Palladium‐Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide

An efficient palladium‐catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high‐value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl‐containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.     

Equilibrium Formation of Stable All‐Silicon Versions of 1,3‐Cyclobutanediyl

Main group analogues of cyclobutane‐1,3‐diyls are fascinating due to their unique reactivity and electronic properties. So far only heteronuclear examples have been isolated. Here we report the isolation and characterization of all‐silicon 1,3‐cyclobutanediyls as stable closed‐shell singlet species from the reversible reactions of cyclotrisilene c‐Si₃Tip₄ (Tip=2,4,6‐triisopropylphenyl) with the N‐heterocyclic silylenes c‐[(CR₂CH₂)(NtBu)₂]Si: (R=H or methyl) with saturated backbones. At elevated temperatures, tetrasilacyclobutenes are obtained from these equilibrium mixtures. The corresponding reaction with the unsaturated N‐heterocyclic silylene c‐(CH)₂(NtBu)₂Si: proceeds directly to the corresponding tetrasilacyclobutene without detection of the assumed 1,3‐cyclobutanediyl intermediate.     

Bounds on absorption times of directionally biased random sequences

A sequence of random variables X₀,X₁, … with values in {0, 1, …, n} representing a general finite-state stochastic process with absorbing state 0 is said to be directionally biased towards 0, if, for all j > 0, ϵ_j: = inf_k>0 {j − E[X_k | X_k−1 = j]} > 0. For such sequences, let t be the expected value of the time to absorption at 0. For a fixed set of biases, the least upper bound for this time can be computed with an algorithm requiring O(n²) steps. Simple upper bounds are described. In particular, t ≤ E[b_x0], where b_i = Σ_j≤i 1/¯ϵ_j and ¯ϵ_j = min_l≥j {ϵ_l}. If all ϵ_j ≤ ϵ_{j + 1} (so ¯ϵ_j = ϵ_j) and ϵ_n < 1, this bound for t is the best possible. For certain finite stochastic processes which we term conditionally independent of X₀ = i, b(i) bounds the expected time given X₀ = i. Similar results are given for lower bounds. The results of this paper were designed to be a useful tool for determining rates of convergence of stochastic optimization algorithms. © 1996 John Wiley & Sons, Inc.     

Chemical Proteomics and Phenotypic Profiling Identifies the Aryl Hydrocarbon Receptor as a Molecular Target of the Utrophin Modulator Ezutromid

Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent K_D of 50 nm  and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies.     

On some generalized sequence spaces of fuzzy numbers defined by a sequence of Orlicz functions

The purpose of the paper is to introduce the concepts of almost λ-statistical convergence and strongly almost λ-convergence of sequences of fuzzy numbers. We establish some connections between these concepts. It is also shown that if a sequence of fuzzy numbers is strongly almost λ-convergent with respect to a sequence of Orlicz funtions then it is almost λ-statistical convergent.     

Interaction-induced collapse of a section of the Fermi sea in the zigzag Hubbard ladder

Using the next-nearest-neighbor (zigzag) Hubbard chain as a one-dimensional model, we investigate the influence of interactions on the position of the Fermi wave vectors with the density-matrix renormalization-group technique. For suitable choices of the hopping parameters we observe that electron-electron correlations induce very different renormalizations for the two different Fermi wave vectors, which ultimately lead to a complete destruction of one section of the Fermi sea in a quantum critical point.     

A beaker without walls: formation of deeply supercooled binary liquid solutions of alcohols from nanoscale amorphous solid films

Layered nanoscale amorphous solid films of methanol and ethanol undergo complete intermixing prior to the onset of measurable desorption at 120 K. This intermixing precedes and inhibits crystallization. Subsequent desorption of the film is described quantitatively by a kinetic model describing evaporation from a continuously mixed ideal binary liquid solution. This occurs at temperatures below the melting point of the binary mixture, indicating ideal behavior for the supercooled liquid solution. This approach provides a new method for preparing and examining deeply supercooled solutions.