Comparative study of the antitumoral activity of phosphine-thiosemicarbazone gold(I) complexes obtained by different methodologies.

A series of phosphino-thiosemicarbazone gold(I) dinuclear complexes obtained by two different synthetic procedures have been prepared. All the compounds have been spectroscopically characterized including single crystal X ray diffraction analysis in some of cases. [Au2(HL1)Cl2] (1), [Au2(HL2)2]Cl2 (2) and [Au2(HL3)2]Cl2 (3) have been prepared by chemical synthesis using a gold(III) salt as precursor; while [Au2(L1)2] (4), [Au2(L2)2]∙2CH3CN (5) and [Au2(L3)2] (6) have been isolated from an electrochemical synthesis (HLn = 2-[2-(diphenylphosphanyl)-benzylidene]-N-R-thiosemicarbazone; HL1: R = methyl, HL2: R = methoxyphenyl, HL3: R = nitrophenyl). The in vitro cytotoxic activity of these gold(I) complexes was tested against some human tumor cell lines: HeLa 229 (cervical epithelial carcinoma), MCF-7 (ovarian adenocarcinoma), NCI-H460 (non-small-cell lung cancer) and MRC5 (normal human lung fibroblast), and the IC50 values compared with those of cisplatin. The neutral methyl-substituted complexes 1 and 4 and methoxyphenyl 5 displayed significant cytotoxic activities in all investigated cancer cell lines, being 1 and 4 the most effective. The ability of complexes 1 and 4 to induce cell death by apoptosis in Hela 229 was also investigated by fluorescence microscopy using the apoptotic DNA fragmentation as marker. These results indicated that the inhibition of cell proliferation is mainly due to an apoptotic process. In order to obtain more information about the mechanism of action of these metallocompounds, the interactions of complexes 1 and 4 with the thioredoxin reductase (TrxR) enzyme were analyzed. Both complexes exhibited a strong inhibition of the thioredoxin reductase activity.

"The Golden Method": Electrochemical Synthesis Is an Efficient Route to Gold Complexes.

Gold compounds to be obtained by the direct electrochemical oxidation of a noble metal are reported. This achievement provides an alternative procedure to obtaining neutral gold compounds with potential medical or catalytic applications.

Alkali-metal-ion-directed self-assembly of redox-active manganese(III) supramolecular boxes.

The ability to organize functional molecules into higher dimensional arrays with well-defined spatial relationships between the components is one of the major goals in supramolecular chemistry. We report here a new route for the preparation of supramolecular boxes, incorporating two types of metal ions: (i) alkali-metal ions, which induce the supramolecular architecture and essentially play a structural role in the final compounds; (ii) manganese(III) ions, which are redox-active systems and give functionality to the new cages. Our results evidence that the size of the cavity inside the box can be tuned depending on the alkali metal used, a characteristic that gives this new family of compounds the potential to act selectively against different substrates. These compounds behave as active catalysts for disproportionation of H2O2 or for water photolysis, but they catalyze neither catecholase reaction nor peroxidase action upon using bulky organic substrates.

Metal self-recognition: a pathway to control the formation of dihelicates and mesocates.

We have studied the factors that affect the formation of different metallosupramolecular architectures by metal direct self-assembly. A synthetic route has been developed to obtain mesocates or dihelicates selectively. For this purpose a series of five bisthiosemicarbazone ligands derived from 1,3-diacetylbenzene were designed and synthesised. Namely H(2)L(Me), H(2)L(Et), H(2)L(Ph), H(2)L(PhN) and H(2)L(PhOMe) with different substituents on the 4-N terminal position of the thiosemicarbazone strands. The Co(II), Zn(II) and Cd(II) complexes of these ligands were prepared by an electrochemical procedure. Crystallographic studies revealed the formation of mesocates for Co(II) and Zn(II) metal ions whereas the Cd(II) complexes gave a bishelical supramolecular structure. Therefore these bisthiosemicarbazone ligands enable the selective isolation of mesocate or dihelicate complexes by using a specific metal ion.

Versatile coordination behaviour of an asymmetric half-salen ligand bearing a dansyl fluorophore.

The coordinative chemistry of the tridentate half-salen ligand 5-(dimethylamino)-N-(2-((2-hydroxybenzylidene)amino)phenyl)naphthalene-1-sulfonamide (H(2)L, 1) has been studied by means of an electrochemical method. All of the complexes have been characterised using analytical and spectroscopic techniques. Ligand 1 and two nickel (6 and 7), copper (9), zinc (12) and cadmium (14) metal complexes have been studied by crystallography. Complexes 6 and 7 are octahedral and tetrahedral nickel(II) complexes, respectively, and both contain an [L](2-) molecule that behaves in an [N(2)O] tridentate manner. Nickel(II) completes its coordination kernel with three water molecules in complex 6, whereas in complex 7 the nickel ion is further bound to a molecule of dansylamine arising from a hydrolysis process. The copper(II) complex 9 is a monomeric compound that contains a bideprotonated ligand thread and a dimethylsulfoxide molecule coordinated through the sulfur atom. The zinc complex 12 is an unusual pentanuclear cluster compound whose structure consists of four anionic ligand units and two hydroxo anions bound to five zinc(II) centres. The appearance of the hydroxo anions in this complex provides new evidence for water reduction electrochemically promoted by zinc metal under mild conditions. The cadmium complex 14 is a dimeric compound that comprises two molecules of the anionic ligand and two dimethylsulfoxide molecules. The great structural variety exhibited by all these complexes demonstrates that the introduction of asymmetry in a salen skeleton by incorporating a dansyl pendant increases the versatility of the resulting ligand on coordination. All complexes are luminescent in solution at room temperature in acetonitrile solutions.

Influence of the geometry around the manganese ion on the peroxidase and catalase activities of Mn(III)-Schiff base complexes.

The peroxidase and catalase activities of eighteen manganese-Schiff base complexes have been studied. A correlation between the structure of the complexes and their catalytic activity is discussed on the basis of the variety of systems studied. Complexes 1-18 have the general formulae [MnL(n)(D)(2)](X)(H(2)O/CH(3)OH)(m), where L(n)=L(1)-L(13); D=H(2)O, CH(3)OH or Cl; m=0-2.5 and X=NO(3)(-), Cl(-), ClO(4)(-), CH(3)COO(-), C(2)H(5)COO(-) or C(5)H(11)COO(-). The dianionic tetradentate Schiff base ligands H(2)L(n) are the result of the condensation of different substituted (OMe-, OEt-, Br-, Cl-) hydroxybenzaldehyde with diverse diamines (1,2-diaminoethane for H(2)L(1)-H(2)L(2); 1,2-diamino-2-methylethane for H(2)L(3)-H(2)L(4); 1,2-diamino-2,2-dimethylethane for H(2)L(5); 1,2-diphenylenediamine for H(2)L(6)-H(2)L(7); 1,3-diaminopropane for H(2)L(8)-H(2)L(11); 1,3-diamino-2,2-dimethylpropane for H(2)L(12)-H(2)L(13)). The new Mn(III) complexes [MnL(1)(H(2)O)Cl](H(2)O)(2.5) (2), [MnL(2)(H(2)O)(2)](NO(3))(H(2)O) (4), [MnL(6)(H(2)O)(2)][MnL(6)(CH(3)OH)(H(2)O)](NO(3))(2)(CH(3)OH) (8), [MnL(6)(H(2)O)(OAc)](H(2)O) (9) and [MnL(7)(H(2)O)(2)](NO(3))(CH(3)OH)(2) (12) were isolated and characterised by elemental analysis, magnetic susceptibility and conductivity measurements, redox studies, ESI spectrometry and UV, IR, paramagnetic (1)H NMR, and EPR spectroscopies. X-ray crystallographic studies of these complexes and of the ligand H(2)L(6) are also reported. The crystal structures of the rest of the complexes have been previously published and herein we have only revised their study by those techniques still not reported (EPR and (1)H NMR for some of these compounds) and which help to establish their structures in solution. Complexes 1-12 behave as more efficient mimics of peroxidase or catalase in contrast with 13-18. The analysis between the catalytic activity and the structure of the compounds emphasises the significance of the existence of a vacant or a labile position in the coordination sphere of the catalyst.

Manganese-Schiff base complexes as catalysts for water photolysis.

Four manganese(III)-Schiff base complexes (1-4) of formula [MnL(n)(H(2)O)(2)](2)(ClO(4))(2)·mH(2)O (n = 1-4; m = 0, 1) have been prepared. The multidentate H(2)L(n) Schiff base ligands consist of 3R,5R-substituted N,N'-bis(salicylidene)-1,2-diimino-2,2-dimethylethane, where R = OEt, OMe, Br or Cl. The complexes have been thoroughly characterized by elemental analysis, mass spectrometry, magnetic susceptibility measurements, IR, UV, paramagnetic (1)H NMR and EPR spectroscopies. Other properties, including redox studies and molar conductivity measurements, have also been assessed. The crystal structure of 1 was solved by X-ray diffraction, which revealed the dimeric nature of the compound through µ-aqua bridges. The ability of these complexes to split water has been studied by water photolysis experiments, with the oxygen evolution measured in aqueous media in the presence of a hydrogen acceptor (p-benzoquinone), the reduction of which was followed by UV-spectroscopy. The discussion of the photolytic behaviour includes advances in the knowledge of the structural motifs and the chemical activity of this type of complex, as revealed by the development of several characterization techniques in the last decade. Parallel-mode Mn(III) EPR shows that complexes 1-4 not only mimic reactivity but also share some structural characteristics from partially assembled natural OEC clusters.

A sequentially assembled grid composed of supramolecular meso-helical nodes.

A unique case of a grid-of-mesocates sequentially assembled by supramolecular cobalt(II) meso-helical units connected through hydrogen bonding is reported.

Endogenous arene hydroxylation promoted by copper(I) cluster helicates.

A novel neutral triple-stranded hexanuclear copper(I) cluster helicate [Cu(I)(6)L(3)]·2CH(3)CN derived from a thiosemicarbazone ligand could be synthesized and crystallographically characterized. The MALDI mass spectrum of this complex suggests that the tetranuclear copper(I) cluster helicate [Cu(I)(4)L(2)] is also present in solution. These copper(I) cluster helicates are capable, in the presence of O(2), of hydroxylating the arene linker of their supporting ligand strands. The resulting dinuclear complex [Cu(II)(2)L'(OH)] is formed by two copper(II) centers, a new ligand arising from the hydroxylation reaction, and one hydroxide group. The magnetic investigation of this compound shows a strong antiferromagnetic coupling between the two Cu(II) centers. The kinetic studies for the hydroxylation process show values of ΔH(≠)=-70 kJ mol(-1), similar to those mediated by the tyrosinase enzymes.

A water reduction process performed by zinc metal under very mild conditions.

Water reduction can be electrochemically promoted by zinc under very mild conditions, as demonstrated by the formation of the complex [Zn(H(2)O)(6)][Zn(3)(L)(3)(mu(3)-O)], whose anion consists of a Zn(3)O(4) cluster incorporating a mu(3)-oxo anion.

The coordination preferences of metal centres modulate superexchange coupling interactions in a metallo-supramolecular helical assembly.

A method to modulate the strength of the superexchange coupling interaction in dinuclear helical assemblies based on the coordination preferences of the metal centres is described.

Sulfonamide-imines as selective fluorescent chemosensors for the fluoride anion.

Two new sulfonamide-type fluorescent chemosensors in organic media are reported. The two receptors, [N,N'-bis(2-tosylaminobenzylidene)-1,2-diaminoethane and N,N'-bis(2-tosylaminobenzylidene)-1,3-diamino-2-propanol], display marked changes in the fluorescence emission intensities as a result of deprotonation by basic anions, and show high selectivity for fluoride over other inorganic anions, such as acetate or dihydrogenphosphate. These results suggest that the presence of the imine group as an intramolecular H-bond acceptor enhances the selectivity of these sensors compared to previous examples in the literature. The deprotonation mechanism has been demonstrated by spectrophotometric and spectrofluorimetric titrations as well as by NMR spectroscopy. The X-ray structures of both receptors are also discussed.

A double-stranded dinuclear cadmium(II) helicate that assembles into chains in the solid state.

A [4+4] double-stranded cadmium dihelicate was afforded from an easily accessible thiosemicarbazone ligand; its crystal structure reveals the assembly of two enantiomers into dihelicate pairs, these pairs being further connected into infinite linear chains.

Coordinative trends of a tridentate thiosemicarbazone ligand: synthesis, characterization, luminescence studies and desulfurization processes.

The coordinative chemistry of the tridentate thiosemicarbazone ligand 2-pyridinecarboxaldehyde 4-N-ethylthiosemicarbazone (HL(Et)) has been explored by using an electrochemical methodology. All the complexes have been characterized using analytical and spectroscopic techniques. In the case of copper we have isolated two different complexes, with Cu(L(Et))(2).4H(2)O (6) and [Cu(2)(L(Et))(2)(SO(4))] (7) formulae. The sulfate group coordinated to the copper atoms in was probably released to the media as a consequence of a desulfurization process. Single X-ray crystallography has been carried out for the ligand HL(Et) and the complexes , [Ag(6)(L(Et))(6)].CH(3)CN (9) and [Pb(L(Et))(2)] (2). The copper(ii) complex is a dimer compound in which two antiparallel monodeprotonated ligands are coordinated to two copper centres by establishment of mu(2)-thiolate bridges and the additional coordination of a sulfate group bridging the two metal atoms. The silver complex is an unusual hexanuclear cluster compound with a wheel-type conformation, while the lead complex is a monomer which exhibits the lone pair effect. A structural comparative study of the electrochemically obtained complexes derived from HL(X) ligands (X= Me, Et and Ph) have been performed. Finally, the solution behaviour of the complexes was checked by NMR, UV and fluorescence studies.

Unprecedent isolation of a mixture of conformational and linkage isomers in a thiosemicarbazone cobalt mesocate.

A cobalt(II) thiosemicarbazonate mesocate has been structurally characterized as an unexpected mixture of conformational and linkage isomers. Moreover, we have shown that the absence of a nitrogen atom in the spacer of the helicand ligand H(2)L(a), enables the assembly of an achiral mesohelical complex in the case of Co(II) ions.

Metal-catalysed oxidation processes in thiosemicarbazones: new complexes with the ligand N-{2-([4-N-ethylthiosemicarbazone]methyl)phenyl}-p-toluenesulfonamide.

The coordination behaviour of a new thiosemicarbazone Schiff-base building block, N-{2-([4-N-ethylthiosemicarbazone]methyl)phenyl}-p-toluenesulfonamide, H2L1 (1), incorporating a bulky tosyl group, towards Mn II, Fe II, Co II, Ni II, Cu II, Zn II, Cd II, Ag I, Sn II, and Pb II has been investigated by means of an electrochemical preparative procedure. Most metal complexes of L1 have the general formula [M(L1)]2.nX (M=Mn, Fe, Co, Ni, Cu, Cd, Pb; n=0-4, X=H2O or CH3CN), as confirmed by the structure of [Pb(L1)]2 (15), in which the lone pair on lead is stereochemically active. This lead(II) complex shows an intense fluorescence emission with a quantum yield of 0.13. In the case of silver, the complex formed was found to possess a stoichiometry of [Ag2(L1)]2.3H2O. During reactions with manganese and copper metals, interesting catalysed processes have been found to take place, with remarkable consequences regarding the ligand skeleton structure. In synthesising the manganese complex, we obtained an unexpected dithiolate thiosemicarbazone tosyl ligand, H2L2, as a side-product, which has been fully characterised, including by X-ray diffraction analysis. In the case of copper, the solid complex has the formula [CuL1]2, but the crystallised product shows the copper atoms coordinated to a new cyclised thiosemicarbazone ligand, H2L3, as in the structures of the complexes [Cu(L3)]2.CH3CN (8) and [Cu(L3)(H2O)]2.CH3CN.H2O (9). The zinc complex [Zn(L1)]4 (12) displays a particular tetranuclear zeolite-type structure capable of hosting small molecules or ions, presumably through hydrogen bonding.

Pentadentate thiosemicarbazones as versatile chelating systems. A comparative structural study of their metallic complexes.

We have prepared some transition and post-transition metal complexes derived from the pentadentate thiosemicarbazone ligand bis(4-N-ethylthiosemicarbazone)-2,6-diacetylpyridine H(2)L(Et), by both chemical and electrochemical procedures. The complexes have been synthesised and fully characterised, including the crystal structures for the ligand H(2)L(Et) and its manganese, cadmium and lead complexes. We have also performed multinuclear (109)Ag, (113)Cd, (119)Sn and (207)Pb studies for silver, cadmium, tin and lead compounds, respectively. Moreover we present here a comparative study on the different structures found for pentadentate thiosemicarbazonate complexes, trying to check the influence of different factors, such as experimental procedure, size of metal, structure of the ligand, and metal oxidation state, on the final structure of the complex formed. Our aim is gaining a better insight into the coordination trends of pentadentate thiosemicarbazone ligands.

Asymmetric self-assembly with atmospheric CO2 fixation of a pentanuclear carbonate NiI) complex based on dissimilar building blocks.

Formation in basic solution of an asymmetric pentanuclear carbonate Ni(II) complex with a compartmental ligand involves atmospheric CO(2) uptake, either by reaction of two slightly different dinuclear precursors that yield its di- and trinuclear "building blocks", or directly, by spontaneous self-organization of metal and ligand starting reactants.

Influence of the metal size in the structure of the complexes derived from a pentadentate [N(3)O(2)] hydrazone.

The influence of the metal size in the nuclearity of the complexes derived from the hydrazone ligand 2,6-bis(1-salicyloylhydrazonoethyl)pyridine [H(4)daps] has been investigated. We have synthesised a series of new complexes [M(H(x)daps)] x yH(2)O, (x = 2,3; y = 0-3) with M = Ag (1), Cd (2), Al (3), Sn (4) and Pb (6), using an electrochemical procedure. The crystal and molecular structures have been determined for the mononuclear complexes [Sn(H(2)daps)(H(2)O)(2)] x 4H(2)O (5) and [Pb(H(2)daps)(CN)][Et(4)N] (7). Complex is the first neutral Sn(II) complex derived from a pentadentate hydrazone Schiff base ligand. Complex shows the lead coordinated to the hydrazone donor set and a cyanide ligand, being the first reported complex with the lead atom coordinated to a monodentate cyanide group. Additionally, we have synthesised the lead complex using chemical conditions, in the presence of sodium cyanide which allowed us to isolate the neutral complex [Pb(H(2)daps)] (8). Evaporation of these mother liquors led the novel compound [Pb(Hdaphs)(CH(3)COO)] (9). Complex 9 shows the initial ligand hydrolysed in one of the imine bonds giving rise to a new tetradentate ligand [H(2)daphs] coordinated to the lead atom and a bidentate acetate group. Moreover, the solution behaviour of the complexes has been investigated by (1)H, (113)Cd, (117)Sn and (207)Pb NMR techniques. In particular multinuclear NMR has provided new useful data to correlate factors such as oxidation state, coordination number and nature of the kernel donor atoms due to the new coordination found in complexes 5 and 7. The comparative study of the structures of the complexes derived from this pentadentate [N(3)O(2)] hydrazone ligand let us to conclude that the metal size is a key factor to control the nuclearity of the complexes derived from the ligand [H(4)daps].

Dinuclear Co(III)/Co(III) and Co(II)/Co(III) mixed-valent complexes: synthetic control of the cobalt oxidation level.

The reactivity of cobalt(II) salts towards H(3)L (2-(2-hydroxyphenyl)-1,3-bis[4-(2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine) was studied in different reaction conditions. Accordingly, the interaction of cobalt(II) acetate with H(3)L in methanol gives rise to the discrete complex [Co(III)(2)L(OAc)(2)(OMe)]*1.5H(2)O.MeOH, 1. Reaction of cobalt(II) acetylacetonate with H(3)L in the presence of dicarboxylic acids was also investigated. Thus, when cobalt(II) acetylacetonate and H(3)L are mixed with terephthalic or malonic acid in 4 : 2 : 1 molar ratios, the mixed valent [Co(II/III)(2)L(acac)(p-O(2)CC(6)H(4)CO(2)H)][Co(II/III)(2)L(acac)(OH)]*2H(2)O*2MeOH, 2 and [Co(II/III)(2)L(acac)(O(2)CCH(2)CO(2)H)][Co(II/III)(2)L(acac)(OH)]*7H(2)O, complexes are isolated. Decreasing the pH of the medium, by addition of a second mol of dicarboxylic acid, leads to [Co(II/III)(2)L(O(2)CCH(2)CO(2))(MeOH)]*2MeOH, 4, while the reaction with terephthalic acid does not proceed. 1, 2 and 4 were crystallographically characterised and all the complexes are dinuclear, with hydrogen bonds that expand the initial nodes. The magnetic characterisation, as well as the NMR spectroscopy, indicates a diamagnetic nature for 1, in agreement with the presence of Co(III), showing the aerial oxidation suffered by the cobalt(II) ions. Nevertheless, are paramagnetic. Temperature variable magnetic measurements were recorded for the crystallographically characterised complexes 2 and 4 and these studies confirm the mixed valence Co(II)/Co(III) nature of the compounds. The best fits of the magnetic data give an axial distortion parameter Delta = 628.7 cm(-1) for 2 and 698.8 cm(-1) for 4, and spin-orbit coupling constant lambda = -117.8 cm(-1) for 2 and -107.0 cm(-1) for 4. Therefore, this study shows that the oxidation degree of the initial cobalt(ii) salt by atmospheric oxygen can be controlled according to the pH of the medium.