Enhancement of selectivity and resolution in the enantioseparation of uncharged compounds using mixtures of oppositely charged cyclodextrins in capillary electrophoresis

The enantiomeric separation of some nonsteroidal anti-inflammatory drugs (NSAIDs) was investigated in capillary electrophoresis (CE) using dual systems with mixtures of charged cyclodextrin (CD) derivatives. A significant enhancement of selectivity and resolution could be achieved in the enantioseparation of these analytes in their uncharged form by the simultaneous addition of two oppositely charged CD derivatives to the background electrolyte. The combination of the single-isomer cationic CD, permethyl-6-monoamino-6-monodeoxy-beta-CD (PMMAbetaCD) and the single-isomer polyanionic CD, heptakis-6-sulfato-beta-cyclodextrin (HSbetaCD) in a pH 2.5 phosphoric acid-triethanolamine buffer, was designed and employed for the enantioseparation of profens. The improvement in selectivity and resolution can be attributed to the fact that the two CDs, which lead to independent and enantioselective complexation with the analyte enantiomers, have not only opposite effects on the electrophoretic mobility of these compounds but also opposite affinity patterns towards the enantiomers of these compounds. Binding constants for these enantiomers with each CD were determined using linear regression approach, in order to be able to predict the effect of the concentrations of the two CDs on enantiomeric selectivity and resolution in such dual systems.     

Synergistic effects of ion-pairing in the enantiomeric separation of basic compounds with cyclodextrin derivatives in nonaqueous capillary electrophoresis

The enantiomeric separation of various kinds of basic pharmaceuticals has been investigated in nonaqueous capillary electrophoresis (NACE) systems using an ion-pairing reagent in combination with cyclodextrins (CDs). The simultaneous addition to the methanolic background electrolyte (BGE) of (+)-S-camphorsulfonate or alkanesulfonates and an anionic beta-cyclodextrin derivative, heptakis(2,3-dimethyl-6-sulfato)-beta-cyclodextrin (HDMS-beta-CD), led to partial or complete enantioresolution in most cases. In the absence of ion-pairing reagent, the enantiomeric resolution obtained with this CD derivative was most often completely lost or strongly reduced, indicating the important role of ion-pairing in the chiral recognition mechanism in these NACE systems. The influence of the nature and concentration of the counterion and the anionic CD derivative on the enantioseparation of basic compounds was studied. Synergistic effects between these two kinds of charged additives were clearly observed.     

A versatile toolbox for variable DNA functionalization at high density

To broaden the applicability of chemically modified DNAs in nano- and biotechnology, material science, sensor development, and molecular recognition, strategies are required for introducing a large variety of different modifications into the same nucleic acid sequence at once. Here, we investigate the scope and limits for obtaining functionalized dsDNA by primer extension and PCR, using a broad variety of chemically modified deoxynucleotide triphosphates (dNTPs), DNA polymerases, and templates. All natural nucleobases in each strand were substituted with up to four different base-modified analogues. We studied the sequence dependence of enzymatic amplification to yield high-density functionalized DNA (fDNA) from modified dNTPs, and of fDNA templates, and found that GC-rich sequences are amplified with decreased efficiency as compared to AT-rich ones. There is also a strong dependence on the polymerase used. While family A polymerases generally performed poorly on "demanding" templates containing consecutive stretches of a particular base, family B polymerases were better suited for this purpose, in particular Pwo and Vent (exo-) DNA polymerase. A systematic analysis of fDNAs modified at increasing densities by CD spectroscopy revealed that single modified bases do not alter the overall B-type DNA structure, regardless of their chemical nature. A density of three modified bases induces conformational changes in the double helix, reflected by an inversion of the CD spectra. Our study provides a basis for establishing a generally applicable toolbox of enzymes, templates, and monomers for generating high-density functionalized DNAs for a broad range of applications.     

Corrosion on prehistoric Cu–Sn-alloys: the influence of artificial environment and storage

The paper contributes to the identification of different corrosion products detected on the cross-section specimens sampled from Bronze Age swords and one helmet found between 60–160 years ago. The objects are kept in 1889 built oak showcases at the Natural History Museum Vienna, having suffered unknown restoration treatments. The identified corrosion products not only affect further eventual treatment in conservation science of copper base objects but also contribute to identify the often unknown find context, which is meant to facilitate archaeological interpretation of the Bronze Age weapons. The analyses of the samples were carried out using SEM-EDXS-EBSD and optical microscopy.     

On applicability of PCA,voxel-wise variance normalization and dimensionality assumptions for sliding temporal window sICA in resting-state fMRI

Subject-level resting-state fMRI (RS-fMRI) spatial independent component analysis (sICA) may provide new ways to analyze the data when performed in the sliding time window. However, whether principal component analysis (PCA) and voxel-wise variance normalization (VN) are applicable pre-processing procedures in the sliding-window context, as they are for regular sICA, has not been addressed so far. Also model order selection requires further studies concerning sliding-window sICA. In this paper we have addressed these concerns. First, we compared PCA-retained subspaces concerning overlapping parts of consecutive temporal windows to answer whether in-window PCA and VN can confound comparisons between sICA analyses in consecutive windows. Second, we compared the PCA subspaces between windowed and full data to assess expected comparability between windowed and full-data sICA results. Third, temporal evolution of dimensionality estimates in RS-fMRI data sets was monitored to identify potential challenges in model order selection in a sliding-window sICA context. Our results illustrate that in-window VN can be safely used, in-window PCA is applicable with most window widths and that comparisons between windowed and full data should not be performed from a subspace similarity point of view. In addition, our studies on dimensionality estimates demonstrated that there are sustained, periodic and very case-specific changes in signal-to-noise ratio within RS-fMRI data sets. Consequently, dimensionality estimation is needed for well-founded model order determination in the sliding-window case. The observed periodic changes correspond to a frequency band of ≤ 0.1 Hz, which is commonly associated with brain activity in RS-fMRI and become on average most pronounced at window widths of 80 and 60 time points (144 and 108 s, respectively). Wider windows provided only slightly better comparability between consecutive windows, and 60 time point or shorter windows also provided the best comparability with full-data results. Further studies are needed to determine the cause for dimensionality variations.     

Enantioselective Syntheses of the Methylene- and Fluoromethylene-Phosphonate Analogues of 3-Phospho-D-Glyceric Acid

Abstract

The racemic methylene analogue of 3-phospho-D-glyceric acid^1–4 has been shown to be a viable substrate for the combined action of 3-phosphoglycerate kinase, PGK, and glyceraldehyde 3-phosphate dehydrogenase, GPD. We have shown that replacement of CH₂ by CHF or CF₂ in a variety of nucleotide analogues^4,5 can lead to improved Performance as enzyme substrates or inhibitors. We have therefore undertaken enantiospecific syntheses of the methylene- and fluoro-methylene-analogues of 3-phospho-D-glyceric acid to investigate their interaction with PGK and GPD and explore whether the fluorine atom in the latter can mimic an oxygen lone-pair in binding to enzymes.     

Fiber crystal growth from the melt for non-linear optical applications

During several years, we have been involved in the growth and characterization of non-linear optical crystals by the two most common techniques for growing single-crystal fibers from the melt: laser-heated pedestal growth and micro-pulling down. Their specific features are presented in this study and their versatility is demonstrated through two typical examples of incongruently melting materials: K₃Li_2?xNb_5+xO_15+2x (solid solution of the ternary system K₂O–Li₂O–Nb₂O₅) and Ca₅(BO₃)₃F which can only be grown from a flux.