Triphenylamine and carbazole‐modified iridiumIII 2‐phenylpyridine complexes: Synthesis,anticaner application and targeted research

Four half‐sandwich iridium^III (Ir^III) triphenylamine or carbazole‐modified 2‐phenylpyridine (TPA/Cz‐PhPy) complexes ([(η⁵‐Cp*)Ir(C^N)Cl]) were synthesized and characterized. Compared with cisplatin, these complexes show higher activity to A549, HepG2 and HeLa cells, with the IC₅₀ values changed from 2.5 ± 0.1 μM to 14.8 ± 2.6 μM. Additionally, complexes could effectively prevent the migration of cancer cells. Ir^III TPA/Cz‐PhPy complexes could bind to protein and transport through serum protein, catalyze the oxidation of nicotinamide‐adenine dinucleotid (NADH) and induce the accumulation of reactive oxygen species, and eventually lead to apoptosis, which was also confirmed by flow cytometry. Moreover, prominent targeted fluorescence property confirmed that Ir^III TPA/Cz‐PhPy complexes were involved in non‐energy dependent intracellular uptake mechanism, effectively accumulated in lysosomes and damage the integrity of acidic lysosomes, and eventually induce cell death. Above all, TPA/Cz‐appended half‐sandwich Ir^III phenylpyridine complexes are promising anticancer agents with dual functions, including migration inhibition and lysosomal damage.     

Lysosome‐targeted potent half‐sandwich iridium(III) α‐diimine antitumor complexes

Fifteen organometallic Ir(III) half‐sandwich complexes ( 1A – 5C ) having the general formula [(η⁵‐Cp^x)Ir(N^N)Cl]PF₆ (Cp^x = Cp*, tetramethyl(phenyl)cyclopentadienyl (Cp^xph) or tetramethyl(biphenyl)cyclopentadienyl (Cp^xbiph); N^N = diamine) have been synthesized and characterized. The molecular structure of 1A was determined using single‐crystal X‐ray diffraction analysis. The hydrolysis of 1A – 5C was monitored using UV–visible spectra. Complexes 3A – 3C showed catalytic activity for the oxidation of NADH to NAD⁺, where 3C showed the highest turnover number of 29.9 within 450 min. Cytotoxicity examination by MTT assay was carried out against two human cancer cell lines (HeLa and A549) after 24 or 48 h drug treatment. The complexes showed high potency, where the most potent complex ( 3C ; IC₅₀ = 3.4 μM) was six times more active than cisplatin against A549 cells after 24 h drug exposure. Cytotoxic potency towards A549 cells increased with phenyl substitution on Cp ring: Cp^xbiph > Cp^xph > Cp*. In addition, the biological studies showed that 3C caused cell apoptosis and cell cycle arrest at G₁ phase in A549 cancer cells. Moreover, 3C increased the level of reactive oxygen species markedly after 24 h, which may provide an important basis for killing cancer cells. Confocal laser scanning microscopy was used to track 3C in A549 cells. The cellular localization experiment showed that 3C targeted lysosomes and caused lysosomal damage.     

Synthesis,spectral, structural characterization and biological activity of new palladium(II) complexes containing 3‐acetyl‐8‐methoxy‐2H‐chromen‐2‐one derived Schiff bases

Four different mononuclear palladium(II) complexes of 3‐acetyl‐8‐methoxycoumarin Schiff bases were synthesized and characterized by spectrochemical techniques. Further analysis through X‐ray crystallography confirmed the structures of the complexes. Their interactive ability with Calf Thymus DNA and protein (Bovine Serum Albumin and Human Serum Albumin) were investigated by means of absorption and emission methods. The intercalative mode of binding with DNA was supported by EB displacement studies and viscosity measurements. Configurational changes that occurred in the proteins have been analysed with the help of 3D fluorescence studies. The complexes were shown to have good antimicrobial activity against the tested bacterial and fungal pathogens. In addition, antiproliferative activity of the complexes was evaluated on A549 and MCF‐7 cell lines and the complexes were comparatively more active than the standard drug cisplatin. Among the compounds, complex 3 was the most effective against MCF‐7 (IC₅₀ value of 5.20 ± 0.15 μM) and A549 (5.09 ± 0.13 μM) compared with the other complexes 1 (6.48 ± 0.17 μM; 5.98 ± 0.09 μM), 2 (5.53 ± 0.12 μM; 5.85 ± 0.11 μM), 4 (6.73 ± 0.19 μM; 6.63 ± 0.16 μM) and cisplatin (16.79 ± 0.08 μM; 15.10 ± 0.05 μM) respectively. LDH and NO release assays confirmed the cytotoxic potential of the synthesized complexes.     

Ruthenium(II)–Polyimine–Coumarin Light‐Harvesting Molecular Arrays: Design Rationale and Application for Triplet–Triplet‐Annihilation‐Based Upconversion

Ru^II–bis‐pyridine complexes typically absorb below 450 nm in the UV spectrum and their molar extinction coefficients are only moderate (ε<16 000 M ^?1 cm^?1). Thus, Ru^II–polyimine complexes that show intense visible‐light absorptions are of great interest. However, no effective light‐harvesting ruthenium(II)/organic chromophore arrays have been reported. Herein, we report the first visible‐light‐harvesting Ru^II–coumarin arrays, which absorb at 475 nm (ε up to 63 300 M ^?1 cm^?1, 4‐fold higher than typical Ru^II–polyimine complexes). The donor excited state in these arrays is efficiently converted into an acceptor excited state (i.e., efficient energy‐transfer) without losses in the phosphorescence quantum yield of the acceptor. Based on steady‐state and time‐resolved spectroscopy and DFT calculations, we proposed a general rule for the design of Ru^II–polypyridine–chromophore light‐harvesting arrays, which states that the ¹IL energy level of the ligand must be close to the respective energy level of the metal‐to‐ligand charge‐transfer (M LCT) states. Lower energy levels of ¹IL/³IL than the corresponding ¹M LCT/³M LCT states frustrate the cascade energy‐transfer process and, as a result, the harvested light energy cannot be efficiently transferred to the acceptor. We have also demonstrated that the light‐harvesting effect can be used to improve the upconversion quantum yield to 15.2 % (with 9,10‐diphenylanthracene as a triplet‐acceptor/annihilator), compared to the parent complex without the coumarin subunit, which showed an upconversion quantum yield of only 0.95 %.     

Three pairs of enantiomers bearing mitochondria‐targeted TPP+ groups as potential anti‐cancer agents

Six complexes with chiral Schiff‐base ligands containing TPP⁺ groups, [VO L ^R,R/^S,S](ClO₄)₂( 1 for RR, 2 for SS), [Ni L ^R,R/S,S](ClO₄)₂·C₂H₅OH ( 3 for RR, 4 for SS) and [CuL^R,R/S,S](ClO₄)₂·CHCl₃·CH₃CH₂OH ( 5 for RR, 6 for SS) ( L ^R,R/S,S = N,N′‐Bis{5‐[(triphenylphosphonium)‐methyl]salicylidine}‐(1R,2R/1S,2S)‐diphenylethane‐1,2‐diamine, were synthesized to serve as mitochondrion‐targeting anticancer drugs. The introduction of TPP⁺ group(s) might markedly influence the properties of complexes. Compounds 3 and 5 were structurally characterized by X‐ray crystallography. Complexes 1–6 could be moderate intercalating agents to CT‐DNA which is determined by several spectroscopy methods. DNA cleavage experiments revealed that all compounds could promote oxidative cleavage of pBR322 plasmid DNA in the presence of H₂O₂. MTT assay indicated 1–6 exhibited effective cytotoxicity on A549 and MCF‐7 cell lines. Notably, the IC₅₀ values of 5 (1.24 ± 0.33 μM) or 6 (1.47 ± 0.52 μM) were approximately 9–11 fold lower than that of cisplatin (IC₅₀ = 13.56 ± 0.88 μM) on A549 cells. 5 and 6 were picked for further study, which indicated that the cytotoxicity seems to result from multiple mechanisms of action, including effectively suppress the growth and proliferation of A549 cells, generation of reactive oxygen species, dissipation of mitochondrial membrane potential, cell cycle perturbation and apoptosis induction. Compounds 1–6 could highly accumulate in the mitochondria by means of ICP‐MS assay. This study demonstrates that 1–6 with mitochondrion‐targeting function could be efficient anticancer drugs.     

Spontaneous CO Release from RuII(CO)2–Protein Complexes in Aqueous Solution,Cells, and Mice

We demonstrate that Ru^II(CO)₂–protein complexes, formed by the reaction of the hydrolytic decomposition products of [fac‐RuCl(κ²‐H₂NCH₂CO₂)(CO)₃] (CORM‐3) with histidine residues exposed on the surface of proteins, spontaneously release CO in aqueous solution, cells, and mice. CO release was detected by mass spectrometry (MS) and confocal microscopy using a CO‐responsive turn‐on fluorescent probe. These findings support our hypothesis that plasma proteins act as CO carriers after in vivo administration of CORM‐3. CO released from a synthetic bovine serum albumin (BSA)–Ru^II(CO)₂ complex leads to downregulation of the cytokines interleukin (IL)‐6, IL‐10, and tumor necrosis factor (TNF)‐α in cancer cells. Finally, administration of BSA–Ru^II(CO)₂ in mice bearing a colon carcinoma tumor results in enhanced CO accumulation at the tumor. Our data suggest the use of Ru^II(CO)₂–protein complexes as viable alternatives for the safe and spatially controlled delivery of therapeutic CO in vivo.     

Ruthenium(II/III)‐Based Compounds with Encouraging Antiproliferative Activity against Non‐small‐Cell Lung Cancer

Hereby we present the synthesis of several ruthenium(II) and ruthenium(III) dithiocarbamato complexes. Proceeding from the Na[trans‐Ru^III(dmso)₂Cl₄] ( 2 ) and cis‐[Ru^II(dmso)₄Cl₂] ( 3 ) precursors, the diamagnetic, mixed‐ligand [Ru^IIL₂(dmso)₂] complexes 4 and 5 , the paramagnetic, neutral [Ru^IIIL₃] monomers 6 and 7 , the antiferromagnetically coupled ionic α‐[Ru^III₂L₅]Cl complexes 8 and 9 as well as the β‐[Ru^III₂L₅]Cl dinuclear species 10 and 11 (L=dimethyl‐ (DMDT) and pyrrolidinedithiocarbamate (PDT)) were obtained. All the compounds were fully characterised by elemental analysis as well as ¹H NMR and FTIR spectroscopy. Moreover, for the first time the crystal structures of the dinuclear β‐[Ru^III₂(dmdt)₅]BF₄ ? CHCl₃ ? CH₃CN and of the novel [Ru^IIL₂(dmso)₂] complexes were also determined and discussed. For both the mono‐ and dinuclear Ru^II and Ru^III complexes the central metal atoms assume a distorted octahedral geometry. Furthermore, in vitro cytotoxicity of the complexes has been evaluated on non‐small‐cell lung cancer (NSCLC) NCI‐H1975 cells. All the mono‐ and dinuclear Ru^III dithiocarbamato compounds (i.e., complexes 6 – 10 ) show interesting cytotoxic activity, up to one order of magnitude higher with respect to cisplatin. Otherwise, no significant antiproliferative effect for either the precursors 2 and 3 or the Ru^II complexes 4 and 5 has been observed.     

Spontaneous CO Release from RuII(CO)2–Protein Complexes in Aqueous Solution,Cells, and Mice

We demonstrate that Ru^II(CO)₂–protein complexes, formed by the reaction of the hydrolytic decomposition products of [fac‐RuCl(κ²‐H₂NCH₂CO₂)(CO)₃] (CORM‐3) with histidine residues exposed on the surface of proteins, spontaneously release CO in aqueous solution, cells, and mice. CO release was detected by mass spectrometry (MS) and confocal microscopy using a CO‐responsive turn‐on fluorescent probe. These findings support our hypothesis that plasma proteins act as CO carriers after in vivo administration of CORM‐3. CO released from a synthetic bovine serum albumin (BSA)–Ru^II(CO)₂ complex leads to downregulation of the cytokines interleukin (IL)‐6, IL‐10, and tumor necrosis factor (TNF)‐α in cancer cells. Finally, administration of BSA–Ru^II(CO)₂ in mice bearing a colon carcinoma tumor results in enhanced CO accumulation at the tumor. Our data suggest the use of Ru^II(CO)₂–protein complexes as viable alternatives for the safe and spatially controlled delivery of therapeutic CO in vivo.     

Light Harvesting and Directional Energy Transfer in Long‐Lived Homo‐ and Heterotrimetallic Complexes of FeII,RuII, and OsII

A new family of trimetallic complexes of the form [(bpy)₂M(phen‐Hbzim‐tpy)M′(tpy‐Hbzim‐phen)M(bpy)₂]⁶⁺ (M=Ru^II, Os; M′=Fe^II, Ru^II, Os; bpy=2,2′‐bipyridine) derived from heteroditopic phenanthroline–terpyridine bridge 2‐{4‐[2,6‐di(pyridin‐2‐yl) pyridine‐4‐yl]phenyl}‐1H‐imidazole[4,5‐f][1,10]phenanthroline (phen‐Hbzim‐tpy) were prepared and fully characterized. Zn²⁺ was used to prepare mixed‐metal trimetallic complexes in situ by coordinating with the free tpy site of the monometallic precursors. The complexes show intense absorptions throughout the UV/Vis region and also exhibit luminescence at room temperature. The redox behavior of the compounds is characterized by several metal‐centered reversible oxidation and ligand‐centered reduction processes. Steady‐state and time‐resolved luminescence data show that the potentially luminescent Ru^II‐ and Os^II‐based triplet metal‐to‐ligand charge‐transfer (³MLCT) excited states in the triads are quantitatively quenched, most likely by intercomponent energy transfer to the lower lying ³MLCT (for Ru and Os) or triplet metal‐centered (³MC) excited states of the Fe^II subunit (nonluminescent). Interestingly, iron did not adversely affect the photophysics of the respective systems. This suggests that the multicomponent molecular‐wire‐like complexes investigated here can behave as efficient light‐harvesting antennas, because all the light absorbed by the various subunits is efficiently channeled to the subunit(s) in which the lowest‐energy excited states are located.     

Synergistic Effects of Metals in a Promising RuII−PtII Assembly for a Combined Anticancer Approach: Theoretical Exploration of the Photophysical Properties

Ru^II?Pt^II complexes are a class of bioactive molecules of interest as anticancer agents that combine a light‐absorbing chromophore with a cisplatin‐like unit. The results of a DFT and TDDFT investigation of a Ru^II complex and its conjugate with a cis‐PtCl₂ moiety reveal that a synergistic effect of the metals makes the assembly a promising multitarget anticancer drug. Inspection of type I and type II photoreactions and spin–orbit coupling computations reveals that the cis‐PtCl₂ moiety improves the photophysical properties of the Ru^II chromophore, ensuring efficient singlet oxygen generation and making the assembly suitable for photodynamic therapy. At the same time, the Ru^II chromophore promotes a new alternative activation mechanism of the Pt^II ligand via a triplet metal‐to‐ligand charge transfer (³M LCT) state, before reaching the biological target. The importance of the supramolecular architecture is accurately derived, opening interesting new perspectives on the use of bimetallic Ru^II?Pt^II assemblies in a combined anticancer approach.     

A Multi‐action and Multi‐target RuII–PtIV Conjugate Combining Cancer‐Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers

Pt^II complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt^IV complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru^II polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt^IV–Ru^II conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt^IV centre is reduced to Pt^II and the axial ligands including the Ru^II complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi‐target and multi‐action effect with (photo‐)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.     

Ferrocene conjugated copper(II) complexes of terpyridine and traditional Chinese medicine (TCM) anticancer ligands showing selective toxicity towards cancer cells

Six novel mixed‐ligand copper(II) complexes, namely, [Cu(R‐tpy)(L)]NO₃ ( 1–6 ), where R‐tpy is 4′‐phenyl‐2,2′:6′,2′′‐terpyridine (Ph‐tpy; 1–3 ) and 4′‐ferrocenyl‐2,2′:6′,2′′‐terpyridine (Fc‐tpy; 4–6 ), L is the bidentate O,O donor monoanion of plumbagin (5‐hydroxy‐2‐methyl‐1,4‐naphthoquinone; plum in 1 , 4 ), chrysin (5,7‐dihydroxyflavone; chry in 2 , 5 ) and curcumin (bis(4‐hydroxy‐3‐methoxyphenyl)‐1,6‐diene‐3,5‐dione; curc in 3 , 6 ) have been synthesized and characterized and their in vitro cytotoxicity against cancer cells is evaluated. The energy optimized structures and the frontier orbitals of the complexes have been obtained from the DFT calculations. Complexes 4–6 with a conjugated ferrocenyl moiety and TCM anticancer ligands, namely, plum (in 4 ), chry (in 5 ) and curc (in 6 ) showed potent cytotoxicity giving respective IC₅₀ values of 1.2 μM, 0.62 μM and 0.21 μM in HeLa and 2.0 μM and 1.0 μM and 0.34 μM in MCF‐7 cancer cells while being much less toxic to MCF‐10A normal cells (IC₅₀: 8.3‐17.1 μM). In contrast, complexes 1–3 with a conjugated phenyl moiety were appreciably less toxic to HeLa cells with respective IC₅₀ values of 10.4 μM, 8.1 μM and 5.5 μM when compared with their ferrocenyl analogues 4–6 . Mechanistic studies using Hoechst staining and Annexin‐V‐FITC assays on cancer cells revealed an apoptotic pathway of cell death induced by the complexes. Fluorescence imaging study showed that complex 6 having curcumin as ligand localized primarily in the mitochondria of HeLa cells. Thus, we demonstrate in this study that ferrocene conjugation to copper(II) complexes of TCM anticancer ligands significantly increases the selectivity and cytotoxicity of the resulting complexes towards cancer cells over normal cells.     

Organometallic ruthenium and iridium phosphorus complexes: Synthesis,cellular imaging,organelle targeting and anticancer applications

The use of metal complexes containing phosphorus ligands as anticancer agents has not been well studied. In this work, eight novel half‐sandwich Ir^III and Ru^II compounds with P^P‐chelating ligands have been synthesized and fully characterized, and alongside two crystal structures were reported. All eight complexes displayed highly potent antiproliferative activity, up to nine times more potent than the clinical anticancer drug cisplatin towards A549 lung cancer cells. Complex Ir1 , which has a simpler structure and highly potent antiproliferative activity, was selected to investigate in further mechanistic studies. No hydrolysis and nucleobase binding occurred for complex Ir1 . In order to elucidate subcellular localization, the self‐luminescence of the complex Ir1 was utilized. Ir1 can specifically target lysosomes and facilitate excessive production of reactive oxygen species, resulting in lysosomal membrane permeabilization in A549 cells. Release of cathepsin B and changes in the mitochondria membrane potential also contributed to the observed cytotoxicity of Ir1 , which demonstrated an anticancer action mechanism that was different from that of cisplatin. The favorable results from biological and chemical research demonstrated that these types of complexes hold significant theranostic potential.     

Synthesis and Anti‐proliferative Activity of Novel Polysubstitued Indazole Derivatives

A simple and efficient process is developed for the synthesis of new N‐(1‐alkyl‐3‐chloro‐4‐ethoxy‐1H‐indazol‐5‐yl)‐arylsulfonamides 4a – d and N‐(1‐alkyl‐3‐chloro‐1H‐indazol‐5‐yl)‐arylsulfonamides 5a – d through the reduction of 1‐alkyl‐3‐chloro‐5‐nitroindazoles 2a , b with SnCl₂ in ethanol followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. All the newly synthesized compounds have been characterized by elemental analysis and spectroscopic data. Some compounds were tested for their in vitro antiproliferative activities against two selected human cancer cell lines A2780 and A549. Among all of these derivatives, compound 5d showed the most potent antiproliferative activity against A2780 (IC₅₀ = 5.47 ± 1.45 μM) and A549 (IC₅₀ = 7.73 ± 1.66 μM) cell lines.     

Synthesis,spectroscopic characterization,biological screening and in vitro cytotoxic studies of 4‐methyl‐3‐thiosemicarbazone derived Schiff bases and their Co (II), Ni (II), Cu (II) and Zn (II) complexes

A series of twenty compounds inclusive of bidentate Schiff bases derived from condensation of 4‐methyl‐3‐thiosemicarbazide with substituted derivatives of napthaldehyde/benzaldehyde/salicylaldehyde and their mononuclear Co (II), Ni (II), Cu (II) and Zn (II) complexes in molar ratio (1:1) were synthesized and characterized. The coordination behavior, modes of bonding and overall geometry of the compounds was known from the elemental analysis, spectral techniques (IR, UV–Vis, ¹H NMR, ¹³C NMR, ESR and ESI‐mass), magnetic moment measurements, molar conductance, thermal and powder XRD studies. The studies revealed octahedral geometry for all the complexes where ligands coordinated in a neutral bidentate manner (NS) via nitrogen atom of azomethine group and sulphur atom of thione group with the metal centre. In vitro biological effects of the compounds were tested against four bacterial species and two fungal strains. The results indicated that the metal complexes showed a marked enhancement in biocidal activity in comparable with the parent Schiff bases. In vitro anticancer activity against the malignant tumor cell lines; human alveolar adenocarcinoma epithelial cell line (A549), human breast adenocarcinoma cell line (MCF7), human prostate cancer cell line (DU145) and human normal lung cell line (MRC‐5) using MTT assay, exposed compound 16 as a leading member with lowest IC₅₀ value of 10.6 ± 0.14 μM against (A549) cell line.     

Synthesis,characterization, and micellization studies of coil‐rod‐coil and ABA ruthenium(II) terpyridine assemblies with π‐conjugated electron acceptor systems

A series of Ru^II heterodinuclear complexes of ABA ‐type with electron‐deficient bis‐terpyridines as building blocks was synthesized by (R‐tpy)Ru^IIICl₃ complexation. These compounds were characterized by NMR spectroscopy, MALDI‐TOF, ESI‐TOF mass spectrometry, and elemental analysis. The results were compared with a coil‐rod‐coil Ru^II metallo‐supramolecular copolymer, which was synthesized by bis‐complex formation between a hydrophilic ω‐terpyridine poly(ethylene glycol) Ru^II mono‐complex and a hydrophobic bis‐terpyridine‐functionalized rigid core. This amphiphilic Ru^II triblock copolymer showed self‐assembly to clusters and micelles in aqueous solution, which was studied by transmission electron microscopy and dynamic light scattering. Applying velocity sedimentation experiments the number of amphiphilic Ru^II ABA triblock copolymer molecules within the micelles could be estimated. Finally, the photophysical properties of the Ru^II supramolecular assemblies were investigated by UV–vis spectroscopy. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Ruthenium–Arene–β‐Carboline Complexes as Potent Inhibitors of Cyclin‐Dependent Kinase 1: Synthesis,Characterization and Anticancer Mechanism Studies

A series of Ru^II–arene complexes ( 1 – 6 ) of the general formula [(η⁶‐arene)Ru(L)Cl]PF₆ (arene=benzene or p‐cymene; L=bidentate β‐carboline derivative, an indole alkaloid with potential cyclin‐dependent kinases (CDKs) inhibitory activities) is reported. All the complexes were fully characterized by classical analytical methods, and three were characterized by X‐ray crystallography. Hydrolytic studies show that β‐carboline ligands play a vital role in their aqueous behaviour. These complexes are highly active in vitro, with the most active complex 6 displaying a 3‐ to 12‐fold higher anticancer activity than cisplatin against several cancer cell lines. Interestingly, the complexes are able to overcome cross‐resistance to cisplatin, and show much lower cytotoxicity against normal cells. Complexes 1 – 6 may directly target CDK1, because they can block cells in the G2M phase, down‐regulate the expression of CDK1 and cyclin B1, and inhibit CDK1/cyclin B in vitro. Further mechanism studies show that the complexes can effectively induce apoptosis through mitochondrial‐related pathways and intracellular reactive oxygen species (ROS) elevation.     

Synthesis,Photophysical, and Electrochemical Properties of RuII Polypyridyl Complexes Bridged with two Tetrapodal Symmetric and one Asymmetric Ligands

Two symmetric tetrapodal ligands L^1–2 and one asymmetric tetrapodal ligand L³ based on 4,5‐diazafluoren have been synthesized and characterized. Ligands L^1–2 formed by the condensation of pentaerythrityl tetratosylate with 4,5‐diazafluoren‐9‐oxime and 9‐(4‐hydroxy)phenylimino‐4,5‐diazafluorene, respectively. L³ was prepared by two steps, 9‐(4‐hydroxy)phenylimino‐4,5‐diazafluorene reacted with pentaerythrityl tetratosylate affording 1,1′,1"‐tris[(4,5‐diazafluoren‐9‐ylimino)phenoxymethyl]‐1"′‐(p‐tosyloxymethyl)‐methane, which reacted with 4,5‐diazafluoren‐9‐oxime affording the asymmetric ligand L³. Three tetranuclear Ru^II complexes [(bpy)₈L^1–3Ru₄](PF₆)₈ (bpy = bipyridine) were obtained by the reaction of Ru(bpy)₂Cl₂ · 2H₂O with ligands L^1–3. Spectroscopic studies of these complexes exhibit metal‐to‐ligand charge transfer absorptions at 440–445 nm and emissions at 575–579 nm. The electrochemical behaviors of these complexes are consistent with one Ru^II‐based oxidation couple and three ligand‐centered reduction couples.     

Controlling the Direction of the Molecular Axis of Rod‐Shaped Binuclear Ruthenium Complexes on Single‐Walled Carbon Nanotubes

We report the synthesis of a mixed‐valence ruthenium complex, bearing pyrene moieties on one side of the ligands as anchor groups. Composites consisting of mixed‐valence ruthenium complexes and SWNTs were prepared by noncovalent π–π interactions between the SWNT surface and the pyrene anchors of the Ru complex. In these composites, the long axis of the Ru complexes was aligned in parallel to the principal direction of the SWNT. The optimized conformation of these complexes on the SWNT surface was calculated by molecular mechanics. The composites were examined by UV/Vis absorption and FT‐IR spectroscopy, XPS, and SEM analysis. Furthermore, their electrochemical properties were evaluated. Cyclic voltammograms of the composites showed reversible oxidation waves at peak oxidation potentials (Ep_ox) = 0.86 and 1.08 V versus Fc⁺/Fc, which were assigned to the Ru^II‐Ru^II/Ru^II‐Ru^III and the Ru^II‐Ru^III/Ru^III‐Ru^III oxidation events of the dinuclear ruthenium complex, respectively. Based on these observations, we concluded that the electrochemical properties and mixed‐valence state of the dinuclear ruthenium complexes were preserved upon attachment to the SWNT surface.     

Imine‐N‐Heterocyclic Carbenes as Versatile Ligands in Ruthenium(II) p‐Cymene Anticancer Complexes: A Structure–Activity Relationship Study

A family of novel imine‐N‐heterocyclic carbene ruthenium(II) complexes of the general formula [(η⁶‐p‐cymene)Ru(C^N)Cl]PF₆⁻ (where C^N is an imine‐N‐heterocyclic carbene chelating ligand with varying substituents) have been prepared and characterized. In this imine‐N‐heterocyclic carbene chelating ligand framework, there are three potential sites that can be modified, which distinguishes this class of ligand and provides a body of flexibilities and opportunities to tune the cytotoxicity of these ruthenium(II) complexes. The influence of substituent effects of three tunable domains on the anticancer activity and catalytic ability in converting coenzyme NADH to NAD⁺ is investigated. This family of complexes displays an exceedingly distinct anticancer activity against A549 cancer cells, despite their close structural similarity. Complex 9 shows the highest anticancer activity in this series against A549 cancer cells (IC₅₀=14.36 μm ), with an approximately 1.5‐fold better activity than the clinical platinum drug cisplatin (IC₅₀=21.30 μm ) in A549 cancer cells. Mechanistic studies reveal that complex 9 mediates cell death mainly through cell stress, including cell cycle arrest, inducing apoptosis, increasing intracellular reactive oxygen species (ROS) levels, and depolarization of the mitochondrial membrane potential (MMP). Furthermore, lysosomal damage is also detected by confocal microscopy.