Bicyclo[2.1.1]hexanes via Intramolecular Formal (3+2)-Cycloaddition.

We report a synthesis of bicyclo[2.1.1]hexanes via an intramolecular formal (3+2) cycloaddition of allylated cyclopropanes bearing a 4-nitrobenzimine substituent.

L-Cysteine-Catalysed Hydration of Activated Alkynes.

Hydration reactions consist of the introduction of a molecule of water into a chemical compound and are particularly useful to transform alkynes into carbonyls, which are strategic intermediates in the synthesis of a plethora of compounds. Herein we demonstrate that L-cysteine can catalyse the hydration of activated alkynes in a very effective and fully regioselective manner to access important building blocks in synthetic chemistry such as β-ketosulfones, amides and esters, in aqueous media. The mild reaction conditions facilitated the integration with enzyme catalysis to access chiral β-hydroxy sulfones from the corresponding alkynes in a one-pot cascade process in good yields and excellent enantiomeric ratios.

Synthesis of 2-Amino-2-deoxy Sugars via Boron-Catalyzed Coupling of Glycosyl Fluorides and Silyl Ether Acceptors.

Although aminosugars are important components in a variety of bioactive molecules, their stereoselective formation is made challenging by the Lewis basic nature of amino substituents. Additionally, the use of -acyl protecting groups is often problematic due to the competing formation of oxazolines during the glycosylation of 2-aminosugar derivatives. Herein, we report a boron-catalyzed strategy utilizing silyl ether glycosyl acceptors and 2-aminosugar donors that employs the 2,2,2-trichloroethoxycarbonyl (Troc) protecting group for the C2 amino functionality in glycosyl fluorides.

Structural Evolution of Photoexcited Methylcobalamin toward a CarH-like Metastable State: Evidence from Time-Resolved X-ray Absorption and X-ray Emission.

CarH is a protein photoreceptor that uses a form of B, adenosylcobalamin (AdoCbl), to sense light via formation of a metastable excited state. Aside from AdoCbl bound to CarH, methylcobalamin (MeCbl) is the only other example─to date─of photoexcited cobalamins forming metastable excited states with lifetimes of nanoseconds or longer. The UV-visible spectra of the excited states of MeCbl and AdoCbl bound to CarH are similar.

Targeted 8-arm PEG Nanosystems for Localization of Choroidal Neovascularization Macular Degeneration Model.

8-arm PEG (polyethylene-glycol) is a highly promising nanoplatform due to its small size (<10 nm), ease-of-conjugation (many functionalized variants are readily available with "click-like" properties), biocompatibility, and optical inactivity. This study evaluates 8-arm PEG uptake into cells () and localization and clearance in vasculature () for targeting of choroidal neovascularization in mice, an animal model of macular degeneration. 8-arm PEG nanoparticles were labeled with fluorescein isothiocyanate (FITC) and functionalized in the absence or presence of pentameric Ar-Gly-Asp (RGD; 4 RGD motifs and a PGC linker), one of the most common peptide motifs used for active targeting.

Nanoclustering in non-ideal ethanol/heptane solutions alters solvation dynamics.

Alcohol/alkane solutions widely used in chemical synthesis and as transportation fuels are highly non-ideal due to the nanoscale clustering of the amphiphilic alcohol molecules within the nonpolar alkanes. Besides impacting reactivity, such as combustion, non-ideal solutions are likely to exhibit unusual solvation dynamics on ultrafast time scales arising from the structurally heterogeneous nature of molecular-scale association. Using a convenient transition metal carbonyl vibrational probe [(C5H5)Mn(CO)3, CMT], linear absorption and nonlinear two-dimensional infrared (2D-IR) spectroscopy reveal composition-dependent solvation dynamics as reported by the frequency fluctuation correlation function in a series of ethanol/heptane solutions.

Iodine/soluble starch cryogel: An iodine-based antiseptic with instant water-solubility, improved stability, and potent bactericidal activity.

Iodine (I) as a broad-spectrum antiseptic has been widely used for treating bacterial infections. However, I has low water-solubility and sublimes under ambient conditions, which limits its practical antibacterial applications. The highly specific and sensitive reaction between I and starch discovered 200 years ago has been extensively applied in analytical chemistry, but the antibacterial activity of the I-starch complex is rarely investigated.

Appended Lewis Acids Enable Dioxygen Reactivity and Catalytic Oxidations with Ni(II).

We disclose a suite of Ni(II) complexes featuring secondary sphere Lewis acids of varied Lewis acidity and tether lengths. Several of these complexes feature atypical behavior of Ni(II): reactivity with O that occurs only in the presence of a tethered Lewis acid. In situ UV-vis spectroscopy revealed that, although adducts are stable at -40 °C, complexes containing 9-borabicyclo[3.

Synthesis of Bufadienolide Cinobufagin via Late-Stage Singlet Oxygen Oxidation/Rearrangement Approach.

This manuscript describes a concise synthesis of cinobufagin, a natural steroid of the bufadienolide family, from readily available dehydroepiandrosterone (DHEA), as well as its α5-epimer derived from 3--andosterone. This synthesis features expedient installation of the 17β-pyrone moiety with the 14β,15β-epoxide and the 16β-acetoxy group using a photochemical regioselective singlet oxygen [4 + 2] cycloaddition followed by CoTPP-promoted endoperoxide rearrangement to provide a 14β,16β--epoxide in 64% yield with a 1.6:1 d.

Microdialysis coupled with droplet microfluidics and mass spectrometry for determination of neurotransmitters with high temporal resolution.

Monitoring the concentration fluctuations of neurotransmitters is valuable for elucidating the chemical signals that underlie brain functions. Microdialysis sampling is a widely used tool for monitoring neurochemicals . The volume requirements of most techniques that have been coupled to microdialysis, such as HPLC, result in fraction collection times of minutes, thus limiting the temporal resolution possible.

Elucidating the polycyclic aromatic hydrocarbons involved in soot inception.

Polycyclic aromatic hydrocarbons are the main precursors to soot particles in combustion systems. A lack of direct experimental evidence has led to controversial theoretical explanations for the transition from gas-phase species to organic soot clusters. This work focuses on sampling infant soot particles from well-defined flames followed by analysis using state-of-the-art mass spectrometry.

Leveraging the Persistent Radical Effect in the Synthesis of trans-2,3-Diaryl Dihydrobenzofurans.

A simple method for accessing trans-2,3-diaryl dihydrobenzofurans is reported. This approach leverages the equilibrium between quinone methide dimers and their persistent radicals. This equilibrium is disrupted by phenols that yield comparatively transient phenoxyl radicals, leading to cross-coupling between the persistent and transient radicals.

Advances in coupling droplet microfluidics to mass spectrometry.

Droplet microfluidics enables development of workflows with low sample consumption and high throughput. Fluorescence-based assays are most used with droplet microfluidics; however, the requirement of a fluorescent reporter restricts applicability of this approach. The coupling of droplets to mass spectrometry (MS) has enabled selective assays on complex mixtures to broaden the analyte scope.

Divalent Benzimidazolium-Based Axles for Self-Reporting Pseudorotaxanes.

Mono- and (bis)benzimidazoliums were evaluated both experimentally and computationally for their potential as pseudopolyrotaxane axle building blocks. Their aggregation and photophysical behavior, along with their potential to form a [2]pseudorotaxane with dibenzyl-24-crown-8, was studied through the synergistic application of 1D/2D and diffusion-ordered NMR spectroscopy, mass spectrometry, ultraviolet-visible and fluorescence spectroscopy, and time-dependent density functional theory. Their photophysical behavior was measured and modeled as a function of protonation state, solvent, and concentration.

Reply to Correspondence on "Synergy and Antagonism between Allosteric and Active-Site Inhibitors of Abl Tyrosine Kinase".

Manley and co-workers provide data demonstrating that, at super-pharmacological concentrations (300 μM), a ternary complex between Abl, asciminib, and ATP-competitive inhibitors is possible. The work in our manuscript concerns the interplay of asciminib (and GNF-2) with ATP-competitive inhibitors at pharmacologically relevant concentrations (C =1.6-3.

Investigations into mechanism and origin of regioselectivity in the metallaphotoredox-catalyzed α-arylation of -alkylbenzamides.

A mechanistic study on the α-arylation of -alkylbenzamides catalyzed by a dual nickel/photoredox system using aryl bromides is reported herein. This study elucidates the origins of site-selectivity of the transformation, which is controlled by the generation of a hydrogen atom transfer (HAT) agent by a photocatalyst and bromide ions in solution. Tetrabutylammonium bromide was identified as a crucial additive and source of a potent HAT agent, which led to increases in yields and a lowering of the stoichiometries of the aryl bromide coupling partner.

Formal Cycloadditions Driven by the Homolytic Opening of Strained, Saturated Ring Systems.

The field of strain-driven, radical formal cycloadditions is experiencing a surge in activity motivated by a renaissance in free radical chemistry and growing demand for sp -rich ring systems. The former has been driven in large part by the rise of photoredox catalysis, and the latter by adoption of the "Escape from Flatland" concept in medicinal chemistry. In the years since these broader trends emerged, dozens of formal cycloadditions, including catalytic, asymmetric variants, have been developed that operate via radical mechanisms.

Photochemical Strategies Enable the Synthesis of Tunable Azetidine-Based Energetic Materials.

Despite their favorable properties, azetidines are often overlooked as lead compounds across multiple industries. This is often attributed to the challenging synthesis of densely functionalized azetidines in an efficient manner. In this work, we report the scalable synthesis and characterization of seven azetidines with varying regio- and stereochemistry and their application as novel azetidine-based energetic materials, enabled by the visible-light-mediated Paternò-Büchi reaction.

Nucleophilic strategies to construct -CF- linkages using borazine-CFAr reagents.

Using a Lewis acid-quenched CFPh reagent, we show C-C bond formation through nucleophilic addition reactions to prepare molecules containing internal -CF- linkages. We demonstrate C(sp)-C(sp) coupling using both SAr reactions and Pd-catalysis. Finally, C(sp)-C(sp) bonds are forged using operationally simple S2 reactions that tolerate medicinally-relevant motifs.

Nickel-Catalyzed Defluorinative Coupling of Aliphatic Aldehydes with Trifluoromethyl Alkenes.

A simple procedure is reported for the nickel-catalyzed defluorinative alkylation of unactivated aliphatic aldehydes. The process involves the catalytic reductive union of trifluoromethyl alkenes with aldehydes using a nickel complex of a 6,6'-disubstituted bipyridine ligand with zinc metal as the terminal reductant. The protocol is distinguished by its broad substrate scope, mild conditions, and simple catalytic setup.

Capillary electrophoresis Western blot using inkjet transfer to membrane.

Traditional Western blots are commonly used to separate and assay proteins; however, they have limitations including a long, cumbersome process and large sample requirements. Here, we describe a system for Western blotting where capillary gel electrophoresis is used to separate sodium dodecyl sulfate-protein complexes. The capillary outlet is threaded into a piezoelectric inkjetting head that deposits the separated proteins in a quasi-continuous stream of <100 pL droplets onto a moving membrane.