Determining membrane capacitance by dynamic control of droplet interface bilayer area

By making dynamic changes to the area of a droplet interface bilayer (DIB), we are able to measure the specific capacitance of lipid bilayers with improved accuracy and precision over existing methods. The dependence of membrane specific capacitance on the chain-length of the alkane oil present in the bilayer is similar to that observed in black lipid membranes. In contrast to conventional artificial bilayers, DIBs are not confined by an aperture, which enables us to determine that the dependence of whole bilayer capacitance on applied potential is predominantly a result of a spontaneous increase in bilayer area. This area change arises from the creation of new bilayer at the three phase interface and is driven by changes in surface tension with applied potential that can be described by the Young-Lippmann equation. By accounting for this area change, we are able to determine the proportion of the capacitance dependence that arises from a change in specific capacitance with applied potential. This method provides a new tool with which to investigate the vertical compression of the bilayer and understand the changes in bilayer thickness with applied potential. We find that, for 1,2-diphytanoyl-sn-glycero-3-phosphocholine membranes in hexadecane, specific bilayer capacitance varies by 0.6-1.5% over an applied potential of ±100 mV.     

Two-dimensional like conjugated copolymers for high efficiency bulk-heterojunction solar cell application:Band gap and energy level engineering

Three two-dimensional like conjugated copolymers PFSDCN,PFSDTA and PFSDCNIO,which consist of alternating fluorene and triphenylamine main chain,and different pendant acceptor groups (malononitrile,1,3-diethtyl-2-thiobarbituric acid and 2-(1,2-dihydro-1-oxoinden-3-ylidene)malononitrile) with thiophene as π-bridge,have been designed,synthesized and characterized.The structure-property relationships of the two-dimensional like conjugated copolymers were systematically investigated.The absorption spectra,band g...     

Compound prioritization methods increase rates of chemical probe discovery in model organisms

Preselection of compounds that are more likely to induce a phenotype can increase the efficiency and reduce the costs for model organism screening. To identify such molecules, we screened ~81,000 compounds in Saccharomyces cerevisiae and identified ~7500 that inhibit cell growth. Screening these growth-inhibitory molecules across a diverse panel of model organisms resulted in an increased phenotypic hit-rate. These data were used to build a model to predict compounds that inhibit yeast growth. Empirical and in silico application of the model enriched the discovery of bioactive compounds in diverse model organisms. To demonstrate the potential of these molecules as lead chemical probes, we used chemogenomic profiling in yeast and identified specific inhibitors of lanosterol synthase and of stearoyl-CoA 9-desaturase. As community resources, the ~7500 growth-inhibitory molecules have been made commercially available and the computational model and filter used are provided.     

Continuous flow enzyme-catalyzed polymerization in a microreactor

Enzymes immobilized on solid supports are increasingly used for greener, more sustainable chemical transformation processes. Here, we used microreactors to study enzyme-catalyzed ring-opening polymerization of ε-caprolactone to polycaprolactone. A novel microreactor design enabled us to perform these heterogeneous reactions in continuous mode, in organic media, and at elevated temperatures. Using microreactors, we achieved faster polymerization and higher molecular mass compared to using batch reactors. While this study focused on polymerization reactions, it is evident that similar microreactor based platforms can readily be extended to other enzyme-based systems, for example, high-throughput screening of new enzymes and to precision measurements of new processes where continuous flow mode is preferred. This is the first reported demonstration of a solid supported enzyme-catalyzed polymerization reaction in continuous mode.     

Reaction development and mechanistic study of a ruthenium catalyzed intramolecular asymmetric reductive amination en route to the dual Orexin inhibitor Suvorexant (MK-4305)

The first example of an intramolecular asymmetric reductive amination of a dialkyl ketone with an aliphatic amine has been developed for the synthesis of Suvorexant (MK-4305), a potent dual Orexin antagonist under development for the treatment of sleep disorders. This challenging transformation is mediated by a novel Ru-based transfer hydrogenation catalyst that provides the desired diazepane ring in 97% yield and 94.5% ee. Mechanistic studies have revealed that CO(2), produced as a necessary byproduct of this transfer hydrogenation reaction, has pronounced effects on the efficiency of the Ru catalyst, the form of the amine product, and the kinetics of the transformation. A simple kinetic model explains how product inhibition by CO(2) leads to overall first-order kinetics, but yields an apparent zero-order dependence on initial substrate concentration. The deleterious effects of CO(2) on reaction rates and product isolation can be overcome by purging CO(2) from the system. Moreover, the rate of ketone hydrogenation can be greatly accelerated by purging of CO(2) or trapping with nucleophilic secondary amines.     

A pyrene-based fluorescent sensor for Zn2+ ions: a molecular 'butterfly'

A simple pyrene-based triazole receptor has been synthesised and shown to self-assemble in the presence of ZnCl(2) in an exclusively 2:1 ratio, whereas a mixture of 2:1 and 1:1 ratios are observed for other Zn(2+) salts. The pyrene units are syn in orientation; this is supported by a strong excimer signal observed at 410 nm in the presence of ZnCl(2) in acetonitrile. DFT calculations and 2D NMR support the proposed structure.     

Free radicals in pyrimidines: E.S.R. of a γ-irradiated single crystal of 5-nitrouracil

Free radicals are observed in γ-irradiated single crystals of 5-nitrouracil with the unpaired electron showing hyperfine interaction with one nitrogen atom. The principal values of hyperfine coupling are A_x = 22·5 g, A_y = 25·2 g, and A_z = 40·0 g, and the principal values of the spectroscopic splitting factor are g_u = 2·0117, g_v = 2·0064 and g_w = 2·0027. The relationship of the directions of the corresponding principal axes to the molecular orientations show that the unpaired electron must be located in an sp ² orbital on either N₍₁₎ or N₍₅₎. Considerations of the mechanism of radical formation and comparison to radiation damage in other molecules make the N₍₁₎ location seem more probable. The π interaction of the nitro group on C₍₅₎ evidently prevents the formulation of free radicals with the unpaired electron on C₍₅₎. That carbon atom is the most common location of unpaired electron density in other pyrimidine free radicals.     

Dispersed mercury microelectrodes using non-conducting polymer coatings

The preparation and use of polymeric dispersed mercury electrodes were investigated. Both micro- and macroelectrodes were considered and it was found that the polymer-coated electrodes have greater chemical and mechanical stability than conventional mercury thin-film electrodes. It was also found that the polymeric microelectrodes display several advantages in performance over the macroelectrode counterpart.