Elena López-Torres

Synthesis, spectroscopic and cyclic voltammetry studies of copper(II) complexes with open chain, cyclic and a new macrocyclic thiosemicarbazones

Abstract New copper complexes have been prepared from benzilbisthiosemicarbazone (L1H6) and from the cyclic 6-methoxi-1,6-diphenyl-4-thio-3,4,5,6-tetrahydro-2,3,5-triazine (L2H2). The complexes were characterized by mass spectrometry, IR, electronic and electron paramagnetic resonance spectra. Complexes from L1H6 (1–5) present 1:1 stoichiometry and show different characteristics with a variable grade of deprotonation in the ligand, depending on the salt used (chloride, nitrate or sulfate) and the presence of acid in the medium. A macrocyclic Schiff base, 3,4,9,10-tetraphenyl-1,2,5,6,8,11-hexaazacyclododeca-7,12-dithione-3,4,9,10-tetraene (L3H2), containing thiosemicarbazone moieties is readily prepared and characterized for the first time, with fairly good yield, from the mesocycle (L2H2) in methanol with copper chloride as template. Near quantitative synthesis of the precursor, L2H2, which is a potential chemotherapeutic agent against cancer, has been achieved by reacting benzil and thiosemicarbazide in the absence of metal salt and using a high dilution technique. Macrocyclic complexes 6 and 7 containing thiosemicarbazone moieties were obtained from L2H2 and copper nitrate and sulfate. Direct reaction between the copper salt and the macrocyclic thiosemicarbazone (L3H2) gave similar complexes but with a lower grade of purity. Macrocyclic complexes 6 and 7 present metal–ligand ratios of 1:2 and 1:1 and the ligand is in a deprotonated form. The redox behaviour was explored by cyclic voltammetry. L1H6 complexes show Cu(II)/Cu(I) couples and quasireversible waves associated with the Cu(III)/Cu(II) process. The reduction/oxidation potential depends on the structure and conformation of the central atom in the coordination compounds.

Spectroscopic and electrochemical properties of nickel(II), iron(III) and cobalt(II) complexes with benzilbisthiosemicarbazone — importance of working conditions and the metal salt used in the final complex

Abstract Reactions of benzilbisthiosemicarbazone (LH6) with nickel, cobalt and iron chloride and nitrate give different complexes depending on the salts used and the working conditions. Reactions from nickel chloride give three complexes, 1, 2 and 3 when the solvent or the pH is modified. Complex 1 is obtained in ethanol under reflux, and in methanol, independently of temperature and also with basic medium. Complex 2 is formed by working in ethanol at room temperature. The ligand acts as a dianion in both complexes. In the presence of hydrochloric acid, the new isolated complex 3 presents the neutral form of the ligand. Reaction from nitrate yields only complex 1. Reactions with iron chloride give two new complexes with different formulae and grade of deprotonation in the ligand. For complex 4, obtained at room temperature, LH6 acts as an anion with a ligand–iron ratio of 2:1 and in its neutral form with a 1:1 ratio in complex 5, working under reflux. Reactions with iron nitrate yield complex 6, with the ligand in an intermediate situation, as anion but a nitrate remains. Complexes 7 and 8, with a 1:1 cobalt–ligand molar ratio are isolated from reactions with cobalt nitrate; both contain nitrate and ethanol or water to complete the co-ordination sphere. Attempts to get a macrocyclic thiosemicarbazone from reaction of benzil and LH6 in the presence of nickel or iron salt gave the complexes obtained, in absence of the dicarbonyl molecule. Electrochemical behaviour of complexes studied by cyclic voltammetry show metal-centred reduction processes for all of them. The reduction/oxidation potential values depend on the structures of complexes. Nickel complexes exhibit waves corresponding to Ni(III)–Ni(II) process. Electrochemical response of iron complexes depends on the presence of chloride ions.

Macrocyclization of cyclic thiosemicarbazones with mercury salts

Abstract A new cyclic Schiff base L1H3 derived from benzil and thiosemicarbazide has been prepared in the presence of NaBH4. Reactions of the new molecule and the cyclic 5-methoxy-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione L2H2 with mercury chloride and nitrate are reported. Complexes of 1:2 stoichiometry are obtained from L1H3, but the reactions from L2H2 yield complexes of the macrocyclic Schiff base 5,6,11,12-tetraphenyl-1,2,4,7,8,10-hexaaza-cyclododeca-4,6,10,12-tetraene-3,9-dithione L3H2, which indicates the macrocyclization of L2H2. A mechanism for the cyclization reaction based on the rupture of the C–N single bond in L2H2 is proposed. The electrochemical results of complex L3Hg makes it and its precursors, L2H2 and L3H2, outstanding candidates for mercury determination by appropriate electrode modification.

Structural diversity of benzil bis(benzoylhydrazone): Mononuclear, binuclear and trinuclear complexes

The coordination behaviour of the Schiff-base, benzil bis(benzoylhydrazone), LH(2) towards divalent nickel, lead, cadmium, zinc and copper ions has been investigated. The complexes have been fully characterized by techniques including (113)Cd and (207)Pb NMR, as well as (13)C and (113)Cd CP/MAS NMR and by single crystal X-ray diffraction. All the complexes have the general formula [ML](n) (n = 1-3 depending on the metal ion), with the ligand doubly deprotonated. The nickel complex [NiL] is a monomeric compound, the lead complex [PbL](2) shows a binuclear structure, whereas zinc [ZnL](3) and copper [CuL](3) complexes are trinuclear helicates. The cadmium complex seems to be a dimer with a structure similar to that of . In the nickel and lead derivatives, the ligand behaves as a tetradentate N(2)O(2) chelate and in complex also as a bridge through one of the O atoms. In the crystal structures of Zn and Cu complexes [ML](3) each metal is in a pentadentate N(3)O(2) environment formed by two different ligands, one tridentate chelate and the other bidentate chelate, giving rise to trinuclear helicates. These results point out the versatility of benzil bis(benzoylhydrazone) on its coordination.

Three novel indium MOFs derived from diphenic acid: synthesis, crystal structures and supramolecular chemistry†

Three In(III) MOFs based on diphenic acid and nitrogen-donor ancillary ligands were obtained as pure phases. Two of them have 1D chain structures, and the third forms 2D zig-zag layers. The different torsion angles adopted by the diphenic ligand along with the existence of several non-covalent interactions govern the crystal packing and determine the formation of a centrosymmetric one-dimensional compound (1) or a non-centrosymmetric helical chain-based compound (3). Reaction with 2,2′-bipyridyl under certain conditions leads also to the formation of two dimeric precursors (compounds 4 and 5). The topological study of all their nets is reported.

The role of unconventional stacking interactions in the supramolecular assemblies of Hg(II) coordination compounds

In this study, nine mercury(II) complexes of the composition [Hg(Ln)(X)2] (X = Cl, Br and I, n = 1–3), (L1 = 2-pyridine piconyl hydrazone); L2 = (2-acetylpyridine piconyl hydrazone) and L3 = (2-phenylpyridine piconyl hydrazone) are synthesized and spectroscopically characterized. Single-crystal X-ray crystallography showed that the molecular complexes can aggregate into larger entities depending upon the anion coordinated to the metal centre. Moreover, Hirshfeld surface (HS) analyses were employed to gain additional insight into interactions responsible for the packing of complexes 1–9. Quantitative examination of 2D fingerprint plots revealed, among others, the dominating participation of H⋯H and H⋯X interactions in the molecular packing. Moreover, C–H⋯X hydrogen bonds, π–π, and chelate-ring–π interactions are described and analysed by means of density functional theory (DFT) calculations since they play an important role in the construction of three-dimensional supramolecular frameworks. The influence of the halide on the energetic features of the assemblies has been also studied.

The structural characterization and biological activity of sulfamethoxazolyl-azo-p-cresol, its copper(II) complex and their theoretical studies

(E)-4-((2-Hydroxy-5-methylphenyl)diazenyl)-N-(5-methylisoxazole-3-yl)benzene sulfonamide (SMX-NN-C6H3(p-Me)-OH, 1) and its Cu(II) complex, [Cu(SMX-NN-C6H3(p-Me)-O)2]n (2), have been characterized by spectroscopic data and single crystal X-ray diffraction studies. The supramolecular 1D chain of 1 is constituted by inter- and intra-molecular hydrogen bonds and also by π⋯π interactions of aromatic rings. Complex 2 has a tetragonally distorted octahedral structure in which ligand 1 serves as an N,O chelator and forms a planar Cu(N,O)2 motif; two axial positions are occupied by the oxazolyl-N of neighbouring units and a 3D structure is formed. The biological activities of these compounds have been evaluated against Gram positive (B. subtilis; IC50: 105 μg ml−1 (1) and 105 μg ml−1 (2)) and Gram negative bacteria (E. coli; IC50: 66.36 μg ml−1 (1) and 62.2 μg ml−1 (2)) and the complexes exhibit better efficiency. Interactions of DNA with 1 and 2 have been examined and the binding constants are Kb(1), 5.920 × 104 M−1 and Kb(2), 4.445 × 104 M−1. The in silico test is used to predict the most favoured binding mode of 1 and 2 with the active site residues of DHPS (dihydropteroate synthetase) of E. coli and of DNA. The Cu(II) complex (2) binds more efficiently (CDOCKER energy, 2, −61.35 a.u.) in the DHPS cavity than ligand 1 (CDOCKER energy, 1, −43.90 a.u.). The electronic structures and spectral properties of 1 and 2 have been investigated by DFT and TD-DFT computation of optimized geometries of the compounds.

Synthesis and antimicrobial activity of tetradentate ligands bearing hydrazone and/or thiosemicarbazone motifs and their diorganotin(IV) complexes.

Four novel ligands derived from 2,3-butanedione have been synthesized, two dissymmetric thiosemicarbazone/3-hydroxy-2-naphthohydrazone ligands, H2L1 (bearing 4-isopropyl-3-thiosemicarbazone) and H2L2 (containing 4-cyclohexyl-3-thiosemicarbazone) and the symmetric H2L3, diacetyl bis(3-hydroxy-2-naphthohydrazone), and H2L4, diacetyl bis(4-cyclohexyl-3-thiosemicarbazone). Their reactivity with SnR2Cl2 (R=methyl, n-butyl and phenyl) was explored and the resulting complexes were characterized by elemental analysis, molar conductivity, mass spectrometry, IR, 1H, 13C and 119Sn NMR and seven of them also by single crystal X-ray diffraction. The results showed that the reactivity of the dissymmetric ligands is strongly different and while the cyclohexyl derivative is very stable, with isopropyl easily undergoes a symmetrization reaction to yield the corresponding symmetric ligands. The antimicrobial activity of the ligands and the corresponding diorganotin(IV) complexes was investigated in vitro against seven species of microorganisms and minimum inhibitory concentrations (MICs) were determined. The results showed that the ligand H2L2 and several of its derivatives, together with methyl and phenyl complexes of H2L1, have the ability of inhibiting the growth of tested bacteria and fungi to different extents. Bacillus subtilis and Staphylococcus aureus Gram positive strains were the most sensitive microorganisms.

Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting

Gold(III) compounds have received increasing attention in cancer research. Three gold complexes of general formula [AuIIIL]Cl, where L is benzil bis(thiosemicarbazonate), compound 1, benzil bis(4-methyl-3-thiosemicarbazonate), compound 2, or benzil bis(4-cyclohexyl-3-thiosemicarbazonate), compound 3, have been synthesized and fully characterized, including the X-ray crystal structure of compound 3, confirming square-planar geometry around the gold(III) centre. Compound 1 showed moderate cytotoxicity and accumulation in MCF7 breast cancer cells but did not inhibit thioredoxin reductase (TrxR) activity and did not induce reactive oxygen species (ROS) production. Compound 2, the least cytotoxic, was found to be capable of modestly inhibiting TrxR activity and produced low levels of ROS in the MCF7 cell line. The most cytotoxic compound, 3, had the highest cellular accumulation and its distribution pattern showed a clear preference for the cytosol and mitochondria of MCF7 cells. It readily hampered intracellular TrxR activity leading to a dramatic alteration of the cellular redox state and to the induction of cell death.

Structural diversity and supramolecular architectures of Zn(II), Cu(II) and Ni(II) complexes by selective control of the degree of deprotonation of diacetyl bis(4-isopropyl-3-thiosemicarbazone)

The reactivity of the new potentially tetradentate ligand diacetyl bis(4-isopropyl-3-thiosemicarbazone) (H2L) with zinc(II), copper(II) and nickel(II) nitrates using different amounts of lithium hydroxide was studied. The results obtained show that with zinc(II), selective ligand deprotonation was completely achieved and complexes [Zn(H2L)(OH2)](NO3)2 (1), [Zn(HL)(EtOH)]NO3 (2) and [ZnL]2 (3) were synthesized, where the ligand acts as a neutral, singly or doubly deprotonated donor, respectively. In contrast, in the case of copper(II), only complexes [Cu(HL)]NO3 (4) and [CuL] (5) were isolated, whereas with nickel(II) the double deprotonation of the ligand took place even in the absence of a base, to yield complex [NiL] (6). The structural preferences of the metals also influence the structure of the complexes; whereas copper(II) and nickel(II) are in a square-planar arrangement, zinc(II) prefers a square-base pyramid geometry. In all the complexes containing a NO3− ion, the ion is not coordinated to the metal and acts as a counter-ion. The different degrees of deprotonation of the ligand, together with the presence or the absence of nitrate and solvent molecules bonded to the metal, make the existence of different supramolecular architectures based on different hydrogen bond arrays possible. The topological analysis shows the formation of 2D (1) and 1D (3 and 5) networks, tetranuclear aggregates (2 and 5·DMF) and dimers (6·DMF), which are linked by other weak interactions to give 2D or 3D nets.