Nazzareno Re

Synthesis, Structures, and Magnetic Properties of Face-Sharing Heterodinuclear Ni(II)−Ln(III) (Ln = Eu, Gd, Tb, Dy) Complexes

Heterodinuclear [(Ni (II)L)Ln (III)(hfac) 2(EtOH)] (H 3L = 1,1,1-tris[(salicylideneamino)methyl]ethane; Ln = Eu, Gd, Tb, and Dy; hfac = hexafluoroacetylacetonate) complexes ( 1.Ln) were prepared by treating [Ni(H 1.5L)]Cl 0.5 ( 1) with [Ln(hfac) 3(H 2O) 2] and triethylamine in ethanol (1:1:1). All 1.Ln complexes ( 1.Eu, 1.Gd, 1.Tb, and 1.Dy) crystallized in the triclinic space group P1 (No. 2) with Z = 2 with very similar structures. Each complex is a face-sharing dinuclear molecule. The Ni (II) ion is coordinated by the L (3-) ligand in a N 3O 3 coordination sphere, and the three phenolate oxygen atoms coordinate to an Ln (III) ion as bridging atoms. The Ln (III) ion is eight-coordinate, with four oxygen atoms of two hfac (-)s, three phenolate oxygen atoms of L (3-), and one ethanol oxygen atom coordinated. Temperature-dependent magnetic susceptibility and field-dependent magnetization measurements showed a ferromagnetic interaction between Ni (II) and Gd (III) in 1.Gd. The Ni (II)-Ln (III) magnetic interactions in 1.Eu, 1.Tb, and 1.Dy were evaluated by comparing their magnetic susceptibilities with those of the isostructural Zn (II)-Ln (III) complexes, [(ZnL)Ln(hfac) 2(EtOH)] ( 2.Ln) containing a diamagnetic Zn (II) ion. A ferromagnetic interaction was indicated in 1.Tb and 1.Dy, while the interaction between Ni (II) and Eu (III) was negligible in 1.Eu. The magnetic behaviors of 1.Dy and 2.Dy were analyzed theoretically to give insight into the sublevel structures of the Dy (III) ion and its coupling with Ni (II). Frequency dependence in the ac susceptibility signals was observed in 1.Dy.

Targeting aquaporin function: potent inhibition of aquaglyceroporin-3 by a gold-based compound

Aquaporins (AQPs) are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have been described as suitable candidates for clinical development. Here we report on the potent inhibition of AQP3 channels by gold(III) complexes screened on human red blood cells (hRBC) and AQP3-transfected PC12 cells by a stopped-flow method. Among the various metal compounds tested, Auphen is the most active on AQP3 (IC50 = 0.8±0.08 µM in hRBC). Interestingly, the compound poorly affects the water permeability of AQP1. The mechanism of gold inhibition is related to the ability of Au(III) to interact with sulphydryls groups of proteins such as the thiolates of cysteine residues. Additional DFT and modeling studies on possible gold compound/AQP adducts provide a tentative description of the system at a molecular level. The mapping of the periplasmic surface of an homology model of human AQP3 evidenced the thiol group of Cys40 as a likely candidate for binding to gold(III) complexes. Moreover, the investigation of non-covalent binding of Au complexes by docking approaches revealed their preferential binding to AQP3 with respect to AQP1. The high selectivity and low concentration dependent inhibitory effect of Auphen (in the nanomolar range) together with its high water solubility makes the compound a suitable drug lead for future in vivo studies. These results may present novel metal-based scaffolds for AQP drug development.

Ferromagnetic NiII–GdIII interactions in complexes with NiGd, NiGdNi, and NiGdGdNi cores supported by tripodal ligands

Dinuclear [(NiL)Gd(hfac)(2)(EtOH)](H(3)L = 1,1,1-tris(N-salicylideneaminomethyl)ethane, Hhfac = hexafluoroacetylacetone), trinuclear [(NiL)(2)Gd(NO(3))], and tetranuclear [(NiL)Gd(CH(3)CO(2))(2)(MeOH)](2) complexes, were prepared by treating [Ni(HL)] with [Gd(hfac)(3)(H(2)O)(2)], Gd(NO(3))(3).6H(2)O, and Gd(CH(3)CO(2))(3).4H(2)O, respectively, in the presence of Et(3)N. All the complexes show that ferromagnetic interactions occur between the Ni(II) and Gd(III) ions.

Titanium-carbon functionalities on an oxo surface defined by a calix [4] arene moiety and its redox chemistry

Abstract Lithiation of [ p -Bu t -calix[4]-(OMe) 2 (OH) 2 ] ( 1 ), followed by reaction with TiCl 3 (thf) 3 or TiCl 4 (thf) 2 , led to the corresponding titanium-calix[4]arene complexes [ p -Bu t -calix[4]-(OMe) 2 (O) 2 ]TiCl] ( 2 ) and [ p -Bu t -calix[4]-(OMe) 2 (O) 2 ]TiCl 2 ] ( 3 ), respectively. Reaction of 1 with TiCl 4 (thf) 2 results in demethylation of the calix[4]arene and the obtention of [ p -Bu t -calix[4]-(OMe) 2 (O) 3 ]TiCl] ( 4 ), whose hydrolysis led to [ p -Bu t -calix[4]-(OMe)(OH) 3 ] ( 6 ). The preparation of 6 can be carried out as a one-pot synthesis. Both 2 and 4 undergo alkylation reactions using conventional procedures, thus forming surprisingly stable organometallic species, namely [ p -Bu t -calix[4]-(OMe) 2 (O) 2 Ti(R)] (R = Me ( 7 ); CH 2 Ph ( 8 ), p -MeC 6 H 4 ( 9 ) and [ p -Bu t -calix[4]-(OMe)(O) 3 Ti(R)] (R = Me ( 10 ); CH 2 Ph ( 11 ); p -MeC 6 H 4 ( 12 )). Complexes 7 and 9 undergo a thermal oxidative conversion into 10 and 12 , occurring with the demethylation of one of the methoxy groups. A solid state structural property of 9 and 12 has been revealed by X-ray analysis showing a self-assembly of the monomeric units into a columnar polymer, where the p -tolyl substituent at the metal functions as a guest group for an adjacent titanium-calixarene. Reductive alkylation of 3 with Mg(CH 2 Ph) 2 gave 8 instead of forming the corresponding dialkyl derivative. Two synthetic routes have been devised for the synthesis of the Ti(III)-Ti(III) dimer [ p -Bu t -calix[4]-(OMe)(O) 3 Ti] 2 ] ( 13 ): the reduction of 4 and the reaction of TiCl 3 (thf) 3 with the lithiated form of 6 . A very strong antiferromagnetic coupling is responsible for the peculiar magnetic behavior of 13 . The proposed structures have been supported by the X-ray analyses of 4, 9, 12 and 13 .

Rearrangement of N-aryl-2-vinylaziridines to benzoazepines and dihydropyrroles: a synthetic and theoretical study.

Herein we report the one-pot synthesis of several N-heterocyclic compounds by rearrangement reactions of N-aryl-2-vinylaziridines. The optimization of the synthetic methodology employed allowed us to obtain differently substituted 2,5-dihydro-1H-benzo[b]azepines in good yields and purities. The relationship between the nature of the starting N-aryl-2-vinylaziridine and the obtained N-heterocycle was also investigated. Finally, to rationalize all the experimental results reported in this paper a theoretical study was performed that casts light on the reaction mechanism.

High Level Theoretical Study of Benzene-Halide Adducts : The Importance of C-H-Anion Hydrogen Bonding

High level ab initio calculations were performed on the interaction of halide anions (F(-), Cl(-), Br(-), and I(-)) to benzene. For these systems recent experimental and theoretical data are rather scarce, in spite of their growingly acknowledged importance for binding in complex biological systems. We have thus explored the complete basis set limit and the effect of counterpoise basis set superposition error corrections on the minimum geometries and energies of benzene-halide adducts in their possible interaction modes. The binding energy and enthalpy values (ranging from -15.3 kcal/mol for fluoride to -6.1 kcal/mol for iodide) show that the hydrogen bonding occurring in these complexes cannot be described as a weak interaction. We have furthermore investigated the topology of the minima and of other selected sections of the potential energy surface, so to gain further insight on the nature of the halide-benzene interaction. In particular, the geometry corresponding to the C(6v) symmetry, although being overall repulsive, has displayed the unprecedented presence of a small flex (a minimum in C(6v) symmetry) with interaction energy close to zero or slightly attractive.

Tantalum–Carbon Functionalities Bonded to a Calix[4]arene-Oxo Matrix: The Chemistry of Mono-, Dialkyl, and Butadiene Derivatives of Tantalum(V)

Tantalum–carbon functionalities bonded over an oxo matrix (here calix[4]arene anions) undergo a variety of multiple migratory insertion reactions which lead to the metal-assisted formation of C–C and CC bonds.

Structural Insight into Peroxisome Proliferator-Activated Receptor γ Binding of Two Ureidofibrate-Like Enantiomers by Molecular Dynamics, Cofactor Interaction Analysis, and Site-Directed Mutagenesis

Molecular dynamics simulations were performed on two ureidofibrate-like enantiomers to gain insight into their different potency and efficacy against PPARgamma. The partial agonism of the S enantiomer seems to be due to its capability to stabilize different regions of the receptor allowing the interaction with both coactivators and corepressors as shown by fluorescence resonance energy transfer (FRET) assays. The recruitment of the corepressor N-CoR1 by the S enantiomer on two different responsive elements of PPARgamma regulated promoters was confirmed by chromatin immunoprecipitation assays. Cell-based transcription assays show that PPARgamma coactivator 1alpha (PGC-1alpha) and cAMP response element binding protein-binding protein (CBP) enhance the basal and ligand-stimulated receptor activity acting as coactivators of PPARgamma, whereas the receptor interacting protein 140 (RIP140) and the nuclear corepressor 1 (N-CoR1) repress the transcriptional activity of PPARgamma. We also tested the importance of the residue Q286 on the transcriptional activity of the receptor by site-directed mutagenesis and confirmed its key role in the stabilization of helix 12. Molecular modeling studies were performed to provide a molecular explanation for the different behavior of the mutants.

Condensation of β‐Diester Titanium Enolates with Carbonyl Substrates: A Combined DFT and Experimental Investigation

The condensation of dialkyl beta-diesters with various aldehydes promoted by TiCl4 has been studied by DFT approaches and experimental methods, including NMR, IR and UV/Vis spectroscopy. Various possible reaction pathways have been investigated and their energy profiles evaluated to find out a plausible mechanism of the reaction. Theoretical results and experimental evidence point to a three-step mechanism: 1) Ti-induced formation of the enolate ion; 2) aldol reaction between the enolate ion and the aldehyde, both coordinated to titanium; and 3) intramolecular elimination that leads to a titanyl complex. The presented mechanistic hypothesis allows one to better understand the pivotal role of titanium(IV) in the reaction.

Aquation of the ruthenium-based anticancer drug NAMI-A: a density functional study.

We carried out density functional theory (DFT) calculations to investigate the thermodynamics and the kinetics of the double aquation reaction of the anticancer drug NAMI-A. Three explicit water molecules were included in the calculations to improve the PB solvation energies. Our calculations show that the chloride substitution reactions on the considered Ru(III) octahedral complex follow a dissociative interchange mechanism, I(d), passing through a loose heptacoordinate transition state. We calculated an activation enthalpy and free energy for the first aquation step of 101.5 and 103.7 kJ mol(-1), respectively, values that are in good agreement with the available experimental results. The activation enthalpy and free energy for the second aquation step were found significantly higher, 118.7 and 125.0 kJ mol(-1), again in agreement with the experimental evidence indicating a slower rate for the second aquation.