Development of a generic micellar electrokinetic chromatography method for the separation of 15 antimalarial drugs as a tool to detect medicine counterfeiting

Since antimalarial drugs counterfeiting is dramatically present on the African market, the development of simple analytical methods for their quality control is of great importance. This work consists in the CE analysis of 15 antimalarials (artesunate, artemether, amodiaquine, chloroquine, piperaquine, primaquine, quinine, cinchonine, mefloquine, halofantrine, sulfadoxine, sulfalen, atovaquone, proguanil, and pyrimethamine). Since all these molecules cannot be ionized at the same pH, MEKC was preferred because it also allows separation of neutral compounds. Preliminary experiments were first carried out to select the most crucial factors affecting the antimalarials separation. Several conditions were tested and four parameters as well as their investigation domain were chosen: pH (5-10), SDS concentration (20-90 mM), ACN proportion (10-40%), and temperature (20-35°C). Then, the experimental design methodology was used and a central composite design was selected. Mathematical modeling of the migration times allowed the prediction of optimal conditions (29°C, pH 6.6, 29 mM SDS, 36% ACN) regarding analyte separation. The prediction at this optimum was verified experimentally and led to the separation of 13 compounds within 8 min. Finally, the method was successfully applied to the quality control of African antimalarial medicines for their qualitative and quantitative content.     

Holography and micro-holography of particle fields: A numerical standard

Holography is an ‘old’ technique for studying the behavior of clouds of droplets which finds a new interest with CCD cameras and real-time numerical reconstruction. Furthermore, the continued progress in camera characteristics (sensitivity, pixel number, digitalization level, and so on) opens the way to more accurate recording of the interference field. To gain a deep understanding of the technique, as well as an evaluation of the performance and limitations of digital holographic particle measurements under various conditions, standard holograms are required. In this paper, a general numerical standard of holograms of fields of particles based on rigorous near-field Lorenz–Mie scattering theory is presented. This theory makes possible the computation of holograms of fields of particles with an arbitrary number of particles of arbitrary size, arbitrary refractive index, arbitrary recording distance (near-field or far-field), and an arbitrary collecting angle (forward, off-axis, or backward scattering light). Several calculation examples are also given for the code validation and possible applications, including a new possible way to simultaneously measure the size, location, and refractive index of particles.     

On the Design of Zinc‐Finger Models with Cyclic Peptides Bearing a Linear Tail

Cyclic peptides with a linear tail (CPLT) have been successfully used to model two zinc fingers (ZFs) adopting the treble‐clef‐ and loosened zinc‐ribbon folds. In this article, we examine the factors that may influence the design of such ZF models: mutations in the sequence, size of the cycle, and size of the tail. For this purpose, several peptides derived from the CPLT‐based models of the treble‐clef‐ and loosened zinc‐ribbon ZF were synthesized and studied. CPLT‐based models appear to be robust toward mutations, accommodate various cycle sizes, and are sensible to the size of the linking region of the tail located between the cycle and the coordinating amino acids. Based on these criteria, we describe the design of a new CPLT‐based model for the zinc‐ribbon ZFs, L_ZR, and compare it to a linear analogue, L_ZR^lin. The model complex Zn ? L_ZR is able to fold correctly around the metal ion contrary to Zn ? L_ZR^lin, suggesting that CPLT‐based models are more likely to yield structurally meaningful models of ZF sites than linear peptide models. Finally, we draw some rules that could allow the design of new CPLT‐based metallopeptides with a controlled fold.     

Suzuki-Miyaura cross-coupling and ring-closing metathesis: a strategic combination to the synthesis of indeno[1,2-c]isoquinolin-5,11-diones

A variety of diversely substituted isoindeno[1,2-c]isoquinolin-5,11-diones has been readily assembled through a sequence involving a Suzuki-Miyaura cross-coupling reaction with enol phosphates combined with a ring-closing metathesis (RCM) reaction. Intramolecular carbocationic annulation reaction and ultimate oxidation of a latent hydroxyl functionality completed the synthesis of the target titled compounds.     

Photochemical electron transfer mediated addition of naphthylamine derivatives to electron-deficient alkenes

Using photochemical electron transfer, N,N-dimethylnaphthylamine derivatives are added to α,β-unsaturated carboxylates. The addition takes place exclusively in the α-position of electron-deficient alkenes and mainly in the 4-position of N,N-dimethylnaphthalen-1-amine. A minor regioisomer results from the addition in the 5-position of this naphthylamine. A physicochemical study reveals that the fluorescence quenching of N,N-dimethylnaphthalen-1-amine is diffusion-controlled and that the back electron transfer is highly efficient. Therefore no transformation is observed at lower concentrations. To overcome this limitation and to induce an efficient transformation, minor amounts of water or another proton donor as well as an excess of the naphthylamine derivative are necessary. A mechanism involving a contact radical ion pair is discussed. Isotopic labeling experiments reveal that no hydrogen is directly transferred between the substrates. The hydrogen transfer to the furanone moiety observed in the overall reaction therefore results from an exchange with the reaction medium. An electrophilic oxoallyl radical generated from the furanone reacts with the naphthylamine used in excess. Concerning some mechanistic details, the reaction is compared with radical and electrophilic aromatic substitutions. The transformation was carried out with a variety of electron-deficient alkenes. Sterically hindered furanone derivatives are less reactive under standard conditions. In a first experiment, such a compound was transformed using heterogeneous electron transfer photocatalysis with TiO(2).     

Evaluating the reliability of analytical results using a probability criterion: a Bayesian perspective

Methods validation is mandatory in order to assess the fitness of purpose of the developed analytical method. Of core importance at the end of the validation is the evaluation of the reliability of the individual results that will be generated during the routine application of the method. Regulatory guidelines provide a general framework to assess the validity of a method, but none address the issue of results reliability. In this study, a Bayesian approach is proposed to address this concern. Results reliability is defined here as "the probability (π) of an analytical method to provide analytical results (X) within predefined acceptance limits (±λ) around their reference or conventional true concentration values (μ(T)) over a defined concentration range and under given environmental and operating conditions." By providing the minimum reliability probability (π(min)) needed for the subsequent routine application of the method, as well as specifications or acceptance limits (±λ), the proposed Bayesian approach provides the effective probability of obtaining reliable future analytical results over the whole concentration range investigated. This is summarised in a single graph: the reliability profile. This Bayesian reliability profile is also compared to two frequentist approaches, the first one derived from the work of Dewé et al. [W. Dewé, B. Govaerts, B. Boulanger, E. Rozet, P. Chiap, Ph. Hubert, Chemometr. Intell. Lab. Syst. 85 (2007) 262-268] and the second proposed by Govaerts et al. [B. Govaerts, W. Dewé, M. Maumy, B. Boulanger, Qual. Reliab. Eng. Int. 24 (2008) 667-680]. Furthermore, to illustrate the applicability of the Bayesian reliability profile, this approach is also applied here to a bioanalytical method dedicated to the determination of ketoglutaric acid (KG) and hydroxymethylfurfural (HMF) in human plasma by SPE-HPLC-UV.     

Dielectric relaxations in polyhydroxyalkanoates/organoclay nanocomposites

Two types of bacterial semi-crystalline copolyesters, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB4HB) are studied neat or with 8 wt% of Cloisite® C30B (C30B) organoclays. Wide Angle X-ray Diffraction (WAXD) and Differential Scanning Calorimetry (DSC) reveal that the nanoclays are partially intercalated, exfoliated and agglomerated. With selected sample preparation, the crystalline phase is unaffected by the C30B presence. Broadband Dielectric Spectroscopy (BDS) measurements showed no influence of the nanoclays on the secondary local relaxations modes of both polymers and on the segmental relaxation of P3HB4HB. Nevertheless, a strong modification of the α relaxation of PHBV has been observed after incorporation of C30B. A strong decrease of the fragility index and of the glass transition temperature revealed an increase of the molecular mobility in the amorphous fraction influenced by the nanoclays.     

A Convenient Synthesis of 3-Aryl-2-Methyl-3,4-Dihydro-1(2H)-Isoquinolones and -1,2,3,4-Tetrahydroisoquinolines

A new methodology for the synthesis of 3-aryl-2-methyl-3,4-dihydro-2H-isoquinolin-l-ones and 3-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines is reported.     

Combination of electrostrictive polymers composites and electrets for energy harvesting capability

More recently, the development of electrostrictive polymers has generated novel opportunities for high‐strain actuators. At present, the investigation of using electrostrictive polymers for energy harvesting is beginning to show potential for this application. Basically, the relative energy gain depends on the current induced by the mechanical strain and frequency. The aim of the present experimental work is to study the composites on the basis of terpolymer P(VDF–TrFE–CFE) filled with low concentrations of copper (Cu) powders. The scanning electron microscopy was performed essentially to verify the dispersion of the fillers within the polymeric matrix. The obtained results showed a relatively homogeneous dispersion for the microsized fillers and the existence of agglomerates for their nanosized counterparts. On the other hand, our experimental data show that the harvested power as well as the current is significantly important for nano‐Cu fillers with respect to micro‐Cu fillers by a factor of 45.9% in the case of the hybridization of electrostrictive polymers and electrets. Copyright © 2014 John Wiley & Sons, Ltd.