N-Heterocyclic Carbene-mediated microfluidic oxidative electrosynthesis of amides from aldehydes

A flow process for N-Heterocyclic Carbene (NHC)-mediated anodic oxidative amidation of aldehydes is described, employing an undivided microfluidic electrolysis cell to oxidize Breslow intermediates. After electrochemical oxidation, the reaction of the intermediate N-acylated thiazolium cation with primary amines is completed by passage through a heating cell to achieve high conversion in a single pass. The flow mixing regimen circumvented the issue of competing imine formation between the aldehyde and amine substrates, which otherwise prevented formation of the desired product. High yields (71–99%), productivities (up to 2.6 g h–1), and current efficiencies (65–91%) were realized for 19 amides

Et3SiH + KOtBu provide multiple reactive intermediates that compete in the reactions and rearrangements of benzylnitriles and indolenines

The combination of potassium tert-butoxide and triethylsilane is unusual because it generates multiple different types of reactive intermediates simultaneously that provide access to (i) silyl radical reactions, (ii) hydrogen atom transfer reactions to closed shell molecules and to radicals, (iii) electron transfer reductions and (iv) hydride ion chemistry, giving scope for unprecedented outcomes. Until now, reactions with this reagent pair have generally been explained by reference to one of the intermediates, but we now highlight the interplay and competition between them

New reductive rearrangement of N-Arylindoles triggered by the Grubbs-Stoltz reagent Et3SiH/KOtBu

N-Arylindoles are transformed into dihydroacridines in a new type of rearrangement, through heating with triethylsilane and potassium tert-butoxide. Studies indicate that the pathway involves (i) the formation of indole radical anions followed by fragmentation of the indole C2-N bond, and (ii) a ring-closing reaction that follows a potassium-ion dependent hydrogen atom transfer step. Unexpected behaviors of ‘radical-trap’ substrates prove very helpful in framing the proposed mechanis

A study of the reactivity of cyclic aminomethylammonium mannich salts

A novel method for the preparation of aminoalkylaminomethyl products was developed utilising novel Mannich-type salts featuring a R 2NCH 2NR 3 + moiety. This methodology showed good nucleophile scope and was successfully employed in reactions under basic, acidic, and neutral conditions. A wide range of diamine products was successfully synthesised, including a neuropeptide Y antagonist

Aerial wetting contact angle measurement using confocal microscopy

A method is presented in which the wetting contact angle of a sessile drop is acquired aerially using confocal techniques to measure the radius and the height of a droplet deposited on a planar surface. The repeatability of this method is typically less than 0.25°, and often less than 0.1°, for droplet diameters less than 1 mm. To evaluate accuracy of this method, an instrument uncertainty budget is developed, which predicts a combined uncertainty of 0.91° for a 1 mm diameter water droplet with a contact angle of 110°. For droplets having diameters less than 1 mm and contact angles between 15° and 160°, these droplets approach spherical shape and their contact angles can be computed analytically with less than 1% error. For larger droplets, gravitational deformation needs to be considered

An exhibition of work by the Victorian tapestry workshop

An exhibition of work by the Victorian tapestry workshop Fine Arts Gallery, University Centre, Churchill Ave., Sandy Bay 24 April - 10 Ma

Mantle heat drives hydrothermal fluids responsible for carbonate-hosted base metal deposits: evidence from 3He/4He of ore fluids in the Irish Pb-Zn ore district

There is little consensus on whether carbonate-hosted base metal deposits, such as the world-class Irish Zn+Pb ore field, formed in collisional or extensional tectonic settings. Helium isotopes have been analysed in ore fluids trapped in sulphides samples from the major base metal deposits of the Irish Zn-Pb ore field in order to quantify the involvement of mantle-derived volatiles, that require melting to be realised, as well as test prevailing models for the genesis of the ore fields. 3He/4He ratios range up to 0.2 Ra, indicating that a small but clear mantle helium contribution is present in the mineralising fluids trapped in galena and marcasite. Sulfides from ore deposits with the highest fluid inclusion temperatures (~200°C) also have the highest 3He/4He (> 0.15 Ra). Similar 3He/4He are recorded in fluids from modern continental regions that are undergoing active extension. By analogy we consider that the hydrothermal fluids responsible for the carbonate-hosted Irish base metal mineralization circulated in thinned continental crust, undergoing extension, and demonstrates that enhanced mantle heat flow is ultimately responsible for driving fluid convection

Improving the practicality of using non-aversive handling methods to reduce background stress and anxiety in laboratory mice

Handling can stimulate stress and anxiety in laboratory animals that negatively impacts welfare and introduces a confounding factor in many areas of research. Picking up mice by the tail is a major source of handling stress that results in strong aversion to the handler, while mice familiarised with being picked up in a tunnel or cupped on the open hand show low stress and anxiety, and actively seek interaction with their handlers. Here we investigate the duration and frequency of handling required for effective familiarisation with these non-aversive handling methods, and test whether this is sufficient to prevent aversion and anxiety when animals then experience immobilisation and a mild procedure (subcutaneous injection). Very brief handling (2 s) was sufficient to familiarise mice with tunnel handling, even when experienced only during cage cleaning. Brief but more frequent handling was needed for familiarisation with cup handling, while pick up by tail induced strong aversion even when handling was brief and infrequent. Experience of repeated immobilisation and subcutaneous injection did not reverse the positive effects of tunnel handling. Our findings demonstrate that replacing tail with tunnel handling during routine cage cleaning and procedures provides a major refinement with little if any cost for familiarisation

A Kernel for Open Source Drug Discovery in Tropical Diseases

Open source drug discovery, a promising alternative avenue to conventional patent-based drug development, has so far remained elusive with few exceptions. A major stumbling block has been the absence of a critical mass of preexisting work that volunteers can improve through a series of granular contributions. This paper introduces the results from a newly assembled computational pipeline for identifying protein targets for drug discovery in ten organisms that cause tropical diseases. We have also experimentally tested two promising targets for their binding to commercially available drugs, validating one and invalidating the other. The resulting kernel provides a base of drug targets and lead candidates around which an open source community can nucleate. We invite readers to donate their judgment and in silico and in vitro experiments to develop these targets to the point where drug optimization can begin