Rhodium-Catalyzed Addition of Aryl Boronic Acids to 2,2-Disubstituted Malononitriles

β-Ketonitriles bearing a quaternary carbon at the 2-position were prepared through Rh-catalyzed addition of aryl boronic acids to 2,2-disubstituted malononitriles. In contrast to the previously described transnitrilative cyanation of aryl boronic acids with dialkylmalononitriles, the present reaction avoids retro-Thorpe collapse of the intermediate addition product through the use of a milder base. The reaction was amenable to a variety of aryl boronic acids and disubstituted malononitriles, providing a diverse array of β-ketonitriles. The products could be further derivatized to valuable chiral α,α-disubstituted-β-aminonitriles through addition reactions to the corresponding N-tert-butanesulfinyl imines.     

A lattice Boltzmann method for thermal nonideal fluids

A Lattice Boltzmann Method for van der Waals fluids with variable temperature is described. Thermo-hydrodynamic equations are correctly reproduced at second order of a Chapman-Enskog expansion. The method is applied to study initial stages of phase separation of a fluid quenched by contact with colder walls. Thermal equilibration is favoured by pressure waves which propagate with the sound velocity.     

A new ternary Cu (II) complex with 4,7-dimethyl-1,10-phenanthroline and NOO-type tridentate Schiff base ligand: Synthesis,crystal structure,biomacromolecular interactions,and radical scavenging activities

NOO-type tridentate Schiff base, N-salicylidene-2-aminobenzoic acid, (H₂L), and its ternary Cu (II) complex containing H₂L Schiff base and 4,7-dimethyl-1,10-phenanthroline (4,7-dmphen), [Cu(4,7-dmphen)(H₂L)]₂7H₂O, have been synthesized and characterized by CHN analysis, ESI-MS, FTIR, and single-crystal X-ray diffraction techniques. The interaction of alone H₂L Schiff base ligand and ternary Cu (II) complex with biomacramolecules {calf thymus DNA (CT-DNA) and bovine serum albumin (BSA)} has been investigated by electronic absorption and fluorescence spectroscopy. The experimental results indicate that H₂L Schiff base ligand and ternary Cu (II) complex bind to CT-DNA by means of a moderate intercalation mode. Furthermore, the fluorescence quenching mechanism between H₂L Schiff base ligand and ternary Cu (II) complex with BSA possesses a static quenching process. Radical scavenging activity of H₂L Schiff base ligand and ternary Cu (II) complex was measured in terms of EC₅₀, using the DPPH and H₂O₂ methods. Biomacromolecule interactions and scavenging activity studies revealed that ternary Cu (II) complex yielded better results than H₂L Schiff base ligand alone.     

Three‐dimensional structure of cyclic antibiotic teicoplanin aglycone using NMR distance and dihedral angle restraints in a DMSO solvation model

The three‐dimensional solution conformation of teicoplanin aglycone was determined using NMR spectroscopy. A combination of NOE and dihedral angle restraints in a DMSO solvation model was used to calculate an ensemble of structures having a root mean square deviation of 0.17 Å. The structures were generated using systematic searches of conformational space for optimal satisfaction of distance and dihedral angle restraints. Comparison of the NMR‐derived structure of teicoplanin aglycone with the X‐ray structure of a teicoplanin aglycone analog revealed a common backbone conformation with deviation of two aromatic side chain substituents. Experimentally determined backbone ¹³C chemical shifts showed good agreement with those computed at the density functional level of theory, providing a cross validation of the backbone conformation. The flexible portion of the molecule was consistent with the region that changes conformation to accommodate protein binding. The results showed that a hydrogen‐bonded DMSO molecule in combination with NMR‐derived restraints together enabled calculation of structures that satisfied experimental data. Copyright © 2015 John Wiley & Sons, Ltd.     

Structure Elucidation of a Complex Faldaprevir‐(±)‐α‐Tocopherol Addition Product Reveals Reactivity of Common Excipient Vitamin E‐TPGS

Vitamin E‐TPGS (d ‐α‐tocopheryl polyethylene glycol succinate) is a common excipient used in drug formulations. This excipient is formed by esterification of Vitamin E succinate with polyethylene glycol. As part of an oral formulation for active pharmaceutical ingredient (API) Faldaprevir, Vitamin E‐TPGS was found to decompose under ambient conditions producing free (±)‐α‐Tocopherol which subsequently formed an adduct composed of α‐Tocopherol and the API. The addition product was isolated using liquid chromatography with collections onto solid‐phase extraction cartridges, and full structure elucidation was achieved using mass spectrometry and nuclear magnetic resonance spectroscopy. The results revealed a regioselective addition of α‐Tocopherol to the API that likely occurs through the formation of a stabilized ortho‐quinone methide intermediate. This finding demonstrates the propensity of the common excipient (Vitamin E‐TPGS) to generate chemically active intermediates that may react with formulation ingredients.     

Correlation Functions by Cluster Variation Method for Ising Model with NN, NNN, and Plaquette Interactions

We consider a procedure for calculating the pair correlation function in the context of cluster variation methods (CVM). As specific cases, we study the pair correlation function in the paramagnetic phase of the Ising model with nearest neighbors, next to nearest neighbors, and plaquette interactions in two and three dimensions. In presence of competing interactions, the so-called disorder line separates in the paramagnetic phase a region where the correlation function has the usual exponential behavior from a region where the correlation has an oscillating, exponentially damped behavior. In two dimensions, using the plaquette as the maximal cluster of the CVM approximation, we calculate the phase diagram and the disorder line for a case where a comparison is possible with known results for the eight-vertex model. In three dimensions, in the CVM cube approximation, we calculate the phase diagram and the disorder line in some cases of particular interest. The relevance of our results for experimental systems like mixtures of oil, water, and surfactant is also discussed.     

Phase-ordering dynamics of binary mixtures with field-dependent mobility in shear flow

The effect of shear flow on the phase-ordering dynamics of a binary mixture with field-dependent mobility is investigated. The problem is addressed in the context of the time-dependent Ginzburg-Landau equation with an external velocity term, studied in self-consistent approximation. Assuming a scaling ansatz for the structure factor, the asymptotic behavior of the observables in the scaling regime can be analytically calculated. All the observables show log-time periodic oscillations which we interpret as due to a cyclical mechanism of stretching and break-up of domains. These oscillations are damped as consequence of the vanishing of the mobility in the bulk phase. Received 13 April 1999     

On the possibility to measure the π0→γγ decay width and the γ?γ→π0 transition form factor with the KLOE-2 experiment

A possibility of KLOE-2 experiment to measure the width \varGamma_{p⁰ ?gg}\varGamma_{\pi^{0} \to\gamma\gamma} and the π ⁰ γγ ^∗ form factor F(Q ²) at low invariant masses of the virtual photon in the space-like region is considered. This measurement is an important test of the strong interaction dynamics at low energies. The feasibility is estimated on the basis of a Monte-Carlo simulation. The expected accuracy for \varGamma_{p⁰ ?gg}\varGamma_{\pi^{0} \to\gamma\gamma} is at a per cent level, which is better than the current experimental world average and theory. The form factor will be measured for the first time at Q ²≤0.1 GeV² in the space-like region. The impact of these measurements on the accuracy of the pion-exchange contribution to the hadronic light-by-light scattering part of the anomalous magnetic moment of the muon is also discussed.