4-Substituted 5-nitroisoquinolin-1-ones from intramolecular Pd-catalysed reaction of N-(2-alkenyl)-2-halo-3-nitrobenzamides

4-Methyl- and 4-benzyl-5-aminoisoquinolin-1-ones are close analogues of the water-soluble PARP-1 inhibitor 5-AIQ. Their synthesis was approached through Pd-catalysed cyclisations of N-(2-alkenyl)-2-iodo-3-nitrobenzamides. Reaction of N,N-diallyl-2-iodo-3-nitrobenzamide with Pd(PPh₃)₄ gave a mixture of 2-allyl-4-methyl-5-nitroisoquinolin-1-one and 2-allyl-4-methylene-5-nitro-3,4-dihydroisoquinolin-1-one. N-Benzhydryl-N-cinnamyl-2-iodo-3-nitrobenzamide similarly gave 2-benzhydryl-4-benzyl-5-nitroisoquinolin-1-one and 2-benzhydryl-4-benzylidene-5-nitro-3,4-dihydroisoquinolin-1-one. The isomeric products are not interconvertible. A deuterium-labelling study indicated that the isomers were formed by different pathways: a π-allyl-Pd route and the classical Heck route. The corresponding secondary amides N-allyl-2-iodo-3-nitrobenzamide and N-((substituted)-cinnamyl)-2-iodo-3-nitrobenzamide gave good yields of the required 4-methyl- and 4-((substituted)-benzyl)-5-nitroisoquinolin-1-ones, respectively, under optimised conditions (Pd(PPh₃)₄, Et₃N, Bu₄NCl, 150 °C, rapid heating). Hydrogenation of the nitro groups gave 4-methyl- and 4-benzyl-5-aminoisoquinolin-1-ones, which were potent inhibitors of PARP-1 activity.     

Instanton moduli as a novel map from tori to K3-surfaces

A map is constructed from the moduli of hyper-Kähler tori to hyper-Kähler K3 surfaces which does not coincide with the Kummer map. The map takes a torus to the moduli space of SO(3) connections on a bundle with nontrivial first Stiefel-Whitney class and first Pontrjagin class equal to –4. This map is shown to intersect the Kummer moduli and also certain subvarieties of singular K3 surfaces. Our map is shown to satisfy the local Torelli theorem, and the K3-surfaces in its image are shown to carry a natural metric which is Calabi-Yau.     

Bicausal isomorphism of Bernoulli processes

Using an idea of Adler and Weiss, automorphisms of Bernoulli processes are constructed where the mapping in one direction is causal with bounded memory and the inverse mapping is causal with memory which is finite w.p.l. Nontrivial such automorphisms exist only when the letter probability distribution has nontrivial symmetry, e.g., the 2-shift.     

Utilization of sterol carrier protein-2 by phytanoyl-CoA 2-hydroxylase in the peroxisomal alpha oxidation of phytanic acid

Since it possesses a 3-methyl group, phytanic acid is degraded by a peroxisomal alpha-oxidation pathway, the first step of which is catalyzed by phytanoyl-CoA 2-hydroxylase (PAHX). Mutations in human PAHX cause phytanic acid accumulations leading to Adult Refsum's Disease (ARD), which is also observed in a sterol carrier protein 2 (SCP-2)-deficient mouse model. Phytanoyl-CoA is efficiently 2-hydroxylated by PAHX in vitro in the presence of mature SCP-2. Other straight-chain fatty acyl-CoA esters were also 2-hydroxylated and the products isolated and characterized. Use of SCP-2 increases discrimination between straight-chain (e.g., hexadecanoyl-CoA) and branched-chain (e.g., phytanoyl-CoA) substrates by PAHX. The results explain the phytanic acid accumulation in the SCP-2-deficient mouse model and suggest that some of the common symptoms of ARD and other peroxisomal diseases may arise in part due to defects in SCP-2 function caused by increased phytanic acid levels.     

Fast temperature-programmed gas chromatography-mass spectrometry for food analysis

Fast temperature-programmed gas chromatography (FTGC) is evaluated. A modified capillary column allowing temperature-program rates as high as 20 degrees C/s is operated with mass spectrometric detection (MSD). FTGC methods are developed for the analysis of off-flavors in water, derivatized sugars, and fatty acid methyl esters. Liquid injection and solid-phase microextraction are evaluated. Although the resolution can be somewhat lower than analysis with a traditional column, time savings are significant. Analysis times range from 2 to 4.5 min compared with 20 to 60 min for conventional methods. MSD allows for the analysis of some coeluting peaks, which allows for quantitation even when peaks coelute.     

Analysis of noise barrier overlap gaps

Sound propagation through the gap produced by two parallel vertical barriers with overlapped ends is formulated for traffic noise sources. The analysis identifies both source and receiver regions according to the mechanisms that influence noise propagation in the vicinity of an overlap gap. A method to account for the contributions from the various source regions for a given receiver location is described. The derived method can be implemented using various equations for sound propagation. The results of using equations approved by the United States Federal Highway Administration for traffic noise propagation are given. Uncalibrated predictions are compared with field measurements for up to 30 receiver positions from each of four overlap gaps. The relative importance of contributions from reflected rays to the noise levels at receiver positions is given. The analysis confirms the initial hypothesis that a commonly used strategy of overlapping barriers by an amount equal to two or three times the overlap width is useful for controlling line-of-sight propagation but ignores the substantial effect of reflections.     

Quantitative analysis and characterization of DNA immobilized on gold

We describe the complementary use of X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy to quantitatively characterize the immobilization of thiolated (dT)(25) single-stranded DNA (ssDNA) on gold. When electron attenuation effects are accurately accounted for in the XPS analysis, the relative coverage values obtained by the two methods are in excellent agreement, and the absolute coverage can be calculated on the basis of the XPS data. The evolution of chemically specific spectral signatures during immobilization indicates that at lower coverages much of the DNA lies flat on the surface, with a substantial fraction of the thymine bases chemisorbed. At higher immobilization densities, the (dT)(25) film consists of randomly coiled ssDNA molecules each anchored via the thiol group and at possibly one or two other bases. We use two examples to demonstrate how the quantitative analysis can be applied to practical problems: the effects of different buffer salts on the immobilization efficiency; the immobilization kinetics. Buffers with divalent salts dramatically increase the efficiency of immobilization and result in very high surface densities (>5 x 10(13)/ cm(2)), densities that may only be possible if the divalent counterions induce strong attractive intermolecular interactions. In contrast with previous reports of alkanethiol adsorption kinetics on gold, ssDNA immobilization in 1 M phosphate buffer does not occur with Langmuir kinetics, a result attributable to rearrangement within the film that follows the initial adsorption.     

Implementation of the quantum Fourier transform

A quantum Fourier transform (QFT) has been implemented on a three qubit nuclear magnetic resonance (NMR) quantum computer to extract the periodicity of an input state. Implementation of a QFT provides a first step towards the realization of Shor's factoring and other quantum algorithms. The experimental implementation of the QFT on a periodic state is presented along with a quantitative measure of its efficiency measured through state tomography. Experimentally realizing the QFT is a clear demonstration of the ability of NMR to control quantum systems.     

Clock synchronization with dispersion cancellation

The dispersion cancellation feature of pulses which are entangled in frequency is employed to synchronize clocks of distant parties. The proposed protocol is insensitive to the pulse distortion caused by transit through a dispersive medium. Since there is cancellation to all orders, also the effects of slowly fluctuating dispersive media are compensated. The experimental setup can be realized with currently available technology, at least for a proof of principle.