- Copper diethyldithiocarbamate as an activator of Nrf2 in cultured vascular endothelial cells
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The interest in organic-inorganic hybrid molecules as molecular probes for biological systems has been growing rapidly. Such hybrid molecules exhibit unique biological activities. Herein, copper(II) bis(diethyldithiocarbamate) (Cu10) was found to activate the transcription factor NF-E2-related factor 2 (Nrf2), which is responsible for regulating antioxidant and phase II xenobiotic enzymes, in vascular endothelial cells. The copper complex rapidly accumulated within cells and induced nuclear translocation of Nrf2, leading to upregulation of the expression of downstream proteins without cytotoxic effects. However, while copper bis(2-hydroxyethyl)dithiocarbamate activated Nrf2, copper ion, diethyldithiocarbamate ligand with or without zinc or iron failed to exhibit this activity. Intracellular accumulation of Cu10 was higher than that of Cu(II) and Cu(I). While the accumulation of copper(II) bis(dimethyldithiocarbamate) was reduced by small interfering RNA (siRNA)-mediated knockdown of the copper transporter CTR1, the knockdown did not affect Cu10 accumulation, indicating that Cu10 rapidly enters vascular endothelial cells via CTR1-independent mechanisms. In addition, copper and iron complexes with other ligands tested could not activate Nrf2, suggesting that the intramolecular interaction between copper and dithiocarbamate ligand is important for the activation of the transcription factor. Cu10 induced the expression of heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, and γ-glutamylcysteine synthetase, downstream proteins of Nrf2. It was suggested that Cu10-induced activation of Nrf2 was due to proteasome inhibition as well as binding to Kelch-like ECH-associated protein 1. Since the effects of Cu10 on vascular endothelial cells are unique and diverse, the copper complex may be a good molecular probe to analyze the functions of the cells.
- Fujie, Tomoya,Murakami, Masaki,Yoshida, Eiko,Tachinami, Tadashi,Shinkai, Yasuhiro,Fujiwara, Yasuyuki,Yamamoto, Chika,Kumagai, Yoshito,Naka, Hiroshi,Kaji, Toshiyuki
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p. 263 - 273
(2016/03/30)
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- Composition and Structure of Complexes in Magnetically Diluted Systems of Copper(II) Dithiocarbamates Cu/M(Dtc)2 (M = Zn, Cd, Hg)
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The magnetically diluted complexes Cu/M(Dtc)2 (where M = Zn, Cd, or Hg, and Dtc is the dibutyl-, pentamethylene-, hexamethylene-, or morpholinedithiocarbamate ligand) were studied by EPR. In these systems, copper(II) forms four types of complexes: the mononuclear Cu(Dtc)2 complexes, the CuM(Dtc)4 dimers, and some heteronuclear species resulting from the substitution of one copper atom for a metal atom in the binuclear or mononuclear parts of the adduct-like polynuclear complexes M2(Dtc)4 · nM(Dtc)2 (n = 1-4). The geometry of the copper(II) coordination polyhedra is discussed for all the complexes identified. Structural instability of some of these magnetically diluted systems is attributed to lability of the polynuclear species.
- Ivanov,Mitrofanova,Rodina
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p. 570 - 574
(2008/10/08)
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- Electron Spin Resonance Study of Some Copper(II) Dithiocarbamates and their Mixed-ligand Complexes
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The e.s.r. spectra of seven copper(II) dithiocarbamates have been recorded in chloroform-ethanol mixtures at room temperature and at 113 K.It has been found that the addition of a range of salts to these dithiocarbamates destroys the complex forming a mixed-ligand complex, , with a new e.s.r. spectrum.When X is Cl or Br the additional interaction of the unpaired electron with a single halogen nucleus is observed.The complex forms a dipole-dipole coupled dimer and a computer simulation of the ΔMs = 2 absorption of this dimer has been obtained.
- Newton, William J.,Tabner, Brian J.
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p. 466 - 471
(2007/10/02)
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- Magnetic and Structural Studies on Copper(II) Dialkyldithiocarbamates
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The magnetic susceptibilities of a series of copper(II) dialkyldithiocarbamates have been measured over the range 4-290 K, the alkyl groups being methyl, ethyl, isopropyl, and n-butyl.Contrary to a previous report of strong ferromagnetic interaction in the diethyl derivative, we find no evidence of any significant exchange interaction in this compound.The dimethyl and di-isopropyl analogues show weak antiferromagnetic interactions.Only the di-n-butyl derivative in the dialkyl series shows evidence of strong magnetic exchange interaction but of an antiferromagnetic nature; this effect is peculiar to the phase recrystallized from chloroform-light petroleum (α), the phase obtained from chloroform-ethanol (β) showing no such interaction.To seek the origin of the exchange interaction in the α derivative, its crystal structure has been determined by single-crystal X-ray diffraction methods at 295 K and refined by least squares to a residual 0.032 for 1976 'observed' reflections.Crystals are triclinic, P1, a=15.29(1), b=9.963(7), c=9.243(7) Angstroem, α=67.94(7), β=82.92(7), γ=71.55(7) deg, and Z=2.The copper environment is the usual pseudo-square-planar array of four sulphur atoms from two bidentate ligands (, 2.31 Angstroem), but there is a long fifth interaction S, 2.899(4) Angstroem> through the inversion centre leading to pseudo-dimer formation.Although similar to the diethyl analogue in this respect, differences are observed in regard to (a) the bridging geometry in the 'dimer' and (b) the proximity to the 'dimer' sulphur ligands of sulphur atoms from neighbouring dimers at ca. 3.8 Angstroem.The likely relative importance of these two features in determining the origin of the antiferromagnetic coupling is discussed.The structure of the β phase has also been determined, the final residual being 0.036 for 1324 'observed' reflections.Crystals are monoclinic, P21/n, a= 14.593(5), b= 7.840(2), c= 10.822(5) Angstroem, β= 101.55(3) deg, and Z= 2.The molecules are located with the copper atoms on crystallographic centres of symmetry, and the only significant intermolecular interactions observed are SH contacts.The CuS4 entity is planar with 2.30 Angstroem.
- Boyd, Peter D. W.,Mitra, Samaresh,Raston, Colin L.,Rowbottom, Graham L.,White, Allan H.
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