Dithiocarbamate Ligands Research Articles

New 3D and 2D supramolecular heteroleptic palladium(II) dithiocarbamates as potent anticancer agents

Three new heteroleptic palladium(II) dithiocarbamates with better in vitro anticancer activity than cisplatin were synthesized and characterized by different analytical techniques, elemental analysis, FTIR, NMR, and single crystal X-ray diffraction analysis. The Pd center is chelated by dithiocarbamate ligand {4-benzylpiperazine-1-carbodithioate (1) and (3) or (4-(2-methoxyphenyl)piperazine-1-carbodithioate (2)}, triorganophosphine {tris-(4-flourophenyl)-phosphine (1) and (2) or tris-(4-chlorophenyl)phosphine (3)}, and a chloro-group, resulting in a square planar geometry. The packing diagram reveals a 3D network (1 and 2) and a 2D network (3) composed of various 1D chains in which the molecules are linked via hydrogen bonds (1–3) and halide⋯π (1, 3) interactions. The anticancer activities of complexes against HeLa cell line varies in the sequence 2 (23.438 μM) > 1 (38.293 μM) > 3 (47.554 μM) > cisplatin (78.075 μM). The cytotoxicity of these complexes is due to their strong induction of oxidative stress and DNA-damage ability leading to apoptosis.

Unusual octahedral Hg(II) dithiocarbamate: Synthesis, spectral and structural studies on Hg(II) complexes with pyrrole based dithiocarbamates and their utility for the preparation of α- and β-HgS

Bis(N-(pyrrol-2-ylmethyl)-N-butyldithiocarbamato-S,S′)mercury(II) (1) and bis(N-(pyrrol-2-ylmethyl)-N-(2-phenylethyl)dithiocarbamato-S,S′)mercury(II) (2) were prepared and characterized by microanalysis, spectroscopy (IR, 1H and 13C NMR) and their structures were elucidated by X-ray crystallography. Complexes 1 and 2 exist as monomer and polymer, respectively. The central mercury atom in 1 is asymmetrically chelated by two dithiocarbamate ligands leading to a distorted tetrahedral geometry. In complex 2, the mercury is six coordinate with distorted octahedral coordination geometry. In this case, both dithiocarbamate ligands function as bridging triconnective ligand. This indicates that small changes in R groups of dithiocarbamate ligand gave different structures. Complexes 1 and 2 were used as single source precursors for the preparation of mercury sulfide nanoparticles. Mercury sulfides were characterized by XRD, TEM, EDAX, IR, UV and fluorescence spectra. Solvothermal decomposition of 1 yielded three different morphological (hexagonal, cube and spherical) α-mercury sulfide nanoparticles and 2 gave only spherical β-mercury sulfide nanoparticles.

Impact of ferrocenyl and pyridyl groups attached to dithiocarbamate moieties on crystal structures and luminescent characteristics of group 12 metal complexes

Metal-directed self assembly of ferrocenyl based pyridyl functionalized dithiocarbamates afforded the novel macrocyclic metal-organic coordination polymers, [M(L)2]∞ (M = Zn(II), L = L2 (N-ferrocenylmethyl-N-pyridin-4-ylmethyl) dithiocarbamate 2, M = Cd(II), L = L1 (N-ferrocenylmethyl-N-pyridin-3-ylmethyl) dithiocarbamate 3); dimers [M(L1)2]2 (M = Zn(II) 1, Hg(II) 4) and a mononuclear [Cd(L2)(phen)], (phen = 1,10-phenanthroline) complex 5. These complexes have been characterised by elemental analysis, IR, UV–Vis., 1H and 13C NMR spectroscopy and their structures have been investigated by X-ray crystallography. In 2 and 3 the metal ions are six-coordinate with two bidentate dithiocarbamate ligands L1 and L2 in an equatorial plane and axially bonded by two Py(N) of the dithiocarbamate ligands on neighbouring molecules thus establishing distorted octahedral geometry (MS4N2) in 2-D polymeric structures. In L1 where the Py(N) is in the 3-position, a centrosymmetric dinuclear complex 1 is formed in which the metal ions adopt square pyramidal geometry. In 1–4, the dithiocarbamate ligands are uniquely bonded to the metal centres in a μ2, κ3-N, S, S bridging-chelating manner. In all the complexes the supramolecular structures are sustained via CH … π (MS2C, chelate) interactions. These unusual interactions have been supported by theoretical calculations. All the complexes show luminescent emissions in the solid phase.

Deubiquitinases as Anticancer Targets of Gold Complexes

AbstractMetal‐based anticancer agents with non‐DNA targets are anticipated for overcoming cisplatin resistance problems. Gold complexes are generally known to undergo ligand exchange or redox reactions with thiols, and hence, are potentially useful agents that could target thiol‐containing enzymes, but not DNA. Recent studies have shown that deubiquitinases (DUBs), key enzymes regulating proteasome‐related protein homeostasis, are potential anticancer targets of both gold(I) and gold(III) complexes. In this review, the current status of gold complexes as DUB inhibitors is discussed. In particular, auranofin and cyclometalated gold(III) complexes containing dithiocarbamate ligands (e.g., [(AuIII(C N)(DEDT)]+, HC N=2‐phenylpyridine, DEDT=diethyldithiocarbamate) are highlighted as examples of DUB inhibitors. The mechanisms of their anticancer action, together with in vitro and/or in vivo antitumor potencies, are also explored.

Distinct coordination geometries in bis-[N,N-bis-(2-meth-oxy-eth-yl)di-thio-carbamato-κ(2) S,S']di-phenyltin(IV) and bis-[N-(2-meth-oxy-eth-yl)-N-methyl-dithio-carbamato-κ(2) S,S']di-phenyl-tin(IV): crystal structures and Hirshfeld surface analysis.

The crystal and mol-ecular structures of two di-phenyl-tin bis-(di-thio-carbamate)s, [Sn(C6H5)2(C5H10NOS2)2], (I), and [Sn(C6H5)2(C7H14NO2S2)2], (II), are described. In (I), in which the metal atom lies on a twofold rotation axis, the di-thio-carbamate ligand coordinates with approximately equal Sn-S bond lengths and the ipso-C atoms of the Sn-bound phenyl groups occupy cis-positions in the resulting octa-hedral C2S4 donor set. A quite distinct coordination geometry is noted in (II), arising as a result of quite disparate Sn-S bond lengths. Here, the four S-donors define a trapezoidal plane with the ipso-C atoms lying over the weaker of the Sn-S bonds so that the C2S4 donor set defines a skewed trapezoidal bipyramid. The packing of (I) features supra-molecular layers in the ab plane sustained by methyl-ene-C-H⋯π(Sn-ar-yl) inter-actions; these stack along the c-axis direction with no specific inter-actions between them. In (II), supra-molecular chains along the b-axis direction are formed by methyl-ene-C-O(ether) inter-actions; these pack with no directional inter-actions between them. A Hirshfeld surface analysis was conducted on both (I) and (II) and revealed the dominance of H⋯H inter-actions contributing to the respective surfaces, i.e. >60% in each case, and other features consistent with the description of the mol-ecular packing above.

Influence of functionalities over polymer, trimer, dimer formation and optical properties of cadmium dithiocarbamates

Homoleptic cadmium(II) bis(dithiocarbamate) complexes having polymeric [Cd(L)2]∞ (L=C7H5O2CH2NCS2CH2C6H5 (L1), 1; C6H4NO2CH2NCS2CH2C4H3O (L2), 2; C6H4FCH2NCS2CH2C4H3O (L3), 3), trinuclear [Cd(L4)2]3 (L4=4-ClC6H4CH2NCS2CH2C4H3O, 4) and dinuclear [Cd(L5)2]2, (L5=3-ClC6H4CH2NCS2CH2C6H5, 5) structures have been synthesized and characterized by elemental analyses, spectroscopy (IR, 1H and 13C {1H} NMR and UV–Vis.) and their structures have been revealed by X-ray crystallography. In 1–3 the dithiocarbamate ligands are uniquely bonded to the Cd atoms in a μ2,κ2 S,S-chelating-bridging fashion, portraying 1D coordination polymeric structures in which the cadmium(II) ions adopt six coordinate distorted octahedral structures. In 4 the six dithiocarbamate ligands are spectacularly arranged about the Cd atoms resulting in a centrosymmetric trinuclear complex in which the central metal adopts an octahedral geometry and the terminal Cd atoms are in square pyramidal environments. Complex 5 has the well-established centrosymmetric dimeric structure in which the metal atoms have a five-coordinate trigonal bipyramidal geometry. Complexes 1–4 are rare examples of polymeric and trinuclear cadmium dithiocarbamate complexes. 1–5 show luminescent characteristics in solution and in the solid state arising from the metal perturbed intra-ligand charge transfer (ILCT) states. Their TG analyses show a single step decomposition with the formation of CdS nanoparticles, which have been examined by PXRD and HRTEM.

23‐ and 27‐Membered Macrocyclic Diorganotin(IV) Bis‐dithiocarbamates: Synthesis, Spectroscopic Characterization, DFT Calculations, and Physicochemical Analysis as Anion Receptors

Four secondary diamines with aromatic spacer groups derived from α,α′‐dibromo‐p‐xylene and 4,4′‐bis(chloromethyl)‐1,1′‐biphenyl have been transformed into bis‐dithiocarbamate ligands and each combined with dimethyl‐, di‐n‐butyl‐, and diphenyltin(IV) dichloride to yield a total of 12 mononuclear diorganotin(IV) bis‐dithiocarbamate complexes with six‐coordinate metal coordination geometries and either 23‐ or 27‐membered macrocyclic structures. The products were fully characterized by IR and NMR (1H, 13C, 119Sn) spectroscopy and high‐resolution ESI+‐TOF mass spectrometry. A representative selection of the macrocyclic complexes was further examined by DFT computational studies and the relative binding energies of the cis and trans isomers of the different diorganotin complexes were calculated and compared. Additionally, four possible conformations of the trans isomers were analyzed. With the purpose of examining whether the complexes can be applied to the recognition of anions, five macrocycles were selected based on criteria that allowed the influence of the aromatic spacer group, the N substituent of the dithiocarbamate ligand, and the organic groups attached to the metal center on the recognition properties to be explored. Among the NMe4+X– salts (X– = F–, Cl–, Br–, I–, NO3–, HSO4–, and CH3COO–) examined, the diorganotin complexes were sensitive to fluoride and carboxylate anions.

Synthesis and spectral studies on Ni(II) complexes involving N-furfuryl-N-substituted benzyldithiocarbamates and PPh3: Anagostic and C–H…π(chelate) interactions in (N-furfuryl-N-(4-fluorobenzyl)dithiocarbamato-S,S′)(thiocyanato-N)(triphenylphosphine)nickel(II)

ABSTRACTTwelve new nickel(II) complexes of functionalized dithiocarabamates [Ni(S2CNRR')2](1-6) and [Ni(S2CNRR')(NCS)(PPh3)](7-12) [where R=furfuryl; R'=2-hydroxy benzyl (1,7), 3-hydroxy benzyl (2,8), 4-hydroxy benzyl (3,9), 4-methoxy benzyl (4,10), 4-fluoro benzyl (5,11), 4-chloro benzyl (6,12)] have been prepared and characterized by elemental analysis, IR, UV-Vis and NMR (1H and 13C) spectroscopy. IR spectra of the complexes support the bidentate coordination of dithiocarbamate ligands. Electronic spectral studies on complexes 1-12 indicate square planar geometry around the nickel(II) central atom. In the 13C NMR spectra, the upfield shift of NCS2 carbon signal for heteroleptic complex (7-12) compared to homoleptic complexes (1-6) is due to the effect of PPh3 on the mesomeric drift of electron density toward nickel through thioureide C-N bond. Single crystal X-ray structural analysis of complex 11 confirms that the coordination geometry about the Ni(II) is distorted square planar. A rare intramolecular anagostic interaction C–H…Ni [Ni⋅⋅⋅H=2.804 Å] is observed. The packing of complex 11 is stabilized by non-conventional C–H…S, C–H⋯F and C–H⋯π(chelate, NiS2C) bonding interactions.

Bis[bis(N-2-hydroxyethyl,N-isopropyl-dithiocarbamato)mercury(II)]2: crystal structure and Hirshfeld surface analysis

Abstract The presence of both κ2-chelating and μ2,κ2-tridentate bridging dithiocarbamate ligands in centrosymmetric {Hg[S2CN(iPr)CH2CH2OH]2}2 (1) leads to globular aggregates that are linked into a three-dimensional architecture via hydroxyl-O–H···O(hydroxy) hydrogen bonding. The structure contrasts that of Hg[S2CN(CH2CH2OH)2]2 (2; this is a literature structure) in which square planar units are connected into supramolecular chains via Hg···S secondary bonding; chains are connected in the crystal structure by hydroxyl-O–H···O(hydroxy) hydrogen bonding. A Hirshfeld surface analysis on 1 and 2 reveal the influence of O–H···O and Hg···S interactions on the molecular packing as well as the distinctive interactions, such as C–H···S interactions in 1 and C–H···π (HgS2C) contacts in 2. A bibliographic survey shows the different structural motifs observed for 1 and 2 are complimented by an additional five motifs for binary mercury(II) dithiocarbamates revealing a fascinating structural diversity for this class of compound.

Supramolecular architecture of organotin(IV) 4-hydroxypiperidine dithiocarbamates: Crystallographic, computational and Hirshfeld surface analyses

Three new organotin(IV) dithiocarbamate complexes viz. [Me2Sn(4-OHPCTDA)2] (1), [n-Bu2Sn(4-OHPCTDA)2] (2) and [Ph3Sn(4-OHPCTDA)] (3) (4-OHPCDTA=4-hydroxypiperidine dithiocarbamate), have been synthesized and characterized by elemental analyses, IR, 1H, 13C, 119Sn NMR spectroscopy and X-ray crystallography. The X-ray analyses for 1 and 2 reveal a skew trapezoidal bipyramid geometry around Sn(IV) which is being satisfied by the two sulfur atoms of the two dithiocarbamate ligands in anisobidentate fashion. In the case of 3 the monodentate coordination by one sulfur atom of the dithiocarbamate ligand imposes distorted tetrahedral geometry around Sn(IV). All three compounds display intermolecular O–H⋯O and C–H⋯S interactions which generate a supramolecular framework. 2 also exhibits intermolecular S⋯S interactions to generate a one dimensional supramolecular architecture. These interactions have been addressed by ab initio, AIM and Hirshfeld surface analyses. Additionally, thermogravimetric analyses of all the three compounds indicates their use as single source precursors for tin sulfide.

Synthesis, characterization, molecular docking and biological studies of self assembled transition metal dithiocarbamates of substituted pyrrole-2-carboxaldehyde

A series of self assembled 3d transition metal dithiocarbamate, M(pdtc) [where M=Mn(II), Fe(II), Co(II), Ni(II) and Cu(II)] have been synthesized and spectroscopically characterized. The bidentate dithiocarbamate ligand Na2pdtc (Disodium-1,4-phenyldiaminobis (pyrrole-1-sulfino)dithioate) was prepared by insertion reaction of carbondisulfide with Schiff base, N,N′-bis-(1H-pyrrol-2-ylmethylene)-benzene-1,4-diamine (L1) in basic medium. The simple substitution reaction between the metal halide and Na2pdtc yielded the title complexes in moderate yields. However, the in situ procedure gives high yield with the formation of single product as evident by TLC. Elemental analysis, IR, 1H and 13C NMR spectra, UV–vis., magnetic susceptibility and conductance measurements were done to characterize the complexes, M(pdtc). All the evidences suggest that the complexes have tetrahedral geometry excepting Cu(II) which is found to be square planar. A symmetrical bidentate coordination of the dithiocarbamato moiety has been observed in all the complexes. The conductivity data show that the complexes are non-electrolyte in nature. The anti-oxidant activity of the ligand, Na2pdtc and its transition metal complexes, M(pdtc) have been carried out using DPPH and Cu(pdtc) was found to be most effective. The anti-microbial activity of the Na2pdtc and M(pdtc) complexes have been carried out and on this basis the molecular docking study of the most effective complex, Cu(pdtc) has also been reported.

Synthesis, spectral, structural and computational studies on NiS4 and NiS2NP chromophores: Anagostic and C–H⋯π (chelate) interactions in [Ni(dtc)(PPh3)(NCS)] (dtc = N-(2-phenylethyl)-N-(4-methoxybenzyl)- dithiocarbamate and N-(2-phenylethyl)-N-(4-chlorobenzyl)dithiocarbamate)

Bis(N-(2-phenylethyl)-N-substituted benzyldithiocarbamato-S,S′)nickel(II) (1–6) and (N-(2-phenylethyl)-N-substituted benzyldithiocarbamato-S,S′)(thiocyanato-N) (triphenylphosphine)nickel(II) (7–12) [substituted benzyl = 2HO–C6H4–CH2– (1,7), 3HO–C6H4–CH2– (2,8), 4HO–C6H4–CH2– (3,9), 4CH3O–C6H4–CH2– (4,10), 4F–C6H4–CH2– (5,11), 4Cl–C6H4–CH2– (6,12)] complexes have been synthesized and characterized by elemental analysis, IR, UV–Vis and NMR (1H and 13C) spectroscopy. In the case of heteroleptic complexes 7–12, the shift in vC-N values to higher wavenumber and the NCS2 carbon signals are shifted to downfield compared to the homoleptic complexes indicating the increasing strength of thioureide vC-N bond due to the presence of π-accepting triphenylphosphine ligand in heteroleptic complexes. Electronic spectral studies on all the complexes (1–12) suggest square planar geometry around the nickel(II). Structures of 10 and 12 have been elucidated by X-ray crystallography. The dithiocarbamate anions in 10 and 12 chelate to the nickel atom. Both the structures reveal C–H⋯Ni intramolecular anagostic interaction. C–H⋯π (chelate) is observed in complexes 10. Supramolecular frame works are stabilised by C–H⋯S, C–H⋯π and C–H⋯Cl non-covalent interaction. The molecular geometry, HOMO-LUMO in the ground state and MEP have been calculated for 10 and 12 using Hartree-Fock (HF) method with LANL2DZ basic set. Molecular electrostatic potential diagram of complexes 10 and 12 support the partial double bond character of C–N (thioureide) bond in dithiocarbamate ligands.

Bis(phosphane)copper(I) and silver(I) dithiocarbamates: crystallography and anti-microbial assay

Abstract The crystal and molecular structures of (Ph3P)2M[S2CN(Me)CH2CH2OH], M=Cu, isolated as a 1:1 dichloromethane solvate (1·CH2Cl2), and M=Ag (4) show the central metal atom to be coordinated by a symmetrically (1·CH2Cl2) and asymmetrically chelating (4) dithiocarbamate ligand. The distorted tetrahedral geometries are completed by two PPh3 ligands. The presence of hydroxyl-O–H···S(dithiocarbamate) hydrogen bonds leads to centrosymmetric dimeric aggregates in each crystal structure. In the molecular packing of 1·CH2Cl2, channels comprising 1 are formed via aryl-C–H···O interactions with the solvent molecules associated with the walls of the channels via methylene-C–H···S, π(aryl) interactions. For 4, the dimeric aggregates are connected via a network of aryl-C–H···π(aryl) interactions. Preliminary screening for anti-microbial activity was conducted. The compounds were only potent against Gram-positive bacteria. Some further selectivity in activity was noted. Most notably, all compounds were active against methicillin resistant Staphylococcus aureus.

Synthesis, characterization and antimicrobial properties of some mixed ligand complexes of Zn(II) dithiocarbamate with different N-donor ligands

In this study, adducts of Zn(II) dithiocarbamates containing different N-donor ligands (pyridine, 2,2′-bipyridine and 1,10-phenanthroline) have been synthesized. The parent dithiocarbamate complex comprise N-methyl-N-phenyl dithiocarbamate (L1) and N-ethyl-N-phenyl dithiocarbamate (L2), and the adducts are represented as [ZnL1L2py], [ZnL1L2bpy], and [ZnL1L2phen] (where py=pyridine, bpy=2,2′-bipyridine, and phen=1,10-phenanthroline). All the compounds have been characterized by elemental analysis and spectroscopic techniques (IR and NMR). In addition, the crystal structure of [ZnL1L2bpy] complex is also reported. The structure indicates that the two dithiocarbamate ligands are disordered in 0.67:0.33 ratio and alternatively bond as monodentate and bidentate ligands. The bipyridine acts as a bidentate ligand, and gives the structure around the Zn atom a distorted square pyramidal geometry. In order to evaluate their antimicrobial properties, the precursor complex and the adducts were screened against six pathogenic bacteria strains and two fungi organisms. The antimicrobial activities of the complexes were in the order [ZnL1L2]>[ZnL1L2py]>[ZnL1L2bpy]>[ZnL1L2phen]. The precursor complex, ZnL1L2, showed the lowest MIC and is considered as the complex with most antimicrobial activity against the selected microorganisms.

Chlorodiphenyltin(IV) dithiocarbamate complexes as chemodosimeters and host for anions and neutral compounds in solution

The chlorodiphenyltin(IV) dithiocarbamate complexes 1–5 with general formula {(Ph2SnCl)dtc} (dtc=R1R2NCS2−; 1, R1=Bn, R2=9-anthrylmethyl; 2, R1=Bn, R2=9-phenanthrylmethyl; 3, R1=Bn, R2=1-pyrenylmethyl; 4, R1=1-naphthylmethyl, R2=1-pyrenylmethyl; 5, R1=R2 1-pyrenylmethyl) have been tested as host for anions and neutral amines in acetonitrile by spectrophotometric UV/Vis titrations. In addition, the titrations of the complexes 1 and 5 were studied in chloroform by 1H and 119Sn NMR spectroscopy. It was found that anions as acetate, benzoate, and dihydrogen phosphate cause a displacement of the dithiocarbamate ligands of metallic center independently of the aromatic nature of the substituents on the nitrogen atom functioning as chemodosimeters in which the indicator is displaced. However, some aliphatic amines and aromatic methylene amines and its aromatic analogs can act as guests with binding constants in the range of 103 to 106M−1. Also, in these cases compound 5 functions as chemodosimeter without displacement of the indicator. According to 1H, 13C, 119Sn NMR data and using DFT (B3LYP) and Poisson–Boltzmann (PB) to model the solvent, structures of the complexes are proposed in which the hydrophobic and π–π interactions are suggested as the dominant interactions.

Ferrocene-Functionalized Cu(I)/Ag(I) Dithiocarbamate Clusters.

A series of compounds, namely, [Cu8(μ4-H){S2CNMeCH2Fc}6](PF6) (1), [Cu7(μ4-H) {S2CN(i)PrCH2Fc}6] (2), [Cu3{S2CN(Bz) (CH2Fc)}2(dppf)2](PF6) (3), and [Ag2{S2CNMe(CH2Fc)}2(PPh3)2] (4) (dppf = 1,1'-bis(diphenylphosphino)ferrocene), supported by multiferrocene assemblies, were synthesized. All the compounds were characterized by (1)H NMR, Fourier transform infrared, elemental analysis, and electrospray ionization mass spectrometry techniques. Single-crystal X-ray structural analysis revealed that 1 is a monocationic octanuclear Cu(I) cluster and that 2 is a neutral heptanuclear Cu(I) cluster with tetracapped tetrahedral (1) and tricapped tetrahedral (2) geometries entrapped with an interstitial hydride, anchored by six ferrocene units at the periphery of the core. Compounds 3 and 4 comprise trimetallic Cu(I) and dimetallic Ag(I) cores enfolded by four and two ferrocene moieties. Interestingly both chelating and bridging modes of binding are observed for dppf ligand in 3. Further the formation and isolation of polyhydrido copper clusters [Cu28H15{S2CN(i)PrCH2Fc}12](PF6) (5) and [Cu28H15{S2CN(n)Bu2}12](PF6) (7), stabilized by bulky ferrocenyl and n-butyl dithiocarbamate ligands, was demonstrated. They are readily identified by (2)H NMR studies on their deuterium analogues, [Cu28D15{S2CN(i)PrCH2Fc}12](PF6) (6) and [Cu28D15{S2CN(n)Bu2}12](PF6) (8). Though the structure details as well as spectroscopic characterizations of 5 are yet to be investigated, the compound 7 is fully characterized by variety of spectroscopy including single-crystal X-ray diffraction. The cyclic voltammetry studies for compounds 1, 2, and 4 display irreversible redox peaks for Fe(2+)/Fe(3+) couple wherein the reduction peaks are not well-resolved due to some adsorption of the complex onto the electrode surface.

Copper diethyldithiocarbamate as an activator of Nrf2 in cultured vascular endothelial cells

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00775-016-1337-z) contains supplementary material, which is available to authorized users.

Crystal structures of (2,2'-bipyridyl-κ(2) N,N')bis-[N,N-bis-(2-hydroxy-eth-yl)di-thio-carbamato-κ(2) S,S']zinc dihydrate and (2,2'-bipyridyl-κ(2) N,N')bis-[N-(2-hydroxy-eth-yl)-N-iso-propyl-dithio-carbamato-κ(2) S,S']zinc.

The common feature of the title compounds, [Zn(C5H10NO2S2)2(C10H8N2)]·2H2O, (I), and [Zn(C6H12NOS2)2(C10H8N2)], (II), is the location of the Zn(II) atoms on a twofold rotation axis. Further, each Zn(II) atom is chelated by two symmetry-equivalent and symmetrically coordinating di-thio-carbamate ligands and a 2,2'-bi-pyridine ligand. The resulting N2S4 coordination geometry is based on a highly distorted octa-hedron in each case. In the mol-ecular packing of (I), supra-molecular ladders mediated by O-H⋯O hydrogen bonding are found whereby the uprights are defined by {⋯HO(water)⋯HO(hy-droxy)⋯} n chains parallel to the a axis and with the rungs defined by 'Zn[S2CN(CH2CH2)2]2'. The water mol-ecules connect the ladders into a supra-molecular layer parallel to the ab plane via water-O-H⋯S and pyridyl-C-H⋯O(water) inter-actions, with the connections between layers being of the type pyridyl-C-H⋯S. In (II), supra-molecular layers parallel to the ab plane are sustained by hy-droxy-O-H⋯S hydrogen bonds with connections between layers being of the type pyridyl-C-H⋯S.

Bis[N-(2-hy-droxy-eth-yl)-N-iso-propyl-dithio-carbamato-κ(2) S,S'](piperazine-κN)cadmium: crystal structure and Hirshfeld surface analysis.

The title compound, [Cd(C6H12NOS2)2(C4H10N2)], features a distorted square-pyramidal coordination geometry about the central Cd(II) atom. The di-thio-carbamate ligands are chelating, forming similar Cd-S bond lengths and define the approximate basal plane. One of the N atoms of the piperazine mol-ecule, which adopts a chair conformation, occupies the apical site. In the crystal, supra-molecular layers propagating in the ac plane are formed via hy-droxy-O-H⋯O(hy-droxy), hy-droxy-O-H⋯N(terminal-piperazine) and coordinated-piperazine-N-H⋯O(hy-droxy) hydrogen bonds; the layers also feature methine-C-H⋯S inter-actions and S⋯S [3.3714 (10) Å] short contacts. The layers stack along the b-axis direction with very weak terminal-piperazine-N-H⋯O(hy-droxy) inter-actions between them. An evaluation of the Hirshfeld surfaces confirms the importance of inter-molecular inter-actions involving oxygen and sulfur atoms.

Bis(N-benzyl-N-methyldithiocarbamato-κ2S,S′)(pyridine-κN)cadmium(II)

The title compound, [Cd(C9H10NS2)2(C5H5N)], features a five-coordinate CdIIatom, being coordinated by two nearly symmetrically chelating dithiocarbamate ligands and a pyridine N atom. The resulting NS4donor set defines a distorted coordination geometry tending toward square pyramidal. In the molecular packing, centrosymmetric ten-membered {...HCNCS}2synthons arise as a result of methylene-C—H...S interactions. These are connected into layers parallel to (10-2)viaweak methyl-C—H...π(phenyl) interactions.