Potentiometric evaluation of calix[4]arene anion receptors in membrane electrodes: phosphate detection

Ion-selective membrane electrodes doped with the urea- or thiourea-functionalised calix[4]arenes, 5,11,17,23-tetra-tert-butyl-25,27-bis[[4-N′-(phenylureido)butyl]oxy]-26,28-dipropoxy calix[4]arene (I) and 5,11,17,23-tetra-tert-butyl-25,27-bis[[4-(N′-phenylthioureido)-butyl]oxy]-26,28-dipropoxy calix[4]arene (II), were evaluated for anion sensing. Potentiometric results show that these calixarene ionophore-based membrane electrodes exhibit a good sensitivity to aqueous solutions of the monohydrogen orthophosphate species HPO₄²⁻ in the concentration range 5.0 × 10⁻⁵ to 1.0 × 10⁻¹ M, with near-Nernstian response slopes of −33.0 and −28.0 mV dec⁻¹ for ionophores I and II, respectively. Selectivity coefficient values for monohydrogen orthophosphate over a range of common anions were determined by the fixed interference and matched potential methods and indicated that these membrane electrodes exhibit a good selectivity for HPO₄²⁻ with respect to the other anions, including sulfate and nitrate.     

Membrane Cholesterol and the Formation of Cholesterol Domains in the Pathogenesis of Cardiovascular Disease

At least three types of cholesterol-rich membrane domains have been described in biological membranes including cholesterol rafts, membrane caveolae and crystalline cholesterol domains,. While clear biological functions have been ascribed to both rafts and caveolae, little attention has been directed to the biological consequences of cholesterol enrichment of cell membranes and the formation of cholesterol domains. Elevated blood cholesterol levels have been shown to result in the enrichment of the cell plasma membrane with cholesterol in arterial smooth muscle cells (SMC), endothelial cells (EC) and cardiac myocytes. In the early period of cholesterol feeding (within days), the cell membrane enriches with cholesterol and membrane viscosity and membrane bilayer width increase. This latter effect severely alters membrane protein function, and recent data indicates that this induces the modulation of vascular cells (SMC and EC) to the atherosclerotic phenotype. In cardiac myocytes these membrane modifications appear to induce alterations in gene expression patterns that lead to the development of a heart failure phenotype. In addition, as the cholesterol content increases, phase separation of cholesterol occurs resulting in the formation of immiscible cholesterol domains within the membrane. These domains likely initiate nucleation of cholesterol crystals which would explain the origin of “cholesterol clefts” in atherosclerotic lesions. Taken together, these membrane alterations secondary to cholesterol enrichment constitute a “membrane lesion” which contribute to the very early pathogenic events underlying major human diseases including coronary artery disease, stroke and heart failure.     

Treatment of intralocular diseases with poly(ortho ester)‐based drug delivery systems

A poly(ortho ester) (POE) has been investigated as a carrier for controlled delivery in intraocular therapy. The intraocular biocompatibility of POE was assessed in the rabbit after intravitreal as well as suprachoroidal injections. In both cases, the injection was feasible and reproducible, and the tolerance of POE was good, with no clinical or cellular signs of inflammation. The polymer degraded slowly within 2 to 3 weeks, with total bioresorption. POE allowed to sustain the release of an antifibroblastic agent in a model of glaucoma filtering surgery in the rabbit. A formulation based on POE and 5‐fluorouracil was administered to prevent the failure of the surgery. This POE formulation was effective in inhibiting the fibrotic response, allowing a local and controlled release of a small amount of the antiproliferative drug, while reducing its toxicity. Based on these results, POE appears to be a promising carrier for sustained drug delivery in treatment of intraocular affections.     

New heteroleptic palladium(II) dithiocarbamates: synthesis,characterization, packing and anticancer activity against five different cancer cell lines

Two new heteroleptic palladium(II) complexes have been synthesized by reacting equimolar quantities of palladium(II) chloride, sodium 4‐(2‐methoxyphenyl)piperazine‐1‐carbodithioate and diphenyl‐p‐tolylphosphine ( 1 ) or tri‐p‐tolylphosphine ( 2 ). Complexes 1 and 2 have been characterized using elemental analysis, Fourier transform infrared spectroscopy, multinuclear NMR (¹H, ¹³C and ³¹P) spectroscopy and single‐crystal X‐ray analysis. The latter technique confirms a pseudo square‐planar geometry in which two adjacent positions are occupied by bidentate dithiocarbamate while chloro and substituted triphenylphosphine are present at the remaining two positions. The anticancer activity of both complexes against five different cancer cell lines (LU – human lung carcinoma, established at UIC, Department of Surgical Oncology; MCF7 – human breast adenocarcinoma, ATCC number HTB‐22?; MDA‐MB‐231 – human breast adenocarcinoma, ATCC number HTB‐26?; Hepa‐1c1c7 – mouse liver hepatoma, ATCC number CRL‐2026?; PC‐3 – human prostate adenocarcinoma, ATCC number CRL‐1435?) was determined by MTT assay, revealing 2 has higher activity than 1 . A drug–calf thymus DNA binding study with UV–visible spectroscopy reveals a higher DNA binding affinity of 2 (3.511 × 10⁴ M^?1) than 1 (4.213 × 10³ M^?1). Density functional theory studies confirm the relatively more stable nature of 2 than 1 . Copyright © 2016 John Wiley & Sons, Ltd.     

Peptide-mediated blood-brain barrier transport of polymersomes

A polymeric nanocarrier: Polymersomes tagged with a dodecamer peptide that recognizes gangliosides GM1 and GT1b are shown to cross the blood-brain barrier, both in an in?vitro model and in?vivo. The combination of polymeric vesicles with a small GM1-binding peptide and GM1/GT1b gangliosides as targeting sites for blood-brain barrier transport is unprecedented.     

Derivation of the near-surface dielectric function of amorphous silicon from photoelectron loss spectra

The near-surface dielectric function ε(?ω) of hydrogenated amorphous silicon (a-Si:H) films has been derived from X-ray photoelectron energy-loss spectra, over the energy range 0–40 eV. Removal of low lying single-electron excitations is a prerequisite step to proceed to the derivation of the single plasmon energy loss function Im[? 1/ε(?ω)] due to collective electron oscillations. Several methods are compared to separate interband transitions from bulk or surface plasmons excitation. The shape of interband excitation loss in the range 1–10 eV can be described by a Henke function; alternatively, its removal using a sigmoid weighting function is a low-noise and reliable method. After deconvolution of multiple plasmon losses and self-consistent elimination of surface plasmon excitation, the single plasmon loss distribution allows recovery of optical (ellipsometry) data measured in the near-UV to visible range.     

1,3-Dipolar cycloaddition reaction of bipyridinium ylides with the propynamido-β-cyclodextrin. A regiospecific synthesis of a new class of fluorescent β-cyclodextrins

The 1,3-dipolar cycloaddition reaction of bipyridinium ylides with the electron deficient propynamido-β-cyclodextrin was studied. This reaction resulted in the regiospecific formation of a new class of fluorescent β-cyclodextrins. The new fluorophore systems were characterized spectroscopically by their absorption and emission maxima and their quantum yields.     

Quantification of the 35S promoter in DNA extracts from genetically modified organisms using real-time polymerase chain reaction and specificity assessment on various genetically modified organisms, part I: operating procedure

A highly sensitive quantitative real-time assay targeted on the 35S promoter of a commercial genetically modified organism (GMO) was characterized (sF/sR primers) and developed for an ABI Prism 7700 Sequence Detection System and TaqMan chemistry. The specificity assessment and performance criteria of sF/sR assay were compared to other P35S-targeted published assays. sF/sR primers amplified a 79 base pair DNA sequence located in a part of P35S that is highly conserved among many caulimovirus strains, i.e., this consensus part of CaMV P35S is likely to be present in many GM events. According to the experimental conditions, the absolute limit of detection for Bt176 corn was estimated between 0.2 and 2 copies of equivalent genome (CEG). The limit of quantification was reached below 0.1% Bt176 content. A Cauliflower Mosaic Virus control (CaMV) qualitative assay targeted on the ORF III of the viral genome was also used as a control (primers 3F/3R) to assess the presence of CaMV in plant-derived products. The specificity of this test was assessed on various CaMV strains, including the Figwort Mosaic Virus (FMV) and solanaceous CaMV strains. Considering the performance of sF/sR quantification test, the highly conserved sequence, and the small size of the amplicon, this assay was tested in a collaborative study in order to be proposed as an international standard.     

Alternative strategies for the stereoselective synthesis of enantioenriched 6-arylated piperidin-2-ones

Two alternative synthetic approaches to a variety of enantioenriched 6-arylated piperidin-2-ones have been developed. The first one is based on the hydrogenation of suitably arylated chiral cyclic enehydrazides. The second approach relies on the asymmetric catalytic hydrogenation of the corresponding N-alkylated precursors.