Development of pharmacophores for inhibitors of the rapid component of the cardiac delayed rectifier potassium current

Blockade of cardiac-delayed rectifier potassium current (I_Kr) is an important mechanism for Class III antiarrhythmic effect. We developed pharmacophores for I_Kr inhibitors starting from structures of known blockers. To obtain the pharmacophores, DISCO module of SYBYL was used. Conformations required for DISCO computations were provided by Multisearch type conformational analyses. A common five-point three-dimensional relationship was identified for the most active compounds, whereas a four-point pharmacophore forming a subset of the former one, could be developed for less potent agents. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 69: 21–30, 1998     

Hierarchy of Order in Liquid Crystalline Polycaps

When outfitted with long alkyl chains , polycaps, capsules along a polymer chain, spontaneously organize themselves into a two-dimensional liquid crystalline phase. Further organization results from shearing or pulling the liquid crystalline samples, producing three-dimensional assemblies of micrometer-wide, infinitely long fibers (see schematic representation).     

Enhanced Catalytic Activity and Unexpected Products from the Oxidation of Cyclohexene by Organic Nanoparticles of 5,10,15,20‐Tetrakis‐(2,3,4,5,6‐pentafluorophenyl)porphyrinatoiron(III) in Water by Using O2

The catalytic oxidation of alkenes by most iron porphyrins using a variety of oxygen sources, but generally not dioxygen, yields the epoxide with minor quantities of other products. The turnover numbers for these catalysts are modest, ranging from a few hundred to a few thousand depending on the porphyrin structure, axial ligands, and other reaction conditions. Halogenation of substituents increases the activity of the metalloporphyrin catalyst and/or makes it more robust to oxidative degradation. Oxidation of cyclohexene by 5,10,15,20‐tetrakis‐(2,3,4,5,6‐pentafluorophenyl)porphyrinato iron(III), ([Fe^III(tppf₂₀)]) and H₂O₂ is typical of the latter: the epoxide is 99 % of the product and turnover numbers are about 350. 1 – 4 Herein, we report that dynamic organic nanoparticles (ONPs) of [Fe^III(tppf₂₀)] with a diameter of 10 nm, formed by host–guest solvent methods, catalytically oxidize cyclohexene with O₂ to yield only 2‐cyclohexene‐1‐one and 2‐cyclohexene‐1‐ol with approximately 10‐fold greater turnover numbers compared to the non‐aggregated metalloporphyrin in acetonitrile/methanol. These ONPs facilitate a greener reaction because the reaction solvent is 89 % water and O₂ is the oxidant in place of synthetic oxygen sources. This reactivity is unexpected because the metalloporphyrins are in close proximity and oxidative degradation of the catalyst should be enhanced, thus causing a significant decrease in catalytic turnovers. The allylic products suggest a different oxidative mechanism compared to that of the solvated metalloporphyrins. These results illustrate the unique properties of some ONPs relative to the component molecules or those attached to supports.     

Generation and detection of gaseous W12O 41 −· and other tungstate anions by laser desorption ionization mass spectrometry

The presence of a peak centered near m/z 2862, observed for the first time for the caged dodecatungstate radical-anion, [W₁₂O₄₁]^−·, enables distinguishing WO₂ from WO₃ by Laser Desorption Ionization mass spectrometry (LDI-MS). In addition to WO₂, laser irradiation of dry deposits made from aqueous ammonium paratungstate, and calcium and lead orthotungstate also produce the [W₁₂O₄₁]^−·. In contrast, spectra recorded from deposits made from aqueous Na₂WO₄, sodium metatungstate, and WO₃, or non-aqueous calcium and lead orthotungstate, and ammonium paratungstate, failed to show the m/z 2862 peak cluster. These observations support the hypothesis that polycondensation reactions to form [W₁₂O₄₁]^−· occur solely in the presence of water. Although dry spots are irradiated for ionization, the solvent used for sample preparation plays an important role on the chemical composition endowed to ions detected. For example, the m/z 2862 peak seen from deposits made from aqueous ammonium paratungstate, and calcium and lead orthotungstate, is absent in the spectra recorded either from pristine deposits or those derived from solutions made with organic solvents such as acetonitrile or ethanol.     

The Lee‐Yang and Pólya‐Schur programs. II. Theory of stable polynomials and applications

In the first part of this series we characterized all linear operators on spaces of multivariate polynomials preserving the property of being nonvanishing in products of open circular domains. For such sets this completes the multivariate generalization of the classification program initiated by Pólya and Schur for univariate real polynomials. We build on these classification theorems to develop here a theory of multivariate stable polynomials. Applications and examples show that this theory provides a natural framework for dealing in a uniform way with Lee‐Yang type problems in statistical mechanics, combinatorics, and geometric function theory in one or several variables. In particular, we answer a question of Hinkkanen on multivariate apolarity. © 2009 Wiley Periodicals, Inc.     

Crystallisation kinetics,glass forming ability and thermal stability in glassy Se100 − xInx chalcogenide alloys

Differential scanning calorimetry (DSC) studies have been done under non-isothermal conditions at different heating rates for glassy Se_100 ? xIn_x (5 ≤ x ≤ 20) alloys. DSC traces with well-defined endothermic and exothermic troughs and peaks at glass transition (T_g), crystallisation (T_c) and melting (T_m) temperatures were observed. The crystallisation kinetics parameters, Avrami index (n), activation energy for crystallisation (E_c) and frequency factor (K_o), have been calculated on the basis of the classical Johnson–Mehl–Avrami (JMA) model and related methods derived by Kissinger, Augis–Bennett and Mahedevan. Activation energy for glass transformation (E_t) has been evaluated on the usual two different non-isothermal methods developed by Moynihan and Kissinger. An extension of the Augis–Bennett method well known for evaluating E_c to calculate E_t has been explored with satisfactory results. Results obtained from these methods are in close agreement with each other. Close correlation between E_t, E_c and heating rate (β) was observed. The glass forming ability (GFA) and thermal stability parameters have been calculated for each glass system. It was found that the proportion of indium additive changed significantly the values of glass/crystal transformation, GFA and thermal stability of the studied system.     

The Lee-Yang and Pólya-Schur programs. I. Linear operators preserving stability

In 1952 Lee and Yang proposed the program of analyzing phase transitions in terms of zeros of partition functions. Linear operators preserving non-vanishing properties are essential in this program and various contexts in complex analysis, probability theory, combinatorics, and matrix theory. We characterize all linear operators on finite or infinite-dimensional spaces of multivariate polynomials preserving the property of being non-vanishing whenever the variables are in prescribed open circular domains. In particular, this solves the higher dimensional counterpart of a long-standing classification problem originating from classical works of Hermite, Laguerre, Hurwitz and Pólya-Schur on univariate polynomials with such properties.     

Moving targets: recognition of alkyl groups

Alkyl chains can adopt seemingly unusual conformations, such as helices, when bound to natural and synthetic hydrophobic receptors. This plasticity allows the alkanes to assume shapes that are congruent to the receptor's space and fill that space properly. We describe here the use of cavitands and capsules as tools that expose the forces involved in the molecular recognition of hydrocarbons. Studies using NMR spectroscopy reveal how attractive interactions and solvophobic forces are maximized in solution through unprecedented contortions of alkanes and hint at a new generation of nanoscale mechanical devices.     

Cavitands with revolving doors regulate binding selectivities and rates in water

A water-soluble self-folding cavitand has been prepared, featuring four benzoate groups attached to the open end. These benzoates act as rapidly "revolving doors" to the cavity. The cavitand shows increased selectivity for small hydrophobic guests and slower rates of guest exchange.     

Competitive homolytic and heterolytic decomposition pathways of gas‐phase negative ions generated from aminobenzoate esters

An alkyl‐radical loss and an alkene loss are two competitive fragmentation pathways that deprotonated aminobenzoate esters undergo upon activation under mass spectrometric conditions. For the meta and para isomers, the alkyl‐radical loss by a homolytic cleavage of the alkyl‐oxygen bond of the ester moiety is the predominant fragmentation pathway, while the contribution from the alkene elimination by a heterolytic pathway is less significant. In contrast, owing to a pronounced charge‐mediated ortho effect, the alkene loss becomes the predominant pathway for the ortho isomers of ethyl and higher esters. Results from isotope‐labeled compounds confirmed that the alkene loss proceeds by a specific γ‐hydrogen transfer mechanism that resembles the McLafferty rearrangement for radical cations. Even for the para compounds, if the alkoxide moiety bears structural motifs required for the elimination of a more stable alkene molecule, the heterolytic pathway becomes the predominant pathway. For example, in the spectrum of deprotonated 2‐phenylethyl 4‐aminobenzoate, m/z 136 peak is the base peak because the alkene eliminated is styrene. Owing to the fact that all deprotonated aminobenzoate esters, irrespective of the size of the alkoxy group, upon activation fragment to form an m/z 135 ion, aminobenzoate esters in mixtures can be quantified by precursor ion discovery mass spectrometric experiments. Copyright © 2016 John Wiley & Sons, Ltd.