: 2,2’‐bipyridine‐6,6’‐dicarboxylate) macrocycle MC3 and its highly water soluble derivative m‐CH2NMe2‐MC3 using a series of ruthenium tris(bipyridine) complexes as photosensitizers under varied reaction conditions. Our investigations showed that the catalytic activities of these Ru macrocycles are significantly affected by the choice of photosensitizer (PS) and reaction media, in addition to buffer concentration, light intensity and concentration of the sensitizer. Our steady‐state and transient spectroscopic studies revealed that the photocatalytic performance of trinuclear Ru(bda) macrocycles is not limited by their intrinsic catalytic activities but rather by the efficiency of photogeneration of oxidant PS+ and its ability to act as an oxidizing agent to the catalysts as both are strongly dependent on the choice of photosensitizer and the amount of employed organic co‐solvent.

Impact of substituents on molecular properties and catalytic activities of trinuclear Ru macrocycles in water oxidation.

Herein we report a broad series of new trinuclear supramolecular Ru(bda) macrocycles bearing different substituents at the axial or equatorial ligands which enabled investigation of substituent effects on the catalytic activities in chemical and photocatalytic water oxidation. Our detailed investigations revealed that the activities of these functionalized macrocycles in water oxidation are significantly affected by the position at which the substituents were introduced. Interestingly, this effect could not be explained based on the redox properties of the catalysts since these are not markedly influenced by the functionalization of the ligands. Instead, detailed investigations by X-ray crystal structure analysis and theoretical simulations showed that conformational changes imparted by the substituents are responsible for the variation of catalytic activities of the Ru macrocycles. For the first time, macrocyclic structure of this class of water oxidation catalysts is unequivocally confirmed and experimental indication for a hydrogen-bonded water network present in the cavity of the macrocycles is provided by crystal structure analysis. We ascribe the high catalytic efficiency of our Ru(bda) macrocycles to cooperative proton abstractions facilitated by such a network of preorganized water molecules in their cavity, which is reminiscent of catalytic activities of enzymes at active sites.

Efficient trinuclear Ru(ii)-Re(i) supramolecular photocatalysts for CO2 reduction based on a new tris-chelating bridging ligand built around a central aromatic ring.

We have designed and synthesized a new tris-chelating polypyridine ligand (bpy3Ph) suitable to be used as a bridging ligand (BL) for constructing various supramolecular photocatalysts. This BL is a phenylene ring with three ethylene chains at 1, 3, and 5 positions, of which the other terminals are connected to 2,2'-bipyridine moieties. The ligand bpy3Ph has been used to prepare, according to a multi-step synthetic protocol, trinuclear supramolecular photocatalysts containing different metal subunits. In particular, the compounds Ru2Re and RuRe2 have been prepared, containing different ratios of components based on Ru(dmb)3 2+-type and Re(dmb)(CO)3Cl-type units (dmb = 4,4'-dimethyl-2,2'-bipyridine), which can play the roles of photosensitizers and catalyst units for photocatalytic CO2 reduction, respectively. The trinuclear model Ru3 and mononuclear and dinuclear Ru and Ru2 precursor metal complexes, containing free chelating sites, have also been synthesized using the same bridging ligand. The absorption spectra, redox behaviour and photophysical properties of the new species indicate that there is no strong electronic interaction among the Ru and Re units. The trinuclear complexes Ru2Re and RuRe2 could photocatalyze CO2 reduction to CO with high selectivity (up to 97%), high efficiency (Φ COs of 28% and 25%, respectively: BIH as a reductant), and high durability (TONCOs of 5232 and 6038, respectively: BIH as a reductant) which are the largest TONs for CO2 reduction using supramolecular photocatalysts in homogeneous solutions. The absence of negligible accumulation of the mono-reduced form of the photosensitizer indicates fast electron transfer to the catalyst unit(s) through the relatively large bridging ligand and is proposed to contribute to the outstanding photocatalytic properties of the new species, including their durability. The relevant photocatalytic behaviour of the new systems indicates new avenues for the design of extended bridging ligands capable of efficiently and functionally integrating photosensitizers and catalysts towards the preparation of new, larger supramolecular photocatalysts for selective CO2 reduction.

Synthesis, characterization, photophysical, and redox properties of three trinuclear Ru(II) polypyridyl complexes possessing 5-amino-1,10-phenanthroline ligands

Three ruthenium(II) polypyridyl complexes with 5-amino-1,10-phenanthroline ligands have been successfully designed and synthesized. They have been fully characterized by ESI-MS, ESI-HRMS, 1H NMR, and elemental analyses. The photophysical and electrochemical properties of the three complexes have been investigated in organic solvent. The geometrical configuration and the electron density distribution in the frontier molecular orbitals of the three complexes have been studied. The three complexes show metal-to-ligand charge transfer (1MLCT) absorption at 445 nm, and intense triplet metal-to-ligand (3MLCT) emission at around 619 nm in fluid solution at 298 K and 580 nm in low-temperature glass. Electrochemical studies of the three complexes are consistent with one RuIII/II reversible couple at around 1.31 V accompanied by three ligand-centered reduction couples.

Substituent Effect of the Bridging Ligand in the Trinuclear Ru Complexes on Photocatalytic Oxygenation of a Sulfide and Alkenes.

To examine the effect of tuning the electron transfer ability between photosensitizers and reaction centers on the activity of visible-light-driven catalysts, a series of trinuclear Ru photocatalysts containing two Ru(II) photosensitizers and a Ru(II) reaction center bridged by a substituted bipyrimidine was prepared. The introduction of electron-donating or electron-withdrawing groups on the ligands was found to affect the photophysical and electrochemical properties of these catalysts. Density functional theory calculations of the mononuclear Ru complexes with nonsubstituted and substituted bipyrimidine ligands, which correspond to the reaction center of the trinuclear complexes, revealed how the electronic effect of the substituents affect the frontier orbital energies. For photocatalytic oxygenation of a sulfide and terminal alkenes, the catalyst with a 5,5'-dibromo-2,2'-bipyrimidine ligand showed higher activity than the catalyst with 5,5'-dimethyl-2,2'-bipyrimidine and nonsubstituted bipyrimidine ligands, as expected according to the electronic effects of these ligands. In contrast, the catalyst with the nonsubstituted bipyrimidine ligand showed the highest activity toward inner alkenes, which may be due to steric effects.

Two trinuclear Ru(II) complexes of hetero-tritopic bridging ligands: synthesis, characterization, theoretical calculations, photophysical and electrochemical properties

Two hetero-tritopic bridging ligands L1 and L2 based on 2,2′-bipyridine and 1,10-phenanthroline moieties, and their corresponding Ru(II) complexes [{Ru(bpy)2}3(µ3−L1)](PF6)6 and [{Ru(bpy)2}3(µ3−L2)](PF6)6 (bpy = 2,2′-bipyridine), were synthesized. The molecular structures of both complexes were deduced by 1H NMR, ESI-MS, ESI-HRMS, elemental analyses, and IR spectroscopy. Quantum calculations on the free bridging ligands and their complexes are also presented. Both complexes display MLCT absorptions at around 454 nm, and emissions at around 613 nm in CH3CN solution at room temperature and at around 590 nm in EtOH–MeOH glassy matrix at 77 K. Cyclic and differential pulse voltammetry studies of both complexes reveal one reversible Ru(II)-centered oxidation and three reversible ligand-centered reductions, in each case.

Photocatalytic Oxygenation of Sulfide and Alkenes by Trinuclear Ruthenium Clusters.

Trinuclear Ru cluster photocatalysts that contain two Ru(II) photosensitizers and a Ru(II) reaction center are prepared, and their activity in the photocatalytic oxygenation of a sufide and alkenes is investigated. Photoirradiation (visible light) and the use of a Co salt ([Co(NH3)5Cl]Cl2, as an electron acceptor) are found to be essential for these catalytic reactions. The O atom of the water solvent (pH 6.8) is transferred to the substrate by a stepwise electron transfer and deprotonation of an aqua ligand at the reaction center. Through these processes, the aqua ligand coordinated at the reaction center is converted to a Ru(V)═O species, which is the active intermediate in the sulfide and alkene oxygenation.

Di- and trinuclear Ru(II) complexes of 1,10-phenanthroline and 2,2′-bipyridine derivatives; synthesis, photophysical and electrochemical properties

Three heterotopic ligands L1, L2, and L3 based on 1,10-phenanthroline and 2,2′-bipyridine moieties have been synthesized and characterized. The Ru(II) complexes [{Ru(bpy)2}3(µ3-L1)](PF6)6, [{Ru(bpy)2}3(µ3-L2)](PF6)6, and [{Ru(bpy)2}2(µ2-L3)](PF6)4 (bpy = 2,2′-bipyridine) have been prepared by refluxing Ru(bpy)2Cl2·2H2O with each ligand in ethanol. All three complexes display MLCT absorptions at around 455 nm and emissions at around 618 nm. Electrochemical studies of the complexes reveal one Ru(II)-centered quasi-reversible oxidation at around 1.32 V and three ligand-centered reductions in each case.

A Cyanuric Acid Platform Based Tripodal Bis-heteroleptic Ru(II) Complex of Click Generated Ligand for Selective Sensing of Phosphates via C-H···Anion Interaction.

A new bis-heteroleptic trinuclear Ru(II) complex (1[PF6]6) has been synthesized from electron deficient cyanuric acid platform based copper-catalyzed azide-alkyne cycloaddition, i.e., CuAAC click generated ligand, 1,3,5-tris [(2-aminoethyl-1H-1,2,3-triazol-4-yl)-pyridine]-1,3,5-triazinane-2,4,6-trione (L1). Complex 1[PF6]6 displays weak luminescence (ϕf = 0.002) at room temperature with a short lifetime of ∼5 ns in acetonitrile. It shows selective sensing of hydrogen pyrophosphate (HP2O7(3-)) through 20-fold enhanced emission intensity (ϕf = 0.039) with a 15 nm red shift in emission maxima even in the presence of a large excess of various competitive anions like F(-), Cl(-), AcO(-), BzO(-), NO3(-), HCO3(-), HSO4(-), HO(-), and H2PO4(-) in acetonitrile. Selective change in the decay profile as well as in the lifetime of 1[PF6]6 in the presence of HP2O7(3-) (108 ns) further supports its selectivity toward HP2O7(3-). UV-vis and photoluminescence titration profiles and corresponding Job's plot analyses suggest 1:3 host-guest stoichiometric binding between 1[PF6]6 and HP2O7(3-). High emission enhancement of 1[PF6]6 in the presence of HP2O7(3-) has resulted in the detection limit of the anion being as low as 0.02 μM. However, 1[PF6]6 shows selectivity toward higher analogues of phosphates (e.g., ATP, ADP, and AMP) over HP2O7(3-)/H2PO4(-) in 10% Tris HCl buffer (10 mM)/acetonitrile medium. Downfield shifting of the triazole C-H in a (1)H NMR titration study confirms that the binding of HP2O7(3-)/H2PO4(-) is occurring via C-H···anion interaction. The single crystal X-ray structure of complex 1 having NO3(-) counteranion, 1[NO3]6 shows binding of NO3(-) with complex 1 via C-H···NO3(-) interactions.

Photoinduced Charge Accumulation in Molecular Systems.

Fuel-forming reactions such as CO2 reduction or water splitting require multiple redox equivalents. When aiming at light-driven production of energy-rich chemicals, nowadays often referred to as solar fuels, it therefore becomes important to master the photoinduced accumulation of electrons or holes on individual molecular components. Featured in this short review are some of the key molecular systems explored in this emerging field of research. This includes for example a trinuclear Ru(II)-Rh(III)-Ru(III) complex or an Ir(III)-sensitized polyoxotungstate hybrid, but also several systems in which electron or hole collection occurs at organic moieties such as perylenebis(dicarboximide), quinone-containing or oligotriarylamine-based units. In many cases the photodriven accumulation of charge requires the use of sacrificial electron donors, but there exist also a handful of studies in which redox equivalents can be accumulated without the use of such additives.

Three trinuclear Ru(II) complexes containing 4,5-diazafluorene and 2,2′-bipyridine: synthesis, absorption spectrum, luminescence, and redox behavior

Three heterotopic ligands L1, L2, and L3 have been prepared by the reaction of 4,4′-bis(bromomethyl)-2,2′-bipyridine with 4,5-diazafluoren-9-oxime, 9-(2-hydroxy)phenylimino-4,5-diazafluorene, and 9-(4-hydroxy)phenylimino-4,5-diazafluorene, respectively, in DMF. The three ligands consist of two 4,5-diazafluorene units and one 2,2′-bipyridine unit. Ru(II) complexes [{Ru(bpy)2}3(μ3-L1−3)](PF6)6 (bpy = 2,2′-bipyridine) were prepared by refluxing Ru(bpy)2Cl2·2H2O and the ligands in 2-methoxyethanol. The three Ru(II) complexes display metal-to-ligand charge-transfer absorption at 445–450 nm and one Ru(II)-centered oxidation at 1.32 V in CH3CN solution at room temperature. Upon excitation into the metal-to-ligand charge-transfer band, the emission intensities of [{Ru(bpy)2}3(μ3-L2)]6+ and [{Ru(bpy)2}3(μ3-L3)]6+ are almost equal to that of [{Ru(bpy)2}3(μ3-L1)]6+ in CH3CN solution at room temperature, but weaker than that of [{Ru(bpy)2}3(μ3-L1)]6+ in EtOH–MeOH (4 : 1, v/v) glassy matrix at 77 K.

Molecular assemblies based on strong axial coordination in metal complexes of saddle-distorted dodecaphenylporphyrins

In this mini-review, we have highlighted our works on metal complexes having saddle-distorted dodecaphenylporphyrin (DPP) and its derivative as ligands in the light of enhancement of the Lewis acidity of a metal center coordinated by the porphyrin. The important point through this mini-review is ill-overlap of the out-of-plane lone pairs of pyrrole nitrogen atoms with σ-orbitals of the metal center bound to the saddle-distorted porphyrin core. The enhanced Lewis acidity of the central metal ions enabled us to construct stable molecular complexes through axial coordination using metal–DPP (M(DPP)) moieties ( M = Mo V or Sn IV ) and molecular or ionic entities with Lewis-basic coordination sites, including Keggin-type polyoxometallates (POM), which are known to have weak Lewis basicity and thus hard to coordinate to metal ions. A discrete 1:2 complex with a Ru -substituted POM performs catalytic substrate oxidation reactions in organic solvents. A 1:1 complex between Sn IV ( DPP ) and a Keggin-type POM exhibited photoinduced electron transfer, in which the Sn IV ( DPP ) moiety acts as an electron donor and the POM as an electron acceptor. Besides POM, other electron acceptors, including μ3-oxo trinuclear Ru III clusters and anthraquinone, having carboxyl groups as a linker unit also formed stable complexes with DPP-metal complexes as axial ligands to perform photoinduced electron transfer. Successful photoreactions of the M(DPP)-acceptor complexes are mainly enabled by the enhanced Lewis acidity of the DPP-metal complexes for the stabilization of the assemblies and also by lowering the oxidation potential of the porphyrin ligand to gain larger driving force of electron transfer to form an electron-transfer state with avoiding intersystem crossing. The stability and photochemical behavior are in sharp contrast to those for metal complexes with planar porphyrins as ligands.

DNA binding properties and cytotoxic activities of two trinuclear ruthenium(II) polypyridyl complexes

The interactions between two trinuclear Ru(II) complexes and calf thymus DNA(CT DNA) were studied via absorption spectroscopy, reverse salt titrations, binding stoichiometry, DNA melting experiments, as well as viscosity measurement. The results indicate that complexes 1 and 2 bind to DNA via the interaction of the planar π-delocalized system of the complexes with intrinsic binding constants of 4.18×105 and 3.85×106 L/mol, respectively, and non-electrostatic binding free energy makes a predominant contribution to the binding free energy. The in vitro cytotoxic activity of complexes 1 and 2 was evaluated by the MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide]_method. Complex 1 shows higher anticancer potency than complex 2 against four tumor cell lines. Further mechanism study indicates that complexes 1 and 2 can cause cell cycle arrest in the G2/M phase.

Preparation, photophysical, and electrochemical properties of three trinuclear Ru(II) complexes: Bridging ligands composed of 2,2′-bipyridine and 4,5-diazafluorene fragments

Three bridging ligands 5,5′-bis[(4,5-diazafluoren-9-ylimino)methyl]-2,2′-bipyridine (L1), 5,5′-bis[2-(4,5-diazafluoren-9-ylimino)phenoxymethyl]-2,2′-bipyridine (L2), 5,5′-bis[4-(4,5-diazafluoren-9-ylimino)phenoxymethyl]-2,2′-bipyridine (L3), and corresponding Ru(II) complexes [(bpy)6Ru3(L1–3)](PF6)6 (bpy=2,2′-bipyridine) have been synthesized. The three ligands have two kinds of nonequivalent chelating sites: one involving the 2,2′-bipyridine moiety, and the other involving the 4,5-diazafluorene moiety. The emission intensities of complexes [(bpy)6Ru3(L2)]6+ and [(bpy)6Ru3(L3)]6+ are almost equal to that of complex [(bpy)6Ru3(L1)]6+ in CH3CN solution at room temperature, but weaker than that of complex [(bpy)6Ru3(L1)]6+ in EtOH–MeOH (4:1, v/v) glassy matrix at 77K. Cyclic voltammetry and differential pulse voltammetry studies of the three complexes show one Ru(II)-centered oxidation at around 1.33V for the RuII/III couple.

PH-responsive luminescence of a new trinuclear Ru(ii) polypyridine complex

Synthesis of a new heteroleptic trinuclear Ru(ii) complex of a ditopic imidazole-based terpyridine bridging ligand and its room temperature luminescence in fluid solution and pH modulated luminescence behaviour is reported.

RNA binding and inhibition of primer extension by a Ru(iii)/Pt(ii) metal complex

AH197, a trinuclear Ru(III)/Pt(II) metal complex, is strikingly more effective than the hallmark anticancer drug cisplatin and the Ru(III) clinical candidate NAMI-A in its binding to RNA and inhibition of primer DNA synthesis. Heteromultinuclear complexes could potentially serve as far better chemotherapeutics than mononuclear complexes.

Dispersed Ru nanoclusters transformed from a grafted trinuclear Ru complex on SiO2 for selective alcohol oxidation

Ru nanoclusters (average diameter = 1.3 ± 0.3 nm) were successfully prepared by using a Ru3 cluster Ru3O(CH3COO)6(H2O)3·(CH3COO) grafted on a pyridine-functionalized SiO2 surface. The pyridine moiety dispersed on the SiO2 surface spread the Ru3 cluster, controlling its surface density, and the nanoclusterization of the Ru cluster proceeded on the surface. The structures of the Ru nanoclusters were characterized by means of elemental analysis; thermogravimetric analysis; FT-IR, UV/vis, and solid-state NMR spectroscopy; BET analysis; X-ray photoelectron spectroscopy; X-ray diffraction; transmission electron microscopy; and Ru K-edge X-ray absorption fine structure analysis. It was found that the catalytic activity for the selective oxidation of alcohol to the corresponding aldehyde using O2 highly depended on the dispersion and structures of the Ru particles, and the Ru nanocluster was found to be efficient in the selective oxidation of a variety of alcohols.