Tetracycline prevents Aβ oligomer toxicity through an atypical supramolecular interaction

The antibiotic tetracycline was reported to possess an anti-amyloidogenic activity on a variety of amyloidogenic proteins both in in vitro and in vivo models. To unveil the mechanism of action of tetracycline on Aβ1-40 and Aβ1-42 at both molecular and supramolecular levels, we carried out a series of experiments using NMR spectroscopy, FTIR spectroscopy, dynamic laser light-scattering (DLS) and atomic force microscopy (AFM). Firstly we showed that the co-incubation of Aβ1-42 oligomers with tetracycline hinders the toxicity towards N2a cell lines in a dose-dependent manner. Therefore, the nature of the interaction between the drug and Aβ oligomers was investigated. To carry out NMR and FTIR studies we have prepared Aβ peptide solutions containing assemblies ranging from monomers to large oligomers. Saturation transfer difference (STD) NMR experiments have shown that tetracycline did not interact with monomers at variance with oligomers. Noteworthy, in this latter case we observed that this interaction was very peculiar since the transfer of magnetization from Aβ oligomers to tetracycline involved all drug protons. In addition, intermolecular cross-peaks between tetracycline and Aβ were not observed in NOESY spectra, indicating the absence of a specific binding site and suggesting the occurrence of a supramolecular interaction. DLS and AFM studies supported this hypothesis since the co-dissolution of Aβ peptides and tetracycline triggered the immediate formation of new aggregates that improved the solubility of Aβ peptides, preventing in this way the progression of the amyloid cascade. Moreover, competitive NMR binding experiments showed for the first time that tetracycline competes with thioflavin T (ThT) in the binding to Aβ peptides. Our data shed light on a novel mechanism of anti-amyloidogenic activity displayed by tetracycline, governed by hydrophobic and charge multiparticle interactions.     

Re(V) and Re(III) complexes with sal2phen and triphenylphosphine: rearrangement, oxidation and reduction

Reactions of Re(V), tetradentate Schiff base complexes with tertiary phosphines have previously yielded both rearranged Re(V) and reduced Re(III) complexes. To further understand this chemistry, the rigid diiminediphenol (N(2)O(2)) Schiff base ligand sal(2)phen (N,N'-o-phenylenebis(salicylaldimine)) was reacted with (n-Bu(4)N)[ReOCl(4)] to yield trans-[ReOCl(sal(2)phen)] (1). On reaction with triphenylphosphine (PPh(3)), a rearranged Re(V) product cis-[ReO(PPh(3))(sal(2)phen*)]PF(6) (2), in which one of the imines was reduced to an amine during the reaction, and the reduced Re(III) products trans-[ReCl(PPh(3))(sal(2)phen)] (4) and trans-[Re(PPh(3))(2)(sal(2)phen)](+) (5) were isolated. Reaction of sal(2)phen with [ReCl(3)(PPh(3))(2)(CH(3)CN)] resulted in the isolation of [ReCl(2)(PPh(3))(2)(salphen)] (3). The compounds were characterized using standard spectroscopic methods, elemental analyses and single crystal X-ray crystallography.     

Hydrogen storage properties and neutron scattering studies of Mg2(dobdc)--a metal-organic framework with open Mg2+ adsorption sites

The hydrogen storage properties of Mg(2)(dobdc) (dobdc(4-) = 2,5-dioxido-1,4-benzenedicarboxylate), a metal-organic framework possessing hexagonal one-dimensional channels decorated with unsaturated Mg(2+) coordination sites, have been examined through low- and high-pressure adsorption experiments, infrared spectroscopy, and neutron scattering studies.     

Ferritin and metallothionein: dangerous liaisons

Ferritin (Ft) interaction with the Zn-complexes of mammalian MT1, MT2 and MT3 metallothioneins (MT) leads to simultaneous Fe(II) and Zn(II) release.     

Sol–gel derived silica-based organic–inorganic hybrid materials as “composite precursors” for the synthesis of highly homogeneous nanostructured mixed oxides: an overview

The present contribution reports on our results concerning the synthesis of different binary and ternary oxide systems by using hybrid materials as “composite” precursors. In the last years, we have developed and explored a valuable strategy to yield a very homogeneous dispersion of nanoparticles of early metal transition oxide, MO₂ (M = Zr, Hf) inside a silica matrix. This route is based on the use of the sol–gel process to obtain organic–inorganic hybrid silica-based materials embedding the oxide precursors (Zr and/or Hf oxoclusters), which are then calcined at high (T > 500 °C) temperatures to give the desired oxides. The “precursor” hybrid materials are prepared by a modified sol–gel process, involving the copolymerisation of the organically modified oxozirconium or oxohafnium clusters (M₄O₂(OMc)₁₂ (M = Zr, Hf and OMc = methacrylate) with (methacryloxymethyl)triethoxysilane (MAMTES) or (methacryloxypropyl)trimethoxysilane (MAPTMS). Free radical copolymerisation of the 12 methacrylate groups of the oxoclusters with the methacrylate-functionalised siloxanes allows a stable anchoring of the oxoclusters to the silica network formed by the hydrolysis and condensation of the alkoxy groups. The sol–gel reactions of the two methacrylate-modified silanes methacryloxymethyltriethoxysilane and methacryloxypropyltrimethoxysilane were followed by using two independent time-resolved spectroscopic methods, viz., IR ATR and NMR with the aim to optimise their pre-hydrolysis times and consequently their use as precursors for hybrid materials. As mentioned, thermal treatment at high temperature of the hybrid yields a very homogeneous dispersion of ZrO₂ and/or HfO₂ nanoparticles in the silica matrix, since the molecular homogeneity of the starting hybrid is retained in the final mixed oxide. This route was successfully applied both to the synthesis of bulk materials and thin films characterised by different compositions (in term of M/Si molar ratios and M nature), heating route (conventional or microwave-assisted) and final temperature of annealing (from RT to 1,100 °C). The first example of the ZrO₂–HfO₂–SiO₂ ternary oxide system was also prepared by this approach. The prepared systems, both in the form of hybrid materials as well as in the final form of binary or ternary oxides, were thoroughly characterised by a wide variety of analytical tools from a compositional, structural, morphological point of view. Moreover, in the case of the binary ZrO₂–SiO₂ bulk materials, also the evolution under heating was followed by different methods. In particular, the composition of the hybrid as well as of the final oxidic materials was determined by X-Ray Photoelectron Spectroscopy and elemental analysis, whereas FT-IR and multinuclear solid-state NMR spectroscopies shed light on the changes occurring in the composition upon thermal heating and the degree of condensation of the silica network. The morphology and the microstructure of the hybrids and of the oxides were studied by nitrogen sorption and Scanning Electron Microscopy. X-Ray Diffraction, Transmission Electron Microscopy and X-ray Absorption Fine Structure Spectroscopy X-ray Absorption Fine Structure Spectroscopy were used to follow the conversion of the amorphous oxides to the final materials consisting of crystalline zirconia or hafnia dispersed in amorphous silica. On selected systems, functional properties (surface reactivity, dielectric properties) were furthermore investigated. The obtained binary oxides were also used as substrates for functionalisation experiments with (1) dialkycarbamates and (2) long alkyl chains to produce functional materials for catalysis and HPLC applications, respectively.     

Effect of alkylimidazolium based ionic liquids on the structure of UV-irradiated cellulose

In this paper, the influence of three alkylimidazolium-based ionic liquids with the same cation (1-ethyl-3-methylimidazolium) and different anions (chloride, tetrafluoroborate and hexafluorophosphate) on the structure and properties of cellulose, have been studied by using Fourier transform infrared spectroscopy measurements, fluorescence microscopy imaging, viscometric and methylene blue sorption tests. Cellulose treated with ionic liquids showed better stability to UV light, as demonstrated by the lower variations of the polymerization degree, carboxyl groups content, moisture index, crystallinity index, lateral order index and allomorph index, with the increase of the UV exposure period, by comparing to non-treated cellulose. The results show that the tested ionic liquids could be effective as “green” plasticizers and UV stabilizers for cellulose-based materials.     

Immobilization of molecularly imprinted polymer nanoparticles in electrospun poly(vinyl alcohol) nanofibers

We describe the fabrication of polymer nanofibers with entrapped molecularly imprinted polymer (MIP) nanoparticles and study their possible use in a fluorescence-based biosensor application. The MIP was imprinted with the fluorescent amino acid derivative dansyl-L-phenylalanine. Poly(vinyl alcohol) was used as a support for MIP nanoparticles because it is water-soluble and can be spun into very thin fibers. The fibers were characterized by atomic force microscopy and optical microscopy, and fluorescence microscopy was used for the characterization of target binding to the MIP. The fibers show close to 100% recovery upon extraction and rebinding of the target molecule. The selectivity of the system has been demonstrated through competitive binding experiments with nonfluorescent analogues boc-L-phenylalanine and boc-D-phenylalanine.     

Charge transfer through modified peptide nucleic acids

We studied the charge transfer properties of bipyridine-modified peptide nucleic acid (PNA) in the absence and presence of Zn(II). Characterization of the PNA in solution showed that Zn(II) interacts with the bipyridine ligands, but the stability of the duplexes was not affected significantly by the binding of Zn(II). The charge transfer properties of these molecules were examined by electrochemistry for self-assembled monolayers of ferrocene-terminated PNAs and by conductive probe atomic force microscopy for cysteine-terminated PNAs. Both electrochemical and single molecular studies showed that the bipyridine modification and Zn(II) binding do not affect significantly the charge transfer of the PNA duplexes.