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.     

Screening and confirmation methods for GHB determination in biological fluids

The purpose of this review is to provide a comprehensive overview of reported methods for screening and confirmation of the low-molecular-weight compound and drug of abuse gamma-hydroxybutyric acid (GHB) in biological fluids. The polarity of the compound, its endogenous presence, its rapid metabolism after ingestion, and its instability during storage (de novo formation and interconversion between GHB and its lactone form gamma-butyrolactone) are challenges for the analyst and for interpretation of a positive result. First, possible screening procedures for GHB are discussed, including colorimetric, enzymatic, and chromatography-based procedures. Confirmation methods for clinical and forensic cases mostly involve gas chromatography (coupled to mass spectrometry), although liquid chromatography and capillary zone electrophoresis have also been used. Before injection, sample-preparation techniques include (a combination of) liquid–liquid, solid-phase, or headspace extraction, and chemical modification of the polar compound. Also simple “dilute-and-shoot” may be sufficient for urine or serum. Advantages, limitations, and trends are discussed.     

Carbon monoxide adsorption on silver doped gold clusters

Well controlled gas phase experiments of the size and dopant dependent reactivity of gold clusters can shed light on the surprising discovery that nanometer sized gold particles are catalytically active. Most studies that investigate the reactivity of gold clusters in the gas phase focused on charged, small sized clusters. Here, reactivity measurements in a low-pressure reaction cell were performed to investigate carbon monoxide adsorption on neutral bare and silver doped gold clusters (Au(n)Ag(m); n = 10-45; m = 0, 1, 2) at 140 K. The size dependence of the reaction probabilities reflects the role of the electronic shells for the carbon monoxide adsorption, with closed electronic shell systems being the most reactive. In addition, the cluster's reaction probability is reduced upon substitution of gold atoms for silver. Inclusion of a single silver atom causes significant changes in the reactivity only for a few cluster sizes, whereas there is a more general reduction in the reactivity with two silver atoms in the cluster. The experimental observations are qualitatively explained on the basis of a Blyholder model, which includes dopant induced features such as electron transfer from silver to gold, reduced s-d hybrization, and changes in the cluster geometry.     

Chromophores from hexeneuronic acids: chemical behavior under peroxide bleaching conditions

Hexeneuronic acids (HexA) are a major cause of discoloration (yellowing/brightness reversion) in pulps from xylan-containing wood, being generated from the xylan’s 4-O-methylglucuronic acid residues. The HexA-derived chromophores, whose identification and structure confirmation have been described in the previous part of this series (Rosenau et al. in Cellulose, 2017), were subject to conditions of peroxide bleaching, i.e. treatment with hydrogen peroxide in alkaline medium. These chromophores, ladder-type oligomers of mixed aromatic-quinoid and mixed furanoid-benzoid character, are degraded relatively quickly to one major product, 2,5-dihydroxy-[1,4]-benzoquinone (DHBQ), and a minor component, 2,5-dihydroxyacetophenone (DHA). These two compounds, which have already been identified as two of the three key chromophores (besides 5,8-dihydroxy-[1,4]-naphthoquinone, DHNQ) in aged cellulosics, are potent chromophores themselves and are subsequently more slowly degraded to non-colored degradation products, according to pathways already described in previous parts of this series. The occurrence of DHBQ and DHA in the bleaching treatment of the HexA-derived chromophores establishes the link between HexA chemistry and the key chromophore classes of residual chromophores found in aged cellulosic materials.     

Objective Vocal Quality in Children Using Cochlear Implants: A Multiparameter Approach

Objectives

The purpose of this study was to determine the objective vocal quality in 36 prelingually deaf children using cochlear implant (CI) with a mean age of 9 years. An additional purpose was to compare the objective vocal quality of these 36 CI users with 25 age-matched children with prelingual severe hearing loss using conventional hearing aids (HAs) and 25 normal hearing (NH) children.

Study Design

The design for this cross-sectional study was a multigroup posttest-only design.

Methods

The objective vocal quality was measured by means of the dysphonia severity index (DSI). Moreover, perceptual voice assessment using the GRBASI scale was performed.

Results

CI children have a vocal quality by means of the DSI of +1.8, corresponding with a DSI% of 68%, indicating a borderline vocal quality situated 2% above the limit of normality. The voice was perceptually characterized by the presence of a very slight grade of hoarseness, roughness, strained phonation, and higher pitch and intensity levels. No significant objective vocal quality differences were measured between the voices of the CI children, HA users, and NH children.

Conclusions

According to the results, one aspect of the vocal approach in children with CI and using HAs must be focused on the improvement of the strained vocal characteristic and the use of a lower pitch and intensity level.     

Growth Mechanism and Chemical Bonding in Scandium‐Doped Copper Clusters: Experimental and Theoretical Study in Concert

Size matters! The electronic structure and size‐dependent stability of neutral and cationic scandium‐doped copper clusters have been investigated by mass spectrometric studies (for the cations) and also quantum chemical computations. The proposed reaction paths ultimately lead to the most stable Frank–Kasper‐shaped Cu₁₆Sc⁺ cluster (shown here), which could be the germ of a new crystallization process.

     

Finding short and implementation-friendly addition chains with evolutionary algorithms

Finding the shortest addition chain for a given exponent is a significant problem in cryptography. In this work, we present a genetic algorithm with a novel encoding of solutions and new crossover and mutation operators to minimize the length of the addition chains corresponding to a given exponent. We also develop a repair strategy that significantly enhances the performance of our approach. The results are compared with respect to those generated by other metaheuristics for exponents of moderate size, but we also investigate values up to \(2^{255} - 21\). For numbers of such size, we were unable to find any results produced by other metaheuristics which could be used for comparison purposes. Therefore, we decided to add three additional strategies to serve as benchmarks. Our results indicate that the proposed approach is a very promising alternative to deal with this problem. We also consider a more practical perspective by taking into account the implementation cost of the chains: we optimize the addition chains with regards to the type of operations as well as the number of instructions required for the implementation.     

Enantiomeric impurity determination in capillary electrophoresis using a highly-sulfated cyclodextrins-based method

Capillary electrophoresis (CE), using highly-sulfated cyclodextrins as chiral selectors, has been applied to determine the chiral purity of pharmaceutical compounds. A chiral separation strategy, developed earlier for racaemic mixtures, was applied on four basic drugs (propranolol, atenolol, chlorpheniramine and tryptophan methylester). The aim was to develop validated separation methods which allow determination of 0.1% impurity levels of the unwanted enantiomers (distomer) in the presence of 99.9% of the active compound (eutomer). The linearity, quantification limits for the trace enantiomers and the precision of the measurements were determined. In a second part, impurity separations have been simulated in order to evaluate the required resolution when assaying impurities. It is shown that a baseline resolution of 1.5, generally accepted for racaemic mixtures, does not always allow good impurity determinations. Two alternative methods to solve this problem have been proposed.