ABSTRACT
Since the potential anticancer activity of auranofin was discovered, gold compounds have attracted interest with a view to developing anticancer agents that follow cytotoxic mechanisms other than cisplatin. Two benzimidazole gold(I) derivatives containing triphenylphosphine (Au(pben)(PPh3)) (1) or triethylphosphine (Au(pben)(PEt3)) (2) were prepared and characterized by standard techniques. X-ray crystal structures for 1 and 2 were solved. The cytotoxicity of 1 and 2 was tested in human neuroblastoma SH-SY5Y cells. Cells were incubated with compounds for 24 h with concentrations ranging from 10 µM to 1 nM, and the half-maximal inhibitory concentration (IC50) was determined. 1 and 2 showed an IC50 of 2.7 and 1.6 µM, respectively. In order to better understand the type of cell death induced by compounds, neuroblastoma cells were stained with Annexin-FITC and propidium iodide. The fluorescence analysis revealed that compounds were inducing apoptosis; however, pre-treatment with the caspase inhibitor Z-VAD did not reduce cell death. Analysis of compound effects on caspase-3 activity and reactive oxygen species (ROS) production in SH-SY5Y cells revealed an antiproliferative ability mediated through oxidative stress and both caspase-dependent and caspase-independent mechanisms.
ABSTRACT
The compound [2bpytmH](2)[I(3)](2)[I(2)], which contains protonated 2bpytm, and four neutral monomeric complexes [CoCl(2)(2bpytm)]·H(2)O (1), [CoBr(2)(2bpytm)] (2), [CoI(2)(2bpytm)]·1/2H(2)O (3) and [NiBr(2)(2bpytm)]·H(2)O (4) have been obtained during a study into the reactivity of the bis(2-pyridylthio)methane (2bpytm) ligand towards cobalt(II) and nickel(II) halides. Furthermore, a cyclic dimer [CuBr(2)(2bpytm)](2) (5) and a 1D polymer [CuBr(2)(2bpytm)](n)·CH(3)CN (6) have been obtained from copper(II)/(I) bromide salts. An unprecedented S-CH(2)-S activation and cleavage in 2bpytm has been observed on using copper(II) salts with organic and voluminous inorganic anions. The cleavage of 2bpytm enabled the isolation of copper(II) complexes containing the in situ generated ligands 2-pyridinethiolate, 2-pyridinesulfenate or 2-pyridinesulfonate.
ABSTRACT
The versatile coordination chemistry of bis(pyrimidin-2-ylthio)methane (bptm) allows the synthesis of a series of different metal complexes with diverse structures. We describe here the synthesis and structural characterization of three kinds of compounds: four cyclic dimers, [Co(2)Cl(4)(bptm)(2)] (1), [Zn(2)I(4)(bptm)(2)] (2), [Cd(2)I(4)(bptm)(2)] (3), [Cu(2)(NO(3))(4)(bptm)(2)] (4); two acyclic dimers, [Cu(2)Br(4)(bptm)(3)] (5), [Cu(2)(AcO)(4)(bptm)(2)] (6); and two 2D coordination polymers, [CuBr(bptm)] (7) and [CuI(bptm)] (8). Different structural models are obtained on making small changes in the building units under different synthetic conditions. The effects of the weak interactions in the crystal packing were also analyzed.
ABSTRACT
The reaction of [ReX(CO)5] with thiosemicarbazones H2L(R) derived from beta-keto esters (X = Cl, Br; R = Me, Ph) allowed the isolation of cyclic trimeric complexes [Re3(pyz(R))3(CO)9], where pyz(R) is the pyrazolonate corresponding to the thiosemicarbazone. Electron spray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) monitoring of the reactions of H2L(Ph) in toluene confirmed that the trimer was formed in the reaction mixture and no higher oligomer was detected. These studies, together with the X-ray structures of the trimeric complexes, afford new insight into the factors influencing the self-assembly of pyrazolonaterhenium(I) complexes.
Subject(s)
Macrocyclic Compounds , Organometallic Compounds , Pyrazolones/chemistry , Rhenium/chemistry , Crystallography, X-Ray , Ligands , Macrocyclic Compounds/chemical synthesis , Macrocyclic Compounds/chemistry , Models, Molecular , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , StereoisomerismABSTRACT
The reactions of methylacetoacetate and ethyl 2-methylacetoacetate thiosemicarbazones (H(2)L(A) and H(2)L(B), respectively) with [ReX(CO)(5)] and [ReX(CO)(3)(CH(3)CN)(2)] (X = Cl, Br) were explored under various experimental conditions. Besides the adducts fac-[ReX(CO)(3)(H(2)L)], in which the rhenium is coordinated to three carbonyl groups, the X anion, and the N,S-bidentate thiosemicarbazone ligand, the following complexes were also isolated: fac-[ReBr(CO)(3)(Hpyz(B))], the tetrameric complexes fac-[Re(pyz(A))(CO)(3)](4) and fac-[Re(pyz(B))(CO)(3)](4), and fac-[Re(pyz(B))(CO)(3)(H(2)O)] (where Hpyz(A) and Hpyz(B) are pyrazolones derived by cyclization of H(2)L(A) and H(2)L(B), respectively). The cyclization reactions were monitored by (1)H NMR spectroscopy and the complexes isolated were identified by elemental analysis, mass spectrometry, IR and (1)H NMR spectroscopy, and in some cases by X-ray diffractometry. The isolation and the full structural identification of the rather unusual fac-[ReBr(CO)(3)(Hpyz(B))], which contains the enol form of the pyrazolone ligand, affords new insight into the cyclization of thiosemicarbazones derived from beta-keto esters.
ABSTRACT
Compounds in which N-phenylpiperazines were linked by a propyloxy chain to position 6 or 7 of a coumarin ring were designed and synthesised, and their affinities for 5-HT(1A) and D(2A) receptors were determined by radioligand binding assays. The influence of para substitution in the phenyl ring, substitution at position 4 of the coumarin system, and the coumarin position at which the piperazinylalkyl chain is linked was explored. Electron-withdrawing phenyl ring substituents para to the piperazine strongly reduced activity at both receptors. Binding at 5HT(1A) was influenced by the bulk of substituents at position 4 of the coumarin system, and binding at D(2A) by their electronic properties. Neither binding affinity was significantly affected by whether the piperazinylalkyl chain was inserted at position 6 or 7 of the coumarin system.
