Enantiomeric Cyclic Peptides with Different Caco‐2 Permeability Suggest Carrier‐Mediated Transport

Recently, oral absorption of cyclic hexapeptides was improved by N‐methylation of their backbone amides. However, the number and position of N‐methylations or of solvent exposed NHs did not correlate to intestinal permeability, measured in a Caco‐2 model. In this study, we investigate enantiomeric pairs of three polar and two lipophilic peptides to demonstrate the participation of carrier‐mediated transporters. As expected, all the enantiomeric peptides exhibited identical lipophilicity (logD_7.4) and passive transcellular permeability determined by the parallel artificial membrane permeability assay (PAMPA). However, the enantiomeric polar peptides exhibited different Caco‐2 permeability (P_app) in both directions a–b and b–a. The same trend was observed for one of the lipophilic peptide, whereas the second lipophilic enantiomer pair showed identical Caco‐2 permeability (within the errors). These findings provide the first evidence for the involvement of carrier‐mediated transport for peptides, especially for those of polar nature.     

Highly Phosphorescent Crystals of Square‐Planar Platinum Complexes with Chiral Organometallic Linkers: Homochiral versus Heterochiral Arrangements,Induced Circular Dichroism,and TD‐DFT Calculations

A novel class of chiral luminescent square‐planar platinum complexes with a π‐bonded chiral thioquinonoid ligand is described. Remarkably the presence of this chiral organometallic ligand controls the aggregation of this square planar luminophor and imposes a homo‐ or hetero‐chiral arrangement at the supramolecular level, displaying non‐covalent Pt–Pt and π–π interactions. Interestingly these complexes are highly luminescent in the crystalline state and their photophysical properties can be traced to their aggregation in the solid state. A TD‐DFT calculation is obtained to rationalize this unique behavior.     

Synthesis by Emulsion Polymerization of Poly(butyl acrylate-co-silver acrylate) Ionomers and Evaluation of their Possible Applications

The synthesis by emulsion polymerization and the characterization by a battery of techniques of poly(butyl acrylate-co-silver acrylate) [poly(BuAc-co-AgAc)] ionomers are reported here. Reaction rates were fast and conversions around 90% were obtained in less than one hour, regardless of the initial ratio of butyl acrylate and silver acrylate employed (BuAc/AgAc = 90/10, 80/20, 70/30). Particle size was in the range of 176 to 200 nm, depending on the BuAc/AgAc ratio. Ionomers’ formation was corroborated by infrared spectroscopy and inferred by differential scanning calorimetry (DSC). DSC disclosed that the poly(BuAc-co-AgAc) has two glass transition temperatures: one at ca. ?49°C due to relaxation of the ionomer backbone domains rich in BuAc and another ca. 35°C due to the relaxation of the backbone domains where the AgAc-units content was higher. Young moduli increased as the copolymers became richer in AgAc. Antibacterial tests against Escherichia coli with the 90/10 (BuAc/AgAc) ionomer revealed that the bacteria population diminishes from 5 log CFU/mL to less than 0.3 MPN/mL after one hour of contact with the ionomers. Also, we demonstrated that the ionomers are excellent compatibilizers for making semiconductive films of n-dodecylbenzene sulfonic acid-doped polyaniline (PANIDBSA)-poly(BuAc-co-AgAc) and poly(n-butyl methacrylate) (PBMA) blends. The electrical conductivity of the blend films, which were homogeneous, rose as the AgAc content in the films increased.     

Synthesis,properties and photopolymerization of liquid crystalline dioxetanes

The synthesis and photopolymerization of various liquid crystalline dioxetanes is described. The effects of the spacer length, structure of the mesogenic group and oxetane group on the liquid crystalline properties, polymerization behaviour and optical properties (birefringence) of the oriented and crosslinked network formed in photo-polymerization are discussed. Thermally stable films with birefringence values up to 0.13 can be formed from these materials. The dioxetanes show significantly lower polymerization shrinkage than do structurally related diacrylates.     

Synthesis of polypyrrole nanoparticles by batch and semicontinuous heterophase polymerizations

Nanoparticles of semiconducting polypyrrole (PPy) were synthesized by batch heterophase (BHP) and semicontinuous heterophase polymerization (SHP) using ferric chloride (FeCl₃), potassium persulfate (KPS), or ammonium persulfate (APS) as the oxidizing agent, sodium dodecyl sulfate (SDS) as surfactant, and ethanol (EtOH) or iso-pentyl alcohol (iC₅OH) as co-surfactants. In all cases, the molar ratios of monomer/oxidizing agent were 1/1. Pyrrol polymerization by BHP and SHP allowed using much lower percentages of surfactant than those employed in microemulsion polymerization of this monomer. The effects of temperature, oxidizing agent, and co-surfactant on conductivity were studied. The polymers were analyzed by transmission electron microscopy (TEM), UV/Visible and Fourier transform infrared (FTIR) spectroscopies, and cyclic voltammetry. Higher PPy conductivities were obtained by polymerizing at 0 °C with FeCl₃ as the oxidizing agent, in the presence of iC₅OH as co-surfactant. When the reaction was carried out by SHP with low reaction times, smaller particles with similar conductivities were obtained compared to those obtained by BHP; the conductivity of PPy decreases with increasing polymerization time, which can be explained by PPy overoxidation.     

Efficient three-step sequence for the deamination of α-aminoesters. Application to the synthesis of CysLT1 antagonists

A practical and efficient three-step sequence for the deamination of α-aminoesters is reported. This method is based on the NaBH₄-mediated selective reduction of α-diazoesters to α-hydrazonoesters and has been successfully applied to the deamination of several representative α-aminoesters including some l-cysteine ethyl ester derivatives, key intermediates in the synthesis of a series of CysLT1 antagonists.     

Simulation of non-Gaussian multivariate stationary processes

Mathematical justifications are given for a simulation technique of multivariate non-Gaussian random processes and fields based on Rosenblatt's transformation of Gaussian processes. Different types of convergences are given for the approaching sequence. Moreover an original numerical method is proposed in order to solve the functional equation yielding the underlying Gaussian process autocorrelation function.