Oxindolimine-copper(II) and zinc(II) complexes that previously have shown to induce apoptosis, with DNA and mitochondria as main targets, exhibit here significant inhibition of kinase CDK1/cyclin B protein. Copper species are more active than the corresponding zinc, and the free ligand shows to be less active, indicating a major influence of coordination in the process, and a further modulation by the coordinated ligand. Molecular docking and classical molecular dynamics provide a better understanding of the effectiveness and kinase inhibition mechanism by these compounds, showing that the metal complex provides a stronger interaction than the free ligand with the ATP-binding site. The metal ion introduces charge in the oxindole species, giving it a more rigid conformation that then becomes more effective in its interactions with the protein active site. Analogous experiments resulted in no significant effect regarding phosphatase inhibition. These results can explain the cytotoxicity of these metal complexes towards different tumor cells, in addition to its capability of binding to DNA, and decreasing membrane potential of mitochondria.
Recebido em 5/7/10; aceito em 17/9/10; publicado na web em 25/10/10 Herein, the immobilization of some Schiff base-copper(II) complexes in smectite clays is described as a strategy for the heterogenization of homogeneous catalysts. The obtained materials were characterized by spectroscopic techniques, mostly UV/Vis, EPR, XANES and luminescence spectroscopy. SWy-2 and synthetic Laponite clays were used for the immobilization of two different complexes that have previously shown catalytic activity in the dismutation of superoxide radicals, and disproportionation of hydrogen peroxide. The obtained results indicated the occurrence of an intriguing intramolecular redox process involving copper and the imine ligand at the surface of the clays. These studies are supported by computational calculations.
Structural and electronic properties of [C12H24S6X], [C13H26S6OX], and [C14H28S6OX] (X: Ag(+), Cd(2+)) crown thioether complexes were investigated within the framework of the density functional theory (DFT) using the projector augmented wave (PAW) method. The theoretical results were compared with time-differential perturbed γ-γ angular correlations (TDPAC) experiments reported in the literature using the (111)Ag→(111)Cd probe. In the case of X=Ag(+), a refinement of the structure was performed and the predicted equilibrium structures compared with available X-ray diffraction experimental data. Structural distortions induced by replacing Ag(+) with Cd(2+) were investigated as well as the electric-field gradient (EFG) tensor at the Cd(2+) sites. Our results suggest that the EFG at Cd(2+) sites corresponds to the Ag(+) coordination sphere structure, i.e., before the structural relaxations of the molecule with X=Cd(2+) are completed. The results are discussed in terms of the characteristics of the TDPAC (111)Ag→(111)Cd probe and the time window of the measurement, and provide an interesting tool with which to probe molecular relaxations.
We compare published TDPAC experiments on 111 Cd in the crown thioether C 6 H 12 S 3 AgCl with ab-initio electronic structure calculations performed within the framework of the Density Functional Theory using the Projector Augmented Wave method. We conclude from this comparison that the Cd atom at the very moment of the TDPAC experiment is positively charged, and we point out to a methodological difference between reproducing experimental electric-field gradients in molecules versus solid metals.
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