A parallel synthesis demonstration library of tri-substituted indazoles containing new antimutagenic/antioxidant hits related to benzydamine

A solution phase strategy for the multiple parallel synthesis of a demonstration library of indazoles is described by which regio-selectivity problems inherent to previous syntheses of this nucleus are largely overcome. Synthesis of selected components proceeded satisfactorily indicating that a fully realized library of indazole analogs could readily be produced using this methodology. Simple modifications of the basic nucleophilic aromatic substitution route unambiguously produce a range of N-1 substitutions (alkyl, aryl and aralkyl) in 50-75% yields. Next a range of substituents was introduced at the C-3 position in 50-80% yields by O-alkylation. Careful choice of reagents and reaction conditions were required to prevent by-product formation due to competing alkylation at N-2 (trace to 15% yields). When present, these contaminants were readily removed by chromofiltration. A third diversity site was sketched in at C-5 in 75-90% yield by reductive alkylation or acylation. Screening of some of the demonstration library members in vitro revealed highly active antioxidants suggesting that producing a full library would be worthwhile.     

Catalytic action of Ni atoms in the formation of carbon nanotubes: a molecular dynamics study

Catalytic action of Ni atoms in the growth of single-wall carbon nanotubes is investigated using tight-binding molecular dynamics and ab initio methods. Our results demonstrate this to be a two step process in which the Ni atom first creates and stabilizes defects in nanotubes. The subsequent incorporation of incoming carbon atoms anneals the Ni-stabilized defects freeing the Ni atom to repeat the catalytic process.     

Velocity fluctuations in a homogeneous 2D granular gas in steady state

We have measured the spectrum of velocity fluctuations in a granular system confined to a vertical plane and driven into a homogeneous, steady state by strong vertical vibration. The distribution of horizontal velocities is not Maxwell-Boltzmann and is given by P(v) = Cexp[-beta(|v|/sigma)(alpha)] where alpha = 1.55+/-0.1 at all frequencies and amplitudes investigated, and also for varying boundary conditions. The deviation from Maxwell-Boltzmann statistics occurs in the absence of spatial clustering and does not result from an inhomogeneous average over regions of varying local density. Surprisingly, P(v) has the same shape over a wide range of densities.     

Simulation of spray combustion in a lean-direct injection combustor

Large-eddy simulation (LES) of a liquid-fueled lean-direct injection (LDI) combustor is carried out by resolving the entire inlet flow path through the swirl vanes and the combustor. A localized dynamic subgrid closure is combined with a subgrid mixing and combustion model so that no adjustable parameters are required for both non-reacting and reacting LES. Time-averaged velocity predictions compare well with the measured data. The unsteady flow features that play a major role in spray dispersion, fuel–air mixing and flame stabilization are identified from the simulation data. It is shown that the vortex breakdown bubble (VBB) is smaller with more intense reverse flow when there is heat release. The swirling shear layer plays a major role in spray dispersion and the VBB provides an efficient flameholding mechanism to stabilize the flame.     

Preparation and physicochemical characterization of carbamazepine (CBMZ): para-sulfonated calix[n]arene inclusion complexes

The formation of inclusion complexes with para-sulfonated calix[n]arene (PSC[n]A) was studied for carbamazepine (CBMZ), a poorly water soluble anticonvulsant drug. The effect of PSC[4]A and PSC[6]A on aqueous solubility of carbamazepine was studied extensively. The complete complexation of the drug was achieved after 48 h of shaking with PSC[n]A in water and evaporation of water to get solid complex. The interaction between PSC[n]A and CBMZ in solid state inclusion complexes was accomplished by aqueous phase solubility studies, HPLC, DSC, PXRD, FTIR, UV–Vis, and FT-Raman spectroscopy. The solubility of CBMZ increases as a function of PSC[n]A concentration. The results of the two phase solubility experiments are in good conformity to signify the formation of 1:1 (PSC[6]A:CBMZ) and 2:1 PSC[4]A:CBMZ complexes. The order of dissolution rate of CBMZ is inclusion complex > physical mixture > drug alone. The purpose of this study was to enhance solubility resulting in high dissolution rate and bioavailability of this essentially water insoluble drug.