Cymene Complexes Research Articles

Microwave-Assisted Transfer Hydrogenation of Carbonyl and ­Nitro Compounds Using Bimetallic Ru(II) Cymene Complexes

AbstractWe report an investigation of the microwave-assisted catalytic transfer hydrogenation (TH) of carbonyl and nitro compounds by employing Ru(II) complexes: bimetallic [(p-cymene)2(RuCl)2L1]2X (X = BF4 (Cat2); X = PF6 (Cat3)) and mononuclear [(p-cymene)(RuCl)L2]BF4 (Cat4) (where L1 = N,N′-(3,3′,5,5′-tetraisopropyl-[1,1′-biphenyl]-4,4′-diyl)bis(1-(pyridin-2-yl)methanimine) and L2 = N-(2,6-diisopropylphenyl)-1-(pyridin-2-yl)methanimine). At a low catalyst loading of 0.01 mol% (Cat2/Cat3), a broad range of substrates, comprising aromatic as well as aliphatic ketones and aldehydes, undergo the TH reaction in a short reaction time of just 10 minutes. Additionally, chemoselective hydrogenation of nitroaromatic compounds is achieved under microwave irradiation in the presence of Cat2 within 5 minutes. Control experiments demonstrate that microwave heating conditions outperform conventional heating in terms of improved catalytic activity and reaction efficiency. The bimetallic catalyst Cat2 is used at a very low loading of 0.001 mol% to achieve high TONs and TOFs of 7.7 × 104 and 2.3 × 105 h–1, respectively, for the TH reaction. Spectrometry experiments involving trapping of intermediates are used to propose a mechanism for the TH of the carbonyl compounds.

Anticancer Properties of Ru and Os Half-Sandwich Complexes of N,S Bidentate Schiff Base Ligands Derived from Phenylthiocarbamide.

The versatile coordinating nature of N,S bidentate ligands is of great importance in medicinal chemistry imparting stability and enhancing biological properties of the metal complexes. Phenylthiocarbamide-based N,S donor Schiff bases converted into RuII /OsII (cymene) complexes and characterized by spectroscopic techniques and elemental analysis. The hydrolytic stability of metal complexes to undergo metal-halide ligand exchange reaction was confirmed both by the DFT and NMR experimentation. The ONIOM (QM/MM) study confirmed the histone protein targeting nature of aqua/hydroxido complex 2 aH with an excellent binding energy of -103.19 kcal/mol. The antiproliferative activity against a panel of cancer cells A549, MCF-7, PC-3, and HepG2 revealed that ruthenium complexes 1 a-3 a were more cytotoxic than osmium complexes and their respective ligands 1-3 as well. Among these ruthenium cymene complex bearing sulfonamide moiety 2 a proved a strong cytotoxic agent and showed excellent correlation of cellular accumulation, lipophilicity, and drug-likeness to the anticancer activity. Moreover, the favorable physiochemical properties such as bioavailability and gastrointestinal absorption of ligand 2 also supported the development of Ru complex 2 a as an orally active anticancer metallodrug.

Ru(II)-p-Cymene Complexes of Furoylthiourea Ligands for Anticancer Applications against Breast Cancer Cells.

Half-sandwich Ru(II) complexes containing nitro-substituted furoylthiourea ligands, bearing the general formula [(η6-p-cymene)RuCl2(L)] (1-6) and [(η6-p-cymene)RuCl(L)(PPh3)]+ (7--12), have been synthesized and characterized. In contrast to the spectroscopic data which revealed monodentate coordination of the ligands to the Ru(II) ion via a "S" atom, single crystal X-ray structures revealed an unusual bidentate N, S coordination with the metal center forming a four-membered ring. Interaction studies by absorption, emission, and viscosity measurements revealed intercalation of the Ru(II) complexes with calf thymus (CT) DNA. The complexes showed good interactions with bovine serum albumin (BSA) as well. Further, their cytotoxicity was explored exclusively against breast cancer cells, namely, MCF-7, T47-D, and MDA-MB-231, wherein all of the complexes were found to display more pronounced activity than their ligand counterparts. Complexes 7-12 bearing triphenylphosphine displayed significant cytotoxicity, among which complex 12 showed IC50 values of 0.6 ± 0.9, 0.1 ± 0.8, and 0.1 ± 0.2 μM against MCF-7, T47-D, and MDA-MB-231 cell lines, respectively. The most active complexes were tested for their mode of cell death through staining assays, which confirmed apoptosis. The upregulation of apoptotic inducing and downregulation of apoptotic suppressing proteins as inferred from the western blot analysis also corroborated the apoptotic mode of cell death. The active complexes effectively generated reactive oxygen species (ROS) in MDA-MB-231 cells as analyzed from the 2',7'-dichlorofluorescein diacetate (DCFH-DA) staining. Finally, in vivo studies of the highly active complexes (6 and 12) were performed on the mice model. Histological analyses revealed that treatment with these complexes at high doses of up to 8 mg/kg did not induce any visible damage to the tested organs.

NRF2 and Bip Interconnection Mediates Resistance to the Organometallic Ruthenium-Cymene Bisdemethoxycurcumin Complex Cytotoxicity in Colon Cancer Cells

Organometallic ruthenium (Ru)(II)-cymene complexes display promising pharmacological properties and might represent alternative therapeutic agents in medical applications. Polyphenols, such as curcumin and curcuminoids, display beneficial properties in medicine, including chemoprevention. Here we analyzed the anticancer effect of a cationic Ruthenium (Ru)(II)-cymene Bisdemethoxycurcumin (Ru-bdcurc) complex. The experimental data show that Ru-bdcurc induced cell death of colon cancer cells in vitro. In response to treatment, cancer cells activated the endoplasmic reticulum (ER)-resident chaperone GRP78/BiP and NRF2, the master regulators of the unfolded protein response (UPR) and the antioxidant response, respectively. Pharmacologic targeting of either NRF2 or BiP potentiated the cytotoxic effect of Ru-bdcurc. We also found that NRF2 and UPR pathways were interconnected as the inhibition of NRF2 reduced BiP protein levels. Mechanistically, the increased Ru-bdcurc-induced cell death, following NRF2 or BiP inhibition, correlated with the upregulation of the UPR apoptotic marker CHOP and with increased H2AX phosphorylation, a marker of DNA damage. The findings reveal that BiP and NRF2 interconnection was a key regulator of colon cancer cells resistance to Ru-bdcurc cytotoxic effect. Targeting that interconnection overcame the protective mechanism and enhanced the antitumor effect of the Ru-bdcurc compound.

Synthesis and anticancer evaluation of trinuclear N^N quinolyl-benzimidazole-based PGM complexes

• Trinuclear N^N quinolyl-benzimidazole-based PGM complexes were prepared. • Comprehensively characterised using various spectroscopic and analytical techniques. • Antiproliferative properties against two human breast cancer cell lines, MCF-7 and MDA-MB-32, were evaluated. • A ruthenium(II) p -cymene complex was found to be the most active complex. The synthesis, characterization and cytotoxicity of a novel tris-benzimidazole-quinoline hybrid ligand and its corresponding cationic trimetallic complexes are described. The synthesis of the ligand was achieved via an acid-catalyzed cyclization-condensation reaction of a tris-benzenediamine precursor with 2-quinolinecarboxaldehyde. The complexation reactions of the bidentate tris-ligand with the appropriate precursor dimers [Ru(η 6 -p-Pr i C 6 H 4 Me)Cl 2 ] 2 , [IrCp*( μ -Cl)Cl] 2 , [RuCl 2 (η 6 -C 6 H 5 OCH 2 CH 2 OH)] 2 and [Os(η 6 -p-Pr i C 6 H 4 Me)Cl 2 ] 2 afforded four new cationic trimetallic complexes. The complexes are moisture and air-stable and were characterized using various spectroscopic techniques ( 1 H, 13 C NMR spectroscopy and FT-IR spectroscopy). UV/Visible spectroscopic studies of the trinuclear metal complexes showed that the complexes are stable in DMSO for 48 h at room temperature and physiological temperature, and are thus compatible for in vitro experiments. The synthesized ligand and complexes were examined for antiproliferative properties against two human breast cancer cell lines: MCF-7 and MDA-MB-231. Preliminary evaluations of the test compounds were conducted at a single dose concentration of the test compounds. The osmium(II) and ruthenium(II) p -cymene complexes showed the greatest anticancer activity of all the synthesized compounds and were selected for multidose screening. The ruthenium(II) p -cymene complex was found to be the most active complex, with IC 50 values of 25.23 μ M and 32.68 μ M in the MCF-7 and MDA-MB-231 cell lines, respectively.

Ruthenium‐p‐cymene Complex Side‐Wall Covalently Bonded to Carbon Nanotubes as Efficient Hybrid Transfer Hydrogenation Catalyst

AbstractA half‐sandwich ruthenium‐p‐cymene organometallic complex has been immobilized at Single Walled Carbon Nanotubes (SWNT) sidewalls through a stepwise covalent chemistry protocol. The introduction of amino groups by means of diazonium‐chemistry protocols leads the grafting at the outer walls of the nanotubes. This hybrid material is active in the transfer hydrogenation of ketones to yield alcohols, using as hydrogen source 2‐propanol. SWNT−NH2−Ru presents a broad scope, performing the reaction under aerobic conditions and can be recycled over 9 consecutive reaction runs without losing activity or leaching ruthenium out. Comparison of the activity with related homogeneous catalysts reveals an improved performance due to the covalent bond between the metal and the material, achieving turnover frequencies as high as 192774 h−1.

Synthesis, Characterization, and Cytotoxicity of Morpholine-Containing Ruthenium(II) p-Cymene Complexes.

Morpholine motif is an important pharmacophore and, depending on the molecular design, may localize in cellular acidic vesicles. To understand the importance of the presence of pendant morpholine in a metal complex, six bidentate N,O-donor ligands with or without a pendant morpholine unit and their corresponding ruthenium(II) p-cymene complexes (1-6) are synthesized, purified, and structurally characterized by various analytical methods including X-ray diffraction. Complexes 2-4 crystallized in the P21/c space group, whereas 5 and 6 crystallized in the P1̅ space group. The solution stability studies using 1H NMR support instantaneous hydrolysis of the native complexes to form monoaquated species in a solution of 3:7 (v/v) dimethyl sulfoxide-d6 and 20 mM phosphate buffer (pH* 7.4, containing 4 mM NaCl). The monoaquated complexes are stable for at least up to 24 h. The complexes display excellent in vitro antiproliferative activity (IC50 ca. 1-14 μM) in various cancer cell lines, viz., MDA-MB-231, MiaPaCa2, and Hep-G2. The presence of the pendant morpholine does not improve the dose efficacy, but rather, with 2-[[(2,6-dimethylphenyl)imino]methyl]phenol (HL1) and its pendant morpholine analogue (HL3) giving complexes 1 and 3, respectively, the antiproliferative activity was poorer with 3. MDA-MB-231 cells treated with the complexes show that the acidic vesicles remain acidic, but the population of acidic vesicles increases or decreases with time of exposure, as observed from the dispersed red puncta, depending on the complex used. The presence of the 2,6-disubstituted aniline and the naphthyl group seems to improve the antiproliferative dose. The complex treated MDA-MB-231 cells show that cathepsin D, which is otherwise present in the cytosolic lysosomes, translocates to the nucleus as a result of exposure to the complexes. Irrespective of the presence of a morpholine motif, the complexes do not activate caspase-3 to induce apoptosis and seem to favor the necrotic pathway of cell killing.

Antibacterial and Cytotoxic Activity of Ruthenium‐p‐cymene Complexes with 2‐Methylquinolin‐8‐ol Derivatives

AbstractEight 5‐aryl‐2‐methylquinolin‐8‐ol ligands (2–9) were prepared by a cross‐coupling Suzuki reaction from precursors brominated at position 5 (10), and positions 5 and 7 (11). These ligands were converted into new ruthenium(II)‐p‐cymene complexes (12–22) (51–94 %). The cytotoxic and antimicrobial activities of all compounds were investigated. Ligands showed higher cytotoxicity (EC50=3.1–4.8 μM) than ruthenium complexes (EC50=5.2–7.8 μM) against human melanoma cancer cells (A375). The most potent compound 7 has been shown to act via apoptosis. Some compounds were more potent as anticancer than cisplatin. Several ruthenium complexes selectively inhibited S. typhimurium and S. aureus (IC50=4.64–146.15 and 9.37–125.95 μg/mL, respectively), while most ligands were potent against C. albicans. Molecular docking studies with a protein from S. aureus suggest four key amino acids interactions, in agreement with the inhibitory potential against this bacterium.

Tunable Anticancer Activity of Furoylthiourea-Based RuII -Arene Complexes and Their Mechanism of Action.

Fourteen new RuII -arene (p-cymene/benzene) complexes (C1-C14) have been synthesized by varying the N-terminal substituent in the furoylthiourea ligand and satisfactorily characterized by using analytical and spectroscopic techniques. Electrostatic potential maps predicted that the electronic effect of the substituents was mostly localized, with some influence seen on the labile chloride ligands. The structure-activity relationships of the Ru-p-cymene and Ru-benzene complexes showed opposite trends. All the complexes were found to be highly toxic towards IMR-32 cancer cells, with C5 (Ru-p-cymene complex containing C6 H2 (CH3 )3 as N-terminal substituent) and C13 (Ru-benzene complex containing C6 H4 (CF3 ) as N-terminal substituent) showing the highest activity among each set of complexes, and hence they were chosen for further study. These complexes showed different behavior in aqueous solutions, and were also found to catalytically oxidize glutathione. They also promoted cell death by apoptosis and cell cycle arrest. Furthermore, the complexes showed good binding ability with the receptors Pim-1 kinase and vascular endothelial growth factor receptor 2, commonly overexpressed in cancer cells.

DNA-Binding Capabilities and Anticancer Activities of Ruthenium(II) Cymene Complexes with (Poly)cyclic Aromatic Diamine Ligands.

Ruthenium(II) arene complexes of the general formula [RuCl(η6-p-cymene)(diamine)]PF6 (diamine = 1,2-diaminobenzene (1), 2,3-diaminonaphthalene (2), 9,10-diaminophenanthrene (3), 2,3-diaminophenazine (4), and 1,2-diaminoanthraquinone (5) were synthesized. Chloro/aqua exchange was evaluated experimentally for complexes 1 and 2. The exchange process was investigated theoretically for all complexes, revealing relatively fast exchange with no significant influence from the polycyclic aromatic diamines. The calf thymus DNA (CT-DNA) binding of the complexes increased dramatically upon extending the aromatic component of the diamines, as evaluated by changes in absorption spectra upon titration with different concentrations of CT-DNA. An intercalation binding mode was established for the complexes using the increase in the relative viscosity of the CT-DNA following addition of complexes 1 and 2. Theoretical studies showed strong preference for replacement of water by guanine for all the complexes, and relatively strong Ru–Nguanine bonds. The plane of the aromatic systems can assume angles that support non-classical interactions with the DNA and covalent binding, leading to higher binding affinities. The ruthenium arenes illustrated in this study have promising anticancer activities, with the half maximal inhibitory concentration (IC50) values comparable to or better than cisplatin against three cell lines.

The interactions of the ruthenium(II)-cymene complexes with lysozyme and cytochrome c.

The reactions of four cymene-capped ruthenium(II) compounds with pro-apoptotic protein, cytochrome c (Cyt), and anti-proliferative protein lysozyme (Ly) in carbonate buffer were investigated by ESI-MS, UV-vis absorption, and CD spectroscopy. The complexes with two chloride ligands (C2 and C3) were more reactive toward proteins than those with only one (C1 and C4), and the complex with S,N-chelating ligand (C4) was less reactive than one with O,N-chelating ligand (C1). Dehalogenated complexes are most likely species, initially coordinating proteins for all tested complexes. During the time, protein adducts vividly exchanged non-arene organic ligand L with CO32- and OH-, while cymene moiety was retained. In water, only dehalogenated adducts were identified suggesting that in vivo, in the presence of various anions, dynamic ligand exchange could generate different intermediate protein species. Although all complexes reduced Cyt, the reduction was not dependent on their reactivity to protein, implying that initially noncovalent binding to Cyt occurs, causing its reduction, followed by coordination to protein. Cyt reduction was accompanied with rupture of ferro-Met 80 and occupation of this hem coordination site by a histidine His-33/26. Therefore, in Cyt with C2 and C3, less intensive reduction of hem iron leaves more unoccupied target residues for Ru coordination, leading to more efficient formation of covalent adducts, in comparison to C1 and C4. This study contributes to development of new protein-targeted Ru(II) cymene complexes, and to the design of new cancer therapies based on targeted delivery of Ru(II) arene complexes bound on pro-apoptotic/anti-proliferative proteins as vehicles.

Electrochemical, mechanistic, and DFT studies of amine derived diphosphines containing Ru(II)-cymene complexes with potent in vitro cytotoxic activity against HeLa and triple-negative breast cancer cells MDA-MB-231.

Complexes with general formula [RuCl(η6-p-cymene)(P-NR-P)]X (R = CH2Py (Py = pyridine) - [1a]+, CH2Ph (Ph = phenyl) - [1b]+, Ph - [1c] and p-tol (p-tol = p-tolyl) - [1d]+; X = PF6- or BF4-) were evaluated as cytotoxic agents against two cancer cell lines (HeLa and MDA-MB-231). All metal complexes are active in the range of concentrations tested (up to 100 μmol L-1). The IC50 (μmol L-1) values for the metal complexes are lower than that found for cisplatin. The activities are up to 6- and 15-fold higher than cisplatin for HeLa and MDA-MB-231 cancer cell lines, respectively. Studies of DNA binding and DNA cleavage were performed. DNA binding studies revealed a modest hypochromic shift in the metal complexes electronic spectra, indicating a weak interaction with Kb values in the range of 1.7 × 103-1.6 × 104. Although the cleavage tests revealed that in the dark DNA is not a biological target for these metal complexes, upon blue light irradiation they are activated causing DNA cleavage. Electrochemical studies showed the presence of two independent redox processes, one attributed to the oxidation process of Ru2+ → Ru3+ (EC process) and the other one to the reduction of Ru2+ → Ru1+, which is further reduced to Ru0 (ECE mechanism). In both processes, coupled chemical reactions were observed. DFT calculations were performed to support the electrochemical/chemical behavior of the complexes. The reactivity of complex [1b]BF4 with CH3CN was evaluated and two complexes were isolated [2b]BF4 and [3b]BF4. The complex mer-[RuCl(CH3CN)3(P-NCH2Ph-P)]BF4 ([2b]BF4) was isolated after refluxing the precursor [1b]BF4 in CH3CN. Isomerization of [2b]BF4 in CH3CN resulted in the formation of fac-[RuCl(CH3CN)3(P-NCH2Ph-P)]BF4. An attempt to isolate the fac-isomer by adding diethyl ether was unsuccessful, and the complex [3b]BF4 was observed as the major component. The complex [Ru2(μ-Cl3)(CH3CN)2(P-NCH2Ph-P)2]BF4 ([3b]BF4) proved to be very stable and can be obtained from both the mer- and the fac-isomers. The molecular structures of [1b]BF4 and [3b]BF4 were solved by single-crystal X-ray diffraction.

Aerobic dehydrogenation of amines to nitriles catalyzed by triazolylidene ruthenium complexes with O2 as terminal oxidant.

Pyridyl-substituted mesoionic triazolylidene ruthenium cymene complexes catalyze the oxidation of both aromatic and aliphatic amines to nitriles with high activity and selectivity under benign conditions using dioxygen as the terminal oxidant. Modification on the pyridyl moiety of the ligand scaffold has negligible effect on the catalytic performance, while substituents on the triazolylidene directly affect the catalytic fitness of the metal center, leading to distinct catalytic profiles. Pre-dissociation of the cymene ligand and formation of a solvento analogue further enhances the catalytic activity towards nitrile formation. Variation of reaction conditions provided valuable mechanistic insights and resulted in a highly efficient protocol for nitrile formation with maximum turnover numbers around 10 000. The turnover frequency reaches up to 400 h-1, providing one of the fastest catalytic systems known to date for this transformation.

Inhibition of 3D colon cancer stem cell spheroids by cytotoxic RuII-p-cymene complexes of mesalazine derivatives.

The Ru(ii) complex of an imidazole-mesalazine Schiff base is a unique example showing growth inhibition of 3D-colon cancer stem cell spheroids and bulk colon cancer cells at lower dosage than salinomycin or oxaliplatin. Unlike oxaliplatin which increases the expression of stemness genes (SOX2, KLF4, HES1 and Oct4), these complexes maintain a tight regulation.

Protein binding affinity of biologically active thiourea based half-sandwich Ru(II) cymene complexes

Half-sandwich (η6-p-cymene) complexes bearing either neutral functionalized N,S-bidentate thiourea ligands or a mono-negative N,N-aminoquinoline ligand were screened for their antibacterial and antifungal activities as well as cell viability against non-malignant HEK293 (human embryonic kidney cells). The haemolysis parameters (HC10 and HC50) were determined to get some information about the compatibility of the toxic compounds with the blood components. The protein binding affinity of hen white egg lysozyme (HEWL), a model protein, towards the synthesized (η6-p-cymene) complexes was investigated by ESI-MS. Metalation of HEWL was achieved through both covalent and non-covalent modes of interaction. To recognize if the metalation site of HEWL is the His15 side chain, the reactions between the complexes and imidazole were theoretically and experimentally studied by quantum chemical calculations, UV–Vis and NMR. Exchange of the nitrogen coordination site of the thiourea ligand from the pyridine to the benzothiazole moiety induced higher potency against Staphylococcus aureus, Candida albicans and Cryptococcus neoformans var. grubii.

Anticancer activity and mechanism of bis-pyrimidine based dimetallic Ru(II)(η6-p-cymene) complex in human non-small cell lung cancer via p53-dependent pathway

Non-small cell lung cancer (NSCLC) is the most common cancer worldwide, which is related with poor prognosis and resistance to chemotherapy. Notably, ruthenium-based complexes have emerged as good alternative to the currently used platinum-based drugs for cancer therapy. In the present study, we synthesized a novel bis-pyrimidine based ligand 1,3-bis(2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)benzene (L) and used it in the synthesis of a dimetallic Ru(II) cymene complex [(Ru(η6-p-cymene)Cl)2(1,3-bis(2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)benzene)] (L-Ru). We checked the stability of this complex in solution state in D2O/DMSO‑d6 mixture and found it to be highly stable under these conditions. We determined the anticancer activity and mechanism of action of L-Ru in human NSCLC A549 and A427 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and related biological analyses. These results revealed that L-Ru exerted a strong inhibitory effect on the cells proliferation,G0/G1-arrest, accompanied with upregulation of p53, p21, p15, cleaved Poly (ADP-ribose) polymerase (PARP) protein and downregulation of cell cycle markers. L-Ru inhibited cell migration and invasion. The mitochondria-mediated apoptosis of NSCLC induced by L-Ru was also observed followed by the increase of apoptosis regulator B-cell lymphoma 2 associated X (BAX), and activation of caspase-3/-9. The effects of L-Ru on the cell viability, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells and Annexin V-positive cells apoptosis induction were remarkably attenuated. This complex induced DNA damage, cell cycle arrest and cell death via caspase-dependent apoptosis involving PARP activation and induction of p53-dependent pathway. These findings suggested that this ruthenium complex might be a potential effective chemotherapeutic agent in NSCLC therapy.

Stacking interactions between ruthenium p-cymene complexes: combined crystallographic and density functional study

Stacking interactions between ruthenium p-cymene complexes are significantly strengthened by additional simultaneous C–H/π interactions of aromatic rings and their substituents.

Biological and catalytic evaluation of Ru(II)‐p‐cymene complexes of Schiff base ligands: Impact of ligand appended moiety on photo‐induced DNA and protein cleavage, cytotoxicity and C‐H activation

Two organometallic Ru(II)‐p‐cymene complexes of the type [Ru(η6‐p‐cymene)(L)Cl]PF6 1 and 2, where L is N,N‐bis(4‐isopropylbenzylidene)ethane‐1,2‐diamine (bien, L1) or N,N‐bis (pyren‐2‐ylmethylene)ethane‐1,2‐diamine (bpen, L2) have been prepared and characterized well. Because of appended pyrenyl groups in coordinated bpen ligand, the complex 2 exhibits higher DNA and protein binding than complex 1 in which isopropylbenzyl groups are incorporated. Interestingly, the luminescent characteristic complex 2 is unique in displaying DNA cleavage after light activation by UVA light at 365 nm through oxygen dependent mechanism. AFM analysis attests the photo‐induced DNA fragmentation ability of complex 2. Also, the complex 2 cleaves the protein after light exposure in a non‐specific manner suggesting that it can act as a protein photo cleaving agent. In contrast to the trend of DNA and protein interaction of complexes, the complex 1 exhibits cytotoxic activity against human breast carcinoma (MCF‐7) and liver carcinoma (HepG2) with potency higher than that of complex 2 due to enhanced hydrophobicity of isopropyl groups present in p‐cymene and bien ligands. Indeed, complex 2 is inactive against MCF‐7 and HepG2 cancer cell lines even up to 200 μM concentration. The AO/EB staining assay reveals that the complex 1 is able to induce late apoptotic mode of cell death in breast cancer cells, which is further confirmed by inter‐nucleosomal DNA cleavage. Furthermore, the complexes 1 and 2 are evaluated for their catalytic activities and found to be working well for the β‐carboline directed C–H arylation to afford the desired products in good yield (40–47%).

Water soluble Ru (II)–p‐cymene complexes of chiral aroylthiourea ligands derived from unprotected D/L‐alanine as proficient catalysts for asymmetric transfer hydrogenation of ketones

The newfangled chiral aroylthiourea ligands (L1‐L6) were produced from unprotected D/L‐alanine and their water soluble Ru (II) organometallic catalysts (1–6) were designed from their reaction with [RuCl2(η6‐p‐cymene)]2. The analytical and spectral methods were used to confirm the structure of the ligands and complexes. The solid state structure of L1, 5 and 6 was confirmed by single crystal XRD. The organometallic compounds (1–6) catalyzed the asymmetric transfer hydrogenation of aromatic, heteroaromatic and bulky ketones to yield respective enantiopure secondary alcohols with admirable conversions (up to 99%) and attractive enantiomeric excesses (ee up to 98%), in presence of formic acid and triethylamine in water medium under non‐inert atmospheric conditions.

Activation by Oxidation: Ferrocene-Functionalized Ru(II)-Arene Complexes with Anticancer, Antibacterial, and Antioxidant Properties.

Organometallic Ru(II)-cymene complexes linked to ferrocene (Fc) via nitrogen heterocycles have been synthesized and studied as cytotoxic agents. These compounds are analogues of Ru(II)-arene piano-stool anticancer complexes such as RAPTA-C. The Ru center was coordinated by pyridine, imidazole, and piperidine with 0-, 1-, or 2-carbon bridges to Fc to give six bimetallic, dinuclear compounds, and the properties of these complexes were compared with their non-Fc-functionalized parent compounds. Crystal structures for five of the compounds, their Ru-cymene parent compounds, and an unusual trinuclear compound were determined. Cyclic voltammetry was used to determine the formal MIII/II potentials of each metal center of the Ru-cymene-Fc complexes, with distinct one-electron waves observed in each case. The Fc-functionalized complexes were found to exhibit good cytotoxicity against HT29 human colon adenocarcinoma cells, whereas the parent compounds were inactive. Similarly, antibacterial activity from the Ru-cymene-Fc compounds was observed against Bacillus subtilis, but not from the unfunctionalized complexes. In both cases, the IC50 values correlated quantitatively with the Fc+/0 reduction potentials. This is consistent with more facile oxidation to give ferrocenium, and subsequent generation of toxic reactive oxygen species, leading to greater cytotoxicity. The antioxidant properties of the complexes were quantified by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. EC50 values indicate that linking of the Ru and Fc centers promotes antioxidant activity.