The α-Effect and Competing Mechanisms: The Gas-Phase Reactions of Microsolvated Anions with Methyl Formate

The enhanced reactivity of α-nucleophiles, which contain an electron lone pair adjacent to the reactive site, has been demonstrated in solution and in the gas phase and, recently, for the gas-phase S_N2 reactions of the microsolvated HOO^–(H₂O) ion with methyl chloride. In the present work, we continue to explore the significance of microsolvation on the α-effect as we compare the gas-phase reactivity of the microsolvated α-nucleophile HOO^–(H₂O) with that of microsolvated normal alkoxy nucleophiles, RO^–(H₂O), in reactions with methyl formate, where three competing reactions are possible. The results reveal enhanced reactivity of HOO^–(H₂O) towards methyl formate, and clearly demonstrate the presence of an overall α-effect for the reactions of the microsolvated α-nucleophile. The association of the nucleophiles with a single water molecule significantly lowers the degree of proton abstraction and increases the S_N2 and B_AC2 reactivity compared with the unsolvated analogs. HOO^–(H₂O) reacts with methyl formate exclusively via the B_AC2 channel. While microsolvation lowers the overall reaction efficiency, it enhances the B_AC2 reaction efficiency for all anions compared with the unsolvated analogs. This may be explained by participation of the solvent water molecule in the B_AC2 reaction in a way that continuously stabilizes the negative charge throughout the reaction.

Linking an α‐Tocopherol Derivative to Cobalt(0) Nanomagnets: Magnetically Responsive Antioxidants with Superior Radical Trapping Activity and Reduced Cytotoxicity

Covalent attachment of a phenolic antioxidant analogue of α‐tocopherol to graphite‐coated magnetic cobalt nanoparticles (CoNPs) provided a novel magnetically responsive antioxidant capable of preventing the autoxidation of organic materials and showing a reduced toxicity toward human cells.     

Polymeric ruthenium bipyridine complexes: New potential materials for polymer solar cells

Methyl methacrylate‐containing bipyridine monomers were synthesized with a hydoxy‐functionalized bipyridine. The 4′‐methyl group of the 2,2′‐bipyridine was used to introduce hydoxy‐functionalized alkyl spacers of two different lengths. Two, different synthetic routes were applied for the preparation of the hydoxy‐functionalized bipyridine via a bromo‐(C₇ spacer) or a silylated‐(C₃ spacer) intermediate. A copolymer of poly(methyl methacrylate) with bipyridine units in the side chains was prepared by free‐radical copolymerization and characterized with ¹H NMR, ultraviolet–visible, and IR spectroscopy as well as gel permeation chromatography. The bipyridine units of the copolymer were reacted with ruthenium bipyridine precursors. The resulting graft copolymers displayed promising photophysical and electrochemical properties, opening interesting perspectives for applications in the field of solar‐cell devices. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 374–385, 2004     

Quantile regression with group lasso for classification

Applications of regression models for binary response are very common and models specific to these problems are widely used. Quantile regression for binary response data has recently attracted attention and regularized quantile regression methods have been proposed for high dimensional problems. When the predictors have a natural group structure, such as in the case of categorical predictors converted into dummy variables, then a group lasso penalty is used in regularized methods. In this paper, we present a Bayesian Gibbs sampling procedure to estimate the parameters of a quantile regression model under a group lasso penalty for classification problems with a binary response. Simulated and real data show a good performance of the proposed method in comparison to mean-based approaches and to quantile-based approaches which do not exploit the group structure of the predictors.     

Cycling a Tether into Multiple Rings: Pt-Bridged Macrocycles for Differentiated Guest Recognition,Pseudorotaxane Transformations,and Guest Capture and Release

Macrocycle engineering is a key topic in supramolecular chemistry. When synthesizing a ring, one can obtain either complex mixtures of macrocycles of different sizes or a single ring if a template is utilized. Here, we unite these approaches along with post-synthetic modifications to transform a single tether into multiple rings—up to five per tether. The macrocycles contain two bridged phenylpyridine ligands that are connected through a Pt atom, which defines the rings’ shape, size, and host activity. All rings undergo redox reactions (between Pt^II and Pt^IV) that allow for large conformational changes. Their reactivity, together with their host performance, is a convenient way to control the capture and release of guests, to mediate ring transformations, and to control pseudorotaxane-to-pseudorotaxane conversions. This novel approach could serve to assemble other libraries of small ring molecules, create cyclic polymers bridged by responsive-at-metal nodes, and produce processable mechanically interlocked molecules.     

Dynamics of vibrational overtone excited pyruvic acid in the gas phase: line broadening through hydrogen-atom chattering

The dynamics of overtone-excited pyruvic acid (PA) is studied using a combination of experimental and theoretical methods. It is experimentally observed that high overtone excitation of the OH-stretching mode of PA in the gas phase leads to a unimolecular decarboxylation reaction. An RRKM analysis of the rate is consistent with previous experiments for the thermal reaction but is inconsistent with the present overtone chemistry; from this it is concluded that the overtone-induced reaction is likely to be a direct reaction. Using a Fourier transform infrared spectrometer and a cavity ring-down spectrometer, the spectrum for the OH-stretch fundamental and overtone transitions is measured. We assign two conformers of PA in the spectrum, the Tc and Tt, corresponding to distinct orientations of the OH-group. The spectral peaks for the Tc-conformer broaden dramatically at the third and fourth overtones while those of the Tt-conformer remain relatively narrow. Using a three-mode quantum mechanical model for the vibrational states, the line positions and intensities are well reproduced by theory. The line widths, and the associated dynamical interpretation, are provided by a direct dynamics calculation, where the potential is computed "on-the-fly" and all degrees of freedom are included. It is found that the line broadening is due to the onset of H-atom chattering between the two O-atoms, an effect that occurs for the Tc-conformer but not the Tt-conformer. This H-atom-transfer process is the first step of the decarboxylation reaction mechanism, which subsequently involves breaking the C-C bond. The theoretical and experimental line widths agree but do not correspond to the full reaction time which is much longer than the initial chattering step.     

Ion channel screening

Ion channels are attractive targets for drug discovery with recent estimates indicating that voltage and ligand-gated channels account for the third and fourth largest gene families represented in company portfolios after the G protein coupled and nuclear hormone receptor families. A historical limitation on ion channel targeted drug discovery in the form of the extremely low throughput nature of the gold standard assay for assessing functional activity, patch clamp electrophysiology in mammalian cells, has been overcome by the implementation of multi-well plate format cell-based screening strategies for ion channels. These have taken advantage of various approaches to monitor ion flux or membrane potential using radioactive, non-radioactive, spectroscopic and fluorescence measurements and have significantly impacted both high-throughput screening and lead optimization efforts. In addition, major advances have been made in the development of automated electrophysiological platforms to increase capacity for cell-based screening using formats aimed at recapitulating the gold standard assay. This review addresses the options available for cell-based screening of ion channels with examples of their utility and presents case studies on the successful implementation of high-throughput screening campaigns for a ligand-gated ion channel using a fluorescent calcium indicator, and a voltage-gated ion channel using a fluorescent membrane potential sensitive dye.