Conformational Studies of Oligosaccharides

The conformation of a molecule strongly affects its function, as demonstrated for peptides and nucleic acids. This correlation is much less established for carbohydrates, the most abundant organic materials in nature. Recent advances in synthetic and analytical techniques have enabled the study of carbohydrates at the molecular level. Recurrent structural features were identified as responsible for particular biological activities or material properties. In this Minireview, recent achievements in the structural characterization of carbohydrates, enabled by systematic studies of chemically defined oligosaccharides, are discussed. These findings can guide the development of more potent glycomimetics. Synthetic carbohydrate materials by design can be envisioned.     

Proximity search heuristics for wind farm optimal layout

A heuristic framework for turbine layout optimization in a wind farm is proposed that combines ad-hoc heuristics and mixed-integer linear programming. In our framework, large-scale mixed-integer programming models are used to iteratively refine the current best solution according to the recently-proposed proximity search paradigm. Computational results on very large scale instances involving up to 20,000 potential turbine sites prove the practical viability of the overall approach.     

Rembrandt's Old Woman Praying, 1629/30: A look below the surface using X-ray fluorescence mapping

Rembrandt's painting Old Woman Praying, 1629/30, is the most valuable and exceptional work of art of the Residenzgalerie Salzburg (RGS). It is painted on a gilded copper plate with dimensions of only approximately 15 × 12 cm. The painting probably belongs to a series of three small-scale tronies, all executed on gilded copper plates. This particular picture preparation, which represents a special feature in Rembrandt's work, is quite unusual in the history of art. Previous investigations on the comparable paintings The Laughing Man, 1629/30, in the Mauritshuis, The Hague and the Self Portrait, 1630, in the National Museum, Stockholm showed that the gilding of the copper plate was applied over a lead white ground. To characterize the painting in the RGS, X-ray fluorescence (XRF) mapping was performed in a collaboration between the Research Office Residenzgalerie, Land Salzburg, the XGLab S.R.L, Milan, and the Conservation Science Department of the Kunsthistorische Museum Vienna (KHM). The results indicate a different structure for this painting than that used for The Laughing Man and the Self Portrait. The gilding was applied directly onto the copper plate, but with three areas with the gilding missing. It seems likely that in these sections, the gold was purposely removed to provide a different darker effect. XRF mapping yielded valuable insights into the structure of the painting and its technique as well as the principal pigments used for its composition.     

Isometric artifacts from polymerase chain reaction-massively parallel sequencing analysis of short tandem repeat loci: An emerging issue from a new technology?

The recent introduction of polymerase chain reaction (PCR)-massively parallel sequencing (MPS) technologies in forensics has changed the approach to allelic short tandem repeat (STR) typing because sequencing cloned PCR fragments enables alleles with identical molecular weights to be distinguished based on their nucleotide sequences. Therefore, because PCR fidelity mainly depends on template integrity, new technical issues could arise in the interpretation of the results obtained from the degraded samples. In this work, a set of DNA samples degraded in vitro was used to investigate whether PCR-MPS could generate “isometric drop-ins” (IDIs; i.e., molecular products having the same length as the original allele but with a different nucleotide sequence within the repeated units). The Precision ID GlobalFiler NGS STR panel kit was used to analyze 0.5 and 1 ng of mock samples in duplicate tests (for a total of 16 PCR-MPS analyses). As expected, several well-known PCR artifacts (such as allelic dropout, stutters above the threshold) were scored; 95 IDIs with an average occurrence of 5.9 IDIs per test (min: 1, max: 11) were scored as well. In total, IDIs represented one of the most frequent artifacts. The coverage of these IDIs reached up to 981 reads (median: 239 reads), and the ratios with the coverage of the original allele ranged from 0.069 to 7.285 (median: 0.221). In addition, approximately 5.2% of the IDIs showed coverage higher than that of the original allele. Molecular analysis of these artifacts showed that they were generated in 96.8% of cases through a single nucleotide change event, with the C > T transition being the most frequent (85.7%). Thus, in a forensic evaluation of evidence, IDIs may represent an actual issue, particularly when DNA mixtures need to be interpreted because they could mislead the operator regarding the number of contributors. Overall, the molecular features of the IDIs described in this work, as well as the performance of duplicate tests, may be useful tools for managing this new class of artifacts otherwise not detected by capillary electrophoresis technology.     

Therapeutic Potential of Highly Selective A3 Adenosine Receptor Ligands in the Central and Peripheral Nervous System

Ligands of the G_i protein-coupled adenosine A₃ receptor (A₃R) are receiving increasing interest as attractive therapeutic tools for the treatment of a number of pathological conditions of the central and peripheral nervous systems (CNS and PNS, respectively). Their safe pharmacological profiles emerging from clinical trials on different pathologies (e.g., rheumatoid arthritis, psoriasis and fatty liver diseases) confer a realistic translational potential to these compounds, thus encouraging the investigation of highly selective agonists and antagonists of A₃R. The present review summarizes information on the effect of latest-generation A₃R ligands, not yet available in commerce, obtained by using different in vitro and in vivo models of various PNS- or CNS-related disorders. This review places particular focus on brain ischemia insults and colitis, where the prototypical A₃R agonist, Cl-IB-MECA, and antagonist, MRS1523, have been used in research studies as reference compounds to explore the effects of latest-generation ligands on this receptor. The advantages and weaknesses of these compounds in terms of therapeutic potential are discussed.     

Synthesis of oligosaccharides corresponding to Vibrio cholerae O139 polysaccharide structures containing dideoxy sugars and a cyclic phosphate

A spacer-equipped tetrasaccharide, p-aminocyclohexylethyl alpha-l-Colp-(1-->2)-beta-d-Galp-(1-->3)-[alpha-l-Colp-(1-->4)]-beta-D-GlcpNAc, containing a 4,6-cyclic phosphate in the galactose residue, has been synthesised. The structure corresponds to a part of the repeating unit of the capsular (and lipo-) polysaccharide of the endemic bacteria Vibrio cholerae type O139 synonym Bengal. The synthetic strategy allows continuous syntheses of the complete O139 hexasaccharide repeating unit as well as of the structurally related repeating unit of serotype O22. Starting from ethyl 2-azido-4,6-O-benzylidene-2-deoxy-1-thio-beta-D-glucopyranoside, a thioglycoside tetrasaccharide donor block was constructed through two orthogonal glycosylations with glycosyl bromide donors. First, a properly protected galactose moiety was introduced using silver triflate as promoter and subsequently the two colitose residues, carrying electron-withdrawing protecting groups for stability reasons, under halide-assisted conditions. The tetrasaccharide block was then linked to the spacer in a NIS-TMSOTf-promoted coupling. Transformation of the azido group into an acetamido group using H2S followed by removal of temporary protecting acetyl groups gave a 4',6'-diol, which was next phosphorylated with methyl dichlorophosphate and deprotected to yield the 4,6-cyclic phosphate tetrasaccharide target structure.     

Combined depletion and electrostatic forces in polymer-induced membrane adhesion: a theoretical model

We develop a semi-quantitative analytical theory to describe adhesion between two identical planar charged surfaces embedded in a polymer-containing electrolyte solution. Polymer chains are uncharged and differ from the solvent by their lower dielectric permittivity. The solution mimics physiological fluids: It contains 0.1 M of monovalent ions and a small number of divalent cations that form tight bonds with the headgroups of charged lipids. The components have heterogeneous spatial distributions. The model was derived self-consistently by combining: (a) a Poisson-Boltzmann like equation for the charge densities, (b) a continuum mean-field theory for the polymer profile, (c) a solvation energy forcing the ions toward the polymer-poor regions, and (d) surface interactions of polymers and electrolytes. We validated the theory via extensive coarse-grained Molecular Dynamics (MD) simulations. The results confirm our analytical model and reveal interesting details not detected by the theory. At high surface charges, polymer chains are mainly excluded from the gap region, while the concentration of ions increases. The model shows a strong coupling between osmotic forces, surface potential and salting-out effects of the slightly polar polymer chains. It highlights some of the key differences in the behaviour of monomeric and polymeric mixed solvents and their responses to Coulomb interactions. Our main findings are: (a) the onset of long-ranged ion-induced polymer depletion force that increases with surface charge density and (b) a polymer-modified repulsive Coulomb force that increases with surface charge density. Overall, the system exhibits homeostatic behaviour, resulting in robustness against variations in the amount of charges. Applications and extensions of the model are briefly discussed.     

Sampling and digestion of waste mobile phones printed circuit boards for Cu,Pb, Ni,and Zn determination

Sampling is the most important procedure in arriving at the value of an electronic scrap. Inappropriate sampling makes other procedures, including assaying, valueless, as the sample must really represent the electronic scrap from which it was taken. The aim of this study was to develop the procedure to investigate the composition of heterogeneous printed circuit boards (PCBs) material and to show its applicability as well as its related limitations. The contents of Cu, Pb, Ni, and Zn in PCBs from wasted mobile phones were determined. Mixtures of aqua regia, hydrogen peroxide and hydrofluoric acid were applied to sample digestion. Open and closed vessel wet digestion with or without heating and microwave-assisted one was realized. For these purposes different sample amounts (0.2, 0.4, and 0.5 g) were applied and on the basis of calculated relative standard deviation values (RSD), the precision of repeated the most effective digestion was evaluated. The microwave-assisted wet digestion and mixture of aqua regia and hydrogen peroxide was found as the most effective one of the compared mixtures and applied conditions. A sample amount of 0.5 g was found as the most suitable. RSD values confirm the importance of electronic waste material sample preparation.     

Mechanistic Studies on the Organocatalytic α‐Chlorination of Aldehydes: The Role and Nature of Off‐Cycle Intermediates

Herein we report the isolation and characterization of aminal intermediates in the organocatalytic α‐chlorination of aldehydes. These species are stable covalent ternary adducts of the substrate, the catalyst and the chlorinating reagent. NMR‐assisted kinetic studies and isotopic labeling experiments with the isolated intermediate did not support its involvement in downstream stereoselective processes as proposed by Blackmond. By tuning the reactivity of the chlorinating reagent, we were able to suppress the accumulation of rate‐limiting off‐cycle intermediates. As a result, an efficient and highly enantioselective catalytic system with a broad functional group tolerance was developed.