Synthesis and Applications of Cinchona Squaramide-Modified Poly(Glycidyl Methacrylate) Microspheres as Recyclable Polymer-Grafted Enantioselective Organocatalysts

This work presents the immobilization of cinchona squaramide organocatalysts on poly(glycidyl methacrylate) solid supports. Preparation of the well-defined monodisperse polymer microspheres was facilitated by comprehensive parameter optimization. By exploiting the reactive epoxy groups of the polymer support, three amino-functionalized cinchona derivatives were immobilized on this carrier. To explore the effect of the amino linker, these structurally varied precatalysts were synthesized by modifying the cinchona skeleton at different positions. The catalytic activities of the immobilized organocatalysts were tested in the Michael addition of pentane-2,4-dione and trans-β-nitrostyrene with excellent yields (up to 98 %) and enantioselectivities (up to 96 % ee). Finally, the catalysts were easily recovered five times by centrifugation without loss of activity.     

Synthesis and antimicrobial activities of some newly 2,4,6-tri-substituted pyridine derivatives

A series of novel 2-(2-(substituted benzylidene)hydrazinyl)-N′-(substituted benzylidene)-6-chloropyridine-4-carbohydrazide (5a–e), 2-(2-cycloalkylidenehydrazinyl)-6-chloro-N’-cyclo-alkylidenepyridine-4-carbohydrazide (6a,b), 2-(2-(1-(4-substituted phenyl)ethylidene)hydrazinyl)-6-chloro-N′-(1-(4-substituted phenyl)ethylidene)pyridine-4-carbohydrazide (7a,b) and 2-(2-(1-(pyridinyl)ethylidene)hydrazinyl)-6-chloro-N′-(1-(pyridinyl) ethylidene)pyridine-4-carbo-hydrazide (8a–c) derivatives have been synthesized by treating treating 2-chloro-6-hydrazinoisonicotinic acid hydrazide 4 with selected active reagents. Their structures were confirmed by spectral and analytical data. The synthesized compounds were investigated for antimicrobial activities. The antimicrobial screening showed that many of these obtained compounds have good activities comparable to Streptomycin and Fusidic acid as reference drugs.     

Miniaturized electrochemical system for cholinesterase inhibitor detection

The utility of a simple, low-cost detection platform for label-free electrochemical characterization of acetylcholinesterase (AChE) inhibition is demonstrated as a potential tool for screening of small-molecule therapeutic agents for Alzheimer's disease (AD). Technique validation was performed against the standard Ellman's colorimetric assay using the clinically established cholinesterase inhibitor (ChEI), Donepezil (Aricept^®). Electrochemical measurements were obtained by differential pulse voltammetry (DPV) performed using a portable potentiostat system for detection of the enzymatic product, thiocholine (TCh), by direct oxidation on unmodified gold screen-printed electrodes. The IC₅₀ profiles for Donepezil measured in vitro were found to be comparable between both colorimetric and electrochemical detection methods for the analysis of purified human erythrocyte-derived AChE (28 ± 7 nM by DPV; 26 ± 8 nM by Ellman's method). The selectivity of this unmodified electrode system was compared to a range of biological sulfur-containing compounds including cysteine, homocysteine, glutathione and methionine as well as ascorbic acid. Preliminary studies also demonstrated the potential applicability of this electrochemical technique for the analysis of Donepezil in crude cholinesterase samples from anterior cortex homogenates of C57BL/6J mice.     

Synthesis of E- and Z-o-Methoxy-Substituted 2,3-Diphenyl Propenoic Acids and Its Methyl Esters

A series of stereoisomeric o-methoxy-substituted 2,3-diphenyl propenoic acids and their methyl esters have been synthesized. The E isomers were prepared by a modified Perkin condensation (substituted benzaldehyde, phenylacetic acid, Et₃N/acetic anhydride). The difficult to access Z isomers were obtained conveniently in good yields when the appropriate coumarin derivatives were allowed to react with KOH and CH₃I in DMSO.     

An economic prediction of refinement coefficients in wavelet‐based adaptive methods for electron structure calculations

The wave function of a many electron system contains inhomogeneously distributed spatial details, which allows to reduce the number of fine detail wavelets in multiresolution analysis approximations. Finding a method for decimating the unnecessary basis functions plays an essential role in avoiding an exponential increase of computational demand in wavelet‐based calculations. We describe an effective prediction algorithm for the next resolution level wavelet coefficients, based on the approximate wave function expanded up to a given level. The prediction results in a reasonable approximation of the wave function and allows to sort out the unnecessary wavelets with a great reliability. © 2012 Wiley Periodicals, Inc.     

DNA‐Catalyzed Lysine Side Chain Modification

Catalyzing the covalent modification of aliphatic amino groups, such as the lysine (Lys) side chain, by nucleic acids has been challenging to achieve. Such catalysis will be valuable, for example, for the practical preparation of Lys‐modified proteins. We previously reported the DNA‐catalyzed modification of the tyrosine and serine hydroxy side chains, but Lys modification has been elusive. Herein, we show that increasing the reactivity of the electrophilic reaction partner by using 5′‐phosphorimidazolide (5′‐Imp) rather than 5′‐triphosphate (5′‐ppp) enables the DNA‐catalyzed modification of Lys in a DNA‐anchored peptide substrate. The DNA‐catalyzed reaction of Lys with 5′‐Imp is observed in an architecture in which the nucleophile and electrophile are not preorganized. In contrast, previous efforts showed that catalysis was not observed when Lys and 5′‐ppp were used in a preorganized arrangement. Therefore, substrate reactivity is more important than preorganization in this context. These findings will assist ongoing efforts to identify DNA catalysts for reactions of protein substrates at lysine side chains.     

Composite Aromatic Boxes for Enzymatic Transformations of Quaternary Ammonium Substrates

Cation–π interactions to cognate ligands in enzymes have key roles in ligand binding and enzymatic catalysis. We have deciphered the key functional role of both charged and aromatic residues within the choline binding subsite of CTP:phosphocholine cytidylyltransferase and choline kinase from Plasmodium falciparum. Comparison of quaternary ammonium binding site structures revealed a general composite aromatic box pattern of enzyme recognition sites, well distinguished from the aromatic box recognition site of receptors.     

Towards Vaporized Molecular Discrimination: A Quartz Crystal Microbalance (QCM) Sensor System Using Cobalt‐Containing Mesoporous Graphitic Carbon

A recent study on nanoporous carbon based materials (J. Am. Chem. Soc.­ 2012 , 134, 2864) showed that the presence of abundant graphitized sp² carbon species in the frameworks led to higher affinity for aromatic hydrocarbons than their aliphatic analogues. Herein, improved understanding of the sensitive and selective detection of aromatic substances by using mesoporous carbon (MPC)‐based materials, combined with a quartz crystal microbalance (QCM) sensor system, was obtained. MPCs were synthesized by direct carbonization of mesoporous polymers prepared from resol through a soft templating approach with Pluronic F127. The carbon‐based frameworks can be graphitized through the addition of a cobalt source to the precursor solution, according to the catalytic activity of the cobalt nanoparticles formed during the carbonization process. From the Raman data, the degree of the graphitization was clearly increased by increasing the cobalt content and elevating the carbonization temperature. From a QCM study, it was proved that the highly graphitized MPCs exhibited a higher affinity for aromatic hydrocarbons than their aliphatic analogues. By increasing the degree of graphitization in the carbon‐based pore walls, the MPCs showed both larger adsorption uptake and faster sensor response towards toxic benzene and toluene vapors.     

Activation Energies of Fragmentations of Disaccharides by Tandem Mass Spectrometry

A simple multiple collision model for collision induced dissociation (CID) in quadrupole was applied for the estimation of the activation energy (E_o) of the fragmentation processes for lithiated and trifluoroacetated disaccharides, such as maltose, cellobiose, isomaltose, gentiobiose, and trehalose. The internal energy-dependent rate constants k(E_int) were calculated using the Rice-Ramsperger-Kassel-Marcus (RRKM) or the Rice-Ramsperger-Kassel (RRK) theory. The E_o values were estimated by fitting the calculated survival yield (SY) curves to the experimental ones. The calculated E_o values of the fragmentation processes for lithiated disaccharides were in the range of 1.4–1.7 eV, and were found to increase in the order trehalose < maltose < isomaltose < cellobiose < gentiobiose.