Flexible aliphatic poly(isocyanurate–oxazolidone) resins based on poly(ethylene glycol) diglycidyl ether and 4,4′‐methylene dicyclohexyl diisocyanate

New flexible aliphatic oxazolidone‐isocyanurate networks (AISOX) are obtained by reacting a low molecular weight diisocyanate (4,4′‐methylene dicyclohexyl diisocyanate, H₁₂MDI) and a macro‐diepoxyde (poly(ethylene glycol) diglycidyl ether, M_n = 526, PEGDGE) in different molar ratio. The curing reaction, carried out from 25 °C to 200 °C, is studied by using DSC and FTIR. The effect of the molar ratio of the two monomers on thermal and mechanical properties of AISOX resins is investigated by DSC, thermogravimetric analysis, stress?strain measurements and optical microscopy. Independently from the feed composition, it is observed that the reaction steps are: (i) partial hydrolysis of isocyanate caused by water traces, (ii) incomplete trimerization of isocyanate to give isocyanurate, and (iii) formation of oxazolidone and complete conversion of isocyanate. At the highest concentration of the soft macrodiepoxyde (PEGDGE), the AISOX resin is in the rubbery state at room temperature and shows an elastomeric behavior. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43404.     

Selenocarbamates As a Prodrug-Based Approach to Carbonic Anhydrase Inhibition

A study on the activity of selenocarbamates as a novel chemotype acting as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors is reported. Undergoing CA-mediated hydrolysis, selenocarbamates release selenolates behaving as zinc binding groups and effectively inhibiting CAs. A series of selenocarbamates characterised by high molecular diversity and complexity have been studied against different human CA isoforms such as hCA I, II, IX and XII. Selenocarbamates behave as masked selenols with potential biological applications as prodrugs for CAs inhibition-based strategies. X-ray studies provided insights into the binding mode of this novel class of CA inhibitors.     

A new potassium-based bioactive glass: Sintering behaviour and possible applications for bioceramic scaffolds

Providing structural support while maintaining bioactivity is one of the most important goals for bioceramic scaffolds, i.e. artificial templates which guide cells to grow in a 3D pattern, facilitating the formation of functional tissues. In the last few years, 45S5 Bioglass^® has been widely investigated as scaffolding material, mainly for its ability to bond to both hard and soft tissues. However, thermal treatments to improve the relatively poor mechanical properties of 45S5 Bioglass^® turn it into a glass-ceramic, decreasing its bioactivity. Therefore, the investigation of new materials as candidates for scaffold applications is necessary. Here a novel glass composition, recently obtained by substituting the sodium oxide with potassium oxide in the 45S5 Bioglass^® formulation, is employed in a feasibility study as scaffolding material. The new glass, named BioK, has the peculiarity to sinter at a relatively low temperature and shows a reduced tendency to crystallize. In this work, BioK has been employed to realize two types of scaffolds. The obtained samples have been fully characterized from a microstructural point of view and compared to each other. Additionally, their excellent bioactivity has been established by means of in vitro tests.     

Absence of expected side-reactions in the dehydration reaction of fructose to HMF in water over niobic acid catalyst

The catalytic dehydration of fructose (FRU) to 5-hydroxymethylfurfural (HMF) usually runs with the formation of several side products. Among these, levulinic acid (LA) is often reported as the product of a consecutive reaction of HMF re-hydration. In this work, side reactions of the dehydration of FRU performed in very green conditions (water as solvent and niobic acid as solid catalyst) are taken into account. Experimental evidences are given that, in the used conditions: i) HMF is a final stable product, ii) no formation of LA, either deriving from a consecutive reaction of HMF or directly from FRU transformation, was observed, and iii) LA does not react to give condensation products with any other chemical species present in the reaction mixture.     

Structure–Activity Relationships of Benzenesulfonamide‐Based Inhibitors towards Carbonic Anhydrase Isoform Specificity

Carbonic anhydrases (CAs) are implicated in a wide range of diseases, including the upregulation of isoforms CA IX and XII in many aggressive cancers. However, effective inhibition of disease‐implicated CAs should minimally affect the ubiquitously expressed isoforms, including CA I and II, to improve directed distribution of the inhibitors to the cancer‐associated isoforms and reduce side effects. Four benzenesulfonamide‐based inhibitors were synthesized by using the tail approach and displayed nanomolar affinities for several CA isoforms. The crystal structures of the inhibitors bound to a CA IX mimic and CA II are presented. Further in silico modeling was performed with the inhibitors docked into CA I and XII to identify residues that contributed to or hindered their binding interactions. These structural studies demonstrated that active‐site residues lining the hydrophobic pocket, especially positions 92 and 131, dictate the positional binding and affinity of inhibitors, whereas the tail groups modulate CA isoform specificity. Geometry optimizations were performed on each ligand in the crystal structures and showed that the energetic penalties of the inhibitor conformations were negligible compared to the gains from active‐site interactions. These studies further our understanding of obtaining isoform specificity when designing small molecule CA inhibitors.     

VDACs Post-Translational Modifications Discovery by Mass Spectrometry: Impact on Their Hub Function

VDAC (voltage-dependent anion selective channel) proteins, also known as mitochondrial porins, are the most abundant proteins of the outer mitochondrial membrane (OMM), where they play a vital role in various cellular processes, in the regulation of metabolism, and in survival pathways. There is increasing consensus about their function as a cellular hub, connecting bioenergetics functions to the rest of the cell. The structural characterization of VDACs presents challenging issues due to their very high hydrophobicity, low solubility, the difficulty to separate them from other mitochondrial proteins of similar hydrophobicity and the practical impossibility to isolate each single isoform. Consequently, it is necessary to analyze them as components of a relatively complex mixture. Due to the experimental difficulties in their structural characterization, post-translational modifications (PTMs) of VDAC proteins represent a little explored field. Only in recent years, the increasing number of tools aimed at identifying and quantifying PTMs has allowed to increase our knowledge in this field and in the mechanisms that regulate functions and interactions of mitochondrial porins. In particular, the development of nano-reversed phase ultra-high performance liquid chromatography (nanoRP-UHPLC) and ultra-sensitive high-resolution mass spectrometry (HRMS) methods has played a key role in this field. The findings obtained on VDAC PTMs using such methodologies, which permitted an in-depth characterization of these very hydrophobic trans-membrane pore proteins, are summarized in this review.     

Peptide-containing aggregates as selective nanocarriers for therapeutics

New nanocarriers are obtained by assembling two amphiphilic monomers: one containing the bioactive peptide CCK8 spaced, by a polydisperse poly(ethylene glycol), from two hydrophobic tails ((C18)2PEG2000CCK8), and the other containing a chelating agent able to give stable radiolabeled indium-111 complexes linked to the same hydrophobic moiety ((C18)2DTPAGlu). The size and shape of the supramolecular aggregates were structurally characterized by dynamic light scattering, small-angle neutron scattering, and cryogenic transmission electronic microscopy. Under the experimental conditions we investigated (pH 7.4 and molar ratio between monomers 30:70), there is the presence of high polydisperse aggregates: rod-like micelles with a radius of approximately 40 A and length >700 A, open bilayer fragments with thickness approximately 65 A, and probably vesicles. The presence of the bioactive peptide well exposed on the external surface of the aggregate allows selective targeting of nanocarriers towards the cholecystokinin receptors overexpressed by the cancerous cells. In vitro binding assays and in vivo biodistribution studies by nuclear medicine experiments using indium-111 are reported. Moreover, preliminary data concerning the drug loading capability of the aggregates and their drug efficiency on the target cells is reported by using the cytotoxic drug doxorubicin. Incubation of receptor-positive and control cells with peptide-containing aggregates filled with doxorubicin shows significantly lower cell survival in receptor-expressing cells relative to the control, for samples incubated in the presence of doxorubicin.