Structure, stereochemistry, and biological activity of integramycin, a novel hexacyclic natural product produced by Actinoplanes sp. that inhibits HIV-1 integrase

[structure: see text] HIV-1 integrase is a critical enzyme for viral replication, and its inhibition is an emerging target for potential antiviral chemotherapy. We have discovered a novel inhibitor, integramycin, from screening of fermentation extracts using an in vitro assay. Integramycin possesses a hexacyclic ring system and exhibited an IC50 value of 4 microM against HIV-1 integrase (strand transfer). The isolation, structure elucidation, stereochemistry, conformation, and biological activity has been described.     

A Ferrofluid with Surface Modified Nanoparticles for Magnetic Hyperthermia and High ROS Production

A ferrofluid with 1,2-Benzenediol-coated iron oxide nanoparticles was synthesized and physicochemically analyzed. This colloidal system was prepared following the typical co-precipitation method, and superparamagnetic nanoparticles of 13.5 nm average diameter, 34 emu/g of magnetic saturation, and 285 K of blocking temperature were obtained. Additionally, the zeta potential showed a suitable colloidal stability for cancer therapy assays and the magneto-calorimetric trails determined a high power absorption density. In addition, the oxidative capability of the ferrofluid was corroborated by performing the Fenton reaction with methylene blue (MB) dissolved in water, where the ferrofluid was suitable for producing reactive oxygen species (ROS), and surprisingly a strong degradation of MB was also observed when it was combined with H₂O₂. The intracellular ROS production was qualitatively corroborated using the HT-29 human cell line, by detecting the fluorescent rise induced in 2,7-dichlorofluorescein diacetate. In other experiments, cell metabolic activity was measured, and no toxicity was observed, even with concentrations of up to 4 mg/mL of magnetic nanoparticles (MNPs). When the cells were treated with magnetic hyperthermia, 80% of cells were dead at 43 °C using 3 mg/mL of MNPs and applying a magnetic field of 530 kHz with 20 kA/m amplitude.     

Preparation of glycopolymer‐coated magnetite nanoparticles for hyperthermia treatment

In this article, magnetite nanoparticles (MNPs) coated with glycopolymer bearing glucose moieties were designed with optimal structural, colloidal, and magnetic properties for biomedical applications. MNPs with an average size of 17 ± 2 nm were synthesized by thermal decomposition process and then their surfaces were modified with active vinyl groups. Two different monomers were immobilized onto the surfaces: dopamine methacrylamide, a monomer with properties inspired on mussels adhesive capacity, or unprotected glycomonomer, 2‐{[(D ‐glucosamin‐2N‐yl)carbonyl]‐oxy}ethyl methacrylate. Afterward, the glycomonomer were polymerized at the interface of both vinyl functionalized MNPs by conventional radical polymerization. The resultant hybrid NPs were water dispersible presenting good stability in aqueous solution for long time periods. Moreover, the high density of carbohydrates at the surface of the magnetic NPs could confer targeting properties to the system as demonstrated by studies of their binding interactions with lectins, where the binding activity is higher as the glycopolymer content augments. The magnetic and magneto‐thermal properties of the synthesized hybrid NPs were evaluated. The magnetization curves reveal superparamagnetic features at 300 K, with high values of saturation magnetization. Furthermore, the hybrid glycoparticles show suitable heat dissipation power when exposed to alternating magnetic field conditions. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

A second order virtual node method for elliptic problems with interfaces and irregular domains in three dimensions

We present a numerical method for the variable coefficient Poisson equation in three-dimensional irregular domains and with interfacial discontinuities. The discretization embeds the domain and interface into a uniform Cartesian grid augmented with virtual degrees of freedom to provide accurate treatment of jump and boundary conditions. The matrix associated with the discretization is symmetric positive definite and equal to the standard 7-point finite difference Poisson stencil away from embedded interfaces and boundaries. Numerical evidence suggests second order accuracy in the L^∞-norm. Our approach improves the treatment of Dirichlet and jump constraints in the recent work of Bedrossian et al. [1] and introduces innovations necessary in three dimensions. Specifically, we construct new constraint-based Lagrange multiplier spaces that significantly improve the conditioning of the associated linear system of equations; we provide a method for cell-local polyhedral approximation to the zero isocontour surface of a level set needed for three-dimensional embedding; and we show that the new Lagrange multiplier spaces naturally lead to a class of easy-to-implement multigrid methods that achieve near optimal efficiency, as shown by numerical examples. For the specific case of a continuous Poisson coefficient in interface problems, we provide an expansive treatment of the construction of a particular solution that satisfies the value jump and flux jump constraints. As in [1], this is used in a discontinuity removal technique that yields the standard 7-point stencil across the interface and only requires a modification to the right-hand side of the linear system.     

Modification of surface properties of a poly(dimethylsiloxane)-based elastomer, RTV11, upon exposure to seawater

Atomic force microscopy (AFM) was combined with surface analytical techniques to investigate the rarely addressed issue of the effect of seawater on the surface properties of a selected fouling-release coating, silicon elastomer RTV11 (trademark of General Electric). The exposure of the RTV11 surface to seawater resulted in a modification of its morphology and mechanical properties, as confirmed by AFM and scanning electron microscopy (SEM). Surface modification was dependent on sample preparation and curing process, namely, curing agent concentration and relative humidity during curing. The RTV11 surface remained largely unaltered for samples cured under 100% relative humidity. SEM and X-ray photoelectron spectroscopy studies confirmed that the modified surface of RTV11 had the same elemental composition as the unexposed surface of the elastomer and showed excess Ca. However, the modified surface deformed plastically under load and was stiffer than the original surface. No major change was found on surfaces exposed to nanopure water during similar times of exposure as in seawater, regardless of curing conditions. The rate of increase in the aggregate formation in seawater can be described by an exponential function, with a decay constant of approximately 4.99 x 10(-)(3) min(-)(1) and a pre-exponential factor of approximately 1.77 x 10(-)(2) microm/min.     

Production of Thermostable Lipase by Thermomyces lanuginosus on Solid-State Fermentation: Selective Hydrolysis of Sardine Oil

A naturally immobilized biocatalyst with lipase activity was produced by Thermomyces lanuginosus on solid-state fermentation with perlite as inert support. Maxima lipase activities (22 and 120 U/g of dry matter, using p-nitrophenyl octanoate and trioctanoine, respectively, as substrates) were obtained after 72 h of solid culture, remaining nearly constant up to 120 h. Maxima lipase activity was found at 60 to 85 °C and pH 10. The biocatalyst was stable at 60 °C for at least 4 h of incubation and a pH from 7 to 10. Energy values of activation and deactivation of lipase were of 26 and 6.7 kJ/mol, respectively. The biocatalyst shows high selectivity for the release of the omega-3 polyunsaturated fatty acids, eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), during the hydrolysis of sardine oil. The EPA/DHA ratio (16:6) released by this biocatalyst was superior to that obtained with the commercial preparations of T. lanuginosus.     

A New Tubular Arrangement of a Dimethylsilyl Bridged Calix[4]resorcinarene

Abstract

The functionalization of calix[4]resorcinarene 1 (R ₁=H, R ₂=Me) with dichlorodimethylsilane leads to the formation of the dimethylsilyl-bridged cavitand 2 which, during the work up of the reaction product, encapsulates a molecule of water 2·H₂O crystallizes in the C2/c system (a = 23.892 Å, b = 8.493 Å, c = 43.035 Å, β = 100.05°, reflections: 5385, 2376 (F>4.0 [sgrave](F)), R=9.17%, calculated density=1.213 Mg/m³) with eight molecules per unit cell. The main feature of the crystal packing is the alternating pairs of up-down disposed cavitands along the c direction and well developed columns in the b direction. The molecules of water are completely encapsulated, but there are some close contacts with the methylene bridge from the upper molecule. Molecular orbital calculations show that the lowest energy conformer of cavitand 2 is that with all four silicon atoms oriented inward and the energies of the other conformers are so high that they cannot be accessed at normal temperature. Ab initio calculated electrostatic potentials correlate well with the relative positions of the cavitands in the crystal structure.     

Study of nitrogen containing compounds in the polar troposphere

Atmospheric nitrogen compounds play a critical role in tropospheric photochemistry and are crucial to understand the chemical and physical evolution of atmospheric pollutants in polar areas. Measurements of these species in remote areas are rare, although their relevance is well established. Sampling campaigns of gaseous and particulate atmospheric trace species were performed in Arctic and in Antarctica during three consecutive years (1997-1999), using a proper combination of annular denuders and filter pack. After sampling, the ionic species were extracted with aqueous solutions and analysed by means of ion chromatography. Quality assurance on the sampling and analytical steps allowed accurate and precise measurements of all relevant compounds, which are thought to be important to nitrogen chemistry, at very low concentration levels. In addition, the measurements also included a multistage low-pressure impactor for the collection of particulate matter in different size regions (0.035-15.9 mm). Results obtained from these campaigns demonstrate that the minor components may be measured at levels as low as a few nanograms per cubic meter. The reported concentrations are to be considered among the first observations of nitrogen containing compounds in polar sites.