Fluorescent Probes from Aromatic Polycyclic Nitrile Oxides: Isoxazoles versus Dihydro-1λ3,3,2λ4-Oxazaborinines

Anthracenenitrile oxide undergoes 1,3-dipolar cycloaddition reaction with propargyl bromide affording the expected isoxazole as single regioisomer, suitably synthetically elaborated and functionalized with a protected triple bond. The introduction of a bromine atom at the position C10 of the anthracene moiety allows for inserting a variety of aromatic and heterocyclic substituents through Suzuki coupling. A two-way synthetic route can lead to simple isoxazole derivatives or, after N−O bond reductive cleavage and BF₃ complexation, enamino ketone boron complexes. The photophysical properties of both the substituted isoxazoles and the corresponding boron complexes were investigated to show the potentialities for the employment as fluorescent tags in imaging techniques. The quite good quantum yield values confirm the suitability of these compounds in the cellular environment. Scope and limitations of the methodology are discussed.     

Low-Barrier Hydrogen Bonds in Negative Thermal Expansion Material H3[Co(CN)6]

The covalent nature of the low-barrier N−H−N hydrogen bonds in the negative thermal expansion material H₃[Co(CN)₆] has been established by using a combination of X-ray and neutron diffraction electron density analysis and theoretical calculations. This finding explains why negative thermal expansion can occur in a material not commonly considered to be built from rigid linkers. The pertinent hydrogen atom is located symmetrically between two nitrogen atoms in a double-well potential with hydrogen above the barrier for proton transfer, thus forming a low-barrier hydrogen bond. Hydrogen is covalently bonded to the two nitrogen atoms, which is the first experimentally confirmed covalent hydrogen bond in a network structure. Source function calculations established that the present N−H−N hydrogen bond follows the trends observed for negatively charge-assisted hydrogen bonds and low-barrier hydrogen bonds previously established for O−H−O hydrogen bonds. The bonding between the cobalt and cyanide ligands was found to be a typical donor–acceptor bond involving a high-field ligand and a transition metal in a low-spin configuration.     

Combining self- and cross-docking as benchmark tools: the performance of DockBench in the D3R Grand Challenge 2

Molecular docking is a powerful tool in the field of computer-aided molecular design. In particular, it is the technique of choice for the prediction of a ligand pose within its target binding site. A multitude of docking methods is available nowadays, whose performance may vary depending on the data set. Therefore, some non-trivial choices should be made before starting a docking simulation. In the same framework, the selection of the target structure to use could be challenging, since the number of available experimental structures is increasing. Both issues have been explored within this work. The pose prediction of a pool of 36 compounds provided by D3R Grand Challenge 2 organizers was preceded by a pipeline to choose the best protein/docking-method couple for each blind ligand. An integrated benchmark approach including ligand shape comparison and cross-docking evaluations was implemented inside our DockBench software. The results are encouraging and show that bringing attention to the choice of the docking simulation fundamental components improves the results of the binding mode predictions.     

Toward sustainable and effective HER electrocatalysts: Strategies for the basal plane site activation of transition metal dichalcogenides

Due to their low cost and overall sustainability, transition metal dichalcogenides (TMDCs) are potential alternatives to noble metals as catalysts to produce green hydrogen. A promising route to improve their performances consists of activating their basal plane, both increasing the number of active sites or their specific activity. This can be accomplished by exploiting point defects, in-plane boundaries and strain. In particular, single atom adsorbed or incorporated into TMDCs have shown remarkable results in electrochemical half-cell tests. Topological curvature or grain boundaries (and related defects) can also be used to further boost the performances. A crucial point for the application of such strategies is related to the development of cost effective and sustainable methods for the scale-up of synthetic protocols.     

Modification of propylene-ethylene copolymers by reactive extrusion

The rheological properties of commercial propylene-ethylene copolymers were modified by reactive extrusion. A dialkyl peroxide was used as initiator of the controlled degradation reaction of the starting polymers. The experiments were carried out in a twin screw extruder at different peroxide concentrations, temperatures, and screw speeds. Gel permeation chromatography was used to estimate the molecular weight distribution of the original and modified copolymers. It has been observed that the estimated molecular weight of the copolymers tends to decrease with the increase in peroxide concentration at all extrusion conditions studied. The linear viscoelastic properties of all the polymers were evaluated at different temperatures and frequencies in a rotational rheometer. Both the viscous and the elastic properties decrease with augmenting peroxide concentration. The Theological behavior of the materials is strongly affected by the global ethylene content of the copolymers. The scanning electron microscopy study did not reveal a significant difference between the morphology of the unmodified and the modified blends for a given composition of the original copolymers. In all the cases the microstructure is composed of a finely dispersed phase of ethylene-propylene copolymer within a continuous polypropylene phase.     

Glycomimetics Targeting Glycosyltransferases: Synthetic,Computational and Structural Studies of Less‐Polar Conjugates

The Leloir donors are nucleotide sugars essential for a variety of glycosyltransferases (GTs) involved in the transfer of a carbohydrate to an acceptor substrate, typically a protein or an oligosaccharide. A series of less‐polar nucleotide sugar analogues derived from uridine have been prepared by replacing one phosphate unit with an alkyl chain. The methodology is based on the radical hydrophosphonylation of alkenes, which allows coupling of allyl glycosyl compounds with a phosphate unit suitable for conjugation to uridine. Two of these compounds, the GalNAc and galactose derivatives, were further tested on a model GT, such as GalNAc‐T2 (an important GT widely distributed in human tissues), to probe that both compounds bound in the medium–high micromolar range. The crystal structure of GalNAc‐T2 with the galactose derivative traps the enzyme in an inactive form; this suggests that compounds only containing the β‐phosphate could be efficient ligands for the enzyme. Computational studies with GalNAc‐T2 corroborate these findings and provide further insights into the mechanism of the catalytic cycle of this family of enzymes.     

Thiol‐ene and thiol‐yne‐based synthesis of glycodendrimers as nanomolar inhibitors of wheat germ agglutinin

Alkene and alkyne functional polyester‐based dendrimers of generation 1 to 4 have been prepared and reacted under free‐radical conditions with 2‐acetamido‐2‐deoxy‐1‐thio‐β‐D ‐glucose (GlcNAc‐SH). As the alkene‐dendrimers underwent the addition of one thiyl radical per ene group whereas each yne group of alkyne‐dendrimers was saturated by two thiyl radicals, a collection of glycodendrimers with glycan density ranging from six to ninety‐six GlcNAc per dendrimer was obtained. The recognition properties of the prepared glycodendrimers toward the wheat germ agglutinin (WGA) were evaluated by enzyme‐linked lectin assay (ELLA). The eight glycodendrimers were excellent ligands showing IC₅₀ values in the nanomolar range and relative potencies per sugar unit up to 2.27 e⁶ when compared to monosaccharidic GlcNAc used as monovalent reference. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2422–2433     

Activation of Carboxylic Acids in Asymmetric Organocatalysis

Organocatalysis, catalysis using small organic molecules, has recently evolved into a general approach for asymmetric synthesis, complementing both metal catalysis and biocatalysis. 1 Its success relies to a large extent upon the introduction of novel and generic activation modes. 2 Remarkably though, while carboxylic acids have been used as catalyst directing groups in supramolecular transition‐metal catalysis, 3 a general and well‐defined activation mode for this useful and abundant substance class is still lacking. Herein we propose the heterodimeric association of carboxylic acids with chiral phosphoric acid catalysts as a new activation principle for organocatalysis. This self‐assembly increases both the acidity of the phosphoric acid catalyst and the reactivity of the carboxylic acid. To illustrate this principle, we apply our concept in a general and highly enantioselective catalytic aziridine‐opening reaction with carboxylic acids as nucleophiles.     

Organocatalytic Asymmetric Hydrolysis of Epoxides

The hydrolytic ring opening of epoxides is an important biosynthetic transformation and is also applied industrially. We report the first organocatalytic variant of this reaction, exploiting our recently discovered activation of carboxylic acids with chiral phosphoric acids via heterodimerization. The methodology mimics the enzymatic mechanism, which involves an enzyme‐bound carboxylate nucleophile. A newly designed phosphoric acid catalyst displays high stereocontrol in the desymmetrization of meso‐epoxides. The methodology shows wide generality with cyclic, acylic, aromatic, and aliphatic substrates. We also apply our method in the first highly enantioselective anti‐dihydroxylation of simple olefins.     

Single‐Molecule Magnetism,Enhanced Magnetocaloric Effect,and Toroidal Magnetic Moments in a Family of Ln4 Squares

Three cationic [Ln₄] squares (Ln=lanthanide) were isolated as single crystals and their structures solved as [Dy₄(μ₄‐OH)(HL)(H₂L)₃(H₂O)₄]Cl₂?(CH₃OH)₄?(H₂O)₈ ( 1 ), [Tb₄(μ₄‐OH)(HL)(H₂L)₃(MeOH)₄]Cl₂?(CH₃OH)₄?(H₂O)₄ ( 2 ) and [Gd₄(μ₄‐OH)(HL)(H₂L)₃(H₂O)₂(MeOH)₂]Br₂?(CH₃OH)₄?(H₂O)₃ ( 3 ). The structures are described as hydroxo‐centered squares of lanthanide ions, with each edge of the square bridged by a doubly deprotonated H₂L^2? ligand. Alternating current magnetic susceptibility measurements show frequency‐dependent out‐of‐phase signals with two different thermally assisted relaxation processes for 1 , whereas no maxima in χ_M“ appears above 2.0 K for complex 2 . For 1 , the estimated effective energy barrier for these two relaxation processes is 29 and 100 K. Detailed ab initio studies reveal that complex 1 possesses a toroidal magnetic moment. The ab initio calculated anisotropies of the metal ions in complex 1 were employed to simulate the magnetic susceptibility by using the Lines model (POLY_ANISO) and this procedure yields J₁=+0.01 and J₂=?0.01 cm^?1 for 1 as the two distinct exchange interactions between the Dy^III ions. Similar parameters are also obtained for complex 1 (and 2 ) from specific heat measurements. A very weak antiferromagnetic super‐exchange interaction (J₁=?0.043 cm^?1 and g=1.99) is observed between the metal centers in 3 . The magnetocaloric effect (MCE) was estimated by using field‐dependent magnetization and temperature‐dependent heat‐capacity measurements. An excellent agreement is found for the ?ΔS_m values extracted from these two measurements for all three complexes. As expected, 3 shows the largest ?ΔS_m variation (23 J Kg^?1 K^?1) among the three complexes. The negligible magnetic anisotropy of Gd indeed ensures near degeneracy in the (2S+1) ground state microstates, and the weak super‐exchange interaction facilitates dense population of low‐lying excited states, all of which are likely to contribute to the MCE, making complex 3 an attractive candidate for cryogenic refrigeration.