Ozonolyse d'olefines perfluorees

We have obtained unusually stable secondaxy ozonides ($\text{2a-c}$) by heating neat perfluoroalkenes ($\text{1a-c}$) with ozone.     

Metallomesogens: Metal Complexes in Organized Fluid Phases

Metallomesogens, metal complexes of organic ligands which exhibit liquid crystalline (mesomorphic) character, combine the variety and range of metal-based coordination chemistry with the extraordinary physical properties exhibited by liquid crystals. Thermotropic metallomesogens have been made incorporating many metals, including representatives of s-, p-, d-and even f-block elements. Both rodlike (calamitic) and disklike (discotic) thermotropic metallomesogens are known, and examples of all the main mesophase types are found. Many different varieties of ligand can be used: monodentate (4-substituted pyridines), bidentate (β-diketonates, dithiolenes, carboxylates, cyclometalated aromatic amines), or polydentate (phthalocyanines, porphyrins). As with organic mesogens, molecular shape and intermolecular forces play an important role, i.e. the ligands are important in determining mesophase character. The chief requirement for a metallomesogen is a rigid core, usually unsaturated and either rod- or disklike in shape, bearing several long hydrocarbon tails. The metal atom is usually at or near the center of gravity of the molecule. In some cases the ligands are themselves mesogenic, but this is not a requirement. The presence of one or more metals opens many exciting possibilities: new shapes, not easily generated by organic compounds, and hence new properties are then accessible. The incorporation of d-block metals brings with it features such as color and paramagnetism. Profound effects arise from the large and polarizable concentration of electron density that every metal atom possesses, since the molecular polarizability is a key factor in determining whether a molecule will form liquid crystals. Enhanced physical properties (e.g. high birefringencies), as well as new and unexpected ones, will result. A major requirement for metallomesogens to find applications in new device technology is that the metal–ligand bonds are strong and inert and the complexes stable; this can be accomplished with, for example, chelating ligands and the 5d metals.     

A Quantitative Spectrometric Assay for the Determination of Solution Concentration of para-sulphonato-calix[n]arenes and Their Derivatives

A spectrometric assay for the determination of concentration of para-sulphonato-calix[n]arenes and their derivatives has been developed using dimethylmethylene blue (DMMB) as a probe. Interaction with para-sulphonato-calix[n]arenes leads to a metachromatic shift in the spectrum of DMMB with appearance of a peak at 536 nm and diminution of the spectral intensity of the peaks at 594 and 649 nm. The method shows good linearity in the concentration range 0–6 μg/ml for para-sulphonato-calix[n]arenes. in final form: 27 December 2004     

Nouveaux trioxophosphetanes generateurs d'oxygene singulet a basse temperature

We have prepared phosphite ozonides $\text{1b}$–$\text{3b}$ which are efficient and clean singlet oxygene generators at low temperature.     

Synthèse et caractérisation d'une série de bis-9,9′(thio-9-acridinyl)-α,ω-alcanes

Some new bis-acridine derivatives have been prepared under phase transfer catalysis conditions. These are α,ω-bis-(9-thioacridinyl)alkanes with or without heteroatoms such as N or O, included into the bridge. In the latter case, general procedure has to be slightly modified due to a side-reaction leading to thiobenzyl derivatives, which increases in the conditions proposed in the first place. The compounds so prepared were characterized by their melting points, ¹H and ¹³C nmr data. Preliminary results referring to activity against P-388 lymphocitic leukemia are presented.     

Prodrugs of HIV protease inhibitors-saquinavir, indinavir and nelfinavir-derived from diglycerides or amino acids: synthesis, stability and anti-HIV activity

With the aim of improving the pharmacological properties of current protease inhibitors (PIs), the synthesis of various acyl and carbamate amino acid- or diglyceride-containing prodrugs derived from saquinavir, indinavir and nelfinavir, their in vitro stability with respect to hydrolysis and their anti-HIV activity in CEM-SS and MT4 cells have been investigated. l-Leucine (Leu) and l-phenylalanine (Phe) were connected through their carboxyl to the PIs while l-tyrosine (Tyr) was conjugated through its aromatic hydroxyl via various spacer units. Hydrolysis of the prodrug with liberation of the active free drug was crucial for antiviral activity. The Leu- and Phe-PI prodrugs released the active free drug very rapidly (half-lives of hydrolysis in buffer at 37 degree C of 3-4 h). The Tyr-PI conjugates with a -C(O)(CH(2))(4)- linker exhibited half-lives in the 40-70 h range and antiviral activities in the 21-325 nM range (from 2 to 22 nM for the free PIs). The chemically very stable carbamate "peptidomimetic" Tyr-PI prodrugs (no hydrolysis detected after 7 days in buffer) displayed a very low anti-HIV activity or were even inactive (EC(50) from 2300 nM to >10 microM). A very low antiviral activity was measured for the diglyceride-substituted saquinavir and for all of the disubstituted indinavir and nelfinavir prodrugs. All these prodrugs probably released the active parent PI too slowly under the antiviral assay conditions. These results combined with those from transepithelial transport studies (Rouquayrol et al., Pharm. Res., 2002, 19, 1704-1712) indicate that conjugation of amino acids (through their carboxyl) to the PIs constitutes a most appealing alternative which could improve the intestinal absorption of the PIs and reduce their recognition by efflux carriers.     

Theoretical analysis of the influence of the adosorption process on the voltammetric curves in the case of a second order adsorption step followed by a first order charge transfer reaction: Part II. Comparison between linear potential sweep voltammetry and steady state cyclic voltammetry

The voltammetric curves for a 2-step sequential reaction involving a 2nd order adsorption process (such as the catalytic mechanism met in the anodic oxidation of hydrogen) are investigated theoretically by computer calculations. Steady state cyclic voltammetry (s.s.c.v.) is particularly treated by repeating forward and backward sweeps as many times as necessary to reach the steady state. For both l.p.s.v. and s.s.c.v., the usual characteristic features are considered, i.e. E_M, θ_M, i_M as a function of sweep rate υ, especially in the range of υ, where the computed data fit the results derived from analytical solution (quasi-reversible charge transfer, and irreversible charge transfer). In s.s.c.v., indications are given to obtain the kinetic parameters (k₁, k₂, α) from experimental plots.     

Ab initio calculations on blocked Pro-Ala dipeptides

The effect of the chirality of the amino acid at position i + 2 on a β-turn was investigated by a grid scan ab initio calculation on the Ac- -Pro- -Ala-NH₂ and Ac- -Pro- -Ala-NH₂ blocked dipeptides. Th6-31G basis set was used to estimate the effect of the alanyl side chain on the conformation of the peptide backbone in a blocked dipeptide as a simple, but complete model for a reverse turn. This study provides a quantum mechanical evaluation of the ability of the NH at the i + 3 residue to form the H-bond that closes the 10 membered ring which stabilizes the turn. The lowest energy of all 64 probed conformations of the -Ala containing peptide corresponded to a good type II β-turn with a hydrogen bond distance between the acetyl oxygen and the amide terminal hydrogen of 2.21 Å. A comparison with the nonblocked dipeptide ab initio study indicates that the presence of the end blocks enhances the propensity of the -Ala-containing dipeptide for a type II β-turn, but does not seem to enhance the propensity of the -Ala-containing dipeptide for a type I β-turn. The energies and geometric parameters for the lowest four optimized conformations identified by the grid scan search for each molecule have been calculated.     

An efficient synthesis of dienic nucleoside analogues via a Mitsunobu reaction

Nucleoside analogues 9 and 12 were obtained in good yields from alcohol 7 which, under Mitsunobu conditions, led to the title products after deprotection steps.