Identification and validation of tetracyclic benzothiazepines as Plasmodium falciparum cytochrome bc1 inhibitors

Here we report the discovery of tetracyclic benzothiazepines (BTZs) as highly potent and selective antimalarials along with the identification of the Plasmodium falciparum cytochrome bc₁ complex as the primary functional target of this novel compound class. Investigation of the structure activity relationship within this previously unexplored chemical scaffold has yielded inhibitors with low nanomolar activity. A combined approach employing genetically modified parasites, biochemical profiling, and resistance selection validated inhibition of cytochrome bc₁ activity, an essential component of the parasite respiratory chain and target of the widely used antimalarial drug atovaquone, as the mode of action of this novel compound class. Resistance to atovaquone is eroding the efficacy of this widely used antimalarial drug. Intriguingly, BTZ-based inhibitors retain activity against atovaquone resistant parasites, suggesting this chemical class may provide an alternative to atovaquone in combination therapy.     

Decarboxylative coupling reactions: a modern strategy for C-C-bond formation

This critical review examines transition metal-catalyzed decarboxylative couplings that have emerged within recent years as a powerful strategy to form carbon-carbon or carbon-heteroatom bonds starting from carboxylic acids. In these reactions, C-C bonds to carboxylate groups are cleaved, and in their place, new carbon-carbon bonds are formed. Decarboxylative cross-couplings constitute advantageous alternatives to traditional cross-coupling or addition reactions involving preformed organometallic reagents. Decarboxylative reaction variants are also known for Heck reactions, direct arylation processes, and carbon-heteroatom bond forming reactions.     

Supermolecular liquid crystals with a six-armed cyclotriphosphazene core: from columnar to cubic phases

New liquid crystals having a non‐conventional structure have been synthesised from a six‐armed cyclotriphosphazene core, [N₃P₃(OC₆H₄OH‐4)₆], which was condensed with polycatenar acids. Reactions were monitored by ³¹P{¹H} and ¹H NMR spectroscopy and the chemical structure of the resulting materials was confirmed by different spectroscopic techniques and mass spectrometry (MALDI‐TOF). Results were in accordance with monodisperse, fully functionalised cyclotriphosphazenes. Thermal and mesomorphic properties were studied by optical microscopy, differential scanning calorimetry and X‐ray diffraction. All of the synthesised phosphazenes, substituted with benzyl ether chains, show a high thermal stability and exhibit mesomorphic properties, which depend on the number and type of alkyl terminal chains located at the periphery of the mesogens. Mesomorphic properties range from Col_h for cph‐A1 and cph‐A2 to a cubic phase detected for cph‐A3 , which has the larger number of alkyl chains. Furthermore, helical order was detected on X‐ray data of cph‐A2 , which has chiral branched chains. Circular dichroism spectra of annealed films at mesophase temperature show a signal attributed to the chiral helical arrangement of the mesogenic chromophores.     

Multi-stage preconcentrator/focuser module designed to enable trace level determinations of trichloroethylene in indoor air with a microfabricated gas chromatograph

This article describes the development and characterization of a multi-stage preconcentrator/focuser (PCF) module designed to be integrated with a microfabricated gas chromatograph (μGC) for autonomous, in situ determinations of volatile organic compounds. The PCF module has been optimized specifically for the determination of trichloroethylene (TCE) vapors at low- or sub-parts-per-billion concentrations in the presence of common indoor air co-contaminants in residences at risk of vapor intrusion (VI) from surrounding TCE-contaminated soil. It consists of three adsorbent-packed devices arranged in series: a pre-trap of conventional (tubular metal) design for capturing interferences with vapor pressures <3 torr; a high-volume sampler, also of conventional design, for capturing (and transferring) TCE and other compounds with vapor pressures within the range of ~3 to 95 torr; and a microfocuser (μF) consisting of a micromachined Si chamber with an integrated microheater for focusing and injecting samples into the separation module. The adsorbent masses, sampling and desorption flow rates, and heating profiles required for selective, quantitative capture and transfer/injection of TCE are determined for each of the devices, and the assembled PCF module is used to analyze a test atmosphere containing 200 parts-per-trillion of TCE and 27 relevant co-contaminants with a conventional downstream capillary column and electron-capture detector. An average TCE transfer efficiency of 107% is achieved for a 20 L air sample, with a preconcentration factor of ~800,000.     

Biorthogonal systems for solving Volterra integral equation systems of the second kind

With the aid of biorthogonal systems in adequate Banach spaces, the problem of approximating the solution of a system of nonlinear Volterra integral equations of the second kind is turned into a numerical method that allows it to be solved numerically.     

Spectroscopic characterization and laser performance of resonantly diode-pumped Er(3+)-doped disordered NaY(WO4)2

We report what is believed to be the first resonantly pumped laser operation based on Er(3+)-doped disordered double tungstate single crystal. Efficient laser operation of an Er(3+):NaY(WO(4))(2) laser at ～1609.6 nm was demonstrated with the naturally wideband, ～20 nm, InGaAsP/InP laser diode pumping at ～1501 nm. Laser wavelength tunability of ～34 nm was also demonstrated based on disorder-broadened emission features of Er(3+):NaY(WO(4))(2) single crystal.     

New dimeric liquid crystals with chiral flexible spacers

In order to obtain chiral compounds of low molecular weight expected to exhibit mesogenic and ferroelectric properties, the asymmetric carbon was introduced into the central part of the molecule. The series consists of nine chiral dimers in which the chiral flexible spacer derives from S-2-chlorosuccinic acid. The mesomorphic properties of the compounds were studied and all of them were found to be mesogenic. From n = 6 onwards the mesophases were chiral smectic C. Some analogous compounds derived from S-2-chloroglutaric acid were also prepared; these were not found to be mesogenic. The thermal instability of the 2-chlorosuccinic acid derivatives prevented the study of their ferroelectric properties. We attempted to perform this study for several mixtures involving 3-methyladipic acid derivatives and both 2-chlorosuccinic and 2-chloroglutaric acids derivatives. All the mixtures studied show chiral smectic C phases. The mixtures containing 2-chlorosuccinoyl derivatives show thermal instability; however those containing 2-chloroglutaroyl derivatives are stable, but do not show significant values of spontaneous polarization.     

Mesogenic behaviour in some pyrazole and isoxazole derivatives

Abstract

Several aromatic β-diketones with a different number of alkyloxy groups in the aromatic rings and their derived pyrazoles, isoxazoles and thallium (I) complexes have been synthesized. The potential mesomorphic properties of these compounds have been investigated by optical microscopy, DSC and X-ray diffraction. The pyrazoles and isoxazoles with one chain in each aromatic ring are mesogenic, showing smectic A and smectic C mesophases, whereas the pyrazoles and isoxazoles with two chains per ring and the β-diketones and thallium complexes are not. The mesogenic potentiality is shown to be related to the molecular linearity and to the number of alkyloxy groups. To the best of our knowledge, this is the first time liquid crystal properties have been described for pyrazole and isoxazole derivatives.     

Dominance relations and ranking of units by using interval number ordering with cross-efficiency intervals

This paper proposes an approach to the cross-efficiency evaluation that considers all the optimal data envelopment analysis (DEA) weights of all the decision-making units (DMUs), thus avoiding the need to make a choice among them according to some alternative secondary goal. To be specific, we develop a couple of models that allow for all the possible weights of all the DMUs simultaneously and yield individual lower and upper bounds for the cross-efficiency scores of the different units. As a result, we have a cross-efficiency interval for the evaluation of each unit. Existing order relations for interval numbers are used to identify dominance relations among DMUs and derive a ranking of units based on the cross-efficiency intervals provided. The approach proposed may also be useful for assessing the stability of the cross-efficiency scores with respect to DEA weights that can be used for their calculation.