Dataset Information

Dicopper(II) and dizinc(II) complexes with nonsymmetric dinucleating ligands based on indolo[3,2-c]quinolines: synthesis, structure, cytotoxicity, and intracellular distribution.

ABSTRACT: Dicopper(II) and dizinc(II) complexes [Cu2((MeOOC)L(COO))(CH3COO)2] (1) and [Zn2((MeOOC)L(COO))(CH3COO)2] (2) were synthesized by reaction of Cu(CH3COO)2·H2O and Zn(CH3COO)2·2H2O with a new nonsymmetric dinucleating ligand (EtOOC)HL(COOEt) prepared by condensation of 6-hydrazinyl-11H-indolo[3,2-c]quinoline with diethyl-2,2'-((3-formyl-2-hydroxy-5-methylbenzyl)azanediyl)diacetate. The design and synthesis of this elaborate ligand was performed with the aim of increasing the aqueous solubility of indolo[3,2-c]quinolines, known as biologically active compounds, and investigating the antiproliferative activity in human cancer cell lines and the cellular distribution by exploring the intrinsic fluorescence of the indoloquinoline scaffold. The compounds have been comprehensively characterized by elemental analysis, spectroscopic methods (IR, UV-vis, (1)H and (13)C NMR spectroscopy), ESI mass spectrometry, magnetic susceptibility measurements, and UV-vis complex formation studies (for 1) as well as by X-ray crystallography (1 and 2). The antiproliferative activity of (EtOOC)HL(COOEt), 1, and 2 was determined by the MTT assay in three human cancer cell lines, namely, A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon adenocarcinoma), yielding IC50 values in the micromolar concentration range and showing dependence on the cell line. The effect of metal coordination on cytotoxicity of (EtOOC)HL(COOEt) is also discussed. The subcellular distribution of (EtOOC)HL(COOEt) and 2 was investigated by fluorescence microscopy, revealing similar localization for both compounds in cytoplasmic structures.

SUBMITTER: Primik MF

PROVIDER: S-EPMC3763518 | biostudies-other | 2013 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Dicopper(II) and dizinc(II) complexes with nonsymmetric dinucleating ligands based on indolo[3,2-c]quinolines: synthesis, structure, cytotoxicity, and intracellular distribution.

Primik Michael F MF Göschl Simone S Meier Samuel M SM Eberherr Nadine N Jakupec Michael A MA Enyedy Éva A É Novitchi Ghenadie G Arion Vladimir B VB

Inorganic chemistry 20130816 17

Dicopper(II) and dizinc(II) complexes [Cu2((MeOOC)L(COO))(CH3COO)2] (1) and [Zn2((MeOOC)L(COO))(CH3COO)2] (2) were synthesized by reaction of Cu(CH3COO)2·H2O and Zn(CH3COO)2·2H2O with a new nonsymmetric dinucleating ligand (EtOOC)HL(COOEt) prepared by condensation of 6-hydrazinyl-11H-indolo[3,2-c]quinoline with diethyl-2,2'-((3-formyl-2-hydroxy-5-methylbenzyl)azanediyl)diacetate. The design and synthesis of this elaborate ligand was performed with the aim of increasing the aqueous solubility of ...[more]

PMID: 23952332

Similar Datasets

Project description:A new family of dicopper(I) complexes [CuI2RL](X)2 (R=H, 1X, R=tBu, 2X and R=NO2, 3X, X=CF3SO3, ClO4, SbF6, or BArF, BArF=[B{3,5-(CF3)2C6H3}4]-), where RL is a Schiff-base ligand containing two tridentate binding sites linked by a xylyl spacer, has been prepared and characterized, and its reaction with O2 has been studied. The complexes were designed with the aim of reproducing structural aspects of the active site of type 3 dicopper proteins; they contain two three-coordinate copper sites and a rather flexible podand ligand backbone. The solid-state structures of 1ClO4, 2CF3SO3, 2ClO4, and 3BArF.CH3CN have been established by single-crystal X-ray diffraction analysis. 1ClO4 adopts a polymeric structure in the solid state while 2CF3SO3, 2ClO4, and 3BArF.CH3CN are monomeric. The complexes have been studied in solution by means of 1H and 19F NMR spectroscopy, which put forward the presence of dynamic processes. 1-3BArF and 1-3CF3SO3 in acetone react rapidly with O2 to generate metaestable [CuIII2(mu-O)2(RL)]2+ 1-3(O2) and [CuIII2(mu-O)2(CF3SO3)(RL)]+ 1-3(O2)(CF3SO3) species, respectively, that have been characterized by UV-vis spectroscopy and resonance Raman analysis. Instead, reaction of 1-3BArF with O2 in CH2Cl2 results in intermolecular O2 binding. DFT methods have been used to study the chemical identities and structural parameters of the O2 adducts, and the relative stability of the CuIII2(mu-O)2 form with respect to the CuII2(mu-eta2:eta2-O2) isomer. The reaction of 1X, X = CF3SO3 and BArF, with O2 in acetone has been studied by stopped-flow UV-vis exhibiting an unexpected very fast reaction rate (k=3.82(4)x10(3) M-1 s-1, DeltaH=4.9+/-0.5 kJ.mol-1, DeltaS=-148+/-5 J.K-1.mol-1), nearly 3 orders of magnitude faster than in the parent [CuI2(m-XYLMeAN)]2+. Thermal decomposition of 1-3(O2) does not result in aromatic hydroxylation. The mechanism and kinetics of O2 binding to 1X (X=CF3SO3 and BArF) are discussed and compared with those associated with selected examples of reported models of O2-processing copper proteins. A synergistic role of the copper ions in O2 binding and activation is clearly established from this analysis.

Project description:The reactions of CuX2 (X = Cl, Br) with dipinodiazafluorenes yielded four new complexes [CuX2L1]2 (X = Cl (1), Br (2), L1 = (1R,3R,8R,10R)-2,2,9,9-Tetramethyl-3,4,7,8,9,10-hexahydro-1H-1,3:8,10-dimethanocyclopenta [1,2-b:5,4-b']diquinolin-12(2H)-one) and [(CuX2)2L2]n (X = Cl (3), Br (4), L2 = (1R,3R,8R,10R,1'R,3'R,8'R,10'R)-2,2,2',2',9,9,9',9'-Octamethyl-1,1',2,2',3,3',4,4',7,7',8,8',9,9',10,10'-hexadecahydro-1,3:1',3':8,10:8',10'-tetramethano-12,12'-bi(cyclopenta [1,2-b:5,4-b']diquinolinylidene). The complexes were characterized by IR and EPR spectroscopy, HR-ESI-MS and elemental analysis. The crystal structures of compounds 1, 2 and 4 were determined by X-ray diffraction (XRD) analysis. Complexes 1-2 have a monomeric structure, while complex 4 has a polymeric structure due to additional coordinating N,N sites in L2. All complexes contain a binuclear fragment {Cu2(μ-X)2×2} (X = Cl, Br) in their structures. Each copper atom has a distorted square-pyramidal coordination environment formed by two nitrogen atoms and three halogen atoms. The Cu-Nax distance is elongated compared to Cu-Neq. The EPR spectra of compounds 1-4 in CH3CN confirm their paramagnetic nature due to the d9 electronic configuration of the copper(II) ion. The magnetic properties of all compounds were studied by the method of static magnetic susceptibility. For complexes 1 and 2, the effective magnetic moments are µeff ≈ 1.87 and 1.83 µB (per each Cu2+ ion), respectively, in the temperature range 50-300 K, which are close to the theoretical spin value (1.73 µB). Ferromagnetic exchange interactions between Cu(II) ions inside {Cu2(μ-X)2X2} (X = Cl, Br) dimers (J/kB ≈ 25 and 31 K for 1 and 2, respectively) or between dimers (θ' ≈ 0.30 and 0.47 K for 1 and 2, respectively) were found at low temperatures. For compounds 3 and 4, the magnetic susceptibility is well described by the Curie-Weiss law in the temperature range 1.77-300 K with µeff ≈ 1.72 and 1.70 µB for 3 and 4, respectively, and weak antiferromagnetic interactions (θ ≈ -0.4 K for 3 and -0.65 K for 4). Complexes 1-4 exhibit high catalytic activity in the oxidation of alkanes and alcohols with peroxides. The maximum yield of cyclohexane oxidation products reached 50% (complex 3). Based on the data on the study of regio- and bond-selectivity, it was concluded that hydroxyl radicals play a decisive role in the oxidation reaction. The initial products in reactions with alkanes are alkyl hydroperoxides.

Dataset Information

Dicopper(II) and dizinc(II) complexes with nonsymmetric dinucleating ligands based on indolo[3,2-c]quinolines: synthesis, structure, cytotoxicity, and intracellular distribution.

Publications

Dicopper(II) and dizinc(II) complexes with nonsymmetric dinucleating ligands based on indolo[3,2-c]quinolines: synthesis, structure, cytotoxicity, and intracellular distribution.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure