Aryl sulfonyl chlorides (e.g. Ts‐Cl) are beloved of organic chemists as the most commonly used SVI electrophiles, and the parent sulfuryl chloride, O2SVICl2, has also been relied on to create ...sulfates and sulfamides. However, the desired halide substitution event is often defeated by destruction of the sulfur electrophile because the SVICl bond is exceedingly sensitive to reductive collapse yielding SIV species and Cl−. Fortunately, the use of sulfur(VI) fluorides (e.g., R‐SO2‐F and SO2F2) leaves only the substitution pathway open. As with most of click chemistry, many essential features of sulfur(VI) fluoride reactivity were discovered long ago in Germany.6a Surprisingly, this extraordinary work faded from view rather abruptly in the mid‐20th century. Here we seek to revive it, along with John Hyatt’s unnoticed 1979 full paper exposition on CH2CH‐SO2‐F, the most perfect Michael acceptor ever found.98 To this history we add several new observations, including that the otherwise very stable gas SO2F2 has excellent reactivity under the right circumstances. We also show that proton or silicon centers can activate the exchange of SF bonds for SO bonds to make functional products, and that the sulfate connector is surprisingly stable toward hydrolysis. Applications of this controllable ligation chemistry to small molecules, polymers, and biomolecules are discussed.
Old chemistry in new glory: Sulfonyl fluoride exchange (SuFEx) forges rugged inorganic links between carbon centers. Like most click reactions, it is an old process now improved to allow the underappreciated sulfate connection to be made for a variety of purposes. The various exchange events uniquely enabled by the use of fluoride are highlighted here in orange.
Sulfur(VI) Fluoride Exchange (SuFEx) is a new family of click chemistry transformations which relies on readily available materials to produce compounds bearing the SVI–F motif. The potential of ...SuFEx in drug discovery has just started to be explored. We report the first method of SuFEx chemistry for the conversion of phenolic compounds to their respective arylfluorosulfate derivatives in situ in 96-well plates. This method is compatible with automated synthesis and screening to quickly assess the biological activities of the in situ generated, crude products. Using this method, we perform late-stage functionalization of a panel of known anticancer drugs to generate the corresponding arylfluorosulfates. These in situ generated arylfluorosulfates are directly tested in a cancer-cell growth inhibition assay in parallel with their phenolic precursors. We discover three arylfluorosulfates that exhibit improved anticancer cell proliferation activities compared to their phenol precursors. Among these three compounds, the fluorosulfate derivative of Fulvestrant possesses significantly enhanced activity to down-regulate estrogen receptor (ER) expression in ER+ breast cancer cell line MCF-7 and the fluorosulfate derivative of Combretastatin A4a general anticancer drug currently being evaluated under clinical trialsexhibits a 70-fold increase in potency in the drug resistant colon cancer cell line HT-29.
Of the various factors influencing kinetically controlled product ratios, the role of nonstatistical dynamics is arguably the least well understood. In this paper, reactions were chosen in which ...dynamics played a dominant role in product selection, by design. Specifically, the reactions studied were the ring openings of cyclopropylidene to allene and tetramethylcyclopropylidene to tetramethylallene (2,4-dimethylpenta-2,3-diene). Both reactions have intrinsic reaction coordinates that bifurcate symmetrically, leading to products that are enantiomeric once the atoms are uniquely labeled. The question addressed in the study was whether the outcomesthat is, which product well on the potential energy surface was selectedcould be predicted from their initial conditions for individual trajectories in quasiclassical dynamics simulations. Hybrid potentials were developed based on cooperative interaction between molecular mechanics and artificial neural networks, trained against data from electronic structure calculations. These potentials allowed simulations of both gas-phase and condensed-phase reactions. The outcome was that, for both reactions, prediction of initial selection of product wells could be made with >95% success from initial conditions of the trajectories in the gas phase. However, when trajectories were run for longer, looking for “final” products for each trajectory, the predictability dropped off dramatically. In the gas-phase simulations, this drop off was caused by trajectories hopping between product wells on the potential energy surface. That behavior could be suppressed in condensed phases, but then new uncertainty was introduced because the intermolecular interactions between solute and bath, necessary to permit intermolecular energy transfer and cooling of the hot initial products, often led to perturbations of the initial directions of trajectories on the potential energy surface. It would consequently appear that a general ability to predict outcomes for reactions in which nonstatistical dynamics dominate remains a challenge even in the age of sophisticated machine-learning capabilities.
Sulfur fluoride exchange (SuFEx) has emerged as the new generation of click chemistry. We report here a SuFEx-enabled, agnostic approach for the discovery and optimization of covalent inhibitors of ...human neutrophil elastase (hNE). Evaluation of our ever-growing collection of SuFExable compounds toward various biological assays unexpectedly revealed a selective and covalent hNE inhibitor: benzene-1,2-disulfonyl fluoride. Synthetic derivatization of the initial hit led to a more potent agent, 2-(fluorosulfonyl)phenyl fluorosulfate with IC50 0.24 μM and greater than 833-fold selectivity over the homologous neutrophil serine protease, cathepsin G. The optimized, yet simple benzenoid probe only modified active hNE and not its denatured form.
This paper describes a new method to monitor end milling tool wear in real-time by tracking force model coefficients during the cutting process. The behavior of these coefficients are shown to be ...independent from the cutting conditions and correlated with the wear state of the cutting tool. The tangential and radial force model coefficients are normalized and combined into a single parameter for wear monitoring. A number of experiments with different workpiece materials are run to investigate the feasibility of tool wear monitoring using this method. We show that this method can be used in real-time to track tool wear and detect the transition point from the gradual wear region to the failure region in which the rate of wear accelerates.
•The coefficients of a cutting force model for milling are shown to change with wear.•An overall tool wear parameter, K, is introduced.•High variability in estimated K is a sign of the cutting tool edge failure.•A control chart is developed to detect the entrance to tool edge failure region.
The central aim of conservation biology is to understand and mitigate the effects of human activities on biodiversity. To successfully achieve this objective, researchers must take an ...interdisciplinary approach that fully considers the effects, both direct and indirect, of anthropogenic disturbances on wildlife physiology and health. A recent surge in research has revealed that host-associated microbiota-the archaeal, bacterial, fungal and viral communities residing on and inside organisms-profoundly influence animal health, and that these microbial communities can be drastically altered by anthropogenic activities. Therefore, conservation practitioners should consider the disruption of host-associated microbial diversity as a serious threat to wildlife populations. Despite the tremendous potential for microbiome research to improve conservation outcomes, few efforts have been made to truly integrate these fields. In this review, we call for the microbial renaissance of conservation biology, where biodiversity of host-associated microbiota is recognized as an essential component of wildlife management practices. Using evidence from the existing literature, we will examine the known effects of anthropogenic activities on the diversity of host-associated microbial communities and integrate approaches for maintaining microbial diversity to successfully achieve conservation objectives.
Capital Redefined HOSSEINI, S A Hamed; Gills, Barry K
2024, Letnik:
1
eBook
Odprti dostop
Capital Redefined presents a unique perspective on the nature of “capital,” departing from the prevailing reductionist accounts. Hosseini and Gills offer an expanded perspective on Marxian value ...theory by addressing its main limitations and building their own integrative value theory. They argue that the current understanding of “value” must be re-examined and liberated from its subservient ties to capital while acknowledging the ways in which capital appropriates value. This is achieved by differentiating between “fetish value” created by capital and “true value” generated through various commons-based forms of coexistence. The authors propose a defetishization of value by rejecting the commonly accepted idea of its objectivity. They introduce their “commonist value theory,” which redefines capital as both the product and process of perverting the fundamental commoning causes of true value into sources of fetish value. Capital is theorized through a “modular” framework, where multiple intersecting processes constitute a comprehensive power structure, a “value regime,” representing an unprecedented degree of the domination of capital over life. Their theory reconciles two apparently incompatible views on the notion of value. One view encompasses all inputs involved in capitalist value production and conflates intrinsic and commodity values. The other warns against this conflation as it treats capital as an entity tightly associated only with commodity production and wage labor. The authors believe that establishing alternative forms of value creation based on normative principles of living in commons is crucial as an analytical base for criticizing existing power structures and economic systems. The book offers a theoretical foundation for transforming our life worlds toward “post-capitalist” futures. It appeals to scholars and students in various fields, such as political economy, capitalism, and post-capitalist studies, economic and political sociology, globalization, development studies, social ecology, and ecological philosophy.
Relatively little is known about the neuropathophysiology of binge-eating disorder (BED). Here, the evidence from neuroimaging, neurocognitive, genetics, and animal studies are reviewed to synthesize ...our current understanding of the pathophysiology of BED. Binge-eating disorder may be conceptualized as an impulsive/compulsive disorder, with altered reward sensitivity and food-related attentional biases. Neuroimaging studies suggest there are corticostriatal circuitry alterations in BED similar to those observed in substance abuse, including altered function of prefrontal, insular, and orbitofrontal cortices and the striatum. Human genetics and animal studies suggest that there are changes in neurotransmitter networks, including dopaminergic and opioidergic systems, associated with binge-eating behaviors. Overall, the current evidence suggests that BED may be related to maladaptation of the corticostriatal circuitry regulating motivation and impulse control similar to that found in other impulsive/compulsive disorders. Further studies are needed to understand the genetics of BED and how neurotransmitter activity and neurocircuitry function are altered in BED and how pharmacotherapies may influence these systems to reduce BED symptoms.
A two-step, on-water procedure for the synthesis of ethenesulfonyl fluoride (ESF) is described. 2-Chloroethanesulfonyl fluoride is made via a neat reaction with an aqueous, nearly saturated potassium ...bifluoride solution from readily available 2-chloroethanesulfonyl chloride. The subsequent dehydrochlorination of 2-chloroethanesulfonyl fluoride proceeds neatly with magnesium oxide as the base in an aqueous suspension to give ESF. This recipe allows the preparation of ESF in 98% yield on a kilogram scale.
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