Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy

An increasing number of pathologies correlates with both toxic and essential metal ions dyshomeostasis. Next to known genetic disorders (e.g., Wilson’s Disease and β-Thalassemia) other pathological states such as neurodegeneration and diabetes are characterized by an imbalance of essential metal ions. Metal ions can enter the human body from the surrounding environment in the form of free metal ions or metal-nanoparticles, and successively translocate to different tissues, where they are accumulated and develop distinct pathologies. There are no characteristic symptoms of metal intoxication, and the exact diagnosis is still difficult. In this review, we present metal-related pathologies with the most common onsets, biomarkers of metal intoxication, and proper techniques of metal qualitative and quantitative analysis. We discuss the possible role of drugs with metal-chelating ability in metal dyshomeostasis, and present recent advances in therapies of metal-related diseases.     

On the adaptation of local impact laws for multiple impact problems

Nonlinear Dynamics - The classical local impact laws of Newton and Poisson are able to capture the behaviour observed in single-impact collisions in many situations. However, in the case of...     

A general route for the synthesis of hydrido-carboxylate complexes of the type MH(CO)(κ-OCOR)(PPh3)2 [M = Ru,Os; R = CH3, CH2Cl,C6H5, CH(CH3)2] and their use as precatalysts for hydrogenation and hydroformylation reactions

The synthesis and solid-state IR, ¹H and ³¹P{¹H} NMR spectroscopic characterization of complexes of the type MH(CO)(κ³-OCOR)(PPh₃)₂ [M = Ru, Os; R = CH₃, CH₂Cl, C₆H₅ and CH(CH₃)₂] are reported in this paper. These compounds were obtained by reaction of the respective cationic complex [MH(CO)(NCMe)₂(PPh₃)₂]BF₄ with the sodium salt of the corresponding carboxylic acid in a 1:1 v/v dichloromethane/methanol solution at room temperature. The spectroscopic data of these complexes and some DFT calculations reveal an octahedral geometry with a bidentated carboxylate, two equivalent triphenylphosphines in a mutually trans positions, a linear hydride and a linear carbonyl both in the cis-positions of the coordination sphere. The catalytic results indicate that these complexes are efficient and regioselective precatalysts for the quinoline hydrogenation and for the hydroformylation of 1-hexene, under mild reaction conditions (130 °C and 4 atm H₂ and 120 °C and 15 atm H₂/CO, respectively). For benzothiophene hydrogenation, the osmium complexes showed low activities whereas the analogous ruthenium complexes were catalytically inactive under somewhat more drastic reaction conditions to those of the quinoline hydrogenation (140 °C and 10 atm H₂).     

Carbonic Anhydrase Activators for Neurodegeneration: An Overview

Carbonic anhydrases (CAs) are a family of ubiquitous metal enzymes catalyzing the reversible conversion of CO₂ and H₂O to HCO₃⁻ with the release of a proton. They play an important role in pH regulation and in the balance of body fluids and are involved in several functions such as homeostasis regulation and cellular respiration. For these reasons, they have been studied as targets for the development of agents for treating several pathologies. CA inhibitors have been used in therapy for a long time, especially as diuretics and for the treatment of glaucoma, and are being investigated for application in other pathologies including obesity, cancer, and epilepsy. On the contrary, CAs activators are still poorly studied. They are proposed to act as additional (other than histidine) proton shuttles in the rate-limiting step of the CA catalytic cycle, which is the generation of the active hydroxylated enzyme. Recent studies highlight the involvement of CAs activation in brain processes essential for the transmission of neuronal signals, suggesting CAs activation might represent a potential therapeutic approach for the treatment of Alzheimer’s disease and other conditions characterized by memory impairment and cognitive problems. Actually, some compounds able to activate CAs have been identified and proposed to potentially resolve problems related to neurodegeneration. This review reports on the primary literature regarding the potential of CA activators for treating neurodegeneration-related diseases.     

γγ interactions with KLOE

Studies of γγ interactions are performed with the KLOE detector,without tagging of the outgoing e+e-.The data sample is from an integrated luminosity of 240 pb-1.It was collected at the φ-factory DAΦNE with e+e-beams colliding at s～(1/2) 1 GeV,below the φ resonance peak.We present preliminary results concerning the observation of the γγ→η process and the evidence for γγ→π0π0 production at low π0π0 invariant masses.     

Synthesis of a novel purine‐containing heterocyclic ring system: 8,10‐Dimethylindolo[2′,3′:5,6][1,2,4]triazino[4,3‐f]purine‐9,11(8H, 10H, 13H)‐dione

The preparation of a novel purine containing heterocyclic ring system, indolotriazinopurine, by the condensation of 8‐hydrazinotheophylline with 5‐substituted isatins via the intermediate hemiaminal and hydrazone derivatives, is described.     

On the permeability of fibre-reinforced porous materials

Biological tissues can be considered as composite materials comprised of a porous matrix filled with interstitial fluid and reinforced by impermeable collagen fibres. Motivated by studies on fluid flow in articular cartilage, we would like to quantify the undeformed configuration permeability of fibre-reinforced composite materials. If there is a sufficient scale separation between the internal structure of the porous matrix and the arrangement of the fibres, the matrix can be taken as a porous continuum at the fibre scale. In this case, the fibres can be treated as inclusions in a porous continuum, and the overall permeability of the composite can be evaluated using homogenisation procedures. For an isotropic homogeneous matrix, the symmetry of the system is governed by the orientation of the fibres. Here, we propose to retrieve the overall permeability through geometrical considerations and directional averaging methods. The special case of transverse isotropy is discussed in detail, with particular attention to the sub-cases of aligned fibres and fibres lying on a plane.     

Stereoselective Double Functionalization of Geminated C(sp3)-Organodimetallic Linchpins

Geminated C(sp³)-organodimetallics can serve as dinucleophilic linchpins for the rapid assembly of complex molecular structures through two consecutive electrophilic substitution reactions with two different electrophiles. Implementation of these double functionalization sequences in a stereoselective manner to develop tools for asymmetric synthesis has attracted considerable interest from the synthetic community over the last decade. The focus has been put mostly on 1,1-bimetallic reagents containing boron, zinc or zirconium, and different strategies have been applied for such a purpose, including the diastereoselective transformation of enantioenriched chiral reagents or the enantioselective conversion of achiral or racemic derivatives. Asymmetric catalysis is at stake in most of the approaches developed. In this review article, we highlight the key advances in the development of 1,1-bimetallic linchpins as tools for asymmetric synthesis, emphasizing the underlying general concepts.     

Comparison of Antibacterial and Antioxidant Properties of Red (cv. Negramaro) and White (cv. Fiano) Skin Pomace Extracts

Wine pomace has attracted the attention of the food industry, due to its high content in bioactive compounds, and its multiple healthy activities. In this work, whole and separated skin pomaces from fermented (red) and un-fermented (white) grape by-products were characterized for their antioxidant and antimicrobial activities in order to exploit them as functional food ingredient. Antioxidant activity, measured by both ORAC and TEAC assays, was higher in whole than in skin pomace extracts. The characterization of phenolic composition in whole and skin pomace extracts confirmed the peculiarity of some compounds such as anthocyanins (107.84 + 10.3 mg/g TP) in red skin pomace and a great amount of flavanols (80.73 + 4.04 mg/g TP) in white skin pomace. Whole and skin pomace extracts displayed the same antibacterial activity at 250 µg gallic acid equivalents (GAE)/mL. Red and white skin pomace extracts showed a Minimum Inhibitory Concentration (MIC) of 31.25–62.5 GAE/mL against Staphylococcus aureus and Enterococcus faecalis. Pseudomonas spp. were more sensitive to red skin pomace extracts rather than white skin pomace extracts. Given these results, both red and white pomace extracts could be exploited for future application in food, pharmaceutical and cosmetic industry.     

A semi-analytical solution for the confined compression of hydrated soft tissue

Confined compression is a common experimental technique aimed at gaining information on the properties of biphasic mixtures comprised of a solid saturated by a fluid, a typical example of which are soft hydrated biological tissues. When the material properties (elastic modulus, permeability) are assumed to be homogeneous, the governing equation in the axial displacement reduces to a Fourier equation which can be solved analytically. For the more realistic case of inhomogeneous material properties, the governing equation does not admit, in general, a solution in closed form. In this work, we propose a semi-analytical alternative to Finite Element analysis for the study of the confined compression of linearly elastic biphasic mixtures. The partial differential equation is discretised in the space variable and kept continuous in the time variable, by use of the Finite Difference Method, and the resulting system of ordinary differential equations is solved by means of the Laplace Transform method.