Palladium-catalyzed Negishi α-arylation of alkylsulfones

A general, mild catalytic system for α-monoarylation of various alkyl sulfones is described that utilizes palladium-catalyzed Negishi cross-coupling approach.     

Hypervalent Silicon Compounds by Coordination of Diphosphine–Silanes to Gold

Coordination of ambiphilic diphosphine–silane ligands [o‐(iPr₂P)C₆H₄]₂Si(R)F (R=F, Ph, Me) to AuCl affords pentacoordinate neutral silicon compounds in which the metal atom acts as a Lewis base. X‐ray diffraction analyses, NMR spectroscopy, and DFT calculations substantiate the presence of Au→Si interactions in these complexes, which result in trigonal‐bipyramidal geometries around silicon. The presence of a single electron‐withdrawing fluorine atom is sufficient to observe coordination of the silane as a σ‐acceptor ligand, provided it is positioned trans to gold. The nature of the second substituent at silicon (R=F, Ph, Me) has very little influence on the magnitude of the Au→Si interaction, in marked contrast to N→Si adducts. According to variable‐temperature and 2D EXSY NMR experiments, the apical/equatorial positions around silicon exchange in the slow regime of the NMR timescale. The two forms, with the fluorine atom in trans or cis position to gold, were characterized spectroscopically and the activation barrier for their interconversion was estimated. The bonding and relative stability of the two isomeric structures were assessed by DFT calculations.     

Highly Fluorescent and Water‐Soluble Diketopyrrolopyrrole Dyes for Bioconjugation

The preparation of highly water‐soluble and strongly fluorescent diketopyrrolopyrrole (DPP) dyes using an unusual taurine‐like sulfonated linker has been achieved. Exchanging a phenyl for a thienyl substituent shifts the emission wavelength to near λ=600 nm. The free carboxylic acid group present in these new derivatives was readily activated and the dyes were subsequently covalently linked to a model protein (bovine serum albumin; BSA). The bioconjugates were characterized by electronic absorption, fluorescence spectroscopy and MALDI‐TOF mass spectrometry, thus enabling precise determination of the labeling density (ratio DPP/BSA about 3 to 8). Outstanding values of fluorescence quantum yield (30 % to 59 %) for these bioconjugates are obtained. The photostability of these DPP dyes is considerably greater than that of fluorescein under the same irradiation conditions. Remarkably low detection limits between 80 and 300 molecules/μm² were found for the BSA bioconjugates by fluorescence imaging with a epifluorescence microscope.     

Electrochemical Monitoring of the Early Events of Hydrogen Peroxide Production by Mitochondria

Mitochondria consume oxygen in the respiratory chain and convert redox energy into ATP. As a side process, they produce reactive oxygen species (ROS), whose physiological activities are still not understood. However, current analytical methods cannot be used to monitor mitochondrial ROS quantitatively and unambiguously. We have developed electrochemical biosensors based on peroxidase‐redox polymer‐modified electrodes, providing selective detection of H₂O₂ with nanomolar sensitivity, linear response over five concentration decades, and fast response time. The release of H₂O₂ by mitochondria was then monitored under phosphorylating or inhibited respiration conditions. We report the detection of two concomitant regimes of H₂O₂ release: large fluxes (hundreds of nM ) under complex III inhibition, and bursts of a few nM immediately following mitochondria activation. These unprecedented bursts of H₂O₂ are assigned to the role of mitochondria as the hub of redox signaling in cells.     

Thiophene systems. 13. The synthesis of novel thienopyranones

The syntheses and spectral properties of novel dimethyl-substituted thieno[3,2-b]-, [3,4-b]- and [2,3-b]pyran-ones are described. The uv spectra of the three systems are distinctly different as supported by HOMO/LUMO calculations. 5,6-Dihydro-5,5-dimethyl-7H-thieno[3,4-b]pyran-7-one ( 10 ) and 5,6-dihydro-6,6-dimethyl-4H-thieno[2,3-b]pyran-4-one ( 20 ) represent the first members of these thienopyranone ring systems.     

Comprehensive and quantitative stability study of ascorbic acid using capillary zone electrophoresis with ultraviolet detection and high‐resolution tandem mass spectrometry

Ascorbic acid is a powerful antioxidant compound involved in many biological functions, and a chronic deficiency is at the origin of scurvy disease. A simple, rapid, and cost‐effective capillary electrophoresis method was developed for the separation and simultaneous quantification of ascorbic acid and the major degradation products: dehydroascorbic acid, furfural, and furoic acid. Systematic optimization of the conditions was performed that enabled baseline separation of the compounds in less than 10 min. In addition to simultaneous quantification of ascorbic acid alongside to the degradation products, stability studies demonstrated the possibility using capillary electrophoresis to separate and identify the major degradation products. Thus, high‐resolution tandem mass spectrometry experiments were conducted in order to identify an unknown degradation product separated by capillary electrophoresis and significantly present in degraded samples. Comparison of mass spectrometry data and capillary electrophoresis electropherograms allowed to identify unambiguously trihydroxy‐keto‐valeraldehyde. Finally, capillary electrophoresis was successfully applied to evaluate the composition of different pharmaceutical preparation of ascorbic acid. Results showed the excellent performance of the capillary electrophoresis method due to the separation of excipients from the compounds of interest, which demonstrated the relevance of using an electrophoretic separation in order to perform comprehensive stability studies of ascorbic acid.     

Synthesis of poly-L-glutamic acid grafted silica nanoparticles and their assembly into macroporous structures

Polypeptide-coated silica nanoparticles represent an interesting class of organic-inorganic hybrids since the ordered secondary structure of the polypeptide grafts imparts functional properties to these nanoparticles. The synthesis of a poly-l-glutamic acid (PLGA) silica nanoparticle hybrid by employing N-carboxyanhydride (NCA) polymerization to synthesize the polypeptide chains and Cu catalyzed azide alkyne cycloaddition reaction to graft these chains onto the silica surface is reported. This methodology enables the synthesis of well-defined polypeptide chains that are attached onto the silica surface at high surface densities. The PLGA-silica conjugate particles are well dispersed in water, and have been thoroughly characterized using multinuclear ((13)C, (29)Si) solid state NMR, thermogravimetric analysis, Fourier transform infrared, dynamic light scattering, and transmission electron microscopy. The pH-dependent reversible aggregation of the PLGA-silica particles, driven by the change in PLGA structure, has also been studied. Preliminary results on the use of aqueous dispersions of silica-PLGA for the preparation of three-dimensional macroporous structures with oriented pores by ice templating methodology are also demonstrated. These macroporous materials, comprising a biocompatible polymer shell covalently attached to rigid inorganic cores, adopts an interesting lamellar structure with fishbone-type architecture.     

UV-mediated DNA strand breaks in corneal epithelial cells assessed using the comet assay procedure

Ultraviolet (UV)-mediated DNA damage in various tissues has been well documented. However, research on the damaging effect of UV irradiation on the DNA of corneal epithelium is scarce, even though this is of interest because the cornea is directly exposed to damaging solar (UV) radiation. In this study, we developed a corneal epithelium Comet assay model to assess the background DNA damage (as strand breaks) in cells retrieved from different layers of the porcine corneal epithelium, and to investigate the effect of UV irradiation on DNA damage in corneal epithelial cells. Results show that the background DNA strand breaks decreased significantly (P < 0.001) toward deeper layers of the epithelium. Exposure to the same intensity (0.216 J/cm2) of UVA, UVB and UVC caused a significant (P < 0.001) increase in DNA strand breaks of deeper-layer cells: mean +/- SD %DNA scores (10 gels per treatment, with 100 irradiated cells scored per gel) were 10.2% +/- 1.4% for UVA, 27.4% +/- 4.6% for UVB, and 14.7% +/- 1.8% for UVC compared with 4.2% +/- 0.5% for controls (ambient room light). This study has shown for the first time that the Comet assay for DNA strand breaks can be used successfully with corneal epithelial cells. This report will support future studies investigating environmental influences on corneal health and the assessment of possible protective strategies, and in applying DNA lesion-specific versions of the Comet assay in this corneal epithelial cell model.