- Solution Chemistry of Copper(II) Binding to Substituted 8-Hydroxyquinolines
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8-Hydroxyquinolines (8HQs) are a family of lipophilic metal ion chelators that have been used in a range of analytical and pharmaceutical applications over the last 100 years. More recently, CQ (clioquinol; 5-chloro-7-iodo-8-hydroxyquinoline) and PBT2 (5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline) have undergone clinical trials for the treatment of Alzheimer's disease and Huntington's disease. Because CQ and PBT2 appear to redistribute metals into cells, these compounds have been redefined as copper and zinc ionophores. Despite the attention surrounding the clinical trials and the clear link between 8HQs and metals, the fundamental solution chemistry of how these compounds bind divalent metals such as copper and zinc, as well as their mechanism(s) of action in mammalian systems, remains poorly understood. In this study, we used a combination of X-ray absorption spectroscopy (XAS), high-energy resolution fluorescence detected (HERFD) XAS, electron paramagnetic resonance (EPR), and UV-visible absorption spectroscopies to investigate the aqueous solution chemistry of a range of 8HQ derivatives. To circumvent the known solubility issues with 8HQ compounds and their complexes with Cu(II), and to avoid the use of abiological organic solvents, we have devised a surfactant buffer system to investigate these Cu(II) complexes in aqueous solution. Our study comprises the first comprehensive investigation of the Cu(II) complexes formed with many 8HQs of interest in aqueous solution, and it provides the first structural information on some of these complexes. We find that halogen substitutions in 8HQ derivatives appear to have little effect on the Cu(II) coordination environment; 5,7-dihalogenated 8HQ conformers all have a pseudo square planar Cu(II) bound by two quinolin-8-olate anions, in agreement with previous studies. Conversely, substituents in the 2-position of the 8HQ moiety appear to cause significant distortions from the typical square-planar-like coordination of most Cu(II)-bis-8HQ complexes, such that the 8HQ moieties in the Cu(II)-bis-8HQ complex are rotated approximately 30-40° apart in a propeller-like arrangement.
- Dolgova, Natalia V.,George, Graham N.,Harris, Hugh H.,James, Ashley K.,Kroll, Thomas,Pickering, Ingrid J.,Pushie, M. Jake,Sokaras, Dimosthenis,Sopasis, George J.,Summers, Kelly L.
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- Conductometric Determination of Some Metal Ions Using Oxine as Reagent
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A simple and sensitive conductometric method for the determination of copper(II), iron(II) and (III), aluminum(III), chromium(III), gold(III), platinum(IV), vanadyl, zirconyl, and uranyl ions with oxine solution in ethanol-water system is described.An average recovery of 100.3percent with standard deviation not exceeding 0.4percent is observed.The effect of solvent, shape of titration curves and molar ratio of the chelates are studied.The proposed method shows good agreement with the conventional method is discussed.
- Zaki, Mohamed Tarek Mohamed,Hanna, Wageh Georgy,Fawzy, Mohamed Hossam
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- Immobilization of Cu-chelate onto SBA-15 for partial oxidation of benzyl alcohol using water as the solvent
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Bis(8-quinolinolato)copper(II) complex immobilized onto SBA-15 catalyst has been synthesized through a stepwise procedure. The characterization results indicated that the BET surface area, total pore volume, and average pore width decrease after stepwise modification of SBA-15, while the structure stays intact. Catalytic tests showed that CuQ2-SBA-15 catalyzes the oxidation reaction well with 32.5 % conversion of benzyl alcohol and 81.8 % selectivity to benzaldehyde when water is used as the solvent. In addition, homogeneous catalyst bis(8-quinolinolato)copper(II) exhibits very bad catalytic behavior using water as the solvent.
- Hu, Jing,Zou, Yongcun,Liu, Jing,Sun, Jian,Yang, Xiaoyuan,Kan, Qiubin,Guan, Jingqi
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- Nanocrystalline mixed ligand complexes of Cu (II), Ni (II), Co(II) with N, O donor ligands: Synthesis, characterization, and antimicrobial activity
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In present investigation nanocrystalline mixed ligand complexes were synthesized using 8-hydroxyquinoline, salicylaldoxime with metals like Cu (II), Ni (II) and Co (II). The metal: ligand ratio was found to be 1:1:1. These complexes were characterized usi
- Kolhe Nitin,Jadhav Shridhar,Shaikh Sajid,Takate Sushama,Aware Dinkar
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- Optical Resolution of DL-Alanine by Formation of Ternary Copper(II) Complexes with L-Isoleucine
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A ternary complex, (D-alaninato)(L-isoleucinato)copper(II) (abbreviated as ), was crystallized selectively at 0 degC from an aqueous solution containing DL-alanine (DL-Ala), L-isoleucine (L-Ile), and copper(II) acetate monohydrate (Cu(OAc)2*H2O) in the molar ratio of 1:1:1.
- Shiraiwa, Tadashi,Fukuoka, Hirofumi,Yoshida, Masahiro,Kurokawa, Hidemoto
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- Heteroleptic complexes: Via solubility control: Examples of Cu(ii), Co(ii), Ni(ii) and Mn(ii) complexes based on the derivatives of terpyridine and hydroxyquinoline
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We describe the construction of synthetically challenging heteroleptic complexes by capitalizing on the solubility properties of their corresponding favored homoleptic complexes. We demonstrate that the formation of a heteroleptic Cu2+ complex based on 2,2′:6′,2′′-terpyridine (Terpy) and 8-hydroxyquinoline (HQ) is not possible due to the insolubility of (HQ)2Cu2+. Replacing HQ with 8-hydroxy-2-quinolinecarbonitrile (HQCN) enabled the solubility of (HQCN)2Cu2+ in acetonitrile, leading to the formation of the heteroleptic complex Terpy(HQCN)Cu2+, TQCu. Applying these conditions to the synthesis of the corresponding heteroleptic Co2+ complex resulted in TerpyCo2+(acetate)2, which is insoluble in acetonitrile. Upon changing the solvent to methanol, the carbonitrile group of HQCN was converted to carboxyimidate HQOMe yielding a heteroleptic complex Terpy(HQOMe)Co2+, TQ′Co. Using this method, we also generated the heteroleptic complex TQ′Ni and the polynuclear heteroleptic complex Q′4Q′′2Mn4 (Q′′ = HQO2Me). Detailed analysis of the complexes included characterization by X-ray diffraction, EPR, UV-Vis, high resolution ESI MS, DFT calculations and electrochemistry. X-ray analysis of TQCu revealed distorted square pyramidal geometry, while TQ′Co and TQ′Ni exhibit distorted octahedral geometry, which includes metal coordination via the carboxyimidate nitrogen site. Interestingly, Q′4Q′′2Mn4 was found to contain a [MnII4(μ3-O)2(μ2-O)4N10]2+ core, which adopts a distorted octahedral geometry, and two types of HQ chelators. Thus, Q′4Q′′2Mn4 is also heteroleptic even though it does not contain a Terpy ligand. Solution studies revealed that while TQCu is stable in solution, TQ′Co and TQ′Ni go through ligand exchange and are partially converted to their corresponding homoleptic complexes. Based on these data we could propose a mechanism for the formation of TQ′Co and TQ′Ni and show that TQ′Co can be prepared directly from Terpy and HQOMe.
- Baskin, Maria,Fridman, Natalia,Kosa, Monica,Maayan, Galia
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supporting information
p. 15330 - 15339
(2017/11/22)
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- Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status
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Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC50?~?1?μM platinum) and insensitive (IC50?>?5?μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC)2, Cu(Pyr)2, Cu(Plum)2 and Cu(8-HQ)2) showed IC50 values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC)2) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC)2) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p??0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs.
- Wehbe, Mohamed,Lo, Cody,Leung, Ada W. Y.,Dragowska, Wieslawa H.,Ryan, Gemma M.,Bally, Marcel B.
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p. 682 - 690
(2017/10/06)
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- Copper-dependent cytotoxicity of 8-hydroxyquinoline derivatives correlates with their hydrophobicity and does not require caspase activation
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This study reports the structure-activity relationship of a series of 8-hydroxoquinoline derivatives (8-HQs) and focuses on the cytotoxic activity of 5-Cl-7-I-8-HQ (clioquinol, CQ) copper complex (Cu(CQ)). 8-HQs alone cause a dose-dependent loss of viability of the human tumor HeLa and PC3 cells, but the coadministration of copper increases the ligands effects, with extensive cell death occurring in both cell lines. Cytotoxic doses of Cu(CQ) promote intracellular copper accumulation and massive endoplasmic reticulum vacuolization that precede a nonapoptotic (paraptotic) cell death. The cytotoxic effect of Cu(CQ) is reproduced in normal human endothelial cells (HUVEC) at concentrations double those effective in tumor cells, pointing to a potential therapeutic window for Cu(CQ). Finally, the results show that the paraptotic cell death induced by Cu(CQ) does not require nor involve caspases, giving an indication for the current clinical assessment of clioquinol as an antineoplastic agent.
- Tardito, Saverio,Barilli, Amelia,Bassanetti, Irene,Tegoni, Matteo,Bussolati, Ovidio,Franchi-Gazzola, Renata,Mucchino, Claudio,Marchiò, Luciano
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p. 10448 - 10459
(2013/02/23)
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- EPR and thermal studies on the reaction of copper acetate with 8-hydroxyquinoline in the solid phase
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Solid-solid reaction of 8-hydroxyquinoline with copper acetate results in the formation of copper quinolinolate in two steps as evidenced from EPR, TG and DSC studies.DSC scans show that the reaction is not a true solid-solid reaction and participation of some liquid phase occurs.Kinetics of the solid state reaction have also been investigated using capillary technique.
- Bassi, P. S.,Chopra, G. S.,Kaur, Kanwaljit
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p. 454 - 457
(2007/10/02)
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- 4-(Dimethylamino)-8-hydroxyquinoline as a new Chelating Ligand and as a Donor-enforced Terminal Group in Podands
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Electron releasing and -withdrawing substituents are introduced into the 4-position of 8-hydroxy-quinoline (oxine) (1), starting with 4-chloro-8-methoxyquinoline (2).The UV/Vis spectra of the oxines 4, 5 and their Ni-, Cu-, and Co-complexes are compared with those of oxine.Intensity increases of the long wave length absorptions are observed with the new ligand 4 compared to oxine itself and with the metal complexes.The substituted oxines are also used as new donor end groups in podands 8-12.The ammonium complexes of the new podands are investigated.
- Voegtle, Fritz,Siebert, Axel
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p. 1556 - 1563
(2007/10/02)
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- The isotropic hyperfine interaction in ternary complexes of copper(II) with 8-hydroxyquinoline and various salicylic acids
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Electron spin resonance and optical absorption studies are carried out on bis(8-hydroxyquinolinato)copper(II) and seven ternary copper(II) complexes with 8-hydroxyquinoline and salicylic acid or substituted salicylic acids.Electron spin resonance spectra of all these complexes give well resolved lines.An unusual splitting of the parallel lines in frozen solution spectra and four line fluid (DMF) solution spectra at room temperature are observed.It is explained on the basis of either partial dissociation of 8-hydroxyquinoline ligand or the solvation effect of DMF which solvates some copper chelate molecules even at room temperatures.This is more prominent on the parallel lines in frozen solution spectra of all the ternary complexes.The molecular orbital coefficient are estimated assuming an axial symmetry and these indicate that the in-plane ? bonding is weak compared to ?-bond in the ternary complexes.The value of χ, which is proportional to hiperfine constants, indicates that it is quite independent of either ligand substitutions or substitutions in the ligand, but purely depends upon the immediate environment which constitutes the coordination around the paramagnetic ion.
- Anjaneyulu, Y.,Rao, N. V. S.,Swamy, R. Y.,Rao, R. P.,Pisipati, V. G. K. M.
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p. 2154 - 2158
(2007/10/02)
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- Formation of Coordination Compounds under Model Conditions of Frictional Contact
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The model used was simultaneous thermal vaporisation in a vacuum of metals and active components of lubricants.Compounds are formed identical with those obtained under conditions of limiting friction.The mechanism of the formation of coordination compounds during friction involves local temperatures above 1000 deg C.
- Kuzharov, A. S.,Kut'kov, A. A.,Suchkov, V. V.
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p. 1784 - 1786
(2007/10/02)
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