RESUMO

Three dinuclear zinc(II) acetate complexes of the general formula [Zn{Ln}(AcO)]2, namely, di-µ-acetato-κ4O:O'-bis[({2-[(pyridin-2-ylmethylidene)amino]phenyl}sulfanido-κ3N,N',S)zinc(II)], [Zn2(C12H9N2S)2(C2H3O2)2] (n = 1), 4, µ-acetato-1:2κ2O:O'-acetato-2κO-[µ-(2-{[1-(pyridin-2-yl)ethylidene]amino}phenyl)sulfanido-1κS:2κ3N,N',S][(2-{[1-(pyridin-2-yl)ethylidene]amino}phenyl)sulfanido-1κ3N,N',S]dizinc(II), [Zn2(C13H11N2S)2(C2H3O2)2] (n = 2), 5, and µ-acetato-1:2κ2O:O'-acetato-2κO-[µ-(2-{[phenyl(pyridin-2-yl)methylidene]amino}phenyl)sulfanido-1κS:2κ3N,N',S][(2-{[phenyl(pyridin-2-yl)methylidene]amino}phenyl)sulfanido-1κ3N,N',S]dizinc(II)-bis(2-aminophenyl) disulfide (2/1), [Zn2(C18H13N2S)2(C2H3O2)2]·0.5C12H12N2S2 (n = 3), 6·0.5(2-APS)2, were obtained from the reaction of 2-R-(pyridin-2-yl)benzothiazoline precursors (R = H, 1; R = Me, 2; R = Ph, 3) with zinc acetate dihydrate in a 1:1 ratio. All the complexes crystallized as dinuclear species and complex 6 cocrystallized with one molecule of bis(2-aminophenyl) disulfide (2-APS)2. The anionic Schiff base ligands {Ln}- displayed a κ2N,κS-tridentate coordination mode with the formation of two five-membered chelate rings. In 4, 5 and 6·0.5(2-APS)2, both ZnII ions are pentacoordinated and the coordination sphere of 4 was different with respect to those in 5 and 6·0.5(2-APS)2. For 4, the X-ray diffraction study showed a dinuclear complex containing two bridging acetate ligands linked to both ZnII ions. For 5 and 6·0.5(2-APS)2, the dinuclear complexes displayed one bridging acetate ligand linked to both ZnII ions, where the first ZnII ion includes a dative bond with one S atom from an adjacent anionic Schiff base {Ln}-, while the second ZnII ion is coordinated to one terminal acetate ligand. In each dinuclear complex, the geometry is the same for both ZnII metal centres. The local geometry of the ZnII cation in 4 is halfway between trigonal bipyramidal and square pyramidal local geometries; in 5 and 6, the local geometries are described as distorted square pyramidal. Hirshfeld surface analysis of 5 and 6 showed the predominance of H...H interactions, as well as the contribution of C-H...C, C-H...O and C-H...S noncovalent interactions to the cohesion of the crystalline network of the ZnII complexes.

RESUMO

Coordination compounds that mimic Purple Acid Phosphatases (PAPs) have drawn attention in the bioinorganic field due to their capacity to cleave phosphodiester bonds. However, their catalytic activity upon phosphate triesters is still unexplored. Thus, we report the synthesis and characterization of two binuclear complexes, [MnIIMnIII(L1)(OAc)2]BF4 (1) and [MnIIFeIII(L1)(OAc)2]BF4 (2) (H2L1 = 2-[N,N-bis-(2- pyridilmethyl)aminomethyl]-4-methyl-6-[N-(2-hydroxy-3-formyl-5-methylbenzyl)-N-(2-pyridylmethyl)aminomethyl]phenol), their hydrolytic activity and antioxidant potential. The complexes were fully characterized, including the X-Ray diffraction (XRD) of 1. Density functional theory (DFT) calculations were performed to better understand their electronic and structural properties and phosphate conjugates. The catalytic activity was analyzed for two model substrates, a diester (BDNPP) and a triester phosphate (DEDNPP). The results suggest enhancement of the hydrolysis reaction by 170 to 1500 times, depending on the substrate and complex. It was possible to accompany the catalytic reaction of DEDNPP hydrolysis by phosphorus nuclear magnetic resonance (31P NMR), showing that both 1 and 2 are efficient catalysts. Moreover, we also addressed that 1 and 2 present a relevant antioxidant potential, protecting the yeast Saccharomyces cerevisiae, used as eukaryotic model of study, against the exposure of cells to acute oxidative stress.

Assuntos

Antioxidantes , Compostos Férricos , Antioxidantes/farmacologia , Cristalografia por Raios X , Compostos Férricos/química , Hidrólise , Fenóis , Fosfatos , Fósforo

RESUMO

The reaction of 2,6-diformyl-4-methylphenol (DFMF) with 1-amino-2-propanol (AP) and tris(hydroxymethyl)aminomethane (THMAM) was investigated in the presence of Cobalt(II) salts, (X = ClO4-, CH3CO2-, Cl-, NO3-), sodium azide (NaN3), and triethylamine (TEA). In one pot, the variation in Cobalt(II) salt results in the self-assembly of dinuclear, tetranuclear, and H-bonding-directed polynuclear coordination complexes of Cobalt(III), Cobalt(II), and mixed-valence CoIICoIII: [Co2III(H2L-1)2(AP-1)(N3)](ClO4)2 (1), [Co4(H2L-1)2(µ3-1,1,1-N3)2(µ-1,1-N3)2Cl2(CH3OH)2]·4CH3OH (2), [Co2IICo2III(HL-2)2(µ-CH3CO2)2(µ3-OH)2](NO3)2·2CH3CH2OH (3), and [Co2IICo2III (H2L12-)2(THMAM-1)2](NO3)4 (4). In 1, two cobalt(III) ions are connected via three single atom bridges; two from deprotonated ethanolic oxygen atoms in the side arms of the ligands and one from the1-amino-2-propanol moiety forming a dinuclear unit with a very short (2.5430(11) Å) Co-Co intermetallic separation with a coordination number of 7, a rare feature for cobalt(III). In 2, two cobalt(II) ions in a dinuclear unit are bridged through phenoxide O and µ3-1,1,1-N3 azido bridges, and the two dinuclear units are interconnected by two µ-1,1-N3 and two µ3-1,1,1-N3 azido bridges generating tetranuclear cationic [Co4(H2L-1)2(µ3-1,1,1-N3)2(µ-1,1-N3)2Cl2(CH3OH)2]2+ units with an incomplete double cubane core, which grow into polynuclear 1D-single chains along the a-axis through H-bonding. In 3, HL2- holds mixed-valent Co(II)/Co(III) ions in a dinuclear unit bridged via phenoxide O, µ-1,3-CH3CO2-, and µ3-OH- bridges, and the dinuclear units are interconnected through two deprotonated ethanolic O in the side arms of the ligands and two µ3-OH- bridges generating cationic tetranuclear [Co2IICo2III(HL-2)2(µ-CH3CO2)2(µ3-OH)2]2+ units with an incomplete double cubane core. In 4, H2L1-2 holds mixed-valent Co(II)/Co(III) ions in dinuclear units which dimerize through two ethanolic O (µ-RO-) in the side arms of the ligands and two ethanolic O (µ3-RO-) of THMAM bridges producing centrosymmetric cationic tetranuclear [Co2IICo2III (H2L1-2)2(THMAM-1)2]4+ units which grow into 2D-sheets along the bc-axis through a network of H-bonding. Bulk magnetization measurements on 2 demonstrate that the magnetic interactions are completely dominated by an overall ferromagnetic coupling occurring between Co(II) ions.

RESUMO

A new series of Cu(II) complexes [bis[{(µ2-chloro)-2-MeO-Ph-CH2-(N=CH)-2,4-tert-butyl-2-OC6H2)}Cu(II)] (Cu1); bis[{(µ2-chloro)-2-MeS-Ph-CH2-(N=CH)-2,4-tert-butyl-2-(OC6H2)}Cu(II)] (Cu2); bis[{(µ2-chloro)-2-MeO-Ph-CH2-(N=CH)-2-(OC10H6)} Cu(II)] (Cu3); bis[{(µ2-chloro)-2-MeS-Ph-CH2-(N=CH)-2-(OC10H6)}Cu(II)] complex (Cu4); bis[{2-MeS-Ph-CH2-(N=CH)-2,4-tert-butyl-2-(OC6H2)}Cu(II)] (Cu5)] have been synthesized and characterized by elemental analysis, IR, UV-Visible and by X-ray crystallography for Cu1, Cu4 and Cu5. In the solid state, Cu1 features of a chloro-bridged dimer complex with κ2 coordination of the monoanionic phenoxy-imine ligand onto the copper center. On the other hand, the molecular structure of Cu4 reveals the naphthoxy-imine ligand with pendant S-group coordinated to the copper atom in tridentate meridional fashion. Treatment of [Cu(OAc)2·H2O] with two equiv. of [2-MeS-Ph-CH2-(N=CH)-2,4-tert-butyl-2-(HOC6H2)] led to a monomeric complex Cu5, with the ONS-donor Schiff base acting as a bidentate ligand. The redox behavior was explored by cyclic voltammetry. The reduction/oxidation potential of Cu(II) complexes depends on the structure and conformation of the central atom in the coordination compounds. Antioxidant activities of the complexes, Cu1 - Cu5, were determined by in vitro assays such as 1,1-diphenyl-2-picryl-hydrazyl free radicals (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radicals (ABTS+). The dinuclear compounds Cu1-Cu4, from the concentration of 5 µM, presented a good activity in scavenging DPPH radical. In addition, most of the Cu(II) complexes showed ABTS.+ radical-scavenging activity. The monomeric complex Cu5 at all concentrations tested showed antioxidant inability. The cytotoxicity of the Cu1 and Cu3 was determined in V79 cell line by reduction of 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay.

Assuntos

Complexos de Coordenação/farmacologia , Sequestradores de Radicais Livres/farmacologia , Bases de Schiff/farmacologia , Animais , Linhagem Celular , Complexos de Coordenação/síntese química , Cobre/química , Cricetulus , Cristalografia por Raios X , Eletroquímica , Sequestradores de Radicais Livres/síntese química , Ligantes , Estrutura Molecular , Oxirredução , Bases de Schiff/síntese química , Relação Estrutura-Atividade

RESUMO

A dinuclear copper(II) complex of formula [{Cu(bipy)(bzt)(OH2)}2(µ-ox)] (1) (where bipy = 2,2'-bipyridine, bzt = benzoate and ox = oxalate) was synthesised and characterised by diffractometric (powder and single-crystal XRD) and thermogravimetric (TG/DTG) analyses, spectroscopic techniques (IR, Raman, electron paramagnetic resonance spectroscopy (EPR) and electronic spectroscopy), magnetic measurements and density functional theory (DFT) calculations. The analysis of the crystal structure revealed that the oxalate ligand is in bis(bidentate) coordination mode between two copper(II) centres. The other four positions of the coordination environment of the copper(II) ion are occupied by one water molecule, a bidentate bipy and a monodentate bzt ligand. An inversion centre located on the ox ligand generates the other half of the dinuclear complex. Intermolecular hydrogen bonds and π-π interactions are responsible for the organisation of the molecules in the solid state. Molar magnetic susceptibility and field dependence magnetisation studies evidenced a weak intramolecular-ferromagnetic interaction (J = +2.9 cm-1) between the metal ions. The sign and magnitude of the calculated J value by density functional theory (DFT) are in agreement with the experimental data.

Assuntos

2,2'-Dipiridil/química , Benzoatos/química , Complexos de Coordenação/síntese química , Cobre/química , Oxalatos/química , Fenômenos Químicos , Técnicas de Química Sintética , Complexos de Coordenação/química , Cristalografia por Raios X , Ligantes , Fenômenos Magnéticos , Estrutura Molecular , Análise Espectral

RESUMO

The cytotoxicity of a dinuclear imine-copper (II) complex 2, and its analogous mononuclear complex 1, toward different melanoma cells, particularly human SKMEL-05 and SKMEL-147, was investigated. Complex 2, a tyrosinase mimic, showed much higher activity in comparison to complex 1, and its reactivity was verified to be remarkably activated by UVB-light, while the mononuclear compound showed a small or negligible effect. Further, a significant dependence on the melanin content in the tumor cells, both from intrinsic pigmentation or stimulated by irradiation, was observed in the case of complex 2. Similar tests with keratinocytes and melanocytes indicated a much lower sensitivity to both copper (II) complexes, even after exposition to UV light. Clonogenic assays attested that the fractions of melanoma cells survival were much lower under treatment with complex 2 compared to complex 1, both with or without previous irradiation of the cells. The process also involves generation of reactive oxygen species (ROS), as verified by EPR spectroscopy, and by using fluorescence indicators. Autophagic assays indicated a remarkable formation of cytoplasmic vacuoles in melanomas treated with complex 2, while this effect was not observed in similar treatment with complex 1. Monitoring of specific protein LC3 corroborated the simultaneous occurrence of autophagy. A balance interplay between different modes of cell death, apoptosis and autophagy, occurs when melanomas were treated with the dinuclear complex 2, in contrast to the mononuclear complex 1. These results pointed out to different mechanisms of action of such complexes, depending on its nuclearity.

Assuntos

Complexos de Coordenação/química , Cobre/química , Iminas/química , Monofenol Mono-Oxigenase/metabolismo , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos da radiação , Humanos , Melaninas/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tubulina (Proteína)/metabolismo , Raios Ultravioleta

RESUMO

A new diMnIII complex, [Mn2L(OAc)2(H2O)](BPh4)·3H2O (1), obtained with the unsymmetrical N3O3-ligand H3L = 1-[N-(2-pyridylmethyl),N-(2-hydroxybenzyl)amino]-3-[N'-(2-hydroxybenzyl),N'-(benzyl)amino]propan-2-ol, has been prepared and characterized. The unsymmetrical hexadentate ligand L3- leads to coordination dissymmetry (dissimilar donor atoms) around each Mn ion (N2O4 and NO4(solvent), respectively) leaving one labile site on one of the two Mn ions that facilitates interaction of the metal center with H2O2, as in Mn catalase. 1 is able to catalyze H2O2 disproportionation in acetonitrile, with second-order rate constant kcat = 23.9(2) M-1 s-1. The accessibility of the MnII2 state and the closeness of the two one-electron reduction processes suggest 1 employs MnIII2/MnII2 oxidation states for catalysis.

Assuntos

Catalase/química , Peróxido de Hidrogênio/química , Manganês/química , Modelos Químicos , Catálise , Domínio Catalítico , Oxirredução

RESUMO

Aroylhydrazones of ortho-hydroxy aldehydes are Schiff base ligands that typically coordinate as a chelate in an O,N,O'-manner. Dinuclear complexes are normally observed, with the phenolate O atom acting as the bridging atom. The switchable protonation state of the tridentate N'-(2-hydroxybenzylidene)benzohydrazide (H2sabhz) ligand can lead to variations in the resulting supramolecular structure. The title compound, [Pb2(C14H10N2O2)2], was prepared by the reaction of [Pb(OAc)2]·3H2O (OAc is acetate) with the benzoylhydrazone derivative of salicylaldehyde, i.e. H2sabhz, in the presence of triethylamine in methanol. In the crystal structure, each Pb(II) atom of the dimer has an NO3 coordination environment, with one sabhz ligand coordinating in an O,N,O'-manner and with the second sabhz ligand coordinating via the bridging phenolate O atom, since the dimers are located on a centre of inversion. It has been found that the dimers are connected by Pb...N interactions, resulting in a two-dimensional supramolecular network which shows the [3(2).5(2),3.5(3)] net topology. The s(2) electron pair of the Pb(II) ion clearly influences the observed intermolecular interactions.

RESUMO

The centrosymmetric dinuclear complex bis-(µ-3-carb-oxy-6-methyl-pyridine-2-carboxyl-ato)-κ(3) N,O (2):O (2);κ(3) O (2):N,O (2)-bis-[(2,2'-bi-pyridine-κ(2) N,N')(nitrato-κO)cadmium] methanol monosolvate, [Cd2(C8H6NO4)2(NO3)2(C10H8N2)2]·CH3OH, was isolated as colourless crystals from the reaction of Cd(NO3)2·4H2O, 6-methyl-pyridine-2,3-di-carb-oxy-lic acid (mepydcH2) and 2,2'-bi-pyridine in methanol. The asymmetric unit consists of a Cd(II) cation bound to a µ-κ(3) N,O (2):O (2)-mepydcH(-) anion, an N,N'-bidentate 2,2'-bi-pyridine group and an O-mono-dentate nitrate anion, and is completed with a methanol solvent mol-ecule at half-occupancy. The Cd complex unit is linked to its centrosymmetric image through a bridging mepydcH(-) carboxyl-ate O atom to complete the dinuclear complex mol-ecule. Despite a significant variation in the coordination angles, indicating a considerable departure from octa-hedral coordination geometry about the Cd(II) atom, the Cd-O and Cd-N distances in this complex are surprisingly similar. The crystal structure consists of O-H⋯O hydrogen-bonded chains parallel to a, further bound by C-H⋯O contacts along b to form planar two-dimensional arrays parallel to (001). The juxtaposed planes form inter-stitial columnar voids that are filled by the methanol solvent mol-ecules. These in turn inter-act with the complex mol-ecules to further stabilize the structure. A search in the literature showed that complexes with the mepydcH(-) ligand are rare and complexes reported previously with this ligand do not adopt the µ-κ(3) coordination mode found in the title compound.

RESUMO

In this work, the influence of two new dinuclear copper(II) complexes in the viability of melanoma cells (B16F10 and TM1MNG3) was investigated, with the aim of verifying possible correlations between their cytotoxicity and their structure. One of the complexes had a polydentate dinucleating amine-imine ligand (complex 2), and the other a tridentate imine and a diamine-bridging ligand (complex 4). The analogous mononuclear copper(II) species (complexes 1 and 3, respectively) were also prepared for comparative studies. Crystal structure determination of complex 2 indicated a square-based pyramidal geometry around each copper, coordinated to three N atoms from the ligand and the remaining sites being occupied by either solvent molecules or counter-ions. Complex 4 has a tetragonal geometry. Interactions of these complexes with human albumin protein (HSA) allowed an estimation of their relative stabilities. Complementary studies of their reactivity towards DNA indicated that all of them are able of causing significant oxidative damage, with single and double strand cleavages, in the presence of hydrogen peroxide. However, nuclease activity of the dinuclear species was very similar and much higher than that of the corresponding mononuclear compounds. Although complex 2, with a more flexible structure, exhibits a much higher tyrosinase activity than complex 4, having a more rigid environment around the metal ion, both complexes showed comparable cytotoxicity towards melanoma cells. Corresponding mononuclear complexes showed to be remarkably less reactive as tyrosinase mimics as well as cytotoxic agents. Moreover, the dinuclear complexes showed higher cytotoxicity towards more melanogenic cells. The obtained results indicated that the structure of these species is decisive for its activity towards the malignant tumor cells tested.

Assuntos

Antineoplásicos/química , Complexos de Coordenação/química , Cobre/química , Desoxirribonucleases/química , Monofenol Mono-Oxigenase/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Dano ao DNA , Desoxirribonucleases/metabolismo , Humanos , Melanoma/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Estresse Oxidativo

RESUMO

Herein, we report the synthesis and characterization of the new di-iron(III) complex [(bbpmp)(H2O)(Cl)Fe(III)(µ-Ophenoxo)Fe(III)(H2O)Cl)]Cl (1), with the symmetrical ligand 2,6-bis{[(2-hydroxybenzyl)(pyridin-2-yl)methylamino]methyl}-4-methylphenol (H3bbpmp). Complexes 2 with the unsymmetrical ligand H2bpbpmp - {2-[[(2-hydroxybenzyl)(2-pyridylmethyl)]aminomethyl]-6-bis(pyridylmethyl) aminomethyl}-4-methylphenol and 3 with the ligand L(1)=4,11-dimethyl-1,8-bis{2-[N-(di-2-pyridylmethyl)amino]ethyl}cyclam were included for comparison purposes. Complex 1 was characterized through elemental analysis, X-ray crystallography, magnetochemistry, electronic spectroscopy, electrochemistry, mass spectrometry and potentiometric titration. The magnetic data show a very weak antiferromagnetic coupling between the two iron centers of the dinuclear complex 1 (J=-0.29cm(-1)). Due to the presence of labile coordination sites in both iron centers the hydrolysis of both the diester model substrate 2,4-BDNPP and DNA was studied in detail. Complex 1 was also able to catalyze the oxidation of the substrate 3,5-di-tert-butylcatechol (3,5-DTBC) to give the corresponding quinone, and thus it can be considered as a catalytically promiscuous system.

Assuntos

Catecol Oxidase/química , Compostos Férricos/síntese química , Hidrolases/química , Compostos de Ferro/síntese química , Catálise , DNA/química , Compostos Férricos/química , Compostos de Ferro/química , Oxirredução , Especificidade por Substrato

RESUMO

The neutral binuclear mol-ecule of the title complex, [V2(C15H12N2O2S)2(CH3O)2O2], exhibits inversion symmetry and consists of two oxidovanadium(V) (VO)(3+) fragments, each coordinated by a dianionic and O,N',O'-chelating N'-(1-benzoyl-prop-1-en-2-yl)thio-phene-2-carbohydrazidate ligand. The V(5+) cations are bridged by two asymmetrically bonding methano-late ligands [V-O = 1.8155 (12) and 2.3950 (13) Å] originating from the deprotonation of the methanol solvent. The coordination sphere of the V(V) atom is distorted octa-hedral, with the equatorial plane defined by the three donor atoms of the thio-phene-2-carbohydrazidate ligand and the O atom of a methano-late unit. The axial positions are occupied by the oxide group and the remaining methano-late ligand. The axially bound methano-late ligand shows a longer V-O bond length due to the trans influence caused by the tightly bonded oxide group. The packing of the complex mol-ecules is dominated by dispersion forces.

RESUMO

Two new Ni(II) complexes involving the ancillary ligand bis[(pyridin-2-yl)methyl]amine (bpma) and two different carboxylate ligands, i.e. homophthalate [hph; systematic name: 2-(2-carboxylatophenyl)acetate] and benzene-1,2,4,5-tetracarboxylate (btc), namely catena-poly[[aqua{bis[(pyridin-2-yl)methyl]amine-κ(3)N,N',N''}nickel(II)]-µ-2-(2-carboxylatophenyl)aceteto-κ(2)O:O'], [Ni(C9H6O4)(C12H13N3)(H2O)]n, and (µ-benzene-1,2,4,5-tetracarboxylato-κ(4)O(1),O(2):O(4),O(5))bis(aqua{bis[(pyridin-2-yl)methyl]amine-κ(3)N,N',N''}nickel(II)) bis(triaqua{bis[(pyridin-2-yl)methyl]amine-κ(3)N,N',N''}nickel(II)) benzene-1,2,4,5-tetracarboxylate hexahydrate, [Ni2(C10H2O8)(C12H13N3)2(H2O)2]·[Ni(C12H13N3)(H2O)3]2(C10H2O8)·6H2O, (II), are presented. Compound (I) is a one-dimensional polymer with hph acting as a bridging ligand and with the chains linked by weak C-H···O interactions. The structure of compound (II) is much more complex, with two independent Ni(II) centres having different environments, one of them as part of centrosymmetric [Ni(bpma)(H2O)]2(btc) dinuclear complexes and the other in mononuclear [Ni(bpma)(H2O)3](2+) cations which (in a 2:1 ratio) provide charge balance for btc(4-) anions. A profuse hydrogen-bonding scheme, where both coordinated and crystal water molecules play a crucial role, provides the supramolecular linkage of the different groups.