Dissolution of Molybdenum in Hydrogen Peroxide: A Thermodynamic, Kinetic and Microscopic Study of a Green Process for 99mTc Production.

99mTc-based radiopharmaceuticals are the most commonly used medical radioactive tracers in nuclear medicine for diagnostic imaging. Due to the expected global shortage of 99Mo, the parent radionuclide from which 99mTc is produced, new production methods should be developed. The SORGENTINA-RF (SRF) project aims at developing a prototypical medium-intensity D-T 14-MeV fusion neutron source specifically designed for production of medical radioisotopes with a focus on 99Mo. The scope of this work was to develop an efficient, cost-effective and green procedure for dissolution of solid molybdenum in hydrogen peroxide solutions compatible for 99mTc production via the SRF neutron source. The dissolution process was extensively studied for two different target geometries: pellets and powder. The first showed better characteristics and properties for the dissolution procedure, and up to 100 g of pellets were successfully dissolved in 250-280 min. The dissolution mechanism on the pellets was investigated by means of scanning electron microscopy and energy-dispersive X-ray spectroscopy. After the procedure, sodium molybdate crystals were characterized via X-ray diffraction, Raman and infrared spectroscopy and the high purity of the compound was established by means of inductively coupled plasma mass spectroscopy. The study confirmed the feasibility of the procedure for production of 99mTc in SRF as it is very cost-effective, with minimal consumption of peroxide and controlled low temperature.

Carnosine inhibits Aß(42) aggregation by perturbing the H-bond network in and around the central hydrophobic cluster.

Aggregation of the amyloid-ß peptide (Aß) into fibrillar structures is a hallmark of Alzheimer's disease. Thus, preventing self-assembly of the Aß peptide is an attractive therapeutic strategy. Here, we used experimental techniques and atomistic simulations to investigate the influence of carnosine, a dipeptide naturally occurring in the brain, on Aß aggregation. Scanning force microscopy, circular dichroism and thioflavin T fluorescence experiments showed that carnosine does not modify the conformational features of Aß42 but nonetheless inhibits amyloid growth. Molecular dynamics (MD) simulations indicated that carnosine interacts transiently with monomeric Aß42 by salt bridges with charged side chains, and van der Waals contacts with residues in and around the central hydrophobic cluster ((17)LVFFA(21)). NMR experiments on the nonaggregative fragment Aß12-28 did not evidence specific intermolecular interactions between the peptide and carnosine, in agreement with MD simulations. However, a close inspection of the spectra revealed that carnosine interferes with the local propensity of the peptide to form backbone hydrogen bonds close to the central hydrophobic cluster (residues E22, S26 and N27). Finally, MD simulations of aggregation-prone Aß heptapeptide segments show that carnosine reduces the propensity to form intermolecular backbone hydrogen bonds in the region 18-24. Taken together, the experimental and simulation results (cumulative MD sampling of 0.2 ms) suggest that, despite the inability of carnosine to form stable contacts with Aß, it might block the pathway toward toxic aggregates by perturbing the hydrogen bond network near residues with key roles in fibrillogenesis.

Beta-amyloid monomers are neuroprotective.

The 42-aa-long beta-amyloid protein--Abeta(1-42)--is thought to play a central role in the pathogenesis of Alzheimer's disease (AD) (Walsh and Selkoe, 2007). Data from AD brain (Shankar et al., 2008), transgenic APP (amyloid precursor protein)-overexpressing mice (Lesné et al., 2006), and neuronal cultures treated with synthetic Abeta peptides (Lambert et al., 1998) indicate that self-association of Abeta(1-42) monomers into soluble oligomers is required for neurotoxicity. The function of monomeric Abeta(1-42) is unknown. The evidence that Abeta(1-42) is present in the brain and CSF of normal individuals suggests that the peptide is physiologically active (Shoji, 2002). Here we show that synthetic Abeta(1-42) monomers support the survival of developing neurons under conditions of trophic deprivation and protect mature neurons against excitotoxic death, a process that contributes to the overall neurodegeneration associated with AD. The neuroprotective action of Abeta(1-42) monomers was mediated by the activation of the PI-3-K (phosphatidylinositol-3-kinase) pathway, and involved the stimulation of IGF-1 (insulin-like growth factor-1) receptors and/or other receptors of the insulin superfamily. Interestingly, monomers of Abeta(1-42) carrying the Arctic mutation (E22G) associated with familiar AD (Nilsberth et al., 2001) were not neuroprotective. We suggest that pathological aggregation of Abeta(1-42) may also cause neurodegeneration by depriving neurons of the protective activity of Abeta(1-42) monomers. This "loss-of-function" hypothesis of neuronal death should be taken into consideration when designing therapies aimed at reducing Abeta burden.

Organoboron polymers for photovoltaic bulk heterojunctions.

We report on the application of three-coordinate organoboron polymers, inherently strong electron acceptors, in flexible photovoltaic (PV) cells. Poly[(1,4-divinylenephenylene)(2,4,6-triisopropylphenylborane)] (PDB) has been blended with poly(3-hexylthiophene-2,5-diyl) (P3HT) to form a thin film bulk heterojunction (BHJ) on PET/ITO substrates. Morphology may be modulated to give a high percentage of domains (10-20 nm in size) allowing exciton separation. The photoelectric properties of the BHJs in devices with aluminium back electrodes were imaged by light beam induced current (LBIC) and light beam induced voltage (LBIV) techniques. Open circuit voltages, short circuit currents and overall external quantum efficiencies obtained are among the highest reported for all-polymer PV cells.

Aqueous Processed Biopolymer Interfaces for Single-Cell Microarrays.

Single-cell microarrays are emerging tools to unravel intrinsic diversity within complex cell populations, opening up new approaches for the in-depth understanding of highly relevant diseases. However, most of the current methods for their fabrication are based on cumbersome patterning approaches, employing organic solvents and/or expensive materials. Here, we demonstrate an unprecedented green-chemistry strategy to produce single-cell capture biochips onto glass surfaces by all-aqueous inkjet printing. At first, a chitosan film is easily inkjet printed and immobilized onto hydroxyl-rich glass surfaces by electrostatic immobilization. In turn, poly(ethylene glycol) diglycidyl ether is grafted on the chitosan film to expose reactive epoxy groups and induce antifouling properties. Subsequently, microscale collagen spots are printed onto the above surface to define the attachment area for single adherent human cancer cells harvesting with high yield. The reported inkjet printing approach enables one to modulate the collagen area available for cell attachment in order to control the number of captured cells per spot, from single-cells up to double- and multiple-cell arrays. Proof-of-principle of the approach includes pharmacological treatment of single-cells by the model drug doxorubicin. The herein presented strategy for single-cell array fabrication can constitute a first step toward an innovative and environmentally friendly generation of aqueous-based inkjet-printed cellular devices.

Protective effects of L- and D-carnosine on alpha-crystallin amyloid fibril formation: implications for cataract disease.

Mildly denaturing conditions induce bovine alpha-crystallin, the major structural lens protein, to self-assemble into fibrillar structures in vitro. The natural dipeptide l-carnosine has been shown to have potential protective and therapeutic significance in many diseases. Carnosine derivatives have been proposed as potent agents for ophthalmic therapies of senile cataracts and diabetic ocular complications. Here we report the inhibitory effect induced by the peptide (l- and d-enantiomeric form) on alpha-crystallin fibrillation and the almost complete restoration of the chaperone activity lost after denaturant and/or heat stress. Scanning force microscopy (SFM), thioflavin T, and a turbidimetry assay have been used to determine the morphology of alpha-crystallin aggregates in the presence and absence of carnosine. DSC and a near-UV CD assay evidenced that the structural precursors of amyloid fibrils are polypeptide chain segments that lack stable structural elements. Moreover, we have found a disassembling effect of carnosine on alpha-crystallin amyloid fibrils. Finally, we show the ability of carnosine to restore most of the lens transparency in organ-cultured rat lenses exposed to similar denaturing conditions that were used for the in vitro experiments.

Self-organization pathways and spatial heterogeneity in insulin amyloid fibril formation.

At high temperature and low pH, the protein hormone insulin is highly prone to form amyloid fibrils, and for this reason it is widely used as a model system to study fibril formation mechanisms. In this work, we focused on insulin aggregation mechanisms occurring in HCl solutions (pH 1.6) at 60 degrees C. By means of in situ Thioflavin T (ThT) staining, the kinetics profiles were characterized as a function of the protein concentration, and two concurrent aggregation pathways were pointed out, being concentration dependent. In correspondence to these pathways, different morphologies of self-assembled protein molecules were detected by atomic force microscopy images also evidencing the presence of secondary nucleation processes as a peculiar mechanism for insulin fibrillation. Moreover, combining ThT fluorescence and light scattering, the early stages of the process were analyzed in the low concentration regime, pointing out a pronounced spatial heterogeneity in the formation of the first stable fibrils in solution and the onset of the secondary nucleation pathways.

The zero field self-organization of cobalt/surfactant nanocomposite thin films.

Cobalt nanostructures have been prepared by a chemical route based on the Co(II) reduction in the confined space of cobalt bis(2-ethylhexyl)sulfosuccinate (Co(DEHSS)(2)) reverse micelles dispersed in n-heptane. This procedure involves the rapid formation of surfactant softly coated Co nanostructures followed by a slow separation process of the magnetic-field responsive Co/surfactant nanocomposites from the liquid phase. The detailed structure of thin films of the Co/surfactant nanocomposites has been investigated by scanning force microscopy (SFM). The thin films were characterized by different anisotropic features. Micrometric long domains of self-aligned ellipsoidal NPs (tens of nanometers in size) have been observed, together with bendable micrometric long homogeneous nanofibers (NFs). The film structures were strongly dependent on the Co/surfactant ratio and, by increasing the Co percentage, the system was forced towards the formation of mutually connected superstructures consisting of anisotropic bands of self-aligned NFs and anisotropic 2D close packed Co-NP super-lattices. Transmission electron microscopy (TEM) showed that the NPs observed by SFM are in effect composed of almost spherical and oxygen-free cobalt nanoparticles, 1-3 nm in size, which typically assemble in larger ellipsoidal systems tens of nanometers in size. Magnetic force microscopy (MFM) demonstrates the magnetic response of these thin films, highlighting the different behavior (attractive/repulsive) of the Co-NPs aggregates towards the oscillating magnetized tip. The above structural findings have been interpreted in terms of nanostructures/matrix interaction along with a fine balance between short-range isotropic repulsions, van der Waals attractions and long-range anisotropic magnetic interactions.

Self-organization and nanostructural control in thin film heterojunctions.

In spite of more than two-decades of studies of molecular self-assembly, the achievement of low cost, easy-to-implement and multi-parameter bottom-up approaches to address the supramolecular morphology in three-dimensional (3D) systems is still missing. In the particular case of molecular thin films, the 3D nanoscale morphology and function are crucial for both fundamental and applied research. Here we show how it is possible to tune the 3D film structure (domain size, branching, etc.) of thin film heterojunctions with nanoscale accuracy together with the modulation of their optoelectronic properties by employing an easy two-step approach. At first we prepared multi-planar heterojunctions with a programmed sequence of nanoscopic layers. In a second step, thermal stimuli have been employed to induce the formation of bulk heterojunctions with bicontinuous and interdigitated phases having a size below the exciton diffusion length. Importantly, the study of luminescence quenching of these systems can be considered as a useful means for the accurate estimation of the exciton diffusion length of semiconductors in nanoscale blends. Finally, nearly a thousand times lower material consumption than spin coating allows a drastic reduction of material wasting and a low-cost implementation, besides the considerable possibility of preparing thin film blends also by employing materials soluble in different solvents.

Polymeric Thin Films for Organic Electronics: Properties and Adaptive Structures.

This review deals with the correlation between morphology, structure and performance of organic electronic devices including thin film transistors and solar cells. In particular, we report on solution processed devices going into the role of the 3D supramolecular organization in determining their electronic properties. A selection of case studies from recent literature are reviewed, relying on solution methods for organic thin-film deposition which allow fine control of the supramolecular aggregation of polymers confined at surfaces in nanoscopic layers. A special focus is given to issues exploiting morphological structures stemming from the intrinsic polymeric dynamic adaptation under non-equilibrium conditions.

Design and synthesis of new trehalose-conjugated pentapeptides as inhibitors of Abeta(1-42) fibrillogenesis and toxicity.

Aggregation of the amyloid Abeta peptide and its accumulation into insoluble deposits (plaques) are believed to be the main cause of neuronal dysfunction associated with Alzheimer's disease (AD); small molecules that can interfere with the Abeta amyloid fibril formation are therefore of interest for a potential therapeutic strategy. Three new trehalose-conjugated peptides of the well known beta-sheet breaker peptide iAbeta5p, were synthesized. The disaccharide was covalently attached to different sites of the LPFFD peptide chain, i.e. at the N-terminus, C-terminus or at the Asp side chain. CD spectroscopy in different solvents was used to assess changes in the peptide conformation of these compounds. The effects of these glycopeptides on the self-assembly and morphology of Abeta aggregates were investigated by ThT fluorescence assay and dynamic Scanning Force Microscopy, respectively. All the synthesized compounds were tested as inhibitors of Abeta toxicity toward pure cultures of rat cortical neurons.