Cobalt(II) complexes with thiosemicarbazone as potential antitumor agents: synthesis,crystal structures,DNA interactions,and cytotoxicity

Two cobalt(II) complexes [Co(QCT)₂]·Cl·1.5H₂O (1) (QCT = quinoline-2-carboxaldehyde thiosemicarbazone) and [Co(QCMT)(CH₃OH)Cl₂] (2) (QCMT = quinoline-2-carboxaldehyde N⁴-methyl-thiosemicarbazone) have been synthesized and structurally characterized. Complex 1 crystallizes in a triclinic system with space group P–1 and complex 2 crystallizes in a monoclinic system with space group P2(1)/n. In both complexes the cobalt(II) center is six coordinated with distorted octahedral geometry. The interactions of two complexes with CT-DNA were investigated by electronic absorption spectra, circular dichroism (CD) spectra and fluorescence spectra. Results suggest that the complexes bind to DNA via groove binding mode, and complex 2 has stronger binding ability than complex 1. The in vitro cytotoxicity has been tested against the human lung adenocarcinoma cell line A-549, cisplatin-resistant cell line A-549/CDDP, and human breast adenocarcinoma cell line MCF-7. Complex 2 is more cytotoxic than complex 1, and both of them show higher cytotoxicity than the parent ligands alone. Compared with cisplatin, the two cobalt(II) complexes are more active against A-549/CDDP and MCF-7 cell lines at most experimental concentrations. Notably, although complex 2 is found to be less effective than cisplatin against the parent cell line A-549, it is much more effective than cisplatin against the resistant cell A-549/CDDP.     

Spectrothermal studies of 1,10-phenanthroline complexes of Co(II), NI(II), Cu(II) and Cd(II) orotates

The 1,10-phenanthroline (phen) complexes of Co(II), Ni(II), Cu(II) and Cd(II) orotates were synthesized and characterized by elemental analysis, magnetic susceptibility, spectral methods (UV-vis and FTIR) and thermal analysis techniques (TG, DTG and DTA). The Co(II), Ni(II), Cu(II) and Cd(II) ions in diaquabis(1,10-phenanthroline)metal(II) diorotate octahedral complexes [M(H₂O)₂(phen)₂](H₂Or)₂·nH₂O (M=Co(II), n=2.25; Ni(II), n=3; Cu(II) and Cd(II), n=2) are coordinated by two aqua ligands and two moles of phen molecules as chelating ligands through their two nitrogen atoms. The monoanionic orotate behaves as a counter ion in the complexes. On the basis of the first DTG_max, the thermal stability of the hydrated complexes follows the order: Cd(II), 68°C 68°C     

The Preparation, Characterization and Biological Activity of Palladium(II) and Platinum(II) Complexes of Tridentate NNS Ligands Derived from S-methyl- and S-benzyldithiocarbazates and the X-ray Crystal Structure of the [Pd(mpasme)Cl] Complex

New complexes of general formula, [M(NNS)Cl] (M = Pd^II, Pt^II; NNS = anionic forms of the 6-methyl-2-formylpyridine Schiff bases of S-methyl- and S-benzyldithiocarbazates) have been prepared and characterized by a variety of physico-chemical techniques. Based on conductance and spectral evidence, a square-planar structure is assigned to these complexes. The crystal and molecular structure of the [Pd(mpasme)Cl] complex (mpasme=anionic form of the 6-methyl-2-formylpyridine Schiff base of S-methyldithiocarbazate) has been determined by X-ray diffraction. The complex has a distorted square-planar geometry with the ligand coordinated to the palladium(II) ion via the pyridine nitrogen atom, the azomethine nitrogen atom and the thiolate sulfur atom; the fourth coordination position around the palladium(II) ion is occupied by the chloride ligand. The distortion from a regular square-planar geometry is ascribed to the restricted bite angle of the ligand. Both the Schiff bases exhibit strong cytotoxicity against the human ovarian cancer (Caov-3) cell lines, the S-methyl derivative being two times more active than the S-benzyl derivative. The [Pt(mpasme)Cl] complex is moderately active but the palladium(II) complex is weakly active against this cancer. None of the complexes of Hmpsbz are active against Caov-3. The Schiff base, Hmpasme exhibits moderate activity against the bacteria, MRSA, P. aeruginosa and S. typhimurium but is inactive against B. subtilis. Coordination of the ligand with palladium(II) substantially reduces its activity. The Schiff base, Hmpasbz and its palladium(II) and platinum(II) complexes are inactive against these bacteria. The Schiff bases and their palladium(II) and platinum (II) complexes are inactive against the pathogenic fungi, C. albican, Aspergillus ochraceous and Saccharomyces cerevisiae.     

Formation of Zinc(II) and Cadmium(II) Complexes with Pyridine Oxime Ligands in Aqueous Solution

Complex formation equilibria involving pyridine-2-carboxaldehyde oxime (1), 1-(2-pyridinyl)ethanone oxime (2) and 6-methylpyridine-2-carboxaldehyde oxime (3), HL, with zinc(II) and cadmium(II) ions were studied in aqueous 0.1 M NaCl solution at 25° C by potentiometric titrations with a glass electrode. Experimental data were analysed with the least-squares computer program SUPERQUAD to determine the complexes formed and their stability constants. With Ligands 1 and 2 the sets of complexes for Zn(II) and Cd(II) are essentially the same, mono- and dinuclear oxime complexes and their deprotonated/hydrolysed products H_pM_q(HL)^2q+p _r. Owing to the steric requirements of the 6-methyl group, sets of complexes formed with 3 are distinctly different. For zinc(II), only dinuclear oximato species H_pZn₂(HL)^4q+p ₂ ( p = ? 2, ? 3, ? 4) are found, while for the larger cadmium(II) ion mononuclear oximato species CdL⁺ and CdL₂ are detected in addition to the dinuclear complex H_pCd₂(HL)^4q+p ₂ ( p = ? 3).     

A DFT investigation on molecular structures of semicarbazone complexes with Co(II), Ni(II) and Zn(II) and reaction energies of their complexation

The structure optimizations of 2-formylpyridine (H2FoPyS), 3-formylpyridine (H3FoPyS), and 4-formylpyridine (H4FoPyS) semicarbazone complexes with Co(II), Ni(II), and Zn(II) were carried out using DFT calculations at the B3LYP/LANL2DZ level of theory. The B3LYP/LANL2DZ-optimized geometry parameters for the H2FoPyS and H3FoPyS complexes show good agreement with their corresponding X-ray crystallographic data. Due to the X-ray crystallographic structures of the [Zn(H3FoPyS)₂]²⁺ complex and the H4FoPyS complexes with Co(II), Ni(II), and Zn(II) and have not yet been observed, their B3LYP/LANL2DZ-optimized structures are therefore theoretically proposed. The reaction energies and thermodynamic properties of complexation for these complexes computed at the same level of theory are reported.     

Copper(II) and nickel(II) complexes of 2-formylpyridine 3-piperidinyl-, 3-hexamethyleneiminyl- and 3-azabicyclo[3.2.2]nonylthiosemicarbazones

Summary Copper(II) and nickel(II) complexes of 2-formylpyridine 3-piperidinyl-, 3-hexamethyleneiminyl- and 3-azabicyclo-[3.2.2]nonylthiosemicarbazones were prepared and characterized spectroscopically. ¹H and ¹³C n.m.r. spectra of the thiosemicarbazones and a diamagnetic nickel(II) complex are reported, together with i.r., electronic and e.s.r. spectra of the metal complexes. The thiosemicarbazones and their copper(II) and nickel(II) complexes exhibit considerable growth inhibitory activity against Paecilomyces variotii, but show minimal activity against Aspergillus niger.     

Synthesis and Characterization of Complexes of Copper(II), Nickel(II) and Cobalt(II) with vic-Dioximes Bearing N''-p-Aminobenzoyl Benzaldehyde Hydrazone

Six different arylhydrazone derivatives of p-aminobenzoic hydrazide of vic-dioximes were synthesized by reaction of chloroglyoxime and dichloroglyoxime with N＇-p-aminobenzoyl benzaldehyde, 4-hydroxybenzaldehyde and 4-methoxybenzaldehyde hydrazones, respectively. Metal-ligand （1 ： 2） complexes of vic-dioxime derivatives with Cu（Ⅱ）, Ni（Ⅱ） and Co（Ⅱ） were prepared from corresponding metal acetates. The ligands and their complexes were characterized on the basis of elemental analyses and spectral data. The complexing abilities of these new vic-dioximes toward transition metals of Co（Ⅱ）, Cu（Ⅱ）, Ni（Ⅱ）, Zn（Ⅱ）, Cd（Ⅱ）, Mn（Ⅱ） and Cr（Ⅲ） were determined by solid-liquid extraction studies.     

Synthesis,characterization, DNA binding/cleavage,and anticancer and antimicrobial activities: Nano-sized Co(II) and Cd(II) complexes and their use as a precursor for CoO and CdO nanoparticles

In the search of effective bioactive compounds, Co(II) ( C1 ) and Cd(II) ( C2 ) complexes of the type [M(FMAPIMP)(H₂O)Cl].nH₂O (where M = Co(II); n = 2, Cd(II); n = 3, and FMAPIMP = ligand[2-((E)-((2-(((E)-furan-2-ylmethylene)amino)phenyl)imino)methyl)phenol]) were synthesized and characterized using elemental analysis, UV–Vis., cyclic voltammetry, Fourier-transform infrared (FT-IR), nuclear magnetic resonance, and mass spectral studies. The thermal stability of nano-sized Co(II) and Cd(II) complexes was studied using thermogravimetric analysis (TGA). Cobalt and cadmium oxides were synthesized using cobalt and cadmium nanoparticle (NP) structure Schiff base complexes as the raw material after calcination for 5 h at 600 °C. According to the results, Co(II) and Cd(II) complexes with mole ratio 1:1 of metal: H-FMAPIMP which octahedral are the most probable geometry for it. On the contrary, synthesized C1 and C2 NPs were used as suitable precursors for the preparation of CoO and CdO NPs. The obtained NPs were characterized using FT-IR, UV–Vis., TGA, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy techniques. PXRD analysis revealed that the obtained oxides were crystalline and corresponded to CoO and CdO phases. Crystal size, shape, and morphology were determined using SEM and TEM. H-FMAPIMP and its two complexes ( C1 and C2 ) were tested against human ovarian cancer cell line (PA-1). The synthesized Co(II) and Cd(II) complexes exhibited enhanced activity against the tested bacterial (Staphylococcus aureus and Escherichia Coli) and fungal strains (Candida albicans and Aspergillus fumigatus) as compared to H-FMAPIMP. The results of the DNA-cleavage activity indicated that the ligand and its two complexes can cleave calf thymus-DNA at different degrees. Further, antituberculosis activity was performed using microplate alamarBlue assay. Among all these synthesized compounds, C1 exhibited good cleaving ability compared to the newly synthesized C2 . Finally, the geometry of H-FMAPIMP and its Co(II) and Cd(II) complexes was optimized using molecular modeling.     

Synthesis and Characterization of Ni(II), Cu(II), Zn(II) and Cd(II) Complexes of a New Vic-Dioxime Ligand

In this study, 1,2-dihydroxyimino-3,7-di-aza-9,10-O-α-methyl benzal decane (LH₂) was synthesized starting from 1,2-O-α-methyl benzal-4-aza-7-amino heptane (RNH₂) and antichloroglyoxime. With this ligand, complexes were synthesized using Ni(II) and Cu(II) salts with a metal:ligand ratio of 1:2. However, the reaction of the ligand with salts of Zn(II) and Cd(II) gave products with metal:ligand ratio of 1:1. Structures of the ligand and its complexes are proposed based on elemental analyses, IR, ¹³C- and ¹H-NMR spectra, magnetic susceptibility measurements and thermogravimetric analyses (TGA).     

Trans‐bis(saccharinato)cadmium(II) Complexes with 2‐Aminomethylpyridine and 2‐Aminoethylpyridine — Synthesis,Crystal Structures,Spectral and Thermal Characterization of trans‐[Cd(sac)2(ampy)2] and trans‐[Cd(sac)2(aepy)2]

Two trans‐bis(saccharinato) (sac) complexes of cadmium(II ) with 2‐aminomethylpyridine (ampy) and 2‐aminoethylpyridine (aepy) were synthesized and characterized by means of elemental analysis, FT‐IR spectroscopy and thermal analysis. In addition, their solid‐state structures were determined by single crystal X‐ray diffraction studies. The [Cd(sac)₂(ampy)₂] ( 1 ) and [Cd(sac)₂(aepy)] ( 2 ) complexes consist of neutral monomeric units and crystallize in the orthorhombic (Pbca) and monoclinic (P2₁/c) crystal systems, respectively. The cadmium(II ) ions in 1 and 2 sit on inversion centres andexhibit distorted octahedral coordination by two sac anions and two aminopyridine ligands. The sac ligands in both complexes are N‐coordinated and located in trans positions, while the ampy and aepy ligands act as a bidentate ligand forming two symmetrically chelate rings around cadmium(II ). IR spectra and thermal decompositions of the complexes are also discussed.     

Synthesis and characterization of heterocyclic Schiff base and its complexes with Cu(II), Ni(II), Co(II), Zn(II), and Cd(II)

A new Schiff base, {1-[(2-hydroxy-naphthalen-1-ylmethylene)-amino]-4-phenyl-2-thioxo-1, 2-dihydro-pyrimidin-5-yl}-phenyl-methanone, has been synthesized from N-amino pyrimidine-2-thione and 2-hydroxynaphthaldehyde. Metal complexes of the Schiff base were prepared from acetate/chloride salts of Cu(II), Co(II), Ni(II), Zn(II), and Cd(II) in methanol. The chemical structures of the Schiff-base ligand and its metal complexes were confirmed by elemental analyses, IR, ¹³C-NMR, ¹H-NMR, API-ES, UV-Visible spectroscopy, magnetic susceptibility, and thermogravimetric analyses. The electronic spectral data and magnetic moment measurements suggest mononuclear octahedral and mononuclear or binuclear square planar structures for the metal complexes. In light of these results, it was suggested that this ligand coordinates to each metal atom by hydroxyl oxygen, azomethine nitrogen, and thione sulfur to form octahedral complexes with Cd(II) and Zn(II).     

Synthesis,Structural, and Antibacterial Studies of Some Mixed Ligand Complexes of Zn(II), Cd(II), and Hg(II) Derived From Citral Thiosemicarbazone and N-Phthaloyl Amino Acids

A series of new mixed ligand complexes of Zn(II), Cd(II), and Hg(II) with cis-3,7-dimethyl-2,6-octadienthiosemicarbazone (CDOTSC; LH) and N-phthaloyl amino acids (AH) have been synthesized by the reaction of metal dichloride with ligands CDOTSC and N-phthaloyl derivative of DL-glycine (A₁H), L-alanine (A₂H), or L-valine (A₃H) in a 1:1:1 molar ratio in dry refluxing ethanol. All the isolated complexes have the general composition [M(L)(A)]. The plausible structure of these newly synthesized complexes has been proposed on the basis of elemental analyses, molar conductances, molecular weight measurement, and various spectral (IR, ¹H NMR, and ¹³C NMR) studies, and four coordinated geometries have been assigned to these complexes. All the complexes and ligands have been screened for their antibacterial activity.     

Synthesis,characterization and susceptibility of bacteria against Sulfamethoxydiazine complexes of copper(II), zinc(II), nickel(II), cadmium(II), chromium(III) and iron(III)

Complexes of sulfamethoxydiazine with Cu(II), Zn(II), Ni(II), Cd(II), Cr(III) and Fe(III) have been synthesized and characterized on the basis of conductivity measurements, elemental analyses, UV, IR, ¹H?NMR and thermal studies. It is shown that sulfamethoxydiazine behaves as a bidentate ligand, binding the metal ion through the sulfonyl oxygen and sulfonamide nitrogen. In vitro susceptibility tests of these complexes against Escherichia coli, Bacillus subtilis, Proteus vulgaris and Staphylococcus aureus were carried out. The results show that the antibacterial activities of the complexes of Zn(II), Cu(II), Cr(III) and Fe(III) are, in general, stronger than that of sulfamethoxydiazine, while the complexes of Cd(II) and Ni(II) are less active.     

Syntheses and spectrothermal studies of triethanolamine complexes of Co(II), Ni(II), Cu(II) and Cd(II) squarates

The triethanolamine complexes, [M(tea)₂]sq·nH₂O, (n=2 for Co(II), n=0 for Ni(II), Cu(II) and n=1 for Cd(II), tea=triethanolamine, sq²⁻=squarate), have been synthesized and characterized by elemental analyses, magnetic susceptibility and conductivity measurements, UV-Vis and IR spectra, and thermal analyses techniques (TG, DTG and DTA). The Co(II), Ni(II) and Cu(II) complexes possess octahedral geometry, while the Cd(II) complex is monocapped trigonal prismatic geometry. Dianionic squarate behaves as a counter ion in the complexes. The thermal decomposition of these complexes takes place in three stages: (i) dehydration, (ii) release of the tea ligands and (iii) burning of organic residue. On the basis of the first DTG_max of the decomposition, the thermal stability of the anhydrous complexes follows the order: Ni(II), 289°C>Co(II), 230°C>Cu(II), 226°C>Cu(II), 170°C in static air atmosphere. The final decomposition products — the respective metal oxides — were identified by FTIR spectroscopy.     

Spectral,thermal and magnetic investigations of Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) 4-methylphthalates

Conditions for the preparation of Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) 4-methylphthalates were investigated and their composition, solubility in water at 295 K and magnetic moments were determined. IR spectra and powder diffraction patterns of the complexes prepared with molar ratio of metal to organic ligand of 1.0:1.0 and general formula: M [ CH₃C₆H₃(CO₂)₂]·nH₂o (n=1-3) were recorded and their decomposition in air were studied. During heating the hydrated complexes are dehydrated in one (Mn, Co, Ni, Zn, Cd) or two steps (Cu) and next the anhydrous complexes decompose to oxides directly (Cu, Zn), with intermediate formation of carbonates (Mn, Cd), oxocarbonates (Ni) or carbonate and free metal (Co). The carboxylate groups in the complexes studied are mono- and bidentate (Co, Ni), bidentate chelating and bridging (Zn) or bidentate chelating (Mn, Cu, Cd). The magnetic moments for paramagnetic complexes of Mn(II), Co(II), Ni(II) and Cu(II) attain values 5.92, 5.05, 3.36 and 1.96 M.B., respectively. This revised version was published online in July 2006 with corrections to the Cover Date.     

A NEW CYCLOBUTANE SUBSTITUTED SCHIFF BASE LIGAND,SYNTHESIS OF ITS Cd(II), Co(II), Cu(II), Ni(II) AND Zn(II) COMPLEXES AND INVESTIGATION OF THEIR STRUCTURE

Abstract

A new, thiazole derivative ligand, 4-(1-phenyl-1-methylcyclobutane-3-yl)-2-(2-hydroxy-5-bromo benzylidenehydrazino) thiazole (LH), has been synthesized by the reaction of 2-hydroxy-5-bromobenzaldehyde, thiosemicarbazide and subsequently 1-phenyl-1-methyl-3-(2-chloro-1-oxoethyl) cyclobutane. Mononuclear complexes with a metal-ligand ratio of 1 : 2 have been prepared with Cd(II), Co(II), Cu(II), Ni(II) and Zn(II). The authenticity of the ligand and its complexes was established by elemental analyses, IR, ¹³C and ¹H NMR spectra, magnetic susceptibility measurements and thermogravimetric analyses (TGA) and differential scanning calorimetry (DSC).     

Synthesis,characterization, DFT calculations and antimicrobial activity of pentagonal-bipyramidal Zn(II) and Cd(II) complexes with 2,6-diacetylpyridine-bis(trimethylammoniumacetohydrazone)

Isothiocyanate complexes of Zn(II) and Cd(II) with the condensation product of 2,6-diacetylpyridine and trimethylammoniumacetohydrazide (Girard’s T reagent) were synthesized, characterized, and their antimicrobial activities were evaluated. The structures of the complexes were determined by elemental analysis, IR, and NMR spectroscopy. The crystal structure of the Zn(II) complex was also determined. Quantum-chemical calculations of the geometry and total energy of isomers of 2,6-diacetylpyridine-bis(trimethylammoniumacetohydrazone) were performed in vacuum and methanol solution, with the aim to explain conformational behavior and E/Z isomerism of this compound. DFT calculations of the molecular structures and the relative stabilities of linkage isomers of the Cd(II) complex showed that the isomer with N–Cd–N coordination of SCN^? is the most stable. Complexes of Zn(II) and Cd(II) exhibited low to moderate activity against the tested microbial strains.     

Synthesis,characterization, computational simulation,biological and anticancer evaluation of Pd(II), Pt(II), Zn(II), Cd(II), and Hg(II) complexes with 2-amino-4-phenyl-5-selenocyanatothiazol ligand

New Pd(II), Pt(II), Zn(II), Cd(II), and Hg(II) complexes were synthesized from the reaction of 4-phenyl-5-selenocyanatothiazol-2-amine (PhSeCNH) with metal chlorides. The produced compounds were characterized by various spectroscopic techniques. The Material Studio program was used to propose the best fit atomic skeletons for the isolated solid compounds by applying density functional theory. Quantum chemical parameters were determined from such modeling. Also, the synthesized complexes were screened for their cytotoxicity in breast adenocarcinoma (MCF-7) and human cervical (HeLa) cell lines. Furthermore, the bactericidal activity of the investigated compounds was also evaluated against Staphylococcus aureus as a Gram-positive bacteria as well as Pseudomonas aeruginosa and Escherichia coli as Gram-negative bacteria.     

Synthesis and characterization of novel Cd(II), Zn(II) and Ni(II) complexes with 2-quinolinecarboxaldehyde selenosemicarbazone. Crystal structure of bis(2-quinolinecarboxaldehyde selenosemicarbazonato)nickel(II)

New complexes of Cd(II), Zn(II) and Ni(II) with 2-quinolinecarboxaldehyde selenosemicarbazone (Hqasesc) were synthesized and structurally characterized. The structure of the ligand, Cd(II) and Zn(II) complexes was determined by NMR and IR spectroscopy, elemental microanalysis and molar conductivity measurements. Both complexes occur in solution in two forms, the major tetrahedral and minor octahedral. In the major Cd(II) complex one qasesc⁻ ligand is coordinated as a tridentate, the fourth coordination site being occupied by acetate, while in the major Zn(II) complex two qasesc⁻ ligands are coordinated as bidentates. In both minor complexes two qasesc⁻ ligands are coordinated as tridentates forming the octahedral geometry around the central metal ion. The only paramagnetic complex in the series is Ni(II) complex for which X-ray structure analysis was performed. The complex has the angularly distorted octahedral geometry with two qasesc⁻ ligands coordinated as tridentates, in a similar way as in the minor complexes of Cd(II) and Zn(II).     

3-[2-(8-Quinolinyl)benzoxazol-5-yl]alanine derivative—a specific fluorophore for transition and rare-earth metal ion detection

A novel aromatic amino acid, 3-[2-(8-quinolinyl)benzoxazol-5-yl]alanine derivative was synthesized as a potential Zn(II) and rare-earth metal, Eu(III) and Tb(III), ion chemosensor. The fluorophore was obtained using lead tetraacetate in DMSO to oxidize the Schiff base obtained from N-Boc-3-amino-tyrosine methyl ester and quinoline-8-carboxaldehyde. Preliminary photophysical properties of this ligand show that it possesses the properties necessary to be an effective chemosensor for Zn²⁺, Tb³⁺ and Eu³⁺ ions.