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.     

New Dual Donor–Acceptor (2D‐π‐2A) Porphyrin Sensitizers for Stable and Cost‐Effective Dye‐Sensitized Solar Cells

A series of porphyrin sensitizers that featured two electron‐donating groups and dual anchoring groups that were connected through a porphine π‐bridging unit have been synthesized and successfully applied in dye‐sensitized solar cells (DSSCs). The presence of electron‐donating groups had a significant influence on their spectroscopic, electrochemical, and photovoltaic properties. Overall, the dual anchoring groups gave tunable electronic properties and stronger attachment to TiO₂. These new dyes were readily synthesized in a minimum number of steps in gram‐scale quantities. Optical and electrochemical data confirmed the advantages of these dyes for use as sensitizers in DSSCs. Porphyrins with electron‐donating amino moieties provided improved charge separation and better charge‐injection efficiencies for the studied dual‐push–pull dyes. Attenuated total reflectance–Fourier‐transform infrared (ATR‐FTIR) and X‐ray photoelectron spectroscopy of the porphyrin dyes on TiO₂ suggest that both p‐carboxyphenyl groups are attached onto TiO₂, thereby resulting in strong attachment. Among these dyes, cis-Zn2BC2A , with two electron‐donating 3,6‐ditertbutyl‐phenyl‐carbazole groups and dual‐anchoring p‐carboxyphenyl groups, showed the highest efficiency of 4.07 %, with J_SC=9.81 mA cm^?2, V_OC=0.63 V, and FF=66 %. Our results also indicated a better photostability of the studied dual‐anchored sensitizers compared to their mono‐anchored analogues under identical conditions. These results provide insight into the developments of a new generation of high‐efficiency and thermally stable porphyrin sensitizers.     

Directing Group-Promoted Inert C−O Bond Activation Using Versatile Boronic Acid as a Coupling Agent

A simple Ni(cod)₂ and carbene mediated strategy facilitates the efficient catalytic cross-coupling of methoxyarenes with a variety of organoboron reagents. Directing groups facilitate the activation of inert C−O bonds in under-utilized aryl methyl ethers enabling their adaptation for C−C cross-coupling reactions as less toxic surrogates to the ubiquitous haloarenes. The method reported enables C−C cross-coupling with readily available and economical arylboronic acid reagents, which is unprecedented, and compares well with other organoboron reagents with similarly high reactivity. Extension to directing group assisted chemo-selective C−O bond cleavage, and further application towards the synthesis of novel bifunctionalized biaryls is reported. Key to the success of this protocol is the use of directing groups proximal to the reaction center to facilitate the activation of the inert C−OMe bond.     

Probing Electronic Symmetry Reduction during Charge Migration via Time-Resolved X-Ray Diffraction

The present work focuses on probing ultrafast charge migration after symmetry-breaking excitation using ultrashort laser pulses. LiCN is chosen as prototypical system because it can be oriented in the laboratory frame and it possesses optically-accessible charge transfer states at low energies. The charge migration is simulated within the hybrid time-dependent density functional theory/configuration interaction framework. Time-resolved electronic current densities and simulated time-resolved x-ray diffraction signals are used to unravel the mechanism of charge migration. Our simulations demonstrate that specific choices of laser polarization lead to a control over the symmetry of the induced charge migration. Moreover, time-resolved x-ray diffraction signals are shown to encode transient symmetry reduction at intermediate times.     

Nickel-mediated cross-coupling via C–O activation assisted by organoaluminum

We report the alkylation and arylation cross-coupling of aryl ethers based on C–O bond activation using a nickel catalyst and organoaluminum reagents. Ni(cod)₂ in combination with 1,2-bis(dicyclohexylphosphino)ethane ligand in toluene solution at 130°C are the best conditions. The naphthyl ether or methoxy pyridine derivatives are suitable substrates for alkylation and arylation reaction with a wider scope of aluminum reagents in good yields. Computational analysis on the pyridine substrate is provided to help delineate the mechanistic pathway and demonstrate the important aspects of the cooperative interaction bimetallic catalysis. First, the coordination of AlMe₃ to the O atom of pyridine is essential for C–O activation. Second, the β-H transfer from methoxy to pyridine could be discouraged through the use of bidentate phosphine as a ligand. Finally, excess AlMe₃ reagent is critical for facilitating a reductive elimination process.