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.     

Coordination and Dehydrogenation of Amine–Boranes at Metal Centers

There have been a number of approaches developed for the catalyzed dehydrogenation of amine–boranes as potential dihydrogen sources for hydrogen storage applications in recent years. Key advances in this area have been recently made thanks to catalytic and stoichiometric studies. In this Minireview, the fate of amine–boranes upon coordination to a metal center is discussed with a particular emphasis on B? H activation pathways. We focus on the few cases in which coordination of the resulting dehydrogenated product could be achieved, which includes the coordination of aminoborane, the simplest unit resulting from dihydrogen release of ammonia–borane.     

Synthesis and complete assignment of the 1H and 13C NMR signals of new acetamido and aminoflavonoid derivatives

The complete ¹H and ¹³C NMR assignment of 9 acetamidochalcones, 18 acetamidoflavones, 18 aminoflavones, 9 acetamidoflavonols and 9 aminoflavonols has been performed using one‐ and two‐dimensional NMR techniques including COSY, HMQC and HMBC experiments. Copyright © 2010 John Wiley & Sons, Ltd.     

Total Synthesis of Isodaphlongamine H: A Possible Biogenetic Conundrum

Herein we describe the first synthetic efforts toward the total synthesis of isodaphlongamine H, a calyciphylline B‐type alkaloid. The strategy employs a chemoenzymatic process for the preparation of a functionalized cyclopentanol with a quaternary center. This molecule is elaborated to form an enantiopure 1‐aza‐perhydrocyclopentalene core, representing rings A and E of all calyciphylline B‐type alkaloids. Further transformations involve the formation of a cyclic enaminone, 1,4‐conjugate addition with a cyclopentenyl subunit, and intramolecular aldol cyclization to achieve a pentacyclic intermediate, ultimately forming isodaphlongamine H in a total of 24 steps from the commercially available compound 2‐carbethoxycyclopentanone. Isodaphlongamine H exhibits promising inhibitory activity against a panel of human cancer cell lines.     

Alkoxyallene‐ynes: Selective Preparation of Bicyclo[5.3.0] Ring Systems Including a δ‐Alkoxy Cyclopentadienone

The development of an intramolecular rhodium(I)‐catalyzed Pauson–Khand reaction of alkoxyallene‐ynes with a proximal alkoxy group is reported. This reaction, in the presence of a [Rh(cycloocta‐1,5‐diene)Cl]₂/propane‐1,3‐diylbis(diphenylphosphane) system under a CO atmosphere, constitutes a powerful tool for selectively accessing carbo‐ and heterobicyclo[5.3.0] frameworks featuring an enol ether moiety. Through this procedure, a straightforward access to guaiane skeletons with a tertiary hydroxy group at the C10 position was achieved.     

Thermodynamic stability of boron: the role of defects and zero point motion

Its low weight, high melting point, and large degree of hardness make elemental boron a technologically interesting material. The large number of allotropes, mostly containing over a hundred atoms in the unit cell, and their difficult characterization challenge both experimentalists and theoreticians. Even the ground state of this element is still under discussion. For over 30 years, scientists have attempted to determine the relative stability of alpha- and beta-rhombohedral boron. We use density functional calculations in the generalized gradient approximation to study a broad range of possible beta-rhombohedral structures containing interstitial atoms and partially occupied sites within a 105 atoms framework. The two most stable structures are practically degenerate in energy and semiconducting. One contains the experimental 320 atoms in the hexagonal unit cell, and the other contains 106 atoms in the triclinic unit cell. When populated with the experimental 320 electrons, the 106 atom structure exhibits a band gap of 1.4 eV and an in-gap hole trap at 0.35 eV above the valence band, consistent with known experiments. The total energy of these two structures is 23 meV/B lower than the original 105 atom framework, but it is still 1 meV/B above the alpha phase. Adding zero point energies finally makes the beta phase the ground state of elemental boron by 3 meV/B. At finite temperatures, the difference becomes even larger.     

Anisotropic Lithium Ion Conductivity in Single‐Ion Diblock Copolymer Electrolyte Thin Films

Well‐defined single‐ion diblock copolymers consisting of a Li‐ion conductive poly(styrenesulfonyllithium(trifluoromethylsulfonyl)imide) (PSLiTFSI) block associated with a glassy polystyrene (PS) block have been synthesized via reversible addition fragmentation chain transfer polymerization. Conductivity anisotropy ratio up to 1000 has been achieved from PS‐b‐PSLiTFSI thin films by comparing Li‐ion conductivities of out‐of‐plane (aligned) and in‐plane (antialigned) cylinder morphologies at 40 °C. Blending of PS‐b‐PSLiTFSI thin films with poly(ethylene oxide) homopolymer (hPEO) enables a substantial improvement of Li‐ion transport within aligned cylindrical domains, since hPEO, preferentially located in PSLiTFSI domains, is an excellent lithium‐solvating material. Results are also compared with unblended and blended PSLiTFSI homopolymer (hPSLiTFSI) homologues, which reveals that ionic conductivity is improved when thin films are nanostructured.

     

Behaviour of Pluronic P84 block copolymer micelles above the gelification temperature as probed by positron annihilation lifetime spectroscopy

The new method based on positron annihilation lifetime spectroscopy (PALS) to determine both the mean core radius, R(core), and aggregation number, N(ag), of micelles is applied to the study of aqueous solutions of the triblock Pluronic P84 copolymer as a function of temperature (T), beyond the gelification point (334 K). Two long-lived components appear in the PALS spectra, ascribed to triplet positronium in the water bulk (o-Ps(aq)) and in the organic core of the micelles (o-Ps(org)). Of the various fitting parameters, only the lifetime of the latter species, tau4, and the micellar parameters, R(core) and N(ag), disclose the occurrence of gelification by first increasing up to 334 K, then decreasing. By contrast to what is known in case of phase transition, none of the parameters shows any abrupt change at 334 K, whereas the macroscopic viscosity of the solutions suffers a drastic increase. This is attributed to the fact that positronium is sensitive to the microviscosity of the solutions. At the transition point, the properties of the polyoxipropylene aggregates forming the organic core of the P84 micelles are not greatly affected. Furthermore, the fact that the experimental N(ag) values coincide with those calculated for spheres, from the R(core) values, indicates that the shape of the P84 cores does not change significantly after gelification. The onset of gelification results from a decrease in the hydrogen bonding interactions in the solution with an ensuing relative increase in the interactions between the polyoxipropylene (PPO) groups, initially forming the corona of the P84 micelles, in an intermicellar mode. This increased solicitation of the PPO groups outside their initial location would result in depletion in the number of surfactant molecules forming the micelles, viz. a decrease in both R(core) and N(ag) above 334 K. From the data, additional information can be gained regarding the local viscosity and surface tension in the micellar cores.     

Control of Redox Potential by Deprotonation of Coordinated 1H‐Imidazole in Complexes of 2‐(1H‐Imidazol‐2‐yl)pyridine

Complexes [ML₃]²⁺ of the bidentate ligand 2‐(1H‐imidazol‐2‐yl)pyridine were prepared with iron(II), cobalt(II), and ruthenium(II). The electronic spectra suggest the ligand to be a weaker σ‐donor and π‐acceptor than the closely related 2,2′‐bipyridine. The complexes are readily deprotonated by addition of base, and the effect of the deprotonation is to lower the M^III/M^II redox potential by roughly 900 mV. This is roughly 75% of the drop observed for related complexes of 2,6‐di‐1H‐imidazol‐2‐ylpyridine, and suggests the effect to be largely coulombic in origin.     

Dressings Loaded with Cyclodextrin–Hamamelitannin Complexes Increase Staphylococcus aureus Susceptibility Toward Antibiotics Both in Single as well as in Mixed Biofilm Communities

Bacteria reside within biofilms at the infection site, making them extremely difficult to eradicate with conventional wound care products. Bacteria use quorum sensing (QS) systems to regulate biofilm formation, and QS inhibitors (QSIs) have been proposed as promising antibiofilm agents. Despite this, few antimicrobial therapies that interfere with QS exist. Nontoxic hydroxypropyl‐β‐cyclodextrin‐functionalized cellulose gauzes releasing a burst of the antibiotic vancomycin and the QSI hamamelitannin are developed, followed by a sustained release of both. The gauzes affect QS and biofilm formation of Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro model of chronic wound infection and can be considered as candidates to be used to prevent wound infection as well as treat infected wounds.