Synthesis and Characterization of 5‐Cyanotetrazolide‐Based Ionic Liquids

New salts based on imidazolium, pyrrolidinium, phosphonium, guanidinium, and ammonium cations together with the 5‐cyanotetrazolide anion [C₂N₅]^? are reported. Depending on the nature of cation–anion interactions, characterized by XRD, the ionic liquids (ILs) have a low viscosity and are liquid at room temperature or have higher melting temperatures. Thermogravimetric analysis, cyclic voltammetry, viscosimetry, and impedance spectroscopy display a thermal stability up to 230 °C, an electrochemical window of 4.5 V, a viscosity of 25 mPa s at 20 °C, and an ionic conductivity of 5.4 mS cm^?1 at 20 °C for the IL 1‐butyl‐1‐methylpyrrolidinium 5‐cyanotetrazolide [BMPyr][C₂N₅]. On the basis of these results, the synthesized compounds are promising electrolytes for lithium‐ion batteries.     

Maximum norms of random sums and transient pattern formation

Many interesting and complicated patterns in the applied sciences are formed through transient pattern formation processes. In this paper we concentrate on the phenomenon of spinodal decomposition in metal alloys as described by the Cahn-Hilliard equation. This model depends on a small parameter, and one is generally interested in establishing sharp lower bounds on the amplitudes of the patterns as the parameter approaches zero. Recent results on spinodal decomposition have produced such lower bounds. Unfortunately, for higher-dimensional base domains these bounds are orders of magnitude smaller than what one would expect from simulations and experiments. The bounds exhibit a dependence on the dimension of the domain, which from a theoretical point of view seemed unavoidable, but which could not be observed in practice.

In this paper we resolve this apparent paradox. By employing probabilistic methods, we can improve the lower bounds for certain domains and remove the dimension dependence. We thereby obtain optimal results which close the gap between analytical methods and numerical observations, and provide more insight into the nature of the decomposition process. We also indicate how our results can be adapted to other situations.

     

An integrated console for capsule-based,automated organic synthesis

The current laboratory practices of organic synthesis are labor intensive, impose safety and environmental hazards, and hamper the implementation of artificial intelligence guided drug discovery. Using a combination of reagent design, hardware engineering, and a simple operating system we provide an instrument capable of executing complex organic reactions with prepacked capsules. The machine conducts coupling reactions and delivers the purified products with minimal user involvement. Two desirable reaction classes – the synthesis of saturated N-heterocycles and reductive amination – were implemented, along with multi-step sequences that provide drug-like organic molecules in a fully automated manner. We envision that this system will serve as a console for developers to provide synthetic methods as integrated, user-friendly packages for conducting organic synthesis in a safe and convenient fashion.

Using a combination of reagent design, hardware engineering, and a simple operating system we provide an instrument capable of executing complex organic reactions using prepacked capsules with minimal user involvement.     

PHOTOSENSITIZATION OF MELANIN: AN ELECTRON SPIN RESONANCE STUDY OF SENSITIZED RADICAL PRODUCTION AND OXYGEN CONSUMPTION

Abstract Rose Bengal is shown to photosensitize free-radical production and oxygen consumption in solutions of melanin from autooxidation of 3,4-dihydroxyphenylalanine (DOPA). In anaerobic solutions the sensitizer enhances rates of free-radical production by up to a factor of 20. In aerobic solutions, rates of oxygen consumption can be increased by a factor of several hundred. The reactions appear to involve the triplet state of the sensitizer. The effect of the sensitizer in increasing oxygen consumption is quenched by low concentrations of azide and enhanced by D₂O, suggesting that a singlet oxygen mechanism is involved.     

A convenient synthesis of 1,3-oxazolidin-4-ones and 1,3-oxazin-4-ones

1,3-Oxazolidin-4-ones and 1,3-oxazin-4-ones were synthesized by formal cyclocondensation of imines with α- or β-hydroxy acids.     

Hierarchical dynamics in allostery following ATP hydrolysis monitored by single molecule FRET measurements and MD simulations

We report on a study that combines advanced fluorescence methods with molecular dynamics (MD) simulations to cover timescales from nanoseconds to milliseconds for a large protein. This allows us to delineate how ATP hydrolysis in a protein causes allosteric changes at a distant protein binding site, using the chaperone Hsp90 as test system. The allosteric process occurs via hierarchical dynamics involving timescales from nano- to milliseconds and length scales from Ångstroms to several nanometers. We find that hydrolysis of one ATP is coupled to a conformational change of Arg380, which in turn passes structural information via the large M-domain α-helix to the whole protein. The resulting structural asymmetry in Hsp90 leads to the collapse of a central folding substrate binding site, causing the formation of a novel collapsed state (closed state B) that we characterise structurally. We presume that similar hierarchical mechanisms are fundamental for information transfer induced by ATP hydrolysis through many other proteins.

We report on a study that combines advanced fluorescence methods with molecular dynamics simulations to cover timescales from nanoseconds to milliseconds for a large protein, the chaperone Hsp90.     

Bioorthogonal organic chemistry in living cells: novel strategies for labeling biomolecules

The chemical labeling of biomolecules continues to be an important tool for the study of their function and cellular fate. Attention is increasingly focused on labeling of biomolecules in living cells, since cell lysis introduces many artefacts. In addition, with the advances in biocompatible synthetic organic chemistry, a whole new field of opportunity has opened up, affording high diversity in the nature of the label as well as a choice of ligation reactions. In recent years, several different two-step labeling strategies have emerged. These rely on the introduction of a bioorthogonal attachment site into a biomolecule, then ligation of a reporter molecule to this site using bioorthogonal organic chemistry. This Perspective focuses on these techniques, their implications and future directions.     

Total synthesis of the ramoplanin A2 and ramoplanose aglycon

A convergent total synthesis of the ramoplanin A2 and ramoplanose aglycon is disclosed. Three key subunits composed of residues 3-9 (heptapeptide 15), pentadepsipeptide 26, and pentapeptide 34 (residues 10-14) were prepared, sequentially coupled, and cyclized to provide the 49-membered depsipeptide core of the aglycon. Key to the preparation of the pentadepsipeptide 26 incorporating the backbone ester was the asymmetric synthesis of an orthogonally protected L-threo-beta-hydroxyasparagine and the development of effective and near-racemization free conditions for esterification of its hindered alcohol (EDCI, DMAP, 0 degrees C). The coupling sites were chosen to maximize the convergency of the synthesis including that of the three subunits, to prevent late stage racemization of carboxylate-activated phenylglycine-derived residues, and to enlist beta-sheet preorganization of an acyclic macrocyclization substrate for 49-membered ring closure. As such, macrocyclization at the chosen Phe(9)-D-Orn(10) site may benefit from both beta-sheet preorganization as well as closure at a D-amine terminus. Deliberate late stage incorporation of the subunit bearing the labile depsipeptide ester and a final stage Asn(1) side chain introduction provides future access to analogues of the aglycons which themselves are reported to be equally potent or more potent than the natural products in antimicrobial assays.     

Isotachophoresis of beta-blockers in a capillary and on a poly(methyl methacrylate) chip

Analysis of the beta-blockers oxprenolol, atenolol, timolol, propranolol, metoprolol, and acebutolol in human urine by a combination of isotachophoresis (ITP) and zone electrophoresis (ZE) was investigated. Methods were developed with a conventional capillary electrophoresis (CE) apparatus and a poly(methyl methacrylate) (PMMA) microchip system. With CE the separation of oxprenolol, atenolol, timolol, and acebutolol from a standard solution containing 5 microg/mL of each compound was accomplished by performing ZE with transient ITP. The electrolyte system consisted of 10 mM sodium morpholinoethane sulfonate (pH 5.5) and 0.1% methylhydroxyethylcellulose as the leading electrolyte and 30 mM ortho-phosphoric acid (pH 2.0) as both the terminating and the ZE background electrolyte. With the microchip system the separation of oxprenolol and acebutolol from a standard solution containing 10 microg/mL of each compound was accomplished by a coupled-channel ITP-ZE device using the same leading electrolyte solution as the CE system but 5 mM glutamic acid (pH 3.4) as terminating and background electrolytes. The systems were used for analyses of patient urine samples. Water-soluble hydrophilic matrix compounds were removed from the urine samples by solid-phase extraction (SPE). Limits of quantification below 5 microg/mL could be achieved. The PMMA ITP-ZE chip has not earlier been used for analyses of any drugs from urine samples.