Microwave-enhanced rhodium-catalyzed conjugate-addition of aryl boronic acids to unprotected maleimides

Various boronic acids were treated with a rhodium (I) catalyst enabling their 1,4-conjugate addition to unprotected maleimide. The scope of the reaction was explored to include both electron-rich and electron poor boronic acids. These reactions were also performed in the microwave resulting in reduced reaction times and improved efficiencies. Additionally, substrates that were recalcitrant under conventional conditions were successfully reacted under microwave conditions. The reaction worked satisfactorily with boronic acids having a free OH or NH group.     

On the distribution of comparisons in sorting algorithms

We considered the following natural conjecture: For every sorting algorithm every key will be involved in(logn) comparisons for some input. We show that this is true for most of the keys and prove matching upper and lower bounds. Every sorting algorithm for some input will involven–n /2+1 keys in at leastlog₂ n comparisons,>0. Further, there exists a sorting algorithm that will for every input involve at mostn–n ^/c keys in greater thanlog₂ n comparisons, wherec is a constant and>0. The conjecture is shown to hold for natural algorithms from the literature.     

Influence of halloysite nanotubes (HNTs) on morphology,crystallization, mechanical and thermal behaviour of PP/ABS blends and its composites in presence and absence of dual compatibilizer

Halloysite nanotubes (HNTs) filled 80/20 (wt/wt) polypropylene (PP)/acrylonitrile butadiene styrene (ABS) blends and its composites in presence and absence of dual compatibilizer (polypropylene grafted maleic anhydride (PP-g-MA), and styrene-ethylene, butylene-styrene triblock copolymer grafted with maleic anhydrite (SEBS-g-MA)) have been prepared using twin screw extruder followed by injection moulding. Significant refinements in dispersed ABS droplets diameter and interparticle distance between dispersed ABS droplets were observed in case of HNTs filled 80/20 (wt/wt) PP/ABS blends and its composites in presence of PP-g-MA and SEBS-g-MA. This has resulted in significant enhancement in tensile and impact properties of HNTs filled 80/20 (wt/wt) PP/ABS blends and its composites in presence of PP-g-MA and SEBS-g-MA. Refinement in morphology of dispersed ABS phase results in decrease in crystallinity of HNTs filled 80/20 (wt/wt) PP/ABS blends and its composites in presence of PP-g-MA and SEBS-g-MA. In addition, HNTs act as heterogeneous nucleating agent for the growth of PP crystals, and hence crystallization rate of HNTs filled 80/20 (wt/wt) PP/ABS blends and its composites in presence and absence of PP-g-MA and SEBS-g-MA increases. Thermal stability also increases in case of HNTs filled 80/20 (wt/wt) PP/ABS blends and its composites in presence and absence of PP-g-MA and SEBS-g-MA.     

Analysis of Chemotherapeutic Drug Delivery at the Single Cell Level Using 3D-MSI-TOF-SIMS

In this work, we show the advantages of label-free, tridimensional mass spectrometry imaging using dual beam analysis (25 keV Bi₃ ⁺) and depth profiling (20 keV with a distribution centered at Ar₁₅₀₀ ⁺) coupled to time of flight secondary ion mass spectrometry (3D-MSI-TOF-SIMS) for the study of A-172 human glioblastoma cell line treated with B-cell lymphoma 2 (Bcl-2) inhibitor ABT-737. The high spatial (~250 nm) and high mass resolution (m/Δm ~10,000) of TOF-SIMS permitted the localization and identification of the intact, unlabeled drug molecular ion (m/z 811.26 C₄₂H₄₄ClN₆O₅S₂ ^– [M – H]^–) as well as characteristic fragment ions. We propose a novel approach based on the inspection of the drug secondary ion yield, which showed a good correlation with the drug concentration during cell treatment at therapeutic dosages (0–200 μM with 4 h incubation). Chemical maps using endogenous molecular markers showed that the ABT-737 is mainly localized in subsurface regions and absent in the nucleus. A semiquantitative workflow is proposed to account for the biological cell diversity based on the spatial distribution of endogenous molecular markers (e.g., nuclei and cytoplasm) and secondary ion confirmation based on the ratio of drug-specific fragments to molecular ion as a function of the therapeutic dosage.

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Graphical Abstract ?

     

G-quadruplex recognition by bis-indole carboxamides

Herein we report the de novo design and synthesis of a geometrically flexible bis-indole carboxamide and a constrained derivative, as a novel class of small molecule scaffold that exhibits high stabilization potential for DNA G-quadruplex sequences associated with the promoters of c-kit2 and c-myc.     

Synthesis of multi‐substituted dibenzo[b,d]furan

The synthesis of multi‐substituted dibenzo[b,d]furan derivatives 7a‐b and 11a‐b from readily available starting materials is described. These compounds are important intermediates for synthesis of molecules having wide therapeutic applications.     

Diarylethynyl amides that recognize the parallel conformation of genomic promoter DNA G-quadruplexes

We report bis-phenylethynyl amide derivatives as a potent G-quadruplex binding small molecule scaffold. The amide derivatives were efficiently prepared in 3 steps by employing Sonogashira coupling, ester hydrolysis and a chemoselective amide coupling. Ligand-quadruplex recognition has been evaluated using a fluorescence resonance energy transfer (FRET) melting assay, surface plasmon resonance (SPR), circular dichroism (CD) and (1)H nuclear magnetic resonance (NMR) spectroscopy. While most of the G-quadruplex ligands reported so far comprise a planar, aromatic core designed to stack on the terminal tetrads of a G-quadruplex, these compounds are neither polycyclic, nor macrocyclic and have free rotation around the triple bond enabling conformational flexibility. Such molecules show very good binding affinity, excellent quadruplex:duplex selectivity and also promising discrimination between intramolecular promoter quadruplexes. Our results indicate that the recognition of the c-kit2 quadruplex by these ligands is achieved through groove binding, which favors the formation of a parallel conformation.     

Novel colorimetric method overcoming phosphorus interference during trace arsenic analysis in soil solution

A sensitive (method detection limit, 2.0 microg As L(-1)) colorimetric determination of trace As(v) and As(iii) concentrations in the presence of soluble phosphorus (P) concentrations in soil/water extracts is presented. The proposed method modifies the malachite green method (MG) originally developed for P in soil and water. Our method relies upon the finding that As(iii) and As(v) do not develop the green color during P analysis using the MG method. When an optimum concentration of ascorbic acid (AA) is added to a sample containing up to 15 times P > As (microM) concentrations, the final sample absorbance due to P will be equal to that of As(v) molecules. The soluble As concentration can then be quantified by the concentration difference between the mixed oxyanion (As + P) absorbance (proposed method) and the MG method absorbance that measures only P. Our method is miniaturized using a 96-well microplate UV-VIS reader that utilizes minute reagent and sample volumes (120 and 200 microL sample(-1), respectively), thus, minimizing waste and offering flexibility in the field. Our method was tested in a suite of As-contaminated soils that successfully measured both As and P in soil water extracts and total digests. Mean% As recoveries ranged between 84 and 117%, corroborating data obtained with high-resolution inductively-coupled plasma mass-spectrometry. The performance of the proposed colorimetric As method was unaffected by the presence of Cu, Zn, Pb, Ni, Fe, Al, Si, and Cr in both neutral and highly-acidic (ca. pH 2) soil extracts. Data from this study provide the proof of concept towards creating a field-deployable, portable As kit.     

A scaling technique for finding the weighted analytic center of a polytope

Let a bounded full dimensional polytope be defined by the systemAx b whereA is anm × n matrix. Leta _i denote theith row of the matrixA, and define theweighted analytic center of the polytope to be the point that minimizes the strictly convex barrier function – _i=1 ^m w _i ln(a _i ^T x –b _i ). The proper selection of weightsw _i can make any desired point in the interior of the polytope become the weighted analytic center. As a result, the weighted analytic center has applications in both linear and general convex programming. For simplicity we assume that the weights are positive integers.If some of thew _i 's are much larger than others, then Newton's method for minimizing the resulting barrier function is very unstable and can be very slow. Previous methods for finding the weighted analytic center relied upon a rather direct application of Newton's method potentially resulting in very slow global convergence. We present a method for finding the weighted analytic center that is based on the scaling technique of Edmonds and Karp and is an enhancement of Newton's method. The scaling algorithm runs in iterations, wherem is the number of constraints defining the polytope andW is the largest weight given on any constraint. Each iteration involves taking a step in the Newton direction and its complexity is dominated by the time needed to solve a system of linear equations.Supported by the Campus Research Board, University of Illinois at Urbana-Champaign.Supported by the National Science Foundation under Grants CCR-9057481 and CCR-9007195.     

AnO(n logn) algorithm for the all-nearest-neighbors Problem

Given a setV ofn points ink-dimensional space, and anL _q -metric (Minkowski metric), the all-nearest-neighbors problem is defined as follows: for each pointp inV, find all those points inV–{p} that are closest top under the distance metricL _q . We give anO(n logn) algorithm for the all-nearest-neighbors problem, for fixed dimensionk and fixed metricL _q . Since there is an (n logn) lower bound, in the algebraic decision-tree model of computation, on the time complexity of any algorithm that solves the all-nearest-neighbors problem (fork=1), the running time of our algorithm is optimal up to a constant factor.This research was supported by a fellowship from the Shell Foundation. The author is currently at AT&T Bell Laboratories, Murray Hill, New Jersey, USA.