Synthesis, mesomorphism and luminescence properties of palladium(II) and platinum(II) complexes with dimeric Schiff base liquid crystals

A series of ortho-metallated Pd and Pt complexes containing dimeric liquid crystals Schiff base as cyclometallated ligands and N-benzoyl thiourea derivatives as co-ligands were prepared and investigated for their liquid crystalline properties. Their structures were assigned based on elemental analysis, IR and ¹H NMR spectroscopy while the mesogenic properties were investigated by DSC and polarising optical microscopy. The complexes show either monotropic or enantiotropic transitions with nematic and smectic A phases being displayed, with the mesomorphic behaviour strongly related to the type of N-benzoyl thiourea as well as the metal center used. The structure of a palladium(II) complex has been solved by X-ray diffraction.The platinum(II) complexes show photoluminescence properties both in solution and in solid state at room temperature, with the emission band centered around 600 nm. These are the first examples of metallomesogens based on Schiff base cyclometallated ligands that display luminescence properties.     

Novel palladium(II) and Zinc(II) Schiff base complexes: Synthesis,biophysical studies,and anticancer activity investigation

BackgroundSchiff base metal complexes are considered promising chemotherapeutic agents due to their potential application in cancer therapy.MethodsThe current work sought to synthesize a brand-new Schiff base ligand obtained from 2-hydroxybenzohydrazide and (E)− 1-(2-(p-tolyl)hydrazono)propan-2-one with metal ions which included Pd(II) and Zn(II) ions. Elemental analyses, FT-IR, mass spectra, 1H NMR, UV-Vis spectrometer, and computational analysis characterized the compound's structure. In vitro, the breast cancer cell line (MCF-7) was tested for its sensitivity to Schiff base (HL) and its Pd(II) and Zn(II) complexes. The half-maximal inhibitory concentration IC₅₀ of the compounds was determined and used to perform the comet assay, which was carried out to reveal the photo-induced DNA damaging ability of the compounds of individual cells. Moreover, the compounds' effects on antioxidant defense systems of enzymes in cells: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and oxidant Malondialdehyde (MDA) were examined in MCF-7 cells.ResultsThe Pd(II) complex displayed approximately the same IC₅₀ as Cisplatin, while Zn(II) complex had better activity than Cisplatin with very low IC₅₀, 1.40 μg/ml. Significant alterations in SOD, CAT, GPx, and MDA production were discovered, inducing oxidative stress, enlarging ROS production, and reducing the antioxidant amount. This change was approximately similar in most compounds. Consequently, it promoted apoptosis, particularly the Zn(II) complex, which demonstrated an improved impact because of its ability to influence the antioxidant defense systems of enzymes, mostly SOD and GPx, besides increasing MDA levels.ConclusionIt can be concluded that Zn(II) complex is the most effective anticancer drug since it induced a very similar genotoxic effect as Cisplatin and has a very low IC₅₀ value.     

Mononuclear nickel(II) and copper(II) complexes with Schiff base ligands derived from 2,6-diformyl-4-methylphenol and S-methylisothiosemicarbazones

Four new square-planar Ni(II) and Cu(II) complexes with [N₂O₂] binding system were synthesized by metal-directed condensation of 2,6-diformyl-4-methylphenol with benzoyl or acetylacetone mono-S-methylisothiosemicarbazone. Only mononuclear “one-armed” complexes were obtained as a consequence of the different reactivity of the two carbonyl groups in the hydroxydialdehyde. The complexes were characterized by elemental analysis, EI MS and UV-Vis spectroscopy. The structural assignment was confirmed by X-ray diffraction analysis and NMR spectroscopy, for the Ni(II) complexes, and by ESR spectroscopy and magnetic measurements, for the Cu(II) complexes.     

Coordination chemistry of the heterotopic 1,2-phenylenebis(thio)diacetic acid ligand: Rhodium(I), palladium(II) and nickel(II) complexes

Starting from the heterotopic multidentate ligand 1,2-phenylenebis(thio)diacetic acid (1), cis-rac-[PdCl₂{1,2-(HOOCCH₂S)₂C₆H₄-κ²S,S′}] (2), cis-rac-[Rh{1,2-(HOOCCH₂S)₂C₆H₄-κ²S,S′}(cod)]BF₄ (3) and cis-rac-[Ni{1,2-(OOCCH₂S)₂C₆H₄-κ⁴O,O′S,S′}{cis-(C₃H₄N₂)}₂] (4) were prepared and characterised by X-ray diffraction and conventional spectroscopic techniques. Compounds 1-4 show extensive hydrogen-bonded networks (XH?O, X = O, N) in the solid state.     

Synthesis and characterization of nickel(II) and copper(II) complexes with tetradentate Schiff base ligands

The 1:1 condensation of 1,2-diaminopropane and 1-phenylbutane-1,3-dione at high dilution gives a mixture of two positional isomers of terdentate mono-condensed Schiff bases 6-amino-3-methyl-1-phenyl-4-aza-2-hepten-1-one (HAMPAH) and 6-amino-3,5-dimethyl-1-phenyl-4-aza-2-hexen-1-one (HADPAH). The mixture of the terdentate ligands has been used for further condensation with pyridine-2-carboxaldehyde or 2-acetylpyridine to obtain the unsymmetrical tetradentate Schiff base ligands. The tetradentate Schiff bases are then allowed to react with the methanol solution of copper(II) and nickel(II) perchlorate separately. The X-ray diffraction confirms the structures of two of the complexes and shows that the condensation site of the diamine with 1-phenylbutane-1,3-dione is the same.     

Some potential anticancer palladium(II) complexes of 2,2'-bipyridine and amino acids

Nine new palladium(II) complexes of the formula [Pd(bipy)(AA)]n+ (where bipy is 2,2'-bipyridine, AA is an anion of L-cysteine, L-aspartic acid, L-glutamic acid, L-methionine, L-histidine, L-arginine, L-phenylalanine, L-tyrosine, or L-tryptophan, and n = 0 or 1) have been synthesized by interaction of [Pd(bipy)Cl2] with an appropriate sodium salt of amino acid in water. These palladium(II) complexes have been characterized by chemical analysis and by visible, infrared, and 1H NMR spectroscopy. The modes of binding of amino acids in these palladium complexes have been ascertained by infrared and 1H NMR spectroscopy. The molar conductances of these complexes in water suggest that they are either nonelectrolytes or 1:1 electrolytes. These palladium complexes have shown growth inhibition against L1210 lymphoid leukemic, P388 lymphocytic leukemic, Sarcama 180, and Ehrlich ascites tumor cells. Some of these complexes show I.D.50 values comparable to or lower than cis-diamminedichloroplatinum(II).     

Unusual dinuclear copper(II) and nickel(II) complexes of a novel Schiff base deriving from 2-aminoethanol

It is generally accepted that copper(II) complexes involving 2-aminoethanol or a Schiff base deriving from this aminoalcohol display a tetranuclear structure with a Cu₄O₄ ‘cubane’ core. Using a Schiff base obtained by reacting 2′-aminoacetophenone with 2-aminoethanol, we have prepared copper(II) and nickel(II) complexes whose properties are fully consistent with a dinuclear structure. The copper complex is characterized by a low antiferromagnetic interaction.     

Mononuclear Ni(II) and Zn(II) complexes of some potentially binucleating Schiff base ligands

Mononuclear Zn(II) and Ni(II) complexes have been prepared from two new Schiff base ligands in which two alternative co-ordination sites (N₂O₂ or O₂O₂) occur. The first ligands is the Schiff base derived from 1,2-diaminobenzene and 2-hydroxy-3-carboxyl-1-napthaldehyde (bopaH₄). The complexes of this ligand contain the metal ions in the N₂O₂ coordination site as a result of the steric requirements of the co-ordinated ligand. The second ligand series are derivatives of X-substituted 1,2-diaminobenzenes, 2-hydroxy-3-carboxy-1-naphthaldehyde and 2-hydroxy-5-methyl isophthaldehyde (X-bolaH₃). In this case Ni(II) occupies the N₂O₂ site in its complexes with the X-bolaH₃ ligands, whereas the Zn(II) complexes are co-ordinate through the O₂O₂ site since the steric restrictions are less severe.     

Metal-assisted light-induced DNA cleavage activity of 2-(methylthio)phenylsalicylaldimine Schiff base copper(II) complexes having planar heterocyclic bases

Ternary copper(II) complexes [CuLL'](ClO(4)), where HL is NSO-donor Schiff base (2-(methylthio)phenyl)salicylaldimine and L' is NN-donor phenanthroline bases like 1,10-phenanthroline (phen), dipyridoquinoxaline (dpq) and 2,9-dimethyl-1,10-phenanthroline (dmp), are prepared and structurally characterized by X-ray crystallography. The complexes have a distorted square-pyramidal (4+1) CuN(3)OS coordination geometry. While [CuL(phen)](ClO(4)) and [CuL(dpq)](ClO(4)) show axial sulfur ligation, [CuL(dmp)](ClO(4)) has the sulfur bonded at the equatorial site. The one-electron paramagnetic complexes exhibit axial electron paramagnetic resonance (EPR) spectra in dimethylformamide glass at 77 K. The complexes are redox active and a quasireversible electron transfer process near 0.0 V vs saturated calomel electrode (SCE) in DMF-Tris buffer (1:4 v/v at pH 7.2) involving Cu(II)/Cu(I) couple is observed for the phen and dpq complexes. The dmp complex exhibits an irreversible reduction process forming bis(dmp)copper(I) species. A profound effect of the substituents of the phenanthroline bases is observed on the binding of the complexes to the calf thymus (CT) and in the cleavage of supercoiled (SC) pUC19 DNA. The phen and dpq complexes show DNA cleavage activity in presence of mercaptopropionic acid (MPA). The dmp complex is cleavage inactive in presence of MPA. All the complexes show photocleavage activity when irradiated with a monochromatic UV light of 312 nm. The dpq complex also cleaves SC DNA on visible light irradiation at 436, 532 and 632.8 nm but with a longer exposure time and higher complex concentration. The cleavage reactions in presence of MPA are found to involve hydroxyl radical. The photocleavage reactions are found to occur under aerobic conditions showing an enhancement of cleavage in D(2)O and inhibition with azide addition suggesting formation of singlet oxygen as a reactive species. The roles of sulfur of the Schiff base as photosensitizer and the phenanthroline bases as minor groove binder, and their influence on the photocleavage activity are discussed. The quinoxaline ligand exhibits significant photosensitizing effect assisted by the copper(II) center.     

Oxidative DNA cleavage by Schiff base tetraazamacrocyclic oxamido nickel(II) complexes

Nickel is considered a weak carcinogen. Some researches have shown that bound proteins or synthetic ligands may increase the toxic effect of nickel ions. A systematic study of ligand effects on the interaction between nickel complexes and DNA is necessary. Here, we compared the interactions between DNA and six closely related Schiff base tetraazamacrocyclic oxamido nickel(II) complexes NiL(1-3a,1-3b). The structure of one of the six complexes, NiL(3b) has been characterized by single crystal X-ray analysis. All of the complexes can cleave plasmid DNA under physiological conditions in the presence of H(2)O(2). NiL(3b) shows the highest DNA cleavage activity. It can convert supercoiled DNA to nicked DNA then linear DNA in a sequential manner as the complex concentration or reaction time is increased. The cleavage reaction is a typical pseudo-first-order consecutive reaction with the rate constants of 3.27+/-0.14h(-1) (k(1)) and 0.0966+/-0.0042h(-1) (k(2)), respectively, when a complex concentration of 0.6mM is used. The cleavage mechanism between the complex and plasmid DNA is likely to involve hydroxyl radicals as reactive oxygen species. Circular dichronism (CD), fluorescence spectroscopy and gel electrophoresis indicate that the complexes bind to DNA by partial intercalative and groove binding modes, but these binding interactions are not the dominant factor in determining the DNA cleavage abilities of the complexes.     

Synthesis and characterization of palladium(II) and platinum(II) complexes with Schiff bases derivatives of 2-pyridincarboxyaldehyde. Study of their interaction with DNA

Several Schiff bases ligand derivatives of 2-pyridincarboxyaldehyde and different amines, together with their palladium(II) and platinum(II) complexes have been synthesised and characterised. The aim of this study is to probe the influence of substituents beared on the pyridyl/toulene ring at different position to their possible antitumor activity. The amines used were o-, m-, p-toluidine and 4-hydroxyaniline. All the compounds were characterised by elemental analysis, FT-IR spectroscopy, 1H and 195Pt NMR spectroscopy and matrix assisted laser desorption/ionization time-of-flight mass spectroscopy. The formation of DNA adducts were analysed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the compounds with plasmid DNA pBR322 were also obtained. In all cases changes in the second and tertiary structure of DNA could be observed as a consequence of the covalent interaction of the palladium(II) or platinum(II) ions with the N of the nucleobases. However, there are not significant differences in the behavior of the complexes related to the position of the methyl groups or the presence of the OH group. Values of IC50 were also calculated for the platinum(II) complexes for several pairs of ovarian tumor cell lines which were either sensitive or resistant to cisplatin. Finally in vitro apoptosis studies for platinum(II) complexes with ovarian tumor cell lines A2780/A2780cisR were carried out. The results indicated interesting antiproliferative activity and significant apoptosis induction.     

Synthesis and cytotoxicity of diam(m)ineplatinum(II) complexes with 2,2-bis(hydroxymethyl)malonate as the leaving group

Six diam(m)ineplatinum(II) complexes with 2,2-bis(hydroxymethyl)malonate as the leaving group were synthesized and characterized by elemental analysis, FAB-MS, FT-IR, (1)H and (13)C NMR along with a single crystal X-ray diffraction for a representative compound. All the complexes were evaluated for the cytotoxicity against human cancer cell lines A549/ATCC, HT-29, SGC-7901. The activity is related to the nature of the am(m)ine ligand. cis-[Pt(II)(1R,2R-Diaminocyclohexane)·2,2-bis(hydroxymethyl)malonate] (complex 5) exhibits the greatest activity among those six complexes, and is even more active than its parent compound oxaliplatin. LD(50) was found to be 115 mg/kg by iv administration to ICR mice, much larger than that of oxaliplatin (LD(50)=19 mg/kg).     

Dinuclear nickel(II) and zinc(II) complexes of 2,6-bis[{bis(2-pyridylmethyl)amino}methyl]-4-methylphenol

Reaction of the symmetrical proligand H₂L with metal(II) acetate and a counteranion to promote crystallisation has given the homodinuclear complexes [Zn₂L(OAc)₂](BF₄)]·2MeOH and [Ni₂L(OAc)₂](BF₄)]·2MeOH the crystal structures of which are reported. These show the presence of a triply bridging (μ-cresolato)bis(μ-carboxylato) dimetal core.     

Copper(I) complexes with Schiff base and 1,2-bis(diphenylphosphino)ethane as ligands: Synthesis, structure and catalytic properties for the amination of aryl halide

Some copper(I) complexes of the type [Cu(L)(dppe)]X (1-4) [where L = (3-trifluoromethylphenyl)pyridine-2-ylmethylene-amine; dppe = 1,2-bis(diphenylphosphino)ethane; X = Cl⁻, CN⁻, ClO₄⁻ and BF₄⁻] have been synthesized by the condensation of 3-aminobenzotrifluoride with 2-pyridinecarboxaldehyde followed by the reaction with CuCl, CuCN, [Cu(MeCN)₄]ClO₄ and [Cu(MeCN)₄]BF₄ in presence of dppe. The complexes 1-4 were then characterized on the basis of elemental analysis, IR, UV-Vis and ¹H NMR spectral studies. The representative complex of the series 4 has been characterized by single crystal X-ray diffraction which reveal that in complex the central copper(I) ion assumes the irregular pseudo-tetrahedral geometry. The catalytic activity of the complexes was tested and it was found that all the complexes worked as effective catalyst in the amination of aryl halide.     

Some iron(III) complexes with polydentate Schiff base ligands

The iron(III) complexes of three Schiff base ligands are studied as their chloride or perchlorate salts and their electronic spectra, EPR spectra, and electrochemical behavior reported. Two of these ligands are formed from reaction between salicylaldehyde and 9 or 12-membered tri- or tetraazalkanes. EPR evidence indicates that one of the complexes, [1,12-bis(2-hydroxybenzylidene)-(1,4,9,12-tetraazadodec- 6-ene)iron(III)]perchlorate-1,5-water, is a spin-crossover species containing both high-spin and low-spin iron(III) in equilibrium. The third ligand comes from pyrrole-2-carboxaldehyde and a tetraazadodecane.     

Antioxidant, pro-oxidant effect of the thiosemicarbazone derivative Schiff base (4-(1-phenylmethylcyclobutane-3-yl)-2-(2-hydroxybenzylidenehydrazino) thiazole) and its metal complexes on rats

Adverse biological activities of thiosemicarbazone (TSC) and Schiff base (SB) derivatives have been widely studied in rats and in other animal species using different doses, times and routes of administration. However, there are few studies describing changes in some biochemical parameters in vivo which are indicative of oxidative stress in biological systems and of morphological changes of tissues. In this study, the rats were injected subcutaneously with a new thiosemicarbazone thiazole ring containing a Schiff base (LH) and its Cu(L)2 and Zn(L)2 complexes (25 mg kg(-1) body weight) and then sacrificed after 1, 2, 4, 8, 16, 32 and 64 days. The aim of this study was to determine the effect of the new compounds on the serum antioxidant vitamins (A, E, C), selenium (Se), malondialdehyde (MDA) levels, erythrocyte GSH-Px enzyme activity and morphological changes in the liver, kidney and adrenal gland tissues. It was observed that erythrocyte GSH-Px activity, serum MDA and vitamins A, E concentrations were statistically changed (p < 0.02), but serum levels of selenium, and vitamin C were not changed. In conclusion, the parameters measured show that Cu(L)2 caused considerable oxidative stress and Zn(L)2 behaved as an antioxidant. No oxidative stress in LH was observed compared to the control group.     

Hydrogen-bonded copper(II) and nickel(II) complexes and coordination polymeric structures containing reduced Schiff base ligands

Complexes [Cu(HSas)(H₂O)] · 2H₂O (H₃Sas = N-(2-hydroxybenzyl)-l-aspartic acid) (1), [Cu(HMeSglu)(H₂O)] · 2H₂O (H₃MeSglu = (N-(2-hydroxy-5-methylbenzyl)-l-glutamic acid) (2), [Cu₂(Smet)₂] (H₂Smet = (N-(2-hydroxybenzyl)-l-methionine) (3), [Ni(HSas)(H₂O)] (4), [Ni₂(Smet)₂(H₂O)₂] (5), and [Ni(HSapg)₂] (H₂Sapg = (N-(2-hydroxybenzyl)-l-aspargine) (6) have been synthesized and characterized by chemical and spectroscopic methods. Structural determination by single crystal X-ray diffraction studies revealed 1D coordination polymeric structures in 2 and 4, and hydrogen-bonded network structure in 5 and 6. In contrast to previously reported coordination compounds with similar ligands, the phenol remains protonated and bonded to the metal ions in 2 and 4, and also probably in 1. However, the phenolic group is non-bonded in 6.     

Effects on rat testes of the thiosemicarbazone derivative Schiff base (4-(1-phenylmethylcyclobutane-3-yl)-2-(2-hydroxybenzylidenehydrazino)thiazole) and its cadmium(II) complex

The aim of this study was to investigate structural and biochemical changes in testes of rats treated with the thiosemicarbazone derivative thiazole ring Schiff base, (4-(1-phenyl-methylcyclobutane-3-yl)-2-(2-hydroxybenzylidene-hydrazino) thiazole (L), and its Cd(II) complex (CdL(2)). The animals were divided into three groups. Group I was designated as control. The rats in groups II and III were injected subcutaneously with L or CdL(2) respectively at 150-mg kg(-1) doses at 3-day intervals for 15 days. At the end of the study, blood samples were collected for biochemical analysis, and testes were removed for histological examinations. Serum levels of vitamin A, E and MDA of the L-injected group were similar to the control group. While CdL(2) treatment decreased serum vitamin A and E levels, it increased the MDA level compared to other groups. Histologically, the testes structures of L-treated animals were similar to the control. Spermatogenic cells in seminiferous tubules of CdL(2)-treated animals displayed necrosis. Nuclei of spermatogonia and primary spermatocytes were pyknotic and heterochromatic. Homogenous pink particles were present in place of the spermatids. The interstitial areas were oedematous and intertubular vessels were plugged. In conclusion, the present results indicate that L does not cause biochemical and morphological alterations, but its Cd(II) complex has degenerative effects in normal rat testes.     

Synthesis, characterization, and antitumor activity of 1,2-bis(diphenylphosphino) ethane platinum(II) and palladium(II) complexes

A number of 1,2-bis(diphenylphosphino)ethane monomeric platinum(II) and palladium(II) complexes have been synthesized in light of their potential antitumor activity. The metal center is coordinated with a number of carboxylate anions in the cis-configuration. These complexes have been characterized by elemental analysis, conductivity measurement, and various spectroscopic techniques [IR and 195Pt NMR]. In vivo screening tests for activity of these complexes were performed against the L1210/0 murine leukemia cancer model, but none displayed a significant level of antitumor activity.