Synthesis,characterization, crystal structure and antiproliferative in vitro activity of long-chain aliphatic thiosemicarbazones and their Ni(II) complexes

In the course of a research on metal-based compounds active on white blood cell cancers (leukemia, lymphoma and myeloma) nine aliphatic thiosemicarbazones and their nickel complexes have been synthesized with the aim to test their effect on histiocytic lymphoma U937 cell proliferation. All compounds were characterized by elemental, IR and NMR spectra analyses and for five of the complexes also by X-ray crystallography diffraction analysis. Heptanal thiosemicarbazone and the corresponding nickel complex were chosen after a solubility/stability test to carry out preliminary experiments in vitro on human leukemia cell line U937. The complex possesses a remarkable biological activity in inhibiting cell growth and in inducing apoptosis.     

Synthesis,characterization, crystal structure and antiproliferative activity of platinum(II) complexes with 2-acetylpyridine-4-cyclohexyl-thiosemicarbazone

New platinum complexes have been synthesized by the reaction of Na₂PtCl₄ with 2-acetylpyridine-4-cyclohexyl-thiosemicarbazone, HAc4CyclHexyl (1). The new complexes [Pt(Ac4CyclHexyl)Cl] (2) and [Pt(Ac4CyclHexyl)₂] (3) have been characterized by elemental analyses and spectroscopic studies. The crystal structure of the complex [Pt(Ac4CyclHexyl)Cl] · DMF has been solved by single-crystal X-ray diffraction. The anion of Ac4CyclHexyl coordinates in a planar conformation to the central platinum(II) through the pyridyl N, azomethine N and thiolato S atoms. The crystal packing is determined by double intermolecular hydrogen interactions, π–π, Pt–C and Pt–π contacts. The cytotoxic activities of 1–3 have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). The compounds 1–3 display IC₅₀ values in a μM range better than that of the antitumor drug cisplatin and are considered as agents with potential antitumor activity candidates for further stages of screening in vitro and/or in vivo.     

Organotin complexes of pyruvic acid thiosemicarbazone: Synthesis,crystal structures and antiproliferative activity of neutral and cationic diorganotin complexes

The synthesis and spectral characterization of novel neutral and cationic organotin complexes with pyruvic acid thiosemicarbazone, H₂pt (1), [SnPh₂(pt)] (2), [SnMe₂(Hpt)(H₂O)]Cl (3) and [SnPh₂(Hpt)(H₂O)]Cl (4) are reported. The crystal structure of the complexes [SnPh₂(pt)] (2) and [SnMe₂(Hpt)(H₂O)]Cl (3) have been solved by single-crystal X-ray diffraction. The crystal structure of complex 2 showed that the ligand is doubly deprotonated at the oxygen and amide nitrogen atoms and is coordinated to the SnPh₂ fragment via two five-membered chelate rings. The monomers of 2 are linked through intermolecular hydrogen bonds of C−H–O type and through π−π intermolecular interactions. The crystal structure of [SnMe₂(Hpt)(H₂O)]Cl (3) showed that the ligand is mono-deprotonated at the oxygen atom and is coordinated to the SnMe₂ fragment via two five-membered chelate rings. The counter ion chloride is participated in intermolecular hydrogen bonds. An extended network of intermolecular hydrogen bonds leads to aggregation and a supramolecular assembly. The IR and NMR spectroscopic data of the complexes are reported. The in vitro cytotoxic activity has been evaluated against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T-24 (bladder cancer cell line), A-549(non-small cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). The most active of all was found the diorganotin complex 2. The cytotoxic activity shown by these compounds against all these cancer cell lines indicates that coupling of 1 with R₂Sn(IV) metal center result in metallic complexes with important biological properties and remarkable cytotoxic activity, since they are display IC₅₀ values in a μM range the same or better to that of the antitumor drug cisplatin. Compound 2 is considered as agent with potential antitumor activity, and can therefore be candidate for further stages of screening in vitro and/or in vivo.     

Synthesis,crystal structures and spectroscopic studies of calcium(II) succinamate(-1) complexes

The reaction of succinamic acid (H₂sucm) with Ca(NO₃)₂·4H₂O yielded compounds [Ca(Hsucm)(NO₃)(H₂O)]_n (1) and [Ca(Hsucm)₂]_n (2). The succinamate(-1) ligand presents two new ligation modes and coordinates through the two carboxylato and the amide O-atoms, thus bridging three Ca^II ions which assemble into zig-zag 1D chains in 1 and 2D networks in 2. Intermolecular hydrogen bonding interactions in the crystal structures of 1 and 2 result in overall 3D framework structures. Both compounds have been characterized by IR and ¹H NMR spectroscopy, and their thermal decomposition was monitored by TG/DTG and DSC measurements. The structural comparison of 1 and 2 with known lanthanide(III) succinamate(-1) complexes reveals differences in the coordination mode of the ligand and in the coordination number of the metal ions; the biological relevance of these differences is discussed.     

In vitro assessment of cytotoxicity, anti-inflammatory, antifungal properties and crystal structures of metallacyclic palladium(II) complexes

Metallacyclic palladium(II) complexes [Pd(L)(R₃P)Cl], L = TIQDTC (1,2,3,4-tetrahydroisoquinolinedithiocarbamate), 4MpipDTC (4-methylpipradinedithiocarbamate), MPizDTC (N-methylpiperazinedithiocarbamate), R₃P = Ph₃P, (o-tolyl)₃P, Ph₂ClP, were synthesized in a 1:1 molar metal-ligand ratio. These complexes were characterized by elemental analyses, FT-IR, multinuclear (¹H, ¹³C and ³¹P) NMR. The X-ray crystal structures of [Pd(TIQDTC)(Ph₃P)Cl] and [Pd(TIQDTC)((o-tolyl)₃P)Cl] show a slightly distorted square planar environment around the Pd(II) ion with S-Pd-S and P-Pd-Cl average bond angles of 74.51 and 92.41, respectively. These complexes were screened for cytotoxic, antifungal, anti-inflammatory and antibacterial activity. Some complexes exhibit a significant activity against fungi.     

Palladium(II) and platinum(II) saccharinate complexes containing pyridine and 3-acetylpyridine: Synthesis, crystal structures, fluorescence and thermal properties

New palladium(II) and platinum(II) complexes of saccharinate (sac), trans-[Pd(py)₂(sac)₂] (1), cis-[Pt(py)₂(sac)₂] (2), trans-[Pd(3-acpy)₂(sac)₂] (3) and cis-[Pt(3-acpy)₂(sac)₂] (4) (py = pyridine and 3-acpy = 3-acetylpyridine) have been synthesized. Elemental analysis, UV-Vis, IR, NMR and TG/DTA characterizations have been carried out. The structures of 1-4 were determined by X-ray diffraction. The palladium(II) and platinum(II) ions are coordinated by two N-bonded sac ligands, and two nitrogen atoms of py or 3-acpy, forming a distorted square-planar geometry. The palladium(II) complexes (1 and 3) are trans isomers, while the platinum(II) complexes (2 and 4) are cis isomers. The mononuclear species in the solid state are connected by weak intermolecular C-H?O hydrogen bonds, C-H?π and π?π stacking interactions. The platinum(II) complexes show significant fluorescence at the room temperature.     

X-ray crystal structures of novel platinum(II) and palladium(II) complexes of dialkyl phosphonated phosphines

Two diethyl phosphonated phosphine ligands of formula Ph₂P(CH₂)₃PO₃Et₂ (ligand L) and Ph₂P(4-C₆H₄PO₃Et₂) (ligand L′) were used to prepare different complexes of platinum(II) (1, cis-PtCl₂L₂; 2, trans-PtCl₂L₂·H₂O; 3A and 3B, cis- and trans-PtCl₂L′₂) and palladium(II) (4, [PdCl₂L]₂; 5, trans-PdCl₂L₂·H₂O; 6, trans-PdCl₂L′₂·CH₂Cl₂). The single-crystal X-ray structure analyses of complexes 1, 2, 4-6 indicate that complexation involved only the phosphine end, whereas the strong polarization of the PO bond was highlighted by the formation of hydrogen bonds with a water molecule in 2 and 5, and with a dichloromethane molecule in 6, with an exceptionally short CH?O hydrogen bond length (C?O separation 3.094(3) Å).     

Synthesis and characterisation of nickel(II) complexes with tripodal ligand tris[4-(3-(5-methylpyrazolyl)-3-aza-3-butenyl] amine (MPz3tren): X-ray crystal structure of [Ni(MPz3tren)](BF4)2·0.5H2O

Nickel(II) complexes of the tripodal ligand (MPz₃tren) of the general formula [Ni(MPz₃tren)]X₂·nH₂O (X=Cl, Br, NO₃, ClO₄ and BF₄; n=0 for Cl and Br; n=0.5 for NO₃, ClO₄ and BF₄) have been prepared by template methodology and characterised by elemental analyses, magnetic susceptibility and conductivity measurements at RT, IR and electronic spectra. The molar conductivities measured in MeOH for all the complexes show them to be 1:2 electrolytes. The hexadentate character of the ligand in all the complexes is inferred from IR spectral studies. The electronic spectra in solid state and in MeOH solution suggest octahedral geometry for all the complexes. The structure of [Ni(MPz₃tren)](BF₄)₂·0.5H₂O has been determined by single-crystal X-ray diffraction studies (monoclinic, c2/c). Nickel(II) is in a trigonal antiprismatic N₆ donor environment and the crystal structure is stabilised by a network of strong H-bonding.     

Synthesis, characterization and crystal structures of palladium(II) complexes containing neutral, one and twofold deprotonated 1,2,4-triazine species

The synthesis and characterization of three new palladium(II) complexes of 4-amino-6-ethyl-1,2,4-triazine-3-thion-5-one (AETTO, H₃L), [PdCl₂(H₃L)]·H₂O (1), [Pd₂Cl₂(H₂L)(PPh₃)₃]NO₃·2CH₃CN (2) and [Pd(HL)(PPh₃)₂] (3), are reported. All the synthesized compounds are air-stable and were characterized by elemental analyses, IR, NMR spectroscopy and mass spectrometry. In addition, the molecular structures of the complexes have been determined by X-ray single crystal diffraction. On the basis of the crystallographic data, the neutral ligand in 1 and the deprotonated ligands in 2 and 3 act as bidentate NS donors. The singly deprotonated ligand in 2 acts as a bridging agent between two metal centers in the binuclear Pd^II-complex.     

Three new thiocyanato-bridged complexes of cadmium(II): syntheses,X-ray crystal structures and thermal properties

Three new thiocyanato-bridged polymers of cadmium(II), [Cd(me₄dpt)(SCN)₂] _n (1) [me₄dpt = 3,3′-iminobis(N,N-dimethylpropylamine], [Cd(me₂tn)(SCN)₂] _n (2) (me₂tn = N,N′-dimethyl-1,3-propanediamine) and [{amphyH} {Cd(SCN)₃}] _n (3) (ampyH = 4-aminopyridinium cation), have been synthesized and their molecular structures determined through X-ray crystallography. In Complex 1 each square pyramidal mononuclear fragment is H-bonded (N ? H…S) to form a 1D supramolecular chain. Complex 2 is a 1D coordination polymer in which each distorted octahedral cadmium(II) ion is linked with the four bridging thiocyanates and one diamine. The structure of 3 reveals anionic [Cd(SCN)₃]^? zigzag chains arranged in an approximately hexagonal array with the 4-aminopyridinum cations occupying triangular channels. Each chain is H-bonded (N?H…N) to form a 2D supramolecular network. Upon heating, 1 and 2 melt and transform to transparent solid masses at ambient temperature over a few days. On scratching, these turn to a fine powder. This phenomenon is repeatable. Complex 3 upon heating loses a 4-aminopyridine molecule and transforms to [H][Cd(SCN)₃] at ??195°C.     

Synthesis,characterization, crystal structures,enzyme inhibition,DNA binding,and electrochemical studies of zinc(II) complexes

Five zinc(II) complexes, [Zn(L¹)₂] (1), [Zn(L¹)₂(phen)H₂O]·H₂O (2), [Zn(L¹)₂(bipy)] (3), [Zn(L²)₂] (4), and [Zn(L²)₂(phen)] (5) (where L¹?=?4-nitrophenylacetate, L²?=?phenylacetate, phen?=?1,10-phenanthroline and bipy?=?2,2′-bipyridine), have been synthesized and characterized by elemental analysis, FT-IR, and multinuclear NMR. Complexes 2, 3, and 4 have been confirmed by single-crystal X-ray diffraction. In 2 and 3, zinc is bonded monodentate to two carboxylates exhibiting distorted trigonal bipyramidal and tetrahedral geometries, respectively, whereas in 4, the carboxylates are bridging bidentate in distorted tetrahedral geometry. The complexes have been screened for electro- and biological activities, including DNA interaction and enzyme inhibition studies. The effect of concentration of 1–5 on the activity of enzyme, alkaline phosphatase, showed that an increase in concentration of complex decreased the activity of the enzyme. Electrochemical behavior of HL¹, 2, and 3 was investigated by cyclic voltammetry and it was observed that ligand-centered electro-activity exhibits a proportionate change on complexation. The UV–visible spectroscopic and viscometric data indicate electrostatic and groove binding of the complexes with DNA. The binding constant and Gibb’s free energy values indicate the feasibility of the complex–DNA interaction and show potent biological activity of the complexes.     

Structural, spectral and antimicrobial studies of copper(II) complexes of 2-benzoylpyridine N(4)-cyclohexyl thiosemicarbazone

Six new copper(II) complexes of 2-benzoylpyridine N(4)-cyclohexyl thiosemicarbazone (HL) have been synthesized and characterized by different physicochemical techniques like molar conductivity measurements, magnetic studies and electronic, infrared and EPR spectral studies. Five of the complexes have been found to possess the stoichiometry [CuLX], where X = Cl (1), Br (2), NO₃ (3), NCS (4), N₃ (5). The complex prepared from copper sulfate has the composition [Cu₂L₂SO₄] · (H₂O)₂ (6). In all the complexes the deprotonated ligand, L and the anion were found to be coordinated to the Cu(II) ion. The terdentate nature of the ligand is evident from the IR spectra. The metal ligand bonding parameters evaluated from the EPR spectra indicate strong in-plane σ and in-plane π bonding. The magnetic and spectroscopic data indicate a square planar geometry for complexes 1, 3, 4 and 5, while the complexes 2 and 6 are assigned a square pyramidal geometry. Crystal structure of the complex [CuLCl] reveals two molecules per asymmetric unit of a monoclinic lattice, with space group symmetry P2₁/n. The complexes [ CuLBr ₂] (2) and [CuLNCS] (4) crystallized into triclinic lattices with space group . Compound 2 exists as a thiolate bridged copper(II) dimer. The antimicrobial activity of the ligand and the copper complexes were tested against five types of bacteria isolated from clinical samples. The complexes were found to be active against Bacillus sp., Vibrio cholera O1, Staphylococcus aurus and Salmonella paratyphi.     

2-Arylnaphthoxazole-derived palladium(II) complexes as phosphine-free catalysts for Heck reactions

Four air- and moisture-stable new palladium(II) complexes 2a–2c and 4 have been synthesized from easily available 2-arylnaphthoxazole derivatives. The detailed structures of 2c and 4 have been determined by single-crystal X-ray analysis. The Pd–N, Pd–C bonds in palladacycle complexes 2a–2c and the Pd–N, Pd–O bonds in complex 4 form the basis for five- and six-membered chelate rings, respectively. These complexes were applied as efficient phosphine-free catalysts for Heck reactions with aryl bromides and ethyl acrylate. Typically, in the presence of two equivalent n-Bu₄NBr, using 0.01% of palladacycle complex 2c as catalyst and two equivalent of K₂CO₃ as base in DMF at 140 °C provided coupled products in moderate to high yields.     

Synthesis,structure, electrochemical properties,and antioxidant activities of copper(II) and zinc(II) complexes with N,N-bis(N-ethyl-2-ylmethylbenzimidazol)allylamine ligand

N,N-bis(N-methyl-2-ylmethylbenzimidazole)aniline (EtAIDB) and its transition metal complexes, [Cu(EtAIDB)Br₂]·EtOH {dibromo[N,N-bis(N-methyl-2-ylmethylbenzimidazole)aniline] copper(II) ethanol} (1) and [Zn(EtAIDB)Br₂] {dibromo[N,N-bis(N-methyl-2-ylmethylbenzimidazole)aniline] zinc(II)} (2), have been synthesized and characterized by elemental analysis, molar conductivity, UV–visible, and IR spectroscopy. The X-ray crystallographic studies of 1 and 2 have shown two different arrangements: 1 is distorted square-based pyramidal, while 2 can be treated as distorted tetrahedral. The cyclic voltammogram of 1 represents quasi-reversible Cu²⁺/Cu⁺ pairs. In vitro antioxidant tests showed that 1 had significant antioxidant activity against superoxide and hydroxy radicals.     

Syntheses, crystal structures and properties of novel zinc(II) complexes obtained by reactions of zinc(II) malonate with flexible multidentate ligands

Complex [Zn₂(bimb)₂(mal)₂(H₂O)₂]·4H₂O (1) (mal=⁻OCOCH₂COO⁻) was obtained by reaction of bidentate ligand 4,4′-bis(imidazole-1-ylmethyl)biphenyl (bimb) with zinc(II) salt of malonate, while the reaction of the same metal salt with 1,3,5-tris(imidazol-1-ylmethyl)-2,4,6-trimethylbenzene (titmb) gives another novel complex [Zn₂(titmb)₂(mal)][mal]·12H₂O (2). The structures of these complexes were determined by X-ray crystallography. The results revealed that 1 is a cyclic dinuclear complex in which the malonate groups act as terminators and prevent further aggregation, while 2 is a 2D honeycomb network in which each independent 2D sheet contains two sub-layers bridged by the malonate groups and complex 2 also contains free malonate as a counteranion connected to the 2D layer by C-H?O hydrogen bonds. The entirely different structure and topology of complexes 1 and 2, on the one hand, indicates that the nature of organic ligands affected the structures of assemblies greatly, and on the other, reveals the versatility of the malonate which can act as a bridging and/or blocking ligand.     

Syntheses and characterization of nickel(II), zinc(II) and palladium(II) complexes derived from three pyrazole-based polydentate ligands

Two pyrazole-based polydentate ligands, 1,3-bis(5-methyl-3-phenylpyrazol-1-yl)-propan-2-ol (Hmppzpo) and 1,3-bis(5-methyl-3-p-isopropylphenylpyrazol-1-yl)-propan-2-ol (Hmcpzpo), have been synthesized. A third ligand, 1,3-bis(3,5-dimethylpyrazol-1-yl)-propan-2-ol (Hdmpzpo), has been synthetically modified. Seven new M(II) coordination compounds of general formula M₂L₂X₂ (M?=?Zn, Ni; X?=?NO₃ or ClO₄; L?=?dmpzpo, mppzpo or mcpzpo) or MLX (M?=?Pd; L?=?dmpzpo; X?=?Cl) were synthesized and structurally characterized by elemental analysis and FT-IR analysis. The crystal structures of [Zn₂(μ-dmpzpo-O,N,N′)₂(NO₃)₂]?·?2H₂O (1?·?2H₂O), [Ni₂(μ-dmpzpo-O,N,N′)₂(CH₃CN)₂](ClO₄)₂ (2) and Pd(μ-dmpzpo-N,N′)Cl₂ (4) were determined by single-crystal X-ray crystallography. The crystal structures show that complexes 1?·?2H₂O and 2 are center-symmetric dinuclear compounds, with two metal ions bridged by two alkoxo groups and each metal ion with a distorted square-pyramidal environment. The palladium complex, 4, displayed square-planar coordination geometry around the Pd(II) ion with trans arrangement.     

Syntheses,structures, and fluorescent properties of three Zn(II) and Cu(II) complexes of different ligands derived from 3,6-bis(2-pyridyl)-1,2-dihydro-1,2,4,5-tetrazine

Three supramolecular complexes [Zn(HL₁ )₂(H₂O)₂(ZnCl₄)₂] (1), [Cu(L₂ )₂Cl₂] (2), and [Zn(L₃ )Cl₂] (3) have been synthesized and characterized by single crystal X-ray diffraction analysis (L₁ = 3,5-di(2-pyridyl)-4-amino-1,2,4-triazole, L₂ = 3,5-di(2-pyridyl)-1,2,4-triazole, and L₃ = 2-pyridinecarboxylic acid (pyridin-2-ylmethylene)-hydrazide). In 1, anion–π interactions between Cl^? and the π-systems of L₁ are observed and anion–π, hydrogen bonding and π–π stacking interactions link the two complex units of [Zn(HL₁ )₂(H₂O)₂]⁴⁺ and [ZnCl₄]^2? to form a 3-D supramolecular network. In 2, π–π stacking interactions between aromatic rings of 1,2,4-triazole and pyridine rings are observed; in 3, hydrogen bonding of Cl ··· H–N and π–π stacking interactions between parallel pyridine rings of L ₃ are observed. The mechanisms of rearrangement reactions of L to L₁ –L₃ are discussed. The fluorescent properties for solid 1 and 3 are also investigated.     

Structural and spectral investigations on some new Ni(II) complexes of di-2-pyridyl ketone N(4)-phenylthiosemicarbazone

Ni(II) complexes (1–5) of di-2-pyridyl ketone N(4)-phenylthiosemicarbazone (HL) have been synthesized and spectrochemically characterized. Elemental analyses revealed a NiL₂ · 2H₂O stoichiometry for compound 1. However, the single crystals isolated revealed a composition NiL₂ · 0.5(H₂O)0.5(DMF). The compound crystallizes into a monoclinic lattice with the space group P2₁/n. Complexes 2, 3 and 4 are observed to show a 1:1:1 ratio of metal:thiosemicarbazone:gegenion, with the general formula NiLX · yH₂O [X = NCS, y = 2 for 2; X = Cl, y = 3 for 3 and X = N₃, y = 4.5 for 4]. Compound 5 is a dimer with a metal:thiosemicarbazone:gegenion ratio of 2:2:1, with the formula [Ni₂L₂(SO₄)] · 4H₂O.