Small‐Molecule Permeation across Membrane Channels: Chemical Modification to Quantify Transport across OmpF

Biological channels facilitate the exchange of molecules across membranes, but general tools to quantify transport are missing. Electrophysiology is the method of choice to study the functional properties of channels. However, analyzing the current fluctuation of channels typically does not identify successful transport, that is, distinguishing translocation from binding. To distinguish both processes, we added an additional barrier at the channel exit acting as a molecular counter. To identify permeation, we compare the molecule residence time in the native channel with one that is chemically modified at the exit. We use the well‐studied outer membrane channel from E. coli, OmpF. Position 181, which is below the constriction region, was subsequently mutated into cysteine (E181C) in an otherwise cysteine‐free system, then functionalized by covalent binding with one of the two blockers MTSES or GLT. We measured the passage of model peptides, mono‐, tri‐, hepta‐arginine and of norfloxacin, as an example for antibiotic permeation.     

Fluorescence properties of Nd3+-doped tellurite glasses

The compositional and concentration dependence of luminescence of the (4)F(3/2)-->(4)I(J) (J=13/2, 11/2 and 9/2) transitions in four Nd(3+)-doped tellurite based glasses has been studied. The free-ion energy levels obtained for 60TeO(2)+39ZnO(2)+1.0Nd(2)O(3) (TZN10) glass have been analysed using the free-ion Hamiltonian model and compared with similar results obtained for Nd(3+):glass systems. The absorption spectrum of TZN10 glass has been analysed using the Judd-Ofelt theory. Relatively longer decay rates have been obtained for Nd(3+)-doped phosphotellurite glasses. The emission characteristics of the (4)F(3/2)-->(4)I(11/2) transition, of the Nd(3+):TZN10 glass, are found to be comparable to those obtained for Nd(3+):phosphate laser glasses. The non-exponential shape of the emission decay curves for the (4)F(3/2)-->(4)I(11/2) transition is attributed to the presence of energy transfer processes between the Nd(3+) ions.     

Time-parallel multiscale/multiphysics framework

We introduce the time-parallel compound wavelet matrix method (tpCWM) for modeling the temporal evolution of multiscale and multiphysics systems. The method couples time parallel (TP) and CWM methods operating at different spatial and temporal scales. We demonstrate the efficiency of our approach on two examples: a chemical reaction kinetic system and a non-linear predator–prey system. Our results indicate that the tpCWM technique is capable of accelerating time-to-solution by 2–3-orders of magnitude and is amenable to efficient parallel implementation.     

Scaling of fracture strength in disordered quasi-brittle materials

The European Physical Journal B - This paper presents two main results. The first result indicates that in materials with broadly distributed microscopic heterogeneities, the fracture strength...     

A convenient access to 2,4-disubstituted quinazolines via one-pot three-component reaction under mild conditions†

Abstract

A new and practical method has been developed for the synthesis of 2,4-disubstituted quinolines via one-pot three-component reaction of o-amino arylketones, aldehydes and ammonium acetate in high yields by using DDQ in CH₃CN under mild conditions. Neutral conditions, atom economy, easy work-up procedures and compatible with different functional groups are the salient features of this protocol.     

Design,Synthesis, and Anti-Proliferative Activity of Quinoxaline Linked 1,2,4-Oxadiazole Hybrids

Russian Journal of General Chemistry - Herein, synthesis of some new quinoxaline-1,2,4-oxadiazole derivatives is presented, and their in vitro anti-cancer activity against four human cancer cell...     

Beneficial Effects of <Emphasis Type="Italic">Phyllanthus amarus</Emphasis> Against High Fructose Diet Induced Insulin Resistance and Hepatic Oxidative Stress in Male Wistar Rats

Insulin resistance (IR) is a characteristic feature of obesity, type 2 diabetes mellitus, and cardiovascular diseases. Emerging evidence suggests that the high-fructose consumption is a potential and important factor responsible for the rising incidence of IR. The present study investigates the beneficial effects of aqueous extract of Phyllanthus amarus (PAAE) on IR and oxidative stress in high-fructose (HF) fed male Wistar rats. HF diet (66% of fructose) and PAAE (200 mg/kg body weight/day) were given concurrently to the rats for a period of 60 days. Fructose-fed rats showed weight gain, hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired insulin sensitivity, dyslipidemia, hyperleptinemia, and hypoadiponectinemia (P < 0.05) after 60 days. Co-administration of PAAE along with HF diet significantly ameliorated all these alterations. Regarding hepatic antioxidant status, higher lipid peroxidation and protein oxidation, lower reduced glutathione levels and lower activities of enzymatic antioxidants, and the histopathological changes like mild to severe distortion of the normal architecture as well as the prominence and widening of the liver sinusoids observed in the HF diet-fed rats were significantly prevented by PAAE treatment. These findings indicate that PAAE is beneficial in improving insulin sensitivity and attenuating metabolic syndrome and hepatic oxidative stress in fructose-fed rats.     

Improved Synthesis of Cyclic α-Hydrazino Acids of Five- to Nine-Membered Rings and Optical Resolution of 5,6,7-Membered Ring Hydrazino Acids

Synthesis of cyclic α-hydrazino acids of five- to nine-membered rings has been described. Di-tert-butyl or dibenzyl malonate was used as starting materials instead of diethyl malonate, which was used in our first report. Deprotection of tert-butyl or benzyl ester of the final compounds was much easier than that of ethyl or methyl esters. Overall yield of these acids were 39, 50, 47, 52, and 51%, respectively. These acids were then converted to the diastereomers either via the formation of peptides with L-phenylalanine methyl ester or via the formation of esters (for five- to seven-membered rings) with L-2-phenylalaninol. All diastereomers were separated except the nine-membered ring by flash chromatography. Hydrolysis of diastereomeric esters generated the optically pure five-, six- and seven-membered cyclic α-hydrazino acids. In this process, both the enantiomers have been isolated and the chiral auxiliary L-2-phenylalaninol was recovered. Absolute stereochemistry was determined from x-ray crystallographic analysis.     

Statistical models of fracture

Disorder and long-range interactions are two of the key components that make material failure an interesting playfield for the application of statistical mechanics. The cornerstone in this respect has been lattice models of the fracture in which a network of elastic beams, bonds, or electrical fuses with random failure thresholds are subject to an increasing external load. These models describe on a qualitative level the failure processes of real, brittle, or quasi-brittle materials. This has been particularly important in solving the classical engineering problems of material strength: the size dependence of maximum stress and its sample-to-sample statistical fluctuations. At the same time, lattice models pose many new fundamental questions in statistical physics, such as the relation between fracture and phase transitions. Experimental results point out to the existence of an intriguing crackling noise in the acoustic emission and of self-affine fractals in the crack surface morphology. Recent advances in computer power have enabled considerable progress in the understanding of such models. Among these partly still controversial issues, are the scaling and size-effects in material strength and accumulated damage, the statistics of avalanches or bursts of microfailures, and the morphology of the crack surface. Here we present an overview of the results obtained with lattice models for fracture, highlighting the relations with statistical physics theories and more conventional fracture mechanics approaches.

Statistical models of fracture

All authors

Mikko J. Alava, Phani K. V. V. Nukala &; Stefano Zapperi

https://doi.org/10.1080/00018730300741518

Published online:

28 November 2010

Table     

Transannular Diels-Alder reactivities of 14-membered macrocylic trienes and their relationship with the conformational preferences of the reactants: a combined quantum chemical and molecular dynamics study

Transannular Diels-Alder (TADA) reactions that occur between the diene and dienophile moieties located on a single macrocyclic triene molecule have been recognized as effective synthetic routes toward realizing complex tricyclic molecules in a single step. In this paper, we report a comprehensive study on the TADA reactions of 14-membered cyclic triene macrocycles to yield A.B.C[6.6.6] tricycles using quantum chemical methods and using classical molecular dynamics simulations. A benchmark study has been performed to examine the reliability of the commonly used ab initio methods and hybrid density functional levels of theory in comparison with results from CCSD(T) calculations to accurately model TADA reactions. The energy barriers obtained using the M06-2X functional were found to be in quantitative agreement with the CCSD(T) level of theory using a reasonably large basis set. Conformational properties of the reactants have been systematically studied using extensive molecular dynamics (MD) simulations. For this purpose, model systems were conceived, and force field parameters corresponding to the dihedral terms in the potential energy function were obtained. Linear relationship between the activation energies corresponding to the TADA reactions and the probability of finding the reactant in certain conformational states was obtained. A clustering method along with optimizations at the molecular mechanics and density functional M06-2X levels has been used to locate the most stable conformation of each of the trienes.