Interfacial supramolecular biomimetic epoxidation catalysed by cyclic dipeptides

We synthesised a library of cis- and trans-cyclic dipeptides and evaluated their efficacy as catalysts in the asymmetric Weitz-Scheffer epoxidation of trans-chalcone. A thorough investigation relying on structure-activity studies and computational studies provided insights into the mechanism of the process. Our results revealed some structural features required for efficient conversion and for introduction of chirality into the product. The cyclic dipeptide acts as a catalyst by templating a supramolecular arrangement at the aqueous-organic interface required for efficient transformations to occur. Among all cyclic dipeptides investigated, cyclo(Leu-Leu) was the most efficient supramolecular catalyst.     

Synthesis and Biological Activity of a Cytostatic Inhibitor of MLLr Leukemia Targeting the DOT1L Protein

Histone methyltransferase DOT1L catalyzes mono-, di- and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect.     

Lewis acid properties of phosphenium and arsenium cations: Study of their adducts with pyridine

In the growing field of dicoordinated Group 15 cations, the quantitative study of the Lewis acid properties of phosphenium or arsenium cations has not yet been undertaken. Moreover, there are only a few described examples of syntheses of arsenium cations. The aim of this work is to enhance this series and to develop a quantitative comparative study of their complexation with Lewis bases such as pyridine. The observation of the ¹³C NMR C-4 variation in the pyridine ring is a good probe to obtain the apparent equilibrium constant K_c and thus a Lewis acidity scale. Phosphenium cations are more acidic than arsenium cations.     

The Exceptional Jordan Eigenvalue Problem

We discuss the eigenvalue problem for 3 ×3 octonionic Hermitian matrices which is relevant to theJordan formulation of quantum mechanics. In contrast tothe eigenvalue problems considered in our previous work, all eigenvalues are real and solve theusual characteristic equation. We give an elementaryconstruction of the corresponding eigenmatrices, and wefurther speculate on a possible application to particle physics.     

Photomodulable Materials. Synthesis and Properties of Photochromic 3H‐Naphtho[2,1‐b]pyrans Linked to Thiophene Units via an Acetylenic Junction

The synthesis of 3H‐naphtho[2,1‐b]pyrans linked to mono‐, di‐, or terthiophene via an acetylenic junction is described (Schemes 2 and 3). The synthetic approaches involve successive Sonogashira coupling reactions. The photochromic properties in solution of these novel materials were investigated under continuous irradiation.     

Aza-Michael silicone cure is accelerated by β-hydroxyalkyl esters

The aza-Michael reaction is proving to be a practical, catalyst free method by which a variety of polymers, including silicones, can be cured. However, its adoption may be compromised by slow cure rates; for many applications is it not practical to accelerate cure by heating. OH groups on the amine, acrylate partner or solvent are known to lead to accelerated rates of aza-Michael reactions. The impact of the location of OH groups on reaction partners is demonstrated using both small molecules and small molecules plus telechelic silicones. While all OH groups are shown to increase reaction rates, a special enhancement is provided by β-hydroxyalkyl acrylate esters, which have significantly higher rates of reaction than simple acrylates per se, and yet higher reactivities in hydroxylic media. Using this motif, in the absence of solvents, silicone elastomer cure based on the β-hydroxyalkyl acrylate motif is facile and complete in less than 30 min at room temperature.     

Enhancing Potency and Selectivity of a DC-SIGN Glycomimetic Ligand by Fragment-Based Design: Structural Basis

Chemical modification of pseudo-dimannoside ligands guided by fragment-based design allowed for the exploitation of an ammonium-binding region in the vicinity of the mannose-binding site of DC-SIGN, leading to the synthesis of a glycomimetic antagonist (compound 16 ) of unprecedented affinity and selectivity against the related lectin langerin. Here, the computational design of pseudo-dimannoside derivatives as DC-SIGN ligands, their synthesis, their evaluation as DC-SIGN selective antagonists, the biophysical characterization of the DC-SIGN/ 16 complex, and the structural basis for the ligand activity are presented. On the way to the characterization of this ligand, an unusual bridging interaction within the crystals shed light on the plasticity and potential secondary binding sites within the DC-SIGN carbohydrate recognition domain.