Synthesis of Hydantoins,Thiohydantoins, and Glycocyamidines Under Solvent-Free Conditions

Hydantoins, thiohydantoins, and glycocyamidines have been prepared in moderate to excellent yields at room temperature under solvent-free conditions. 3N-amino and carboamide derivatives of hydantoin (7–8) were prepared in single step by condensing benzil with semicarbazide and biuret respectively.     

Magnetization of Fe‐oxide based nanocomposite tuned by surface charging

Aiming at a voltage‐control of magnetism, the magnetization of a porous γ‐Fe₂O₃–Pt nanocomposite is studied under the influence of charging the surfaces of the porous structure in an electrolyte. Reversible variations of the magnetization of up to 10.4% could be achieved upon charging in the regime where electrochemical adsorption and desorption occurs. The observed variation of the magnetization with electrochemical charging is assigned to the γ‐Fe₂O₃ nanoparticles whereas the conductive network of Pt nanoparticles is necessary for charging. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Isolation and characterization of novel antibacterial compound from an untapped plant,Stereospermum fimbriatum

Abstract

Stereospermum fimbriatum or locally known as “Chicha” is traditionally used for itchy skin, earache, stomachache and postpartum treatments. This study was designed to evaluate the antimicrobial potential of S. fimbriatum’s stem bark against 11 pathogens and isolate its bioactive compound. Successive soxhlet extraction was conducted using n-hexane, dichloromethane (DCM) and methanol. Disc diffusion, minimum inhibitory and bactericidal concentration (MIC & MBC) assays were done to examine the antimicrobial activity. Bioassay-guided isolation was conducted on S. fimbriatum’s extract. The DCM extract of stem bark (DS) was the most potent extract followed by n-hexane extract of the stem bark (NS). A novel compound was isolated and coded as C1 which demonstrated potent antibacterial effects with the MIC values as low as 3.13?µg/mL to 6.25?µg/mL, against S. epidermidis, MRSA and S. aureus. Thus, S. fimbriatum could be a potential source of antimicrobial agents for the treatment of skin infections, specifically, MRSA.     

Static analysis of functionally graded beams using higher order shear deformation theory

Displacement field based on higher order shear deformation theory is implemented to study the static behavior of functionally graded metal–ceramic (FGM) beams under ambient temperature. FGM beams with variation of volume fraction of metal or ceramic based on power law exponent are considered. Using the principle of stationary potential energy, the finite element form of static equilibrium equation for FGM beam is presented. Two stiffness matrices are thus derived so that one among them will reflect the influence of rotation of the normal and the other shear rotation. Numerical results on the transverse deflection, axial and shear stresses in a moderately thick FGM beam under uniform distributed load for clamped–clamped and simply supported boundary conditions are discussed in depth. The effect of power law exponent for various combination of metal–ceramic FGM beam on the deflection and stresses are also commented. The studies reveal that, depending on whether the loading is on the ceramic rich face or metal rich face of the beam, the static deflection and the static stresses in the beam do not remain the same.     

Apoptosis mechanisms related to the increased sensitivity of Jurkat T-cells vs A431 epidermoid cells to photodynamic therapy with the phthalocyanine Pc 4

To examine the clinical applicability of Pc 4, a promising second-generation photosensitizer, for the photodynamic treatment of lymphocyte-mediated skin diseases, we studied the A431 and Jurkat cell lines, commonly used as surrogates for human keratinocyte-derived carcinomas and lymphocytes, respectively. As revealed by ethyl acetate extraction and absorption spectrophotometry, uptake of Pc 4 into the two cell lines was linear with Pc 4 concentration and similar on a per cell basis but greater in Jurkat cells on a per mass basis. Flow cytometry showed that uptake was linear at low doses; variations in the dose-response for uptake measured by fluorescence supported differential aggregation of Pc 4 in the two cell types. As detected by confocal microscopy, Pc 4 localized to mitochondria and endoplasmic reticulum in both cell lines. Jurkat cells were much more sensitive to the lethal effects of phthalocyanine photodynamic therapy (Pc 4-PDT) than were A431 cells, as measured by a tetrazolium dye reduction assay, and more readily underwent morphological apoptosis. In a search for molecular factors to explain the greater photosensitivity of Jurkat cells, the fate of important Bcl-2 family members was monitored. Jurkat cells were more sensitive to the induction of immediate photodamage to Bcl-2, but the difference was insufficient to account fully for their greater sensitivity. The antiapoptotic protein Mcl-1 was extensively cleaved in a dose- and caspase-dependent manner in Jurkat, but not in A431, cells exposed to Pc 4-PDT. Thus, the greater killing by Pc 4-PDT in Jurkat compared with A431 cells correlated with greater Bcl-2 photodamage and more strongly to the more extensive Mcl-1 degradation. Pc 4-PDT may offer therapeutic advantages in targeting inflammatory cells over normal keratinocytes in the treatment of T-cell-mediated skin diseases, such as cutaneous lymphomas, dermatitis, lichenoid tissue reactions and psoriasis, and it will be instructive to evaluate the role of Bcl-2 family proteins, especially Mcl-1, in the therapeutic response.     

A general method for copper-catalyzed arylation of arene C-H bonds

A general method for copper-catalyzed arylation of sp (2) C-H bonds with p K a's below 35 has been developed. The method employs aryl halide as the coupling partner, lithium alkoxide or K 3PO 4 base, and DMF, DMPU, or mixed DMF/xylenes solvent. A variety of electron-rich and electron-poor heterocycles such as azoles, caffeine, thiophenes, benzofuran, pyridine oxides, pyridazine, and pyrimidine can be arylated. Furthermore, electron-poor arenes possessing at least two electron-withdrawing groups on a benzene ring can also be arylated. Two arylcopper-phenanthroline complex intermediates were independently synthesized.     

Automated molecular simulation based binding affinity calculator for ligand-bound HIV-1 proteases

The successful application of high throughput molecular simulations to determine biochemical properties would be of great importance to the biomedical community if such simulations could be turned around in a clinically relevant timescale. An important example is the determination of antiretroviral inhibitor efficacy against varying strains of HIV through calculation of drug-protein binding affinities. We describe the Binding Affinity Calculator (BAC), a tool for the automated calculation of HIV-1 protease-ligand binding affinities. The tool employs fully atomistic molecular simulations alongside the well established molecular mechanics Poisson-Boltzmann solvent accessible surface area (MMPBSA) free energy methodology to enable the calculation of the binding free energy of several ligand-protease complexes, including all nine FDA approved inhibitors of HIV-1 protease and seven of the natural substrates cleaved by the protease. This enables the efficacy of these inhibitors to be ranked across several mutant strains of the protease relative to the wildtype. BAC is a tool that utilizes the power provided by a computational grid to automate all of the stages required to compute free energies of binding: model preparation, equilibration, simulation, postprocessing, and data-marshaling around the generally widely distributed compute resources utilized. Such automation enables the molecular dynamics methodology to be used in a high throughput manner not achievable by manual methods. This paper describes the architecture and workflow management of BAC and the function of each of its components. Given adequate compute resources, BAC can yield quantitative information regarding drug resistance at the molecular level within 96 h. Such a timescale is of direct clinical relevance and can assist in decision support for the assessment of patient-specific optimal drug treatment and the subsequent response to therapy for any given genotype.     

HIV/AIDS epidemic fractional-order model

In this paper a non-linear mathematical model with fractional order ?, 0 < ? ≤ 1 is presented for analyzing and controlling the spread of HIV/AIDS. Both the disease-free equilibrium E₀ and the endemic equilibrium E^* are found and their stability is discussed using the stability theorem of fractional order differential equations. The basic reproduction number R₀ plays an essential role in the stability properties of our system. When R₀ < 1 the disease-free equilibrium E₀ is attractor, but when R₀ > 1, E₀ is unstable and the endemic equilibrium (EE) E^* exists and it is an attractor. Finally numerical Simulations are also established to investigate the influence of the system parameter on the spread of the disease.     

Synthesis, Isolation, Characterization, and Reactivity of High-Energy Stereogenic-at-Ru Carbenes: Stereochemical Inversion through Olefin Metathesis and Other Pathways

The synthesis, isolation, purification (routine silica gel chromatography), and spectroscopic characterization of high-energy endo stereogenic-at-Ru complex isomers, generated by ring-opening/cross-metathesis (ROCM) reaction of the corresponding exo carbenes, are disclosed. We provide experimental evidence showing that an endo isomer can undergo thermal or Br?nsted acid-catalyzed polytopal rearrangement, causing conversion to the energetically favored exo carbene.