A Sustainable Freeze‐Drying Route to Porous Polysaccharides with Tailored Hierarchical Meso‐ and Macroporosity

Bio‐derived polysaccharide aerogels are of interest for a broad range of applications. To date, these aerogels have been obtained through the time‐ and solvent‐intensive procedure of hydrogel fomation, solvent exchange, and scCO2 drying, which offers little control over meso/macropore distribution. A simpler and more versatile route is developed, using freeze drying to produce highly mesoporous polysaccharide aerogels with various degrees of macroporosity. The hierarchical pore distribution is controlled by addition of different quantities of t‐butanol (TBA) to hydrogels before drying. Through a systematic study an interesting relationship between the mesoporosity and t‐butanol/water phase diagram is found, linking mesoporosity maxima with eutectic points for all polysaccharides studied (pectin, starch, and alginic acid). Moreover, direct gelation of polysaccharides in aqueous TBA offers additional time savings and the potential for solvent reuse. This finding is a doorway to more accessible polysaccharide aerogels for research and industrial scale production, due to the widespread accessibility of the freeze drying technology and the simplicity of the method.

     

Enantioselective Synthesis of Acyclic Orthogonally Functionalized Compounds Bearing a Quaternary Stereocenter Using Chiral Ammonium Salt Catalysis

We herein report an asymmetric protocol to access a series of orthogonally functionalized acyclic chiral target molecules containing a quaternary stereogenic center by carrying out the enantioselective α-alkylation of novel orthogonally functionalized dioxolane-containing cyanoacetates under chiral ammonium salt catalysis. By using just 1 mol % of Maruoka's spirocyclic ammonium salt catalysts enantioselectivities up to e.r.=97.5 : 2.5 could be achieved and further functional group manipulations of the products were carried out as well.     

Extract from the Marine Seaweed Padina pavonica Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides

The identification of compounds which protect the double-membrane of mitochondrial organelles from disruption by toxic confomers of amyloid proteins may offer a therapeutic strategy to combat human neurodegenerative diseases. Here, we exploited an extract from the marine brown seaweed Padina pavonica (PPE) as a vital source of natural bioactive compounds to protect mitochondrial membranes against insult by oligomeric aggregates of the amyloidogenic proteins amyloid-β (Aβ), α-synuclein (α-syn) and tau, which are currently considered to be major targets for drug discovery in Alzheimer’s disease (AD) and Parkinson’s disease (PD). We show that PPE manifested a significant inhibitory effect against swelling of isolated mitochondria exposed to the amyloid oligomers, and attenuated the release of cytochrome c from the mitochondria. Using cardiolipin-enriched synthetic lipid membranes, we also show that dye leakage from fluorophore-loaded vesicles and formation of channel-like pores in planar bilayer membranes are largely prevented by incubating the oligomeric aggregates with PPE. Lastly, we demonstrate that PPE curtails the ability of Aβ42 and α-syn monomers to self-assemble into larger β-aggregate structures, as well as potently disrupts their respective amyloid fibrils. In conclusion, the mito-protective and anti-aggregator biological activities of Padina pavonica extract may be of therapeutic value in neurodegenerative proteinopathies, such as AD and PD.     

Characterization of Food Packaging Films with Blackcurrant Fruit Waste as a Source of Antioxidant and Color Sensing Intelligent Material

Chitosan and pectin films were enriched with blackcurrant pomace powder (10 and 20% (w/w)), as bio-based material, to minimize food production losses and to increase the functional properties of produced films aimed at food coatings and wrappers. Water vapor permeability of active films increased up to 25%, moisture content for 27% in pectin-based ones, but water solubility was not significantly modified. Mechanical properties (tensile strength, elongation at break and Young’s modulus) were mainly decreased due to the residual insoluble particles present in blackcurrant waste. FTIR analysis showed no significant changes between the film samples. The degradation temperatures, determined by DSC, were reduced by 18 °C for chitosan-based samples and of 32 °C lower for the pectin-based samples with blackcurrant powder, indicating a disturbance in polymer stability. The antioxidant activity of active films was increased up to 30-fold. Lightness and redness of dry films significantly changed depending on the polymer type. Significant color changes, especially in chitosan film formulations, were observed after exposure to different pH buffers. This effect is further explored in formulations that were used as color change indicators for intelligent biopackaging.     

Color Stabilization of Apulian Red Wines through the Sequential Inoculation of Starmerella bacillaris and Saccharomyces cerevisiae

Mixed fermentation using Starmerella bacillaris and Saccharomyces cerevisiae has gained attention in recent years due to their ability to modulate the qualitative parameters of enological interest, such as the color intensity and stability of wine. In this study, three of the most important red Apulian varieties were fermented through two pure inoculations of Saccharomyces cerevisiae strains or the sequential inoculation of Saccharomyces cerevisiae after 48 h from Starmerella bacillaris. The evolution of anthocyanin profiles and chromatic characteristics were determined in the produced wines at draining off and after 18 months of bottle aging in order to assess the impact of the different fermentation protocols on the potential color stabilization and shelf-life. The chemical composition analysis showed titratable acidity and ethanol content exhibiting marked differences among wines after fermentation and aging. The 48 h inoculation delay produced wines with higher values of color intensity and color stability. This was ascribed to the increased presence of compounds, such as stable A-type vitisins and reddish/violet ethylidene-bridge flavonol-anthocyanin adducts, in the mixed fermentation. Our results proved that the sequential fermentation of Starmerella bacillaris and Saccharomyces cerevisiae could enhance the chromatic profile as well as the stability of the red wines, thus improving their organoleptic quality.     

Pixel-by-pixel analysis of DCE MRI curve patterns and an illustration of its application to the imaging of the musculoskeletal system

Dynamic contrast enhanced (DCE) MRI is a widespread method that has found broad application in the imaging of the musculoskeletal (MSK) system. A common way of analyzing DCE MRI images is to look at the shape of the time-intensity curve (TIC) in pixels selected after drawing an ROI in a highly enhanced area. Although often applied to a number of MSK affections, shape analysis has so far not led to a unanimous correlation between these TIC patterns and pathology. We hypothesize that this might be a result of the subjective ROI approach. To overcome the shortcomings of the ROI approach (sampling error and interuser variability, among others), we created a method for a fast and simple classification of DCE MRI where time-curve enhancement shapes are classified pixel by pixel according to their shape. The result of the analysis is rendered in multislice, 2D color-coded images. With this approach, we show not only that differences on a short distance range of the TIC patterns are significant and cannot be appreciated with a conventional ROI analysis but also that the information that shape maps and conventional standard DCE MRI parameter maps convey are substantially different.     

Serendipitous Discovery of a Potent Influenza Virus A Neuraminidase Inhibitor

We have previously reported a potent neuraminidase inhibitor that comprises a carbocyclic analogue of zanamivir in which the hydrophilic glycerol side chain is replaced by the hydrophobic 3‐pentyloxy group of oseltamivir. This hybrid inhibitor showed excellent inhibitory properties in the neuraminidase inhibition assay (K_i=0.46 nM ; K_{i (zanamivir)}=0.16 nM ) and in the viral replication inhibition assay in cell culture at 10^?8 M . As part of this lead optimization, we now report a novel spirolactam that shows comparable inhibitory activity in the cell culture assay to that of our lead compound at 10^?7 M . The compound was discovered serendipitously during the attempted synthesis of the isothiourea derivative of the original candidate. The X‐ray crystal structure of the spirolactam in complex with the N8 subtype neuraminidase offers insight into the mode of inhibition.     

Molecular Recognition of Nucleotides in Water by Scorpiand‐Type Receptors Based on Nucleobase Discrimination

The detection of nucleotides is of crucial importance because they are the basic building blocks of nucleic acids. Scorpiand‐based polyamine receptors functionalized with pyridine or anthracene units are able to form stable complexes with nucleotides in water, based on coulombic, π–π stacking, and hydrogen‐bonding interactions. This behavior has been rationalized by means of an exploration with NMR spectroscopy and DFT calculations. Binding constants were determined by potentiometry. Fluorescence spectroscopy studies have revealed the potential of these receptors as sensors to effectively and selectively distinguish guanosine‐5′‐triphosphate (GTP) from adenosine‐5′‐triphosphate (ATP).     

Enzymatic Building-Block Synthesis for Solid-Phase Automated Glycan Assembly

Automated chemical oligosaccharide synthesis is an attractive concept that has been successfully applied to a large number of target structures, but requires excess quantities of suitably protected and activated building blocks. Herein we demonstrate the use of biocatalysis to supply such reagents for automated synthesis. By using the promiscuous NmLgtB-B β1-4 galactosyltransferase from Neisseria meningitidis we demonstrate fast and robust access to the LacNAc motif, common to many cell-surface glycans, starting from either lactose or sucrose as glycosyl donors. The enzymatic product was shown to be successfully incorporated as a complete unit into a tetrasaccharide target by automated assembly.