A regioselective approach toward the synthesis of pharmacologically important quinone-containing heterocyclic systems

An inexpensive and regioselective approach to dihydrothieno[3,2-g]quinoline-4,9-dione is reported. A combination of a mild version of Skraup reaction with a sequential substitution/Michael addition allowed the selective preparation in acceptable yield of a pharmacologically important quinone derivative, previously obtained only in trace and together with the other regioisomer.     

Calculations of overtone NIR and NIR-VCD spectra in the local mode approximation: Camphor and Camphorquinone

We present a method to calculate near-infrared (NIR) and NIR-vibrational circular dichroism (NIR-VCD) spectra up to the second CH-stretching overtone region in the local mode approximation. Atomic polar tensors and atomic axial tensors are first evaluated by DFT methodology for all CH stretching coordinates with systematic positive and negative displacements off-equilibrium and therefrom anharmonic dipole moment functions are constructed by polynomial interpolations. No adjustable parameters are employed up to this point. Rotational and dipole strengths are finally calculated by evaluating transition moments of Morse-type wave-functions. The method is applied to the case of Camphor and Camphorquinone, for which relevant differences in the vibrational circular dichroism (VCD) data are observed, which are predicted by our approach. Further steps are still to be made for a more complete treatment: the ab initio evaluation of mechanical anharmonicity and the introduction of mechanical and electrical coupling between local modes.     

Poly(ε-caprolactone) modified by functional groups: Preparation and chemical–physical investigation

Functionalization of polymers is a particular relevant approach in the field of biodegradable polymers, where modifications are often required to allow these materials to replace more conventional, not biodegradable polymers in a wider range of applications. This article will report on functionalization of poly(ε-caprolactone) with unsaturated monomers bearing either anhydride groups (PCL-g-(MA-GMA)) or tertiary amines (PCL-g-DMAEA), obtained through radical grafting in a Brabender mixer. Crystallization kinetics parameters have been determined with several techniques (rheology, optical microscopy and differential scanning calorimetry) and the results obtained are in good agreement. It was observed that the crystallization rate significantly increases in the case of the modified polymers.     

A kinematically coupled time-splitting scheme for fluid–structure interaction in blood flow

We present a new time-splitting scheme for the numerical simulation of fluid–structure interaction between blood flow and vascular walls. This scheme deals in a successful way with the problem of the added mass effect. The scheme is modular and it embodies the stability properties of implicit schemes at the low computational cost of loosely coupled ones.     

Positive solutions for some Schrödinger equations having partially periodic potentials

This paper is concerned with the problem of finding positive solutions of the equation −Δu+(a_∞+a(x))u=|u|^q−2u, where q is subcritical, Ω is either RN or an unbounded domain which is periodic in the first p coordinates and whose complement is contained in a cylinder , a_∞>0, a∈C(RN,R) is periodic in the first p coordinates, infx∈RN(a_∞+a(x))>0 and a(x^′,x^″)→0 as |x^″|→∞ uniformly in x^′. The cases a?0 and a?0 are considered and it is shown that, under appropriate assumptions on a, the problem has one solution in the first case and p+1 solutions in the second case when p?N−2.     

On solving the Lagrangian dual of integer programs via an incremental approach

The Lagrangian dual of an integer program can be formulated as a min-max problem where the objective function is convex, piecewise affine and, hence, nonsmooth. It is usually tackled by means of subgradient algorithms, or multiplier adjustment techniques, or even more sophisticated nonsmooth optimization methods such as bundle-type algorithms. Recently a new approach to solving unconstrained convex finite min-max problems has been proposed, which has the nice property of working almost independently of the exact evaluation of the objective function at every iterate-point.     

A nonlinear theory for shells with slowly varying thickness

We study the Γ-limit of 3d nonlinear elasticity for shells of small, variable thickness, around an arbitrary smooth 2d surface. To cite this article: M. Lewicka et al., C. R. Acad. Sci. Paris, Ser. I 347 (2009).     

A designed glycoprotein analogue of Gc-MAF exhibits native-like phagocytic activity

Rational protein design has been successfully used to create mimics of natural proteins that retain native activity. In the present work, de novo protein engineering is explored to develop a mini-protein analogue of Gc-MAF, a glycoprotein involved in the immune system activation that has shown anticancer activity in mice. Gc-MAF is derived in vivo from vitamin D binding protein (VDBP) via enzymatic processing of its glycosaccharide to leave a single GalNAc residue located on an exposed loop. We used molecular modeling tools in conjunction with structural analysis to splice the glycosylated loop onto a stable three-helix bundle (alpha3W, PDB entry 1LQ7). The resulting 69-residue model peptide, MM1, has been successfully synthesized by solid-phase synthesis both in the aglycosylated and the glycosylated (GalNAc-MM1) form. Circular dichroism spectroscopy confirmed the expected alpha-helical secondary structure. The thermodynamic stability as evaluated from chemical and thermal denaturation is comparable with that of the scaffold protein, alpha3W, indicating that the insertion of the exogenous loop of Gc-MAF did not significantly perturb the overall structure. GalNAc-MM1 retains the macrophage stimulation activity of natural Gc-MAF; in vitro tests show an identical enhancement of Fc-receptor-mediated phagocytosis in primary macrophages. GalNAc-MM1 provides a framework for the development of mutants with increased activity that could be used in place of Gc-MAF as an immunomodulatory agent in therapy.     

Impact of reductive cleavage of an intramolecular disulfide bond containing cationic gemini surfactant in monolayers and bilayers

The properties of a novel disulfide-bond-containing gemini surfactant bis[N,N-dimethyl-N-hexadecyl-N-(2-mercaptoethyl)ammonium bromide] disulfide (DSP) were studied using a Langmuir balance, supported monolayers, differential scanning calorimetry, giant vesicles, and LUVs. In 150 mM NaCl the cmc for DSP was 7.5 microM whereas that of the monomer N,N-dimethyl-N-hexadecyl-N-(2-mercaptoethyl)ammonium bromide (MSP) was 12.1 microM. Both surfactants exhibited single endotherms upon DSC, with peak temperatures Tm at 21.7 and 20.1 degrees C for DSP and MSP, respectively. The endotherm for MSP was significantly broader indicating less cooperative melting. Both in monolayers and in vesicles reductive cleavage of the disulfide bond of DSP could be obtained by glutathione (GSH). For Langmuir films of DSP the addition of GSH into the subphase led to a decrease in surface pressure pi as well as surface dipole potential psi. Although the cleavage by GSH was significantly slower in the presence of a charge saturating concentration of DNA, it did not prevent the reaction. The resulting monomers detached from supported monolayers, leading to loss of affinity of the surface for DNA. Disruption of giant vesicles containing DSP within approximately 30 s following a local injection of GSH was observed, revealing membrane destabilization.     

Role of the spacer stereochemistry on the aggregation properties of cationic gemini surfactants

The preparation and characterization of three stereoisomeric cationic gemini surfactants, 2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonio)butane dibromide, are described. The aggregation properties have been studied by fluorescence, electrical conductivity, and quasi-elastic light scattering. A conformational study of the surfactant headgroups has been performed by molecular mechanics calculations to investigate the effect of the stereogenic centers on the surfactant molecular shape and therefore on the different organizations of the monomers in the aggregates. Results show that the stereochemistry of the spacer strongly influences the aggregation behavior of the diasteromeric gemini in water.