Gating motions in voltage-gated potassium channels revealed by coarse-grained molecular dynamics simulations

Voltage-gated potassium (Kv) channels are ubiquitous transmembrane proteins involved in electric signaling of excitable tissues. A fundamental property of these channels is the ability to open or close in response to changes in the membrane potential. To date, their structure-based activation mechanism remains unclear, and there is a large controversy on how these gates function at the molecular level, in particular, how movements of the voltage sensor domain are coupled to channel gating. So far, all mechanisms proposed for this coupling are based on the crystal structure of the open voltage-gated Kv1.2 channel and structural models of the closed form based on electrophysiology experiments. Here, we use coarse-grain (CG) molecular dynamics simulations that allow conformational changes from the open to the closed form of the channel (embedded in its membrane environment) to be followed. Despite the low specificity of the CG force field, the obtained closed structure satisfies several experimental constraints. The overall results suggest a gating mechanism in which a lateral displacement the S4-S5 linker leads to a closing of the gate. Only a small up-down movement of the S4 helices is noticed. Additionally, the study suggests a peculiar upward motion of the intracellular tetramerization domain of the channel, hence providing a molecular view on how this domain may further regulate conduction in Kv channels.     

A high performance oxidation method for secondary alcohols by inductive activation of TEMPO in combination with pyridine-bromine complexes

A new TEMPO-mediated catalytic oxidation method in combination with Py·HBr₃ (stoichiometric) is developed for oxidation of secondary alcohols to the corresponding ketones. The performance of this oxidizing system is better compared with that of TEMPO method combined with R₄NBr₃. Poly(4-vinylpyridine)·HBr₃ can be used in place of Py·HBr₃. The electron-withdrawing substituent at the C-4 position of TEMPO increases the reactivity of TEMPO significantly in the oxidation of electron-deficient alcohols such as polyhaloalkylmethanols. Inductive effect of the substituent of TEMPO is discussed through the characterization of the redox potential of N-O radical by cyclic voltammetry.     

Hygrometric Determination of Water Activities and Osmotic and Activity Coefficients of NH4Cl–KCl–H2O at 25°C

Relative humidities have been measured for mixed aqueous electrolyte system of ammonium and potassium chlorides by the hygrometric method at total molalities from 0.3 to 6 mol-kg^–1for ionic-strength fractions yof NH₄Cl of 1/3, 1/2, and 2/3 at 25°C. The data allow the calculation of new water activities and osmotic coefficients. The proposed ECA (extended composed additivity) rule of calculation of water activity in mixed aqueous electrolyte solutions from the water activities of a single component is extended to this system. The experimental results and the predictions of the ECA rule are compared with the Robinson–Stokes, Reilly–Wood–Robinson, the Pitzer, and the Lietzke–Stoughton II models. Predictions made using these models are, in general, consistent with our results. From these measurements, the Pitzer mixing ionic parameters are determined and used to predict the solute activity coefficients in the mixture for different ionic-strength fractions.     

One-dimensional heat equation with discontinuous conductance

We study a second-order parabolic equation with divergence form elliptic operator,having a piecewise constant diffusion coefficient with two points of discontinuity.Such partial differential equations appear in the modelization of diffusion phenomena in medium consisting of three kinds of materials.Using probabilistic methods,we present an explicit expression of the fundamental solution under certain conditions.We also derive small-time asymptotic expansion of the PDE’s solutions in the general case.The obtained results are directly usable in applications.     

A mathematical analysis and elucidation of AB(2k,1ϕ) thermophotochromic kinetics: Analytical solutions using pure kinetic data and considering as unknown the rate constants,quantum yield,and both species' spectra

A new spectrokinetic method is described that determines the absolute values of all five unknown parameters (ε_A, ε_B, ?_AB, k_AB, k_BA) of AB(2k,1?) thermophotoreactive chromic systems. For the first time, solely kinetic data are used to perform complete analytical elucidations. Also, the method addresses realistic situations by considering that both absorption spectra of the reactive species are unknown and partially or totally overlap, solving the identifiability problem, and using a single set of experimental data (for the thermal and photochemical reactions). The absolute values for the five unknown parameters that make up the true kinetic solution are readily obtained by the application of five analytically defined algebraic equations. The method is independent of experimental conditions relating to initial concentration, temperature, threshold of incident light intensity, and the wavelength at which the kinetic traces are measured. The detailed mathematical algorithm also allows the determination of the reaction quantum yield at any (isosbestic and nonisosbestic) irradiation wavelength and proposes a new colorability expression for these systems. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 41: 255–264, 2009     

On Semicomplete Cones

We give here characterizations of relatively bounded maps, of normal cones, nuclear and well based cones. We also discuss two notions of semi-complete considered by Mokobodzki.      

On the Discrete Spectrum of a Spatial Quantum Waveguide with a Disc Window

In this study we investigate the bound states of the Hamiltonian describing a quantum particle living on three dimensional straight strip of width d. We impose the Neumann boundary condition on a disc window of radius a and Dirichlet boundary conditions on the remained part of the boundary of the strip. We prove that such system exhibits discrete eigenvalues below the essential spectrum for any a > 0. We give also a numeric estimation of the number of discrete eigenvalue as a function of \fracad\frac{a}{d}. When a tends to the infinity, the asymptotic of the eigenvalue is given.     

Electron Ionization Mass Spectra of Organophosphorus Compounds Part I: The Mass Fragmentation Pathways of Cyclic α-Aminophosphonates Monoester Containing 1,2,4-Triazinone Moiety

Abstract

The electron impact induced fragmentation reactions of 3-(4-chlorophenyl)-3,4- dihydro-2-ethoxy-2-oxido-7-methyl-2H,6H-[1,2,4]triazino[4,3-e][1,4,5,2]thiadiazaphosphin in-6-one (1), 3,7-dimethyl-2-ethoxy-2-oxido-1,2,3,4-tetrahydro-6H-[1,2,4]triazino[4,3-b][1,2,4,5]triazaphosphinin-6-one (2), and 9-amino-3,7-dimethyl-4-ethoxy-4-oxido-2,3,4,9-tetrahydro-8H-[1,2,4]triazino[3,2-c][1,2,4,5]triazaphosphinin-8-one (3) are presented and compared. The 1,2,4-triazine rings have almost identical fragmentation routes. The 1,2,4-triazine rings are rather stable relative to the phosphorus rings. Therefore, fragmentation of the phosphorus rings is more favorable for the compounds than the stable 1,2,4-triazine rings.     

Surface modification of TiO2 nanoparticles with AHAPS aminosilane: distinction between physisorption and chemisorption

This paper addresses the surface modification of TiO₂ nanoparticles with n-(6-aminohexyl)aminopropyltrimethoxysilane (AHAPS) using various initial aminosilane concentrations. The main objective of this article is to show experimentally the importance of the physisorption during the grafting process. The distinction between chemisorbed and physisorbed aminosilane molecules on TiO₂ is thoroughly analyzed. The surface of bare and modified TiO₂ particles has been characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) to gain a better understanding of the adsorption mechanism of AHAPS on TiO₂. Quantitative information on surface energy of TiO₂, in terms of adsorption energy sites and heterogeneity, has been investigated by quasi-equilibrium low-pressure adsorption technique using nitrogen and argon as probe molecules. The FTIR and XPS data are combined to estimate and discuss the chemisorbed and physisorbed contribution. The results demonstrate that both physisorption and chemisorption occurs but they display a different behavior. The physisorbed amounts are much higher than the chemisorbed amounts. This shows that the main part of the adsorbed layer is composed of physisorbed molecules. The physisorbed uptake depends highly on the AHAPS concentration while the chemisorbed amount remains constant. Quasi-equilibrium Ar derivative adsorption isotherms reveal that the AHAPS molecules are mostly located on the {101} and {001} faces of titania and that the two faces display the same reactivity toward AHAPS sorption. Nitrogen adsorption experiments show that the sorption takes place on the three polar surface sites of high energy. The molecules are chemisorbed onto the site displaying the highest energy while they are physisorbed on the two lower energy sites.     

2-Dienylphenacyloxazolones and an intramolecular Diels-Alder approach to the A-B-C ring system of phenanthridone alkaloids

A general route to the A-B-C ring system of phenanthridone alkaloids is available by acylation of 2-oxa-zolone with a 2-butadienylbenzoic acid derivative, followed by an intramolecular Diels-Alder reaction and hydrolysis.