Total syntheses of (±)-securinine and (±)- allosecurinine

Total syntheses of (±)-securinine and (±)-allosecurinine that employ a tandem rhodium carbenoid-initiated Claisen/α-ketol rearrangement sequence as a key step are described.     

An improved method for the synthesis of F-BODIPYs from dipyrrins and bis(dipyrrin)s

An improved methodology for the synthesis of F-BODIPYs from dipyrrins and bis(dipyrrin)s is reported. This strategy employs lithium salts of dipyrrins as intermediates that are then treated with only 1 equiv of boron trifluoride diethyletherate to obtain the corresponding F-BODIPYs. This scalable route to F-BODIPYs renders high yields with a facile purification process involving merely filtration of the reaction mixture through Celite in many cases.     

Pharmacophore fingerprint-based approach to binding site subpocket similarity and its application to bioisostere replacement

Bioisosteres have been defined as structurally different molecules or substructures that can form comparable intermolecular interactions, and therefore, fragments that bind to similar protein structures exhibit a degree of bioisosterism. We present KRIPO (Key Representation of Interaction in POckets): a new method for quantifying the similarities of binding site subpockets based on pharmacophore fingerprints. The binding site fingerprints have been optimized to improve their performance for both intra- and interprotein family comparisons. A range of attributes of the fingerprints was considered in the optimization, including the placement of pharmacophore features, whether or not the fingerprints are fuzzified, and the resolution and complexity of the pharmacophore fingerprints (2-, 3-, and 4-point fingerprints). Fuzzy 3-point pharmacophore fingerprints were found to represent the optimal balance between computational resource requirements and the identification of potential replacements. The complete PDB was converted into a database comprising almost 300?000 optimized fingerprints of local binding sites together with their associated ligand fragments. The value of the approach is demonstrated by application to two crystal structures from the Protein Data Bank: (1) a MAP kinase P38 structure in complex with a pyridinylimidazole inhibitor ( 1A9U ) and (2) a complex of thrombin with melagatran ( 1K22 ). Potentially valuable bioisosteric replacements for all subpockets of the two studied protein are identified.     

Quantification of phytochelatins and their metal(loid) complexes: critical assessment of current analytical methodology

Whilst there are a variety of methods available for the quantification of biothiols in sample extracts, each has their own inherent advantages and limitations. The ease with which thiols readily oxidise not only hinders their quantification but also alters the speciation profile. The challenge faced by the analyst is not only to preserve the speciation of the sample, but also to select a method which allows the retrieval of the desired information. Given that sulfur is not a chromophore and that it cannot easily be monitored by ICP-MS, a number of direct and indirect methods have been developed for this purpose. In order to assess these methods, they are compared in the context of the measurement of arsenic–phytochelatin complexes in plant extracts. The inherent instability of such complexes, along with the instabilities of reduced glutathione and phytochelatin species,necessitates a rapid and sensitive analytical protocol. Whilst being a specific example, the points raised and discussed in this review will also be applicable to the quantification of biothiols and thiol–metal(loid) species in a wide range of systems other than just the analysis of arsenic–phytochelatin species in plant extracts.     

Fluoropolymer‐based clear and white paint coatings composition analysis by X‐Ray fluorescence

A new method for the quantification of organic and inorganic phase fractions was developed for fluoropolymer/acrylic‐blend paints – clear and white paint coatings – on aluminum panels by using wavelength dispersive X‐ray fluorescence spectrometry (WDXRF). The method was developed for clear coat samples (only containing fluoropolymer and acrylic phases) as well as white paint samples by also measuring silica and titanium dioxide levels. Both WDXRF and X‐ray photoelectron spectroscopy (XPS), a surface technique, were investigated. For clear coat samples, we found that WDXRF provided far superior quantitative results to XPS, likely related to the extreme surface sensitivity of XPS, in this case a drawback more than a strength. For white paint samples, the X‐ray fluorescence spectrometry method achieved a relative accuracy typically better than 5% for the organic phases and better than 2% for the inorganic phases, for measurements on 8‐mm diameter samples. Copyright © 2013 John Wiley & Sons, Ltd.     

Guided wave measurements for characterization of sol-gel layers

Sol-gel applications require very thick layers with a good understanding of the interfaces. To address this problem, we have installed at CEA Le Ripault a characterization bench using guided waves with assistance from the IM2NP lab in Marseille. This bench allows us to measure the thickness and the refractive index and determine the extinction coefficient of a thin layer. We can distinguish losses at interfaces from those in the bulk according to the chosen propagation mode. This allows us to know if we can stack elementary layers to make thick layers without incurring problems.     

Melting curve of copper measured to 16 GPa using a multi-anvil press

The melting temperature, T _m, of copper has been determined from ambient pressure to 16 GPa using multi-anvil techniques. The melting curve obtained (T _m=1355(5)+44.5(31)P?0.61(21)P ², with T _m in Kelvin and P in GPa) is in good agreement with both the previous experimental studies and with recent ab initio calculations.     

E.P.R. of free radicals in an adamantane matrix

Benzyl radicals and the isoelectronic azabenzyl radicals were prepared in an adamantane matrix and their isotropic E.P.R. spectra observed and analysed. The proton hyperfine splittings were assigned by specific deuteration and by analogy with the benzyl radical. The spin density distribution is strongly affected by non-symmetrical nitrogen substitution, but is only weakly affected by symmetrical substitution. INDO calculations on the radicals predict only small deviations from the benzyl radical spin density distribution for all of the azabenzyl radicals. However, the trends in the experimental values can be rationalized in terms of the electronegativity difference between carbon and nitrogen and its effect on the molecular orbitals of benzyl radical. Furthermore the observed trend in the g values not only lends support to this view of the structure but also allows estimation of the approximate energy of the first nπ* excited states.     

Screening phosphatidylcholine biomarkers in mouse liver extracts from a hypercholesterolemia study using ESI-MS and chemometrics

When fed a high-fat, high-cholesterol diet (HFD), homozygous LDL receptor knockout mice exhibit extremely high levels of plasma cholesterol that are expected to influence liver metabolism. One step in the investigation of potential hepatic alterations was the analysis of organic extracts of livers from these and control mice by electrospray mass spectrometry (ESI-MS). Chemometrics (bioinformatics) analysis shows that the sample spectra cluster into two groups: one from mice with plasma cholesterol levels in excess of 900 mg dL⁻¹ and one from animals with cholesterol levels of 60–250 mg dL⁻¹. The loadings plot of the first PC in the principal-components analysis (PCA) reveals the chemical basis for clustering, i.e., biomarkers present at different concentrations in the different groups. The exact masses of the key peaks in this loadings plot indicate these species are phosphatidylcholines (PtdChos). This assignment is confirmed by tandem MS. Partial least-squares (PLS) with variable selection shows that the spectra are well correlated with plasma total cholesterol, HDL cholesterol, and triglyceride (TG) levels.     

An efficient synthesis of 9H-pyrrolo[1,2-a]indoles

A novel and effective method has been developed for the synthesis of 9H-pyrrolo[1,2-a]indoles by treatment of 3-substituted-4,6-dimethoxyindoles with chalcones in the presence of hydrochloric acid.