Identification and functional characterization of a novel α-conotoxin (EIIA) from Conus ermineus

Nicotinic acetylcholine receptors (nAChRs) are one of the most important families in the ligand-gated ion channel superfamily due to their involvement in primordial brain functions and in several neurodegenerative pathologies. The discovery of new ligands which can bind with high affinity and selectivity to nAChR subtypes is of prime interest in order to study these receptors and to potentially discover new drugs for treating various pathologies. Predatory cone snails of the genus Conus hunt their prey using venoms containing a large number of small, highly structured peptides called conotoxins. Conotoxins are classified in different structural families and target a large panel of receptors and ion channels. Interestingly, nAChRs represent the only subgroup for which Conus has developed seven distinct families of conotoxins. Conus venoms have thus received much attention as they could represent a potential source of selective ligands of nAChR subtypes. We describe the mass spectrometric-based approaches which led to the discovery of a novel α-conotoxin targeting muscular nAChR from the venom of Conus ermineus. The presence of several posttranslational modifications complicated the N-terminal sequencing. To discriminate between the different possible sequences, analogs with variable N-terminus were synthesized and fragmented by MS/MS. Understanding the fragmentation pathways in the low m/z range appeared crucial to determine the right sequence. The biological activity of this novel α-conotoxin (α-EIIA) that belongs to the unusual α4/4 subfamily was determined by binding experiments. The results revealed not only its selectivity for the muscular nAChR, but also a clear discrimination between the two binding sites described for this receptor.     

Synthesis of dodecavalent fullerene-based glycoclusters and evaluation of their binding properties towards a bacterial lectin

Multivalency is playing a major role in biological processes and particularly in lectin-carbohydrate interactions. The design of high-affinity ligands of lectins should provide molecules capable of interfering with these biological processes and potentially inhibit bacterial or viral infections. Azide-alkyne "click" chemistry was applied to the synthesis of dodecavalent fullerene-based glycoclusters. The conjugation could be efficiently performed from alkyne or azide functions on either partners (i.e. hexakis-fullerene adduct or glycoside). PA-IL is a bacterial lectin from the opportunistic pathogen Pseudomonas aeruginosa and is involved in the recognition of glycoconjugates on human tissues. The glycoclusters obtained were evaluated as ligands of PA-IL and for their potential for competing with its binding to glycosylated surfaces. The affinities measured by hemagglutination inhibition assay (HIA), enzyme-linked lectin assay (ELLA), and surface plasmon resonance (SPR) displayed a significant "glycoside cluster effect" with up to a 12,000-fold increase in binding when comparing a monovalent carbohydrate reference probe with a dodecavalent fullerene-based glycocluster, albeit with some differences depending on the analytical technique.     

Ecdysteroid glycosides: identification, chromatographic properties, and biological significance

Ecdysteroid glycosides are found in both animals and plants. The chromatographic behavior of these molecules is characteristic, as they appear much more polar than their corresponding free aglycones when analyzed by normal-phase high-performance liquid chromatography (HPLC), whereas the presence of glycosidic moieties has a very limited (if any) impact on polarity when using reversed-phase HPLC. Biological activity is greatly reduced because the presence of this bulky substituent probably impairs the interaction with ecdysteroid receptor(s). 2-Deoxy-20-hydroxyecdysone 22-O-beta-D-glucopyranoside, which has been isolated from the dried aerial parts of Silene nutans (Caryophyllaceae), is used as a model compound to describe the rationale of ecdysteroid glycoside purification and identification.     

Two minor phytoecdysteroids of the plant Silene viridiflora

Chemical investigations of Silene viridiflora (L.) yielded a new ecdysteroid, 20-hydroxyecdysone 20,22-monoacetonide-25-acetate (1), and a known ecdysteroid, 2-deoxypolypodine B-3-beta-D-glucoside (2). The elucidation of the chemical structures was established by 1D and 2D NMR experiments.     

A unique single carboxylate-bridged spin-frustrated chiral Mn(II) metallatriangle

The reaction between Hmbpymca ligand (prepared in situ from the hydrolysis of 5-methyl-4-cyano-bispyrimidine with NaOH and further neutralization with 2 M HCl) and Mn(ClO(4))(2)·4H(2)O in 1:1 molar ratio afforded the triangulo-trimanganese(II) complex [Mn(3)(bpymca)(3)(H(2)O)(6)]Cl(3)·6H(2)O 1. The chloride anions in this complex come from the HCl used in the neutralization process. The molecular structure of 1 consists of cationic molecular triangles [Mn(3)(μ-mbpymca)(3)(H(2)O)(6)](3+) with C(3) symmetry, chloride anions and crystallization water molecules, all of them involved in an extensive network of hydrogen bonds, leading to a chiral network. Within the [Mn(3)(μ-mbpymca)(3)(H(2)O)(6)](3+) cations, seven-coordinated Mn(II) ions are bridged by both oxygen atoms of the carboxylate groups and exhibit a MnO(5)N(2) compressed pentagonal bipyramidal coordination environment. The temperature dependence of the magnetic susceptibility shows the presence of weak antiferromagnetic interactions between Mn(II) ions mediated by the carboxylate group of the mbpymca ligand and the existence of a 3D antiferromagnetic ordering below 4 K, which has its origin in the AF inter-trimer exchange interactions mediated by the strong hydrogen bonds present in the crystal of 1. The experimental magnetic susceptibility data above 7 K could be satisfactorily fitted to the theoretical analytical expression derived from the spin Hamiltonian H = -J(S(1)S(2) + S(1)S(3) + S(2)S(3)) with J = -0.782(3) cm(-1) and g = 2.092(3). The model predicts a degenerate ground state with an S = 1/2, which is typical of triangular trimetallic spin frustrated systems containing metal with non-integer spins. DFT calculations were performed on the molecular structure as found in the solid state to support the experimental J value and the Mn-O(carb)-Mn as the primarily exchange pathway.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

Amorphous structure and electronic properties of the Ge1Sb2Te4 phase change material

Ge1Sb2Te4 is one of the most commonly used phase change materials, due to the large optical and electrical contrast between a metastable crystalline phase and the amorphous phase. We use ab initio molecular dynamics to generate an amorphous Ge1Sb2Te4 structure. By analysing the distance distributions, we show that the structure can be analysed in terms of 21% of tetrahedrally coordinated Ge atoms and 79% of 3-fold Ge atoms. These are involved in distorted octahedral shells with bond length correlations that are similar to the a-GeTe structure as a consequence of a Peierls-distortion. The electronic properties are shown to be in reasonable agreement with the experiment with an electronic gap of 0.45 eV with. The optical conductivity curve is also in agreement with the experiment, with a maximal conductivity at an energy of ～3 eV.     

Multiscale dynamics of 1H and 19F in confined ionogels for lithium batteries

We present the first results of the nuclear magnetic relaxation dispersion (NMRD) of the confined proton-bearing cation (BMI) and fluorine-bearing anion (TFSI) pair of ionic liquids (Li⁺-ionogels) confined within a silica-like mesoporous matrices designed for lithium batteries. These results are in favour of a very-correlated dynamical motion of the anion–cation pair within the solid and disordered silica matrix.     

Design of metal oxide nanoparticles: Control of size,shape, crystalline structure and functionalization by aqueous chemistry

The aim of this paper is to show that a very simple but well controlled chemistry in an aqueous medium allows one to efficiently control the main characteristics of oxide nanoparticles. Examples concerning titania, alumina, iron and manganese oxides are discussed to illustrate various effects on the control of size, shape and structure of nanoparticles. Some examples of functionalization of these particles are also illustrated. Experimental data, procedures and detailed references can be found in the cited literature.     

CuLn complexes with a single μ-oximato bridge

Two original dinuclear (LnYb, 3 and LnEr, 4) and one trinuclear Cu^IILn^IIICu^II (LnGd, 5) complexes derived from a polydentate non symmetrical Schiff base ligand H₂L have been prepared. The ligand possesses two functions (phenol and oxime) able to coordinate the Ln ions, but structural studies (X-ray diffraction and powder X-ray diffraction) show that the Cu^II and Ln^III ions are only bridged by the oximato (NO) pair. The missing phenoxo bridge is replaced by a surprising pseudo-bridge involving one oxygen atom of the nitrato anion linked to the Cu and Ln ions according to a η²: η¹: μ mode. Although this latter contact has no role from the magnetic point of view, it introduces a large deformation of the unique bridging network. The CuYb complex 3 and the trinuclear CuGdCu complex 5 present antiferromagnetic interactions, with a J_CuGd interaction equal to ?1.25 cm^?1 in 5. The genuine single bridge can be considered as responsible for the antiferromagnetic character of the interaction.