Properties and ATRP activity of copper complexes with substituted tris(2-pyridylmethyl)amine-based ligands.

Synthesis, characterization, electrochemical studies, and ATRP activity of a series of novel copper(I and II) complexes with TPMA-based ligands containing 4-methoxy-3,5-dimethyl-substituted pyridine arms were reported. In the solid state, Cu(I)(TPMA*(1))Br, Cu(I)(TPMA*(2))Br, and Cu(I)(TPMA*(3))Br complexes were found to be distorted tetrahedral in geometry and contained coordinated bromide anions. Pseudo-coordination of the aliphatic nitrogen atom to the copper(I) center was observed in Cu(I)(TPMA*(2))Br and Cu(I)(TPMA*(3))Br complexes, whereas pyridine arm dissociation occurred in Cu(I)(TPMA*(1))Br. All copper(I) complexes with substituted TPMA ligands exhibited a high degree of fluxionality in solution. At low temperature, Cu(I)(TPMA*(1))Br was found to be symmetrical and monomeric, while dissociation of either unsubstituted pyridine and/or 4-methoxy-3,5-dimethyl-substituted pyridine arms was observed in Cu(I)(TPMA*(2))Br and Cu(I)(TPMA*(3))Br. On the other hand, the geometry of the copper(II) complexes in the solid state deviated from ideal trigonal bipyramidal, as confirmed by a decrease in τ values ([Cu(II)(TPMA*(1))Br][Br] (τ = 0.92) > [Cu(II)(TPMA*(3))Br][Br] (τ = 0.77) > [Cu(II)(TPMA*(2))Br][Br] (τ = 0.72)). Furthermore, cyclic voltammetry studies indicated a nearly stepwise decrease (ΔE ≈ 60 mV) of E1/2 values relative to SCE (TPMA (-240 mV) > TPMA*(1) (-310 mV) > TPMA*(2) (-360 mV) > TPMA*(3) (-420 mV)) on going from [Cu(II)(TPMA)Br][Br] to [Cu(II)(TPMA*(3))Br][Br], confirming that the presence of electron-donating groups in the 4 (-OMe) and 3,5 (-Me) positions of the pyridine rings in TPMA increases the reducing ability of the corresponding copper(I) complexes. This increase was mostly the result of a stronger influence of substituted TPMA ligands toward stabilization of the copper(II) oxidation state (log ß(I) = 13.4 ± 0.2, log ß(II) = 19.3 (TPMA*(1)), 20.5 (TPMA*(2)), and 21.5 (TPMA*(3))). Lastly, ARGET ATRP kinetic studies show that with more reducing catalysts an induction period is observed. This was attributed to slow regeneration of Cu(I) species from the corresponding Cu(II).

Functional characterization of bovine viral diarrhea virus nonstructural protein 5A by reverse genetic analysis and live cell imaging.

Nonstructural protein 5A (NS5A) of bovine viral diarrhea virus (BVDV) is a hydrophilic phosphoprotein with RNA binding activity and a critical component of the viral replicase. In silico analysis suggests that NS5A encompasses three domains interconnected by two low-complexity sequences (LCSs). While domain I harbors two functional determinants, an N-terminal amphipathic helix important for membrane association, and a Zn-binding site essential for RNA replication, the structure and function of the C-terminal half of NS5A are still ill defined. In this study, we introduced a panel of 10 amino acid deletions covering the C-terminal half of NS5A. In the context of a highly efficient monocistronic replicon, deletions in LCS I and the N-terminal part of domain II, as well as in domain III, were tolerated with regard to RNA replication. When introduced into a bicistronic replicon, only deletions in LCS I and the N-terminal part of domain II were tolerated. In the context of the viral full-length genome, these mutations allowed residual virion morphogenesis. Based on these data, a functional monocistronic BVDV replicon coding for an NS5A variant with an insertion of the fluorescent protein mCherry was constructed. Live cell imaging demonstrated that a fraction of NS5A-mCherry localizes to the surface of lipid droplets. Taken together, this study provides novel insights into the functions of BVDV NS5A. Moreover, we established the first pestiviral replicon expressing fluorescent NS5A-mCherry to directly visualize functional viral replication complexes by live cell imaging.

Highly Active Bipyridine-Based Ligands for Atom Transfer Radical Polymerization.

A series of 2,2'-bipyridines with 4,4'-substituents (R-bpy) were investigated for atom transfer radical polymerization (ATRP) of methyl acrylate (MA) and methyl methacrylate (MMA). Ligand substituents with a large range of Hammett parameters (R = Cl, H, Me, dinonyl (dN), MeO, and (Me)2N) were studied with cyclic voltammetry (CV), revealing that increasing the strength of electron donating groups (EDGs) resulted in more stable CuII complexes and larger ATRP equilibrium constants. Normal ATRP experiments confirmed the obtained CV data by showing the fastest rates of polymerization with R-bpy ligands containing EDGs ((Me)2N and MeO) and the slowest with electron withdrawing Cl. A 400-fold increase in the polymerization rate was observed with bpy ligands containing p-(Me)2N compared to H substituents. Linear increases in molecular weight with monomer conversion, and narrow molecular weight distributions were obtained with (Me)2N-bpy and MeO-bpy ligands. Low catalyst concentrations of 50 to 100 parts-per-million (ppm) were successfully employed with highly active R-bpy ligands (R = MeO and (Me)2N) and found to be effective in polymerizing MA and MMA, respectively, with narrow molecular weight distributions <1.3.

Substituted Tris(2-pyridylmethyl)amine Ligands for Highly Active ATRP Catalysts.

The synthesis and application of a very active catalyst for copper-catalyzed atom transfer radical polymerizations (ATRP) with tris([(4-methoxy-2,5-dimethyl)-2-pyridyl] methyl)amine (TPMA*) ligand is reported. Catalysts with TPMA* ligands are approximately 3 orders of magnitude more active than those with tris(2-pyridylmethyl)amine (TPMA). Catalyst activity was evaluated by cyclic voltammetry, stopped-flow, and ATRP kinetics. Catalysts with TPMA* ligands perform better than those with TPMA ligands, especially at low catalyst concentrations.

Visible Light and Sunlight Photoinduced ATRP with ppm of Cu Catalyst.

Photochemically induced ATRP was performed with visible light and sunlight in the presence of parts per million (ppm) copper catalysts. Illumination of the reaction mixture yielded polymerization in case of 392 and 450 nm light but not for 631 nm light. Sunlight was also a viable source for the photoinduced ATRP. Control experiments suggest photoreduction of the CuII complex (ligand to metal charge transfer in the excited state), yielding a CuI complex, and a bromine radical that can initiate polymerization. No photoactivation of CuI complex was detected. This implies that the mechanism of ATRP in the presence of light is a hybrid of ICAR and ARGET ATRP. The method was also used to synthesize block copolymers and polymerizations in water.

Homogeneous catalysis using iron complexes: recent developments in selective reductions.

With respect to its availability, low toxicity, and price iron should be one of the most used metals in homogeneous catalysis. Surprisingly, so far the application of iron is underdeveloped in comparison to other transition metals. Herein, we highlight promising attempts obtained in hydrogenation, transfer hydrogenation and hydrosilylation, which nicely illustrate the potential of iron and hopefully initialize a ferric future for catalysis.

Design of and mechanistic studies on a biomimetic iron-imidazole catalyst system for epoxidation of olefins with hydrogen peroxide.

Novel iron catalysts, both defined and in situ generated, for the epoxidation of aromatic and aliphatic olefins with hydrogen peroxide as terminal oxidant are described. Our catalyst approach is based on bio-inspired 1-aryl-substituted imidazoles in combination with cheap and abundant iron trichloride hexahydrate. We show that the free 2-position of the imidazole ligand motif plays a key role for catalytic activity, as substitution leads to a dramatic depletion of yield and conversion. X-ray studies, UV/Vis titrations, and NMR studies were carried out to clarify the mechanism.

Preparation of novel unsymmetrical bisindoles under solvent-free conditions: synthesis, crystal structures, and mechanistic aspects.

Indole aziridines and their hydroxyl derivatives have been used for the preparation of a small library of novel functionalized bisindoles. Diversification of these building blocks by solvent-free C-C-bond formation on solid support yielded annulated Hymenialdisine analogues under mild reaction conditions. Indoles as C-nucleophiles form potentially pharmacologically active bisindoles through an electrophilic aromatic substitution pathway in good to excellent yields. Further transformations of the indole aziridines with H-, N-, and O-nucleophiles demonstrate their versatility as key intermediates in diversity oriented synthesis. The hydroxyl precursor leads also to unsymmetrical bisindoles under similar reaction conditions. Important intermediates and final library compounds were confirmed by X-ray analysis. Theoretical studies on these systems show the possible cationic intermediate in the substitution pathway.