Die Anwendung von Kaliummanganat in der quantitativen Analyse

Zusammenfassung Die oxydimetrische Analyse einer großen Anzahl von organischen und anorganischen Verbindungen mit Kaliummanganat bei 60°C in 1–3 m Lauge wurde untersucht. In vielen Fällen ergaben sich stöchiometrische Reaktionen, die eine genaue quantitative Bestimmung ermöglichen, z. B. bei Ameisensäure, Milchsäure, Glykolsäure, Äpfelsäure, Brenztraubensäure, verschiedenen Zuckern, Alkoholen, Formaldehyd, Cyanid und einigen schwefelhaltigen anorganischen Verbindungen. Bei Weinsäure, Fumarsäure und Maleinsäure wurden um einige Prozent zu niedrige Ergebnisse erhalten, während die Analyse von Äthanol und Citronensäure überhaupt nicht möglich war.Bei den schwer oxydierbaren Verbindungen erwies sich die Stabilität der Manganatlösungen in Lauge während längerer Zeit bei erhöhter Temperatur als ein großer Vorteil. Insbesondere bei der Bestimmung kleiner Mengen solcher Stoffe ist Manganat in alkalischer Lösung dem Permanganat in saurer Lösung weit überlegen.     

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.     

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.     

Time-resolved vibrational spectroscopy of a molecular shuttle

Time-resolved vibrational spectroscopy is used to investigate the inter-component motion of an ultraviolet-triggered two-station molecular shuttle. The operation cycle of this molecular shuttle involves several intermediate species, which are observable in the amide I and amide II regions of the mid-IR spectrum. Using ab initio calculations on specific parts of the rotaxane, and by comparing the transient spectra of the normal rotaxane with that of the N-deuterated version, we can assign the observed vibrational modes of each species occurring during the shuttling cycle in an unambiguous way. The complete time- and frequency-dependent data set is analyzed using singular value decomposition (SVD). Using a kinetic model to describe the time-dependent concentrations of the transient species, we derive the absorption spectra associated with each stage in the operation cycle of the molecular shuttle, including the recombination of the charged species.     

Cohen’s linearly weighted kappa is a weighted average

An n × n agreement table F?=?{f _ij } with n ?? 3 ordered categories can for fixed m?(2??? m??? n ? 1) be collapsed into ${\binom{n-1}{m-1}}$ distinct m × m tables by combining adjacent categories. It is shown that the components (observed and expected agreement) of Cohen??s weighted kappa with linear weights can be obtained from the m × m subtables. A consequence is that weighted kappa with linear weights can be interpreted as a weighted average of the linearly weighted kappas corresponding to the m?× m tables, where the weights are the denominators of the kappas. Moreover, weighted kappa with linear weights can be interpreted as a weighted average of the linearly weighted kappas corresponding to all nontrivial subtables.     

Chiral separation strategy in polar organic solvent chromatography and performance comparison with normal-phase liquid and supercritical-fluid chromatography

A strategy, including a rapid screening and several optimisation steps, for the separation of chiral molecules of pharmaceutical interest by polar organic solvent chromatography (POSC), using four polysaccharide-based stationary phases, is proposed and compared with previously reported strategies in normal-phase (NPLC) and supercritical fluid chromatography (SFC). In a first part of this paper, different examples demonstrate the effectiveness of the POSC strategy for fast method development. Optimisation is based on the use of experimental design to map the experimental domain in an efficient way. In the second part, the best screening results, obtained after performance of earlier defined chromatographic screening strategies in NPLC and SFC, are compared to those obtained in POSC. The three techniques show complementary separation results and allowed baseline separation of 23 of 25 compounds. POSC is found to be a very interesting separation mode compared to NPLC, because of the many fast (< 10 min) baseline separations obtained.