Electrophoretic separation strategy for chiral pharmaceuticals using highly-sulfated and neutral cyclodextrins based dual selector systems

The enantiomeric separation of chiral pharmaceuticals was investigated using dual systems with mixtures of cyclodextrin derivatives. The dual cyclodextrin systems, consisting of one highly-sulfated (α-, β-, and γ-HSCD) and one neutral cyclodextrin, i.e. either heptakis (2,3,6-tri-O-methyl)-β-CD (TMCD), heptakis (2,6-di-O-methyl)-β-CD (DMCD) or hydroxypropyl-β-CD (HPCD), are tested on 25 pharmaceutical compounds with different acid-basic properties (16 basics, 8 acids and 1 neutral). The influence on the separation of the type and concentration of neutral CD in highly-sulfated cyclodextrins-based dual selector systems, is investigated. For 11 of 16 basic compounds, a better separation is obtained with the CD mixtures compared to the use of only a highly-sulfated CD. Mixtures with TMCD give better results than those with DMCD and HPCD. Results showed that dual CD systems are useful to achieve and to optimise chiral separations of compounds not (sufficiently) separated with HSCDs alone. For example, ibuprofen was not resolved with α-, β- or γ-HSCD, but could be separated with the mixture 25 mM TMCD and 5% HS-β-CD. Based on the obtained results, a dual CD systems based separation strategy is defined.     

Fragment‐Based Drug Design Facilitated by Protein‐Templated Click Chemistry: Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin

There is an urgent need for the development of efficient methodologies that accelerate drug discovery. We demonstrate that the strategic combination of fragment linking/optimization and protein‐templated click chemistry is an efficient and powerful method that accelerates the hit‐identification process for the aspartic protease endothiapepsin. The best binder, which inhibits endothiapepsin with an IC₅₀ value of 43 μm , represents the first example of triazole‐based inhibitors of endothiapepsin. Our strategy could find application on a whole range of drug targets.     

Efficient purification and metabolite analysis of radiotracers using high-performance liquid chromatography and on-line solid-phase extraction

This study describes an efficient method using on-line solid-phase extraction (SPE) (Oasis HLB) for preparative HPLC purification of short-lived radiotracers for positron emission tomography (PET) and for HPLC analysis of radiotracers and their metabolites in cell homogenates, plasma and urine samples. The radiochemical purity of tracers (fluorine-18 labeled) purified using this method (Oasis column) was >99% compared to 90% when no Oasis column was used. Radiometabolites of several fluorine-18 and carbon-11-labeled tracers and one technetium-99m tracer were quantified in cell homogenates, plasma and urine samples. Samples were analyzed using Oasis column and analytical HPLC system without prior precipitation of proteins or removal of other biological matrices. The metabolites observed for the evaluated tracers were all polar relative to the unchanged tracer. The extraction repeatability was found to be good (RSD 2.2%) and recoveries of Oasis column/HPLC-injected radioactivity (plasma) were found to be high (mean recovery >91%). The same Oasis column was used for several times without back pressure build-up or decrease of the HPLC separation characteristics.     

Can block copolymers be synthesized by a single-step chemoenzymatic route in supercritical carbon dioxide?

We demonstrate the single-step one-pot synthesis of block copolymers by simultaneous enzymatic ring-opening polymerization and chemically catalyzed atom transfer radical polymerization in supercritical carbon dioxide. Both catalyst systems function simultaneously under these conditions, providing a simple route to the formation of block copolymers of dissimilar monomers.     

Intramolecular switching between dipolar resonance structures in singlet and triplet excited states detected by TRMC

Transient changes in the real and imaginary component of the complex permittivity of a flash-photolyzed solution can be monitored with nanosecond time resolution using the time-resolved microwave conductivity (TRMC) technique. Effects caused by rapid (picosecond), flip—flop switching between dipolar resonance structures in the S₁ and T₁ states of molecules with mirror symmetry have been observed.     

Quantitative determination of carbon concentration profiles by GD‐OES for the study of decarburization in low‐carbon steels

In this study, the quantification of decarburization induced during the annealing process for the fabrication of electrical steels was carried out using glow discharge optical emission spectroscopy (GD‐OES). Different calibration methods, based on external and internal standard references, were examined to optimize the quantification of carbon concentration. Accurate calibration curves for carbon at low concentration ranges were achieved by the use of carbon intensity calibrated by the internal reference, i.e. iron intensity line. This methodology was found to be beneficial for long GD‐OES measurements, providing a better correction over changes in the overall emission intensity with the sputter time. The good depth resolution obtained by the GD‐OES technique enabled the identification of specific features in the steel microstructure related to carbide coarseness. Quantitative carbon concentration profiles were obtained by GD‐OES to evaluate the decarburization effect on the microstructure of low‐carbon steels considering different initial microstructures. The effect of the spatial distribution of carbides in these microstructures on the decarburization kinetics was also studied. Through quantitative determination of carbon elemental profiles by GD‐OES, information about the morphology of the cementite in the microstructure and its development in relation to decarburization was acquired. The depth of decarburization can accurately be determined. On the basis of the global results, GD‐OES thus emerged as being a fast and reliable technique for a better understanding of decarburization kinetics. Copyright © 2015 John Wiley & Sons, Ltd.     

Collective adjustment of pension rights in ALM models

Collective adjustment of pension rights is a way to keep defined benefit systems tenable. In asset liability management (ALM) models presented in the literature these decisions are modeled both at the aggregate level of the liabilities as a whole and at a more detailed level. In this paper we compare the approximate aggregate approach to the accurate detailed approach for the average earnings scheme with conditional indexation. We prove that the aggregate approach leads to one-sided errors. Moreover, we show that for semi-realistic data these biases are considerable.