Thermodynamic study of transthyretin association (wild‐type and senile forms) with heparan sulfate proteoglycan: pH effect and implication of the reactive histidine residue

The tetramer destabilization of transthyretin into monomers and its fibrillation are phenomena leading to amyloid deposition. Heparan sulfate proteoglycan (HSPG) has been found in all amyloid deposits. A chromatographic approach was developed to compare binding parameters between wild‐type transthyretin (wtTTR) and an amyloidogenic transthyretin (sTTR). Results showed a greater affinity of sTTR for HSPG at pH 7.4 compared with wtTTR owing to the monomeric form of sTTR. Analysis of the thermodynamic parameters showed that van der Waals interactions were involved at the complex interface for both transthyretin forms. For sTTR, results from the plot representing the number of protons exchanged vs pH showed that the binding mechanism was pH‐dependent with a critical value at a pH 6.5. This observation was due to the protonation of a histidine residue as an imidazolium cation, which was not accessible when TTR was in its tetrameric structure. At pH >6.5, dehydration at the binding interface and several contacts between nonpolar groups of sTTR and HSPG were also coupled to binding for an optimal hydrogen‐bond network. At pH <6.5, the protonation of the His residue from sTTR monomer when pH decreased broke the hydrogen‐bond network, leading to its destabilization and thus producing slight conformational changes in the sTTR monomer structure. Copyright © 2014 John Wiley & Sons, Ltd.     

Mixed-metal cluster chemistry. 28. Core enlargement of tungsten-iridium clusters with alkynyl, ethyndiyl, and butadiyndiyl reagents

Reaction of [WIr3(mu-CO)3(CO)8(eta-C5Me5)] (1c) with [W(C[triple bond]CPh)(CO)3(eta-C5H5)] afforded the edge-bridged tetrahedral cluster [W2Ir3(mu4-eta2-C2Ph)(mu-CO)(CO)9(eta-C5H5)(eta-C5Me5)] (3) and the edge-bridged trigonal-bipyramidal cluster [W3Ir3(mu4-eta2-C2Ph)(mu-eta2-C=CHPh)(Cl)(CO)8(eta-C5Me5)(eta-C5H5)2] (4) in poor to fair yield. Cluster 3 forms by insertion of [W(C[triple bond]CPh)(CO)3(eta-C5H5)] into Ir-Ir and W-Ir bonds, accompanied by a change in coordination mode from a terminally bonded alkynyl to a mu4-eta2 alkynyl ligand. Cluster 4 contains an alkynyl ligand interacting with two iridium atoms and two tungsten atoms in a mu4-eta2 fashion, as well as a vinylidene ligand bridging a W-W bond. Reaction of [WIr3(CO)11(eta-C5H5)] (1a) or 1c with [(eta-C5H5)(CO)2 Ru(C[triple bond]C)Ru(CO)2(eta-C5H5)] afforded [Ru2WIr3(mu5-eta2-C2)(mu-CO)3(CO)7(eta-C5H5)2(eta-C5R5)] [R = H (5a), Me (5c)] in low yield, a structural study of 5a revealing a WIr3 butterfly core capped and spiked by Ru atoms; the diruthenium ethyndiyl precursor has undergone Ru-C scission, with insertion of the C2 unit into a W-Ir bond of the cluster precursor. Reaction of [W2Ir2(CO)10(eta-C5H5)2] with the diruthenium ethyndiyl reagent gave [RuW2Ir2{mu4-eta2-(C2C[triple bond]C)Ru(CO)2(eta-C5H5)}(mu-CO)2(CO)6(eta-C5H5)3] (6) in low yield, a structural study of 6 revealing a butterfly W2Ir2 unit capped by a Ru(eta-C5H5) group resulting from Ru-C scission; the terminal C2 of a new ruthenium-bound butadiyndiyl ligand has been inserted into the W-Ir bond. Reaction between 1a, [WIr3(CO)11(eta-C5H4Me)] (1b), or 1c and [(eta-C5H5)(CO)3W(C[triple bond]CC[triple bond]C)W(CO)3(eta-C5H5)] afforded [W2Ir3{mu4-eta2-(C2C[triple bond]C)W(CO)3(eta-C5H5)}(mu-CO)2(CO)2(eta-C5H5)(eta-C5R5)] [R = H (7a), Me (7c); R5 = H4Me (7b)] in good yield, a structural study of 7c revealing it to be a metallaethynyl analogue of 3.     

Synthesis, linear, and quadratic-nonlinear optical properties of octupolar D3 and D2d bipyridyl metal complexes

A series of D3 (Fe(II), Ru(II), Zn(II), Hg(II)) and D2d (Cu(I), Ag(I), Zn(II)) octupolar metal complexes featuring different functionalized bipyridyl ligands has been synthesized, and their thermal, linear (absorption and emission), and nonlinear optical (NLO) properties were determined. Their quadratic NLO susceptibilities were determined by harmonic light scattering at 1.91 microm, and the molecular hyperpolarizability (beta0) values are in the range of 200-657 x 10(-30) esu for octahedral complexes and 70-157 x 10(-30) esu for tetrahedral complexes. The octahedral zinc(II) complex 1 e, which contains a 4,4'-oligophenylenevinylene-functionalized 2,2'-bipyridine, exhibits the highest quadratic hyperpolarizability ever reported for an octupolar derivative (lambdamax=482 nm, beta1.91(1 e)=870 x 10(-30) esu, beta0(1 e)=657 x 10(-30) esu). Herein, we demonstrate that the optical and nonlinear optical (NLO) properties are strongly influenced by the symmetry of the complexes, the nature of the ligands (donor endgroups and pi linkers), and the nature of the metallic centers. For example, the length of the pi-conjugated backbone, the Lewis acidity of the metal ion, and the increase of ligand-to-metal ratio result in a substantial enhancement of beta. The contribution of the metal-to-ligand (MLCT) transition to the molecular hyperpolarizability is also discussed with respect to octahedral d6 complexes (M=Fe, Ru).     

Thiophosphorylated cavitand: structure and affinity towards soft metal ions

The iiii stereoisomer of the tetrathiophosphonate-calix[4]resorcinarene host 1 exhibited excellent extraction properties towards soft metal ions, with a better affinity for Ag⁺ (91%), than for Tl⁺ (38%) and Hg²⁺ (16%). The extraction of other picrate salts (Cu²⁺, Ni²⁺, Co²⁺, Zn²⁺, Cd²⁺, Pb²⁺) was not detected. The stoichiometry and the structure of the Hg²⁺, Tl⁺ and Ag⁺ complexes were studied by NMR in solution and gave respectively 1:1, 1:1 and 1:2 host-guest complexes. The formation of the self-assembled 1₂·(AgPic)₄ complex was independent on the anion and only observed with silver(I) ion.     

Macrocyclic 14-Membered Ring Diketal Dilactams: Evaluation of their Divalent Cation Binding Properties

The binding abilities of a new class of 14-membered ring ligands bearing diketal dilactam functions were explored by UV-visible spectrophotometry. Their formation constants, determined in THF solution, showed appreciable complexation with divalent cations (stability order: Sr²⁺≥Ca²⁺>Zn²⁺≥Mg²⁺>Ba²⁺) whereas no association was observed with monovalent cations. The stoichiometry of the complexes formed was essentially 1:1 although sometimes a low percentage (<10%) of 1:2 (cation–ligand) species was detected. The corresponding formation constants determined by computation (STAR program) were in the range 1.5<log?β ¹¹<4.8 and 4.4<log?β ¹²<7.1. They depend significantly on the nature of the substituents. In addition, solvent extractions carried out in a water–chloroform system showed the highest constants (log K ^ex) for the most substituted macrocycles 7b and 7c (norephedrine series) with a lipophilic skeleton.     

Firsts lysidinyl- and lysidinium-triphosphines Pd(II) complexes

The preparation of first lysidinyl-triphosphine ligand (named Triphosline) is described in three steps which are first a Michael type addition of imidazolidine (or lysidine) to diethylvinylphosphonate, second a phosphonate reduction with LiAlH₄ and third an anti-Markovnikov radical addition of the primary phosphine to diphenylvinylphosphine. The Triphosline behaves as a tridentate P-coordinating ligand in palladium(II) complexes. The dangling lysidine function is then cleanly and totally alkylated by methyl iodide to lead to a new kind of lysidinium-triphosphine complexes. Subsequent anion exchange with TlPF₆ affords the first example of a chloride free lysidinium-triphosphine palladium complex which has been fully characterized by spectroscopic and analytical methods.     

General mechanism for the meandering instability of rivulets of Newtonian fluids

A rivulet flowing down an inclined plane often does not follow a straight path, but starts to meander spontaneously. Here we show that this instability is the result of two key ingredients: fluid inertia and anisotropy of the friction between rivulet and substrate. Meandering only occurs if the motion normal to the instantaneous flow direction is more difficult than parallel to it. We give a quantitative criterion for the onset of meandering and confirm it by comparing to the flow of a rivulet between two glass plates which are wetted completely. Above the threshold, the rivulet follows an irregular pattern with a typical wavelength of a few cm.     

Preparation of solid alkaline fuel cell binders based on fluorinated poly(diallyldimethylammonium chloride)s [poly(DADMAC)] or poly(chlorotrifluoroethylene‐co‐DADMAC) copolymers

A membrane or an electrode binder to be used in a solid alkaline fuel cell (SAFC) needs to (i) be insoluble in both aqueous solutions and the required fuels, and (ii) exhibit an hydroxide ion conductivity. To achieve these goals, two pathways were employed: (i) one consists of the radical copolymerization of diallyldimethylammonium chloride (DADMAC) with chlorotrifluoroethylene (CTFE) while (ii) the other one is based on the counter‐ion exchange of a poly(DADMAC) by fluorinated anions. First, the radical copolymerization of CTFE with DADMAC under various experimental conditions was achieved in yields up to 85%, and DADMAC percentages in the copolymers were higher than those in the feed compositions. To obtain insoluble copolymers, high CTFE feed contents (>70 mol %) were required. The other route consisting in the partial replacement of the Cl^? counter‐ions in the water‐soluble poly(DADMAC) by bistrifluoromethanesulfonimide (TFSI^?) did confer the starting material insolubility in water while maintaining its conductivity. When the fluorinated poly(DADMAC) was obtained from concentrated solutions of fluorinated surfactant, it was observed that the amount of counter‐ions exchanged was difficult to control, which limits optimization. Nevertheless, under diluted conditions, membranes with ion exchange capacity up to 0.7 meq g^?1, and conductivities close to 1 mS cm^?1 were obtained. Although their conductivities were low, these membranes fulfill the requirements for a SAFC membrane in terms of solubility in DMSO, water insolubility, and thermal stability (T_d,10% > 320 °C). When used in a fuel cell, as a binder in the membrane‐electrode assembly (MEA), significant improvements were noted (+50% of the open circuit voltage, +580% in current density, and +540% in accessible power). © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2043–2058, 2009     

A Particulate Biochromatographic Support for the Research of Arginase Inhibitors Doped with Nanomaterials: Differences Observed Between Carbon and Boron Nitride Nanotubes. Application to Three Plant Extracts

The arginase enzyme was bound to porous silica using a reactive polymer where two types of nanomaterials were entrapped, i.e., carbon nanotubes (CNTs) and boron nitride nanotubes (BNNTs). For the first time, it was shown that BNNTs were highly efficient for increasing the performance of a particulate bioactive support. Also, we demonstrated that BNNTs enhanced more strongly this effect in comparison with CNTs. In addition, with this novel bioactive support, the relative IC50 values of the well-known arginase inhibitors were found to be in agreement with those derived by the conventional spectrometric method. It was shown the ethylacetate extract of the roots of Spirotropis longifolia (SL) and of the ethanol extract of sunflower (Helianthus annuus) seed (SS) and Lonicera japonica Thunb, i.e., honeysuckle (H) on the arginase activity inhibited the enzyme activity.     

Photoisomerizable bipyridine ligands and macroligands: absorption, photoisomerization properties and theoretical study.

Two 2,2'-bipyridines, substituted at the 4,4'-positions by p-dialkylaminophenylazostyryl moieties p-R2N-C6H4-N=N-C6H4-CH=CH-[6 a, R2N=nBu2N; 6 b, R2N=(nBu)(C4H8OTHP)N; 6 c, R2N=(nBu)(C4H8OH)N], were successfully synthesized by using Wadworth-Emmons reactions. The X-ray structure of 6 a has been determined. Esterification of 6 c with 2-bromoisobutyroylbromide afforded 6 d. This ligand was used as an initiator for the living radical polymerization of methylmethacrylate (MMA) and gave rise to macroligand 6 e. Thin films of good optical quality were obtained by the spin-coating technique. Photoisomerization experiments were carried out on 6 a in solution and on 6 e in both solution and film, and the kinetics of photochemical (E/Z) and thermal (Z/E) isomerization were investigated. They were found to show Z-E back isomerization typical of aminoazobenzene-type rather than of push-pull-type molecules. Density functional theoretical (TD-DFT) calculations were performed on model compound 6 a' (R2N=Me2N) to understand the structural and electronic transitions of the corresponding E-E, E-Z and Z-Z isomers. It was found that the E-E isomer is almost planar as observed experimentally by X-ray diffraction, whereas the Z-Z isomer, which is 35.4 kcal mol(-1) less stable than the E-E isomer, is nonplanar. The theoretical studies also reveal that several transitions of pi-pi*, n-pi* and charge-transfer (CT) types, are involved in the long-wavelength transition of 6 a (E-E). The same observations can be made for the (Z-Z) isomer, and the TD-DFT simulated spectrum fits quite nicely to the experimental, reproducing and explaining the apparition of a blue-shifted charge-transfer band at 390 nm.