Silver(I)‐Catalyzed Hydroazidation of Ethynyl Carbinols: Synthesis of 2‐Azidoallyl Alcohols

The hydroazidation of alkynes is the most straightforward pathway to synthetically useful vinyl azides. However, a general hydroazidation of alkynes remains elusive. Herein, a chemo‐ and regioselective transformation of ethynyl carbinols into vinyl azides is described. This reaction produces a wide variety of 2‐azidoallyl alcohols with high efficiency and in good to excellent yields. These compounds constitute a new class of densely functionalized synthetic intermediates. Their synthetic potential has been demonstrated by further transformations into NH aziridines. The mechanistic aspects of the reaction will attract the attention of chemists working on alkyne chemistry and silver catalysis. The findings that are described in this paper represent significant advances in the regioselective hydroelementation of alkynes and open a new reaction manifold for exploitation.     

Interaction with the Surrounding Water Plays a Key Role in Determining the Aggregation Propensity of Proteins

Understanding the molecular determinants of the relative propensities of proteins to aggregate in a cellular environment is a central issue for treating protein‐aggregation diseases and developing peptide‐based therapeutics. Despite the expectation that protein aggregation can largely be attributed to direct protein–protein interactions, a crucial role the surrounding water in determining the aggregation propensity of proteins both in vitro and in vivo was identified. The overall protein hydrophobicity, defined solely by the hydration free energy of a protein in its monomeric state sampling its equilibrium structures, was shown to be the predominant determinant of protein aggregation propensity in aqueous solution. Striking discrimination of positively and negatively charged residues by the surrounding water was also found. This effect depends on the protein net charge and plays a crucial role in regulating the solubility of the protein. These results pave the way for the design of aggregation‐resistant proteins as biotherapeutics.     

Hexafluoroantimonic Acid Catalysis: Formal [3+2+2] Cycloaddition of Aziridines with Two Alkynes

A practical method for the synthesis of azepine derivatives, a typical seven‐membered heterocyclic ring system, was developed and involves the use of hexafluoroantimonic acid to catalyze a formal [3+2+2] cycloaddition of aziridines with two alkynes. This method was applicable to two of the same or different terminal alkynes for the [3+2+2] cycloaddition with unactivated aziridines, and furnished the corresponding azepine derivatives in good yields with good levels of chemo‐ and regioselectivity. The mechanism was also discussed according to the results of the in situ HRMS and ¹H NMR analysis.     

Self‐Assembly of Pyridinium‐Functionalized Anthracenes: Molecular‐Skeleton‐Directed Formation of Microsheets and Microtubes

Two amphiphilic regioisomers, 9‐AP (1‐[11‐(9‐anthracenylmethoxy)‐11‐oxoundecyl]pyridinium bromide), and 2‐AP (1‐[11‐(2‐anthracenyl methoxy)‐11‐oxoundecyl]pyridinium bromide), were synthesized and their assembly behaviors were studied. Due to the anisotropic features of the anthracene structure, different substituted positions on the anthracene ring lead 9‐AP and 2‐AP to adapt “shaver” and “spatula”‐like molecular shapes, respectively, which consequently dictate the structure of their final assemblies. While “shaver”‐shaped 9‐AP assembled into microsheets, driven by π–π interactions, “spatula”‐shaped 2‐AP assembled into microtubular structures, promoted primarily by charge‐transfer interactions.     

Sponge Phase Producing Porous CeO2 for Catalytic Oxidation of CO

The aggregation behavior of mixtures of the alkaline amino acid L ‐Arginine (L ‐Arg) and bis(2‐ethylhexyl)phosphoric acid (DEHPA) in water was studied in detail. At a fixed L ‐Arg concentration, a phase sequence of micellar phase (L₁ phase), vesicle phase (L_αv phase), planar lamellar phase (L_αl phase), and sponge phase (L₃ phase) was obtained with increasing DEHPA concentration due to changes in the packing parameter. The phase transition of the lamellar structures was determined by freeze‐fracture TEM and ²H NMR spectroscopy. Rheological measurements reflected the phase transition through significant variations of both the elastic modulus and the viscous modulus. Porous CeO₂ materials were produced by utilizing the L₃ phase as template, and the porous CeO₂ exhibited excellent catalytic oxidation activity toward CO due to its high surface area, which provides more active sites for CO conversion.     

Rhodium(III)‐Catalyzed N‐Nitroso‐Directed CH Addition to Ethyl 2‐Oxoacetate for Cycloaddition/Fragmentation Synthesis of Indazoles

Rh^III‐catalyzed N‐nitroso‐directed C?H addition to ethyl 2‐oxoacetate allows subsequent construction of indazoles, a privileged heterocycle scaffold in synthetic chemistry, through the exploitation of reactivity between the directing group and installed group. The formal [2+2] cycloaddition/fragmentation reaction pathway identified herein, a unique reactivity pattern hitherto elusive for the N‐nitroso group, emphasizes the importance of forward reactivity analysis in the development of useful C?H functionalization‐based synthetic tools. The synthetic utility of the protocol is demonstrated with the synthesis of a tricyclic‐fused ring system. The diversity of covalent linkages available for the nitroso group should enable the extension of the genre of reactivity reported herein to the synthesis of other types of heterocycles.     

Magnetically Encoded Luminescent Composite Nanoparticles through Layer‐by‐Layer Self‐Assembly

Sensitive and rapid detection of multiple analytes and the collection of components from complex samples are important in fields ranging from bioassays/chemical assays, clinical diagnosis, to environmental monitoring. A convenient strategy for creating magnetically encoded luminescent CdTe@SiO₂@n Fe₃O₄ composite nanoparticles, by using a layer‐by‐layer self‐assembly approach based on electrostatic interactions, is described. Silica‐coated CdTe quantum dots (CdTe@SiO₂) serve as core templates for the deposition of alternating layers of Fe₃O₄ magnetic nanoparticles and poly(dimethyldiallyl ammonium chloride), to construct CdTe@SiO₂@n Fe₃O₄ (n=1, 2, 3, …?) composite nanoparticles with a defined number (n) of Fe₃O₄ layers. Composite nanoparticles were characterized by zeta‐potential analysis, fluorescence spectroscopy, vibrating sample magnetometry, and transmission electron microscopy, which showed that the CdTe@SiO₂@n Fe₃O₄ composite nanoparticles exhibited excellent luminescence properties coupled with well‐defined magnetic responses. To demonstrate the utility of these magnetically encoded nanoparticles for near‐simultaneous detection and separation of multiple components from complex samples, three different fluorescently labeled IgG proteins, as model targets, were identified and collected from a mixture by using the CdTe@SiO₂@n Fe₃O₄ nanoparticles.     

Design of Enzymatically Cleavable Prodrugs of a Potent Platinum‐Containing Anticancer Agent

Using a versatile synthetic approach, a new class of potential ester prodrugs of highly potent, but systemically too toxic, platinum–acridine anticancer agents was generated. The new hybrids contain a hydroxyl group, which has been masked with a cleavable lipophilic acyl moiety. Both butanoic (butyric) and bulkier 2‐propanepentanoic (valproic) esters were introduced. The goals of this design were to improve the drug‐like properties (e.g., logD) and to reduce the systemic toxicity of the pharmacophore. Two distinct pathways by which the target compounds undergo effective ester hydrolysis, the proposed activating step, have been confirmed: platinum‐assisted, self‐immolative ester cleavage in a low‐chloride environment (LC‐ESMS, NMR spectroscopy) and enzymatic cleavage by human carboxylesterase‐2 (hCES‐2) (LC‐ESMS). The valproic acid ester derivatives are the first example of a metal‐containing agent cleavable by the prodrug‐converting enzyme. They show excellent chemical stability and reduced systemic toxicity. Preliminary results from screening in lung adenocarcinoma cell lines (A549, NCI‐H1435) suggest that the mechanism of the valproic esters may involve intracellular deesterification.     

Study on the interaction between urea and cellulose by combining solid-state 13C CP/MAS NMR and extended Hückel charges

In this article, solid-state ¹³C CP/MAS NMR combined with extended Hückel charges was applied to investigate the interaction between urea and cellulose in the NaOH/urea aqueous solvent system. Direct experimental evidence was provided to support the interaction between urea and cellulose. The solid-state ¹³C CP/MAS NMR results revealed that complicated complexes are formed by urea, NaOH and cellulose in the solution. Excess urea exists in a free state, which explains why 7 wt% NaOH/12 wt% urea/81 wt% H₂O is the optimal ratio selection to dissolve cellulose. Based on the correlation in which the computed extended Hückel charge on carbon of urea is approximately inversely proportional to its ¹³C chemical shift, a possible interaction model of cellulose, NaOH and urea was proposed. Interactions exist between any two of urea, NaOH and cellulose, which results in the cellulose chain being surrounded by NaOH and urea molecules. NaOH and urea may be in the same surface layer of cellulose chains.