Cyclization of protected N-acylhydroxyguanidine to 3-amino-1,2,4-oxadiazole

The acid mediated cyclization of a protected N-acylhydroxyguanidine into the corresponding 3-amino-1,2,4-oxadiazole and confirmation of its structure by single crystal X-ray crystallography is reported herein. The yield of the cyclization is comparable to literature reports utilizing alternative procedures. Importantly, these new conditions provide complementary chemoselectivity to current synthetic procedures which may be useful for the synthesis of 3-amino-1,2,4-oxadiazoles in general.     

Mechanism and origins of regio- and enantioselectivities in RhI-catalyzed hydrogenative couplings of 1,3-diynes and activated carbonyl partners: intervention of a cumulene intermediate

The mechanism of the rhodium-catalyzed reductive coupling of 1,3-diynes and vicinal dicarbonyl compounds employing H(2) as reductant was investigated by density functional theory. Oxidative coupling through 1,4-addition of the Rh(I)-bound dicarbonyl to the conjugated diyne via a seven-membered cyclic cumulene transition state leads to exclusive formation of linear adducts. Diyne 1,4-addition is much faster than the 1,2-addition to simple alkynes. The 1,2-dicarbonyl compound is bound to rhodium in a bidentate fashion during the oxidative coupling event. The chemo-, regio-, and enantioselectivities of this reaction were investigated and are attributed to this unique 1,4-addition pathway. The close proximity of the ligand and the alkyne substituent distal to the forming C-C bond controls the regio- and enantioselectivity: coupling occurs at the sterically more demanding alkyne terminus, which minimizes nonbonded interaction with the ligand. A stereochemical model is proposed that accounts for preferential formation of the (R)-configurated coupling product when (R)-biaryl phosphine ligands are used.     

Aggregation and dispersion of silver nanoparticles in exposure media for aquatic toxicity tests

Silver nanoparticles (AgNPs) are currently being very widely used in industry, mainly because of their anti-bacterial properties, with applications in many areas. Once released into the environment, the mobility, bioavailability, and toxicity of AgNPs in any ecosystem are dominated by colloidal stability. There have been studies on the stability or the aggregation of various nanoparticles (NPs) under a range of environmental conditions, but there is little information on fully characterised AgNPs in media used in (eco)toxicity studies. In this study, monodisperse 7, 10 and 20 nm citrate-stabilised AgNPs were synthesised, characterised and then fractionated and sized by flow field-flow fractionation (FFF) and measured with dynamic light scattering (DLS) in different dilutions of the media recommended by OECD for Daphnia magna (water flea) toxicity testing. Stability of NPs was assessed over 24 h, and less so over 21 days, similar time periods to the OECD acute and chronic toxicity tests for D. magna. All particles aggregated quickly in the media with high ionic strength (media1), resulting in a loss of colour from the solution. The size of particles could be measured by DLS in most cases after 24h, although a fractogram by FFF could not be obtained due to aggregation and polydispersity of the sample. After diluting the media by a factor of 2, 5 or 10, aggregation was reduced, although the smallest NPs were unstable under all media conditions. Media diluted up to 10-fold in the absence of AgNPs did not induce any loss of mobility or fecundity in D. magna. These results confirm that standard OECD media causes aggregation of AgNPs, which result in changes in organism exposure levels and the nature of the exposed particles compared to exposure to fully dispersed particles. Setting aside questions of dose metrics, significant and substantial reduction in concentration over exposure period suggests that literature data are in the main improperly interpreted and nanoparticles are likely to have far greater biological effects than suggested thus far by poorly controlled exposures. We recommend that the standard OECD media is diluted by a factor of ca. 10 for use with these NPs and this test media, which reduces AgNP aggregation without affecting the viability of the text organism.     

Improving Physical Properties via C?H Oxidation: Chemical and Enzymatic Approaches

Physicochemical properties constitute a key factor for the success of a drug candidate. Whereas many strategies to improve the physicochemical properties of small heterocycle‐type leads exist, complex hydrocarbon skeletons are more challenging to derivatize because of the absence of functional groups. A variety of C H oxidation methods have been explored on the betulin skeleton to improve the solubility of this very bioactive, yet poorly water‐soluble, natural product. Capitalizing on the innate reactivity of the molecule, as well as the few molecular handles present on the core, allowed oxidations at different positions across the pentacyclic structure. Enzymatic oxidations afforded several orthogonal oxidations to chemical methods. Solubility measurements showed an enhancement for many of the synthesized compounds.     

MEXIT: Maximal un-coupling times for stochastic processes

Classical coupling constructions arrange for copies of the same Markov process started at two different initial states to become equal as soon as possible. In this paper, we consider an alternative coupling framework in which one seeks to arrange for two different Markov (or other stochastic) processes to remain equal for as long as possible, when started in the same state. We refer to this “un-coupling” or “maximal agreement” construction as MEXIT, standing for “maximal exit”. After highlighting the importance of un-coupling arguments in a few key statistical and probabilistic settings, we develop an explicit MEXIT construction for stochastic processes in discrete time with countable state-space. This construction is generalized to random processes on general state-space running in continuous time, and then exemplified by discussion of MEXIT for Brownian motions with two different constant drifts.     

Cavity Volume and Free Energy in Many-Body Systems

Most models for the spread of an invasive species into a new environment are based on Fisher’s reaction–diffusion equation. They assume that habitat quality is independent of the presence or absence of the invading population. Ecosystem engineers are species that modify their environment to make it (more) suitable for them. A potentially more appropriate modeling approach for such an invasive species is to adapt the well-known Stefan problem of melting ice. Ahead of the front, the habitat is unsuitable for the species (the ice); behind the front, the habitat is suitable (the open water). The engineering action of the population moves the boundary ahead (the melting). This approach leads to a free boundary problem. In this paper, we study the well-posedness of a novel free boundary model for the spread of ecosystem engineers that was recently derived from an individual random walk model. The Stefan condition for the moving boundary is replaced by a biologically derived two-sided condition that models the movement behavior of individuals at the boundary as well as the process by which the population moves the boundary to expand their territory. Our proofs consist of several new and novel ideas that can be used in broader contexts. We assign a convex functional to this problem so that the evolution system governed by this convex potential is exactly the system of evolution equations describing the above model. We then apply variational and fixed-point methods to deal with this free boundary problem.

     

Modified Bridgman anvils for high pressure synthesis and neutron scattering

ABSTRACT

A simple modified Bridgman design for large volume pressure anvils usable in the Paris-Edinburgh (PE) press has been demonstrated at Oak Ridge National Laboratory Spallation Neutron Source. The design shows advantages over the toroidal anvils typically used in the PE press, mainly rapid compression/decompression rates, complete absence of blow-outs upon drastic phase transitions, simplified cooling, high reliability, and relative low loads (～40 tons) corresponding to relatively high pressures (～20?GPa). It also shows advantages over existing large-volume diamond cells as sample volumes of ～2–3?mm³ can be easily and rapidly synthesized. The anvils thus allow sample sizes sufficient for in situ neutron diffraction as well as rapid synthesis of adequate amounts of new materials for ex situ analysis via total neutron scattering and neutron spectroscopy.