Ferrocene-linked thymine/uracil conjugates: base pairing directed self-assembly and supramolecular packing

Ferrocene-linked bis(nucleobase) (1a-c) and chimeric nucleobase (1d) conjugates have been synthesized from mono- and bis(hydroxybutyl)ferrocene 6 via Mitsunobu reaction as the key step. X-ray crystallographic studies of ferrocene bis(nucleobase) conjugates reveal two-dimensional supramolecular organizations of backbones through self-assembled Watson-Crick and reverse Watson-Crick type pairs. Ferrocene-bis(thymine) conjugate self-assembles by reverse Watson-Crick pairing, while the corresponding bis(uracil) conjugate self-assembles by alternating WC and reverse WC type pairing. Such continuous assemblies are not seen in monosubstituted ferrocene nucleobase conjugates which form only planar sheets. The results are interesting from the point of understanding and engineering supramolecular assemblies through rational design of base pairing patterns.     

Kinetic evaluation of highly active supported gold catalysts prepared from monolayer-protected clusters: an experimental Michaelis-Menten approach for determining the oxygen binding constant during CO oxidation catalysis

Thiol monolayer-protected Au clusters (MPCs) were prepared using dendrimer templates, deposited onto a high-surface-area titania, and then the thiol stabilizers were removed under H2/N2. The resulting Au catalysts were characterized with transmission electron microscopy, X-ray photoelectron spectroscopy, and infrared spectroscopy of adsorbed CO. The Au catalysts prepared via this route displayed minimal particle agglomeration during the deposition and activation steps. Structural data obtained from the physical characterization of the Au catalysts were comparable to features exhibited from a traditionally prepared standard Au catalyst obtained from the World Gold Council (WGC). A differential kinetic study of CO oxidation catalysis by the MPC-prepared Au and the standard WGC catalyst showed that these two catalyst systems have essentially the same reaction order and Arrhenius apparent activation energies (28 kJ/mol). However, the MPC-prepared Au catalyst shows 50% greater activity for CO oxidation. Using a Michaelis-Menten approach, the oxygen binding constants for the two catalyst systems were determined and found to be essentially the same within experimental error. To our knowledge, this kinetic evaluation is the first experimental determination of oxygen binding by supported Au nanoparticle catalysts under working conditions. The values for the oxygen binding equilibrium constant obtained from the Michaelis-Menten treatment (ca. 29-39) are consistent with ultra-high-vacuum measurements on model catalyst systems and support density functional theory calculations for oxygen binding at corner or edge atoms on Au nanoparticles and clusters.     

Kinetics of folding and binding of an intrinsically disordered protein: the inhibitor of yeast aspartic proteinase YPrA

The 68 residue peptide IA 3 is an intrinsically unstructured protein that serves as an endogenous inhibitor of the yeast aspartic proteinase A (YPrA). Although unstructured in free solution, IA 3 forms an N-terminal alpha helix as it binds to YPrA, leading to subnanomolar inhibition of the protease. Equilibrium structural and inhibition studies provide little insight into the mechanism and kinetics of the coupled folding and binding interaction. We have used laser temperature jump spectroscopy to study the kinetics of folding of free IA 3 and of the interaction between IA 3 and YPrA. Inducing folding with trifluoroethanol cosolvent allows us to determine the folding rate (kf approximately 0.3 (micros)(-1)) and the unfolding rate (ku approximately 3 (micros)(-1)) for free IA 3 in water at 25 degrees C. A substantially faster relaxation process is observed in the presence of the proteinase; this process appears to be the kinetic signature of an intermediate binding step in the coupled folding and binding interaction of IA 3 and YPrA.     

Influence of Nd:Zn codoping in near-stoichiometric lithium niobate

Near-stoichiometric lithium niobate (SLN) crystals doped with up to 1.6 mol % Zn and codoped with various Nd concentrations in the melt (0.2, 0.5, 0.9, and 1.5 mol %) (Nd:Zn:SLN) are grown from 58.6 mol % Li(2)O using conventional Czochralski technique. Crystals are pulled at the rate of 0.35 mmh with seed rotation at 9 rpm. Concentrations of Zn and Nd in the crystal are varied by adding appropriate amounts of ZnO and Nd(2)O(3) to the starting composition. Unit cell parameters of the grown crystals are calculated by Rietveld refinement method using FULLPROFF software. Domain structure studies are carried out by chemical etching followed by microscopic examination. Dielectric studies reveal the existence of piezoelectric resonance at high frequencies. Enhancement in dielectric constant and tan delta in Nd doped samples has been attributed to the space charge polarization. Nd doped samples exhibit reduction in the relative permittivity after oxygen annealing. Transmission spectra of Nd:Zn:SLN crystals in the UV region exhibit blueshift in the cutoff wavelength. In Mid Infrared (MIR) region crystals doped with 1.6 mol % Zn have shift in the OH absorption peak from 2873 to 2833 nm. Judd-Ofelt analysis carried out on the absorption spectra of codoped crystal yields the lifetime of 104 mus for the metastable state (4)F(32). The branching ratio for the electronic transition from (4)F(32) to (4)I(112) is high compared to that for (4)F(32) to (4)I(132), indicating a higher emission cross section for the former transition. Laser damage threshold evaluated using 532 nm, 5 ns pulsed neodymium doped yttrium aluminum garnet laser, shows an increase by two orders of magnitude for crystals doped with 1.6 mol % Zn. Photorefractive damage threshold for these crystals shows an enhancement of four orders of magnitude due to increase in the photoconductivity.     

Use of enantiomerically pure 7-azabicyclo[2.2.1]heptan-2-ol as a chiral template for the synthesis of aminocyclitols

Using enantiopure 7-azabicyclo[2.2.1]heptane-2-ol, the synthesis of cis- as well as trans-2-aminocyclohexanols, dihydroconduramine E-1, and ent-conduramine F-1 has been described.     

Comparative study of machine-learning and chemometric tools for analysis of in-vivo high-throughput screening data

High-throughput screening (HTS) has become a central tool of many pharmaceutical and crop-protection discovery operations. If HTS screening is carried out at the level of the intact organism, as is commonly done in crop protection, this strategy has the potential of uncovering a completely new mechanism of actions. The challenge in running a cost-effective HTS operation is to identify ways in which to improve the overall success rate in discovering new biologically active compounds. To this end, we describe our efforts directed at making full use of the data stream arising from HTS. This paper describes a comparative study in which several machine learning and chemometric methodologies were used to develop classifiers on the same data sets derived from in vivo HTS campaigns and their predictive performances compared in terms of false negative and false positive error profiles.     

Metal-mediated transport of electrons across molecular films

Electron transfer (ET) to a redox probe in solution across the self-assembled monolayers (SAMs) of a tris-(2-pyridylmethyl)amine-based ligand on gold electrodes is greatly enhanced by Cu-binding.     

Synthetic and Structural Studies on Novel 4,3′-Bicoumarins

Abstract

A series of directly linked 4-3′ bicoumarins have been synthesized by both Knoevenagel and Perkin reactions. This single-step transformation was accomplished by the reaction of coumarin-4-acetates with substituted salicylaldehydes in presence of piperidine using ethanol as solvent and by the reaction of coumarin-4-acetic acids with substituted salicylaldehydes in the presence of sodium hydride in acetic anhydride. Greater yields have been obtained in the sodium hydride and acetic anhydride condition. An intermediate chalcone with an ortho-hydroxyl group, which is a precursor for lactone formation, has been isolated and its structure has been confirmed by x-ray analysis. The nonplanar S-cis arrangement of two C4-C3’ double bonds has been confirmed by nuclear Overhauser spectroscopy (NOE) and x-ray studies. The UV-fluorescence studies support the formation of a conjugated bicoumarin system.     

Y(OTf)3 catalyzed substitution dependent oxidative C(sp)–C(sp) cleavage and regioselective dehydration of β-allyl-β-hydroxydithioesters: alternate route to α,β-unsaturated ketones and functionalized dienes

β-Allyl-β-hydroxydithioesters have been generated by the regioselective Grignard addition to the β-oxodithioesters. They have been successfully employed in selective C(sp³)–C(sp³) bond cleavage to construct α,β-unsaturated ketone residues by the treatment of an emerging catalyst yttrium(III)triflate for the first time. On the other hand, hetaryl substituted β-allyl-β-hydroxydithioesters led to the useful diene precursors through selective dehydration under the similar conditions.     

CLOVES: A cluster-and-search heuristic to solve the vehicle routing problem with delivery and pick-up

This paper addresses the vehicle routing problem with sequence-constrained delivery and pick-up (VRPDP). We propose a multi-phase constructive heuristic that clusters nodes based on proximity, orients them along a route using shrink-wrap algorithm and allots vehicles using generalized assignment procedure. We employ genetic algorithm for an intensive final search. Trials on a large number of test-problems have yielded encouraging results.