Alkylsquarates as key intermediates for the rapid preparation of original drug-inspired compounds

Many natural privileged scaffolds contain a basic nitrogen atom, which often is a key element of pharmacophore and a chemically reactive centre as well. In our ongoing research program devoted to the design of targeted libraries based on acidic templates, we developed methods to convert privileged basic compounds -like natural alkaloids or drugs into acidic compounds. This conversion led to a profound alteration of the pharmacophore, without changing the overall shape and lipophilicity of the molecule. We expect such modifications to generate unexpected biological activities. Recently, we focused on derivatives of squaric acid, a vinylogous carboxylic acid. Two series were studied. First we describe a new, selective parallel synthesis of squaramic acids from a dissymmetric diester (3-tert-butoxy-4-ethoxy-cyclobut-3-en-1,2-dione). This efficient procedure avoids the synthesis of the undesired squaramides. Secondly we describe a microplate parallel synthesis (15 micromol-scale) of squaric acid hydroxamate amides from a squaric hydroxamate ester.     

Ethane‐1,1,2‐trisphosphonic acid hemihydrate

Ethane‐1,1,2‐trisphosphonic acid crystallizes as a hemihydrate, C₂H₉O₉P₃·0.5H₂O, in which the water O atom lies on an inversion centre in the space group P2₁/c. The acid component, which contains a short but noncentred O—H...O hydrogen bond, adopts a gauche conformation. The acid components are linked by an extensive series of O—H...O hydrogen bonds to form layers, which are linked into pairs by the water molecules.     

Metal Ion Controlled Self-Assembly of a Chemically Reengineered Protein Drug Studied by Small-Angle X-ray Scattering

Precise control of the oligomeric state of proteins is of central importance for biological function and for the properties of biopharmaceutical drugs. Here, the self-assembly of 2,2'-bipyridine conjugated monomeric insulin analogues, induced through coordination to divalent metal ions, was studied. This protein drug system was designed to form non-native homo-oligomers through selective coordination of two divalent metal ions, Fe(II) and Zn(II), respectively. The insulin type chosen for this study is a variant designed for a reduced tendency toward native dimer formation at physiological concentrations. A small-angle X-ray scattering analysis of the bipyridine-modified insulin system confirmed an organization into a novel well-ordered structure based on insulin trimers, as induced by the addition of Fe(II). In contrast, unmodified monomeric insulin formed larger and more randomly structured assemblies upon addition of Fe(II). The addition of Zn(II), on the other hand, led to the formation of small quantities of insulin hexamers for both the bipyridine-modified and the unmodified monomeric insulin. Interestingly, the location of the bipyridine-modification significantly affects the tendency to hexamer formation as compared to the unmodified insulin. Our study shows how combining a structural study and chemical design can be used to obtain molecular understanding and control of the self-assembly of a protein drug. This knowledge may eventually be employed to develop an optimized in vivo drug release profile.     

Plasma-based processes for surface wettability modification

In this article, we describe a method to create rough features on silicon surfaces by reactive etching of a photoresist layer. The roughness and, consequently, the wettability of the surfaces can be modified by modifying the duration of plasma etching. Hydrophobic materials deposited on the rough silicon surface can be modified until a superhydrophobic behavior is obtained, whereas hydrophilic materials become more hydrophilic. The elaboration technique described herein offers an inexpensive and rapid method for the creation of tunable roughness on silicon surfaces with large areas.     

Organophosphorus insecticides extraction and heterogeneous oxidation on column for analysis with an acetylcholinesterase (AChE) biosensor

This paper presents an analysis method for organophosphorus insecticides based on AChE biosensors coupled with a preconcentration and oxidation on a solid phase column. Three organic solvents, acetonitrile (ACN), ethanol and methanol were tested for their influence on AChE activity, insecticide inhibition and their ability to elute the adsorbed insecticides. Our results showed that ACN in a concentration of 5% (v/v) had the less negative effect on biosensor analysis and was the most appropriate organic solvent for the column elution. The presence of the organic solvent in the incubation media of the biosensor was found to induce a reduction of the inhibition percentages. The inhibition of the biosensors was performed in phosphate buffer with 5% (v/v) ACN, while the initial and remaining response of the biosensors were measured in PBS. In these conditions, the LODs of paraoxon and dichlorvos were measured with or without a preconcentration step. The LODs of the AChE biosensor without sample preconcentration were 8 × 10⁻⁸ M for paraoxon and 1 × 10⁻⁷ M dichlorvos and the LOD obtained after the preconcentration step were 2.5 × 10⁻⁸ M for paraoxon and 2.5 × 10⁻⁸ M for dichlorvos. Moreover, the use of the column allowed the heterogeneous oxidation of organophosphorus insecticides for improved LOD.     

Insertion of Amides into a Polyoxometalate

POM alert : The incorporation of an amide oxygen atom into the framework of the Dawson‐type polyoxometalate (POM) cluster [P₂V₃W₁₅O₆₂]^9? (see picture) allows the communication of electronic effects between the organic and the inorganic parts of the molecule, including fine‐tuning of the redox properties of the entire hybrid POM by the organic components, and transmission of the POM's electron‐attracting properties to the organic moiety.

     

Universal fluctuations in correlated systems

The probability density function (PDF) of a global measure in a large class of highly correlated systems has been suggested to be of the same functional form. Here, we identify the analytical form of the PDF of one such measure, the order parameter in the low temperature phase of the 2D XY model. We demonstrate that this function describes the fluctuations of global quantities in other correlated equilibrium and nonequilibrium systems. These include a coupled rotor model, Ising and percolation models, models of forest fires, sandpiles, avalanches, and granular media in a self-organized critical state. We discuss the relationship with both Gaussian and extremal statistics.