Physicochemical characteristics and bronchial epithelial cell cytotoxicity of Folpan 80 WG® and Myco 500®, two commercial forms of folpet

Background

Pesticides, in particular folpet, have been found in rural and urban air in France in the past few years. Folpet is a contact fungicide and has been widely used for the past 50 years in vineyards in France. Slightly water-soluble and mostly present as particles in the environment, it has been measured at average concentration of 40.1 μg/m³ during its spraying, 0.16–1.2 μg/m³ in rural air and around 0.01 μg/m³ in urban air, potentially exposing both the workers and the general population. However, no study on its penetration by inhalation and on its respiratory toxicity has been published. The objective of this study was to determine the physicochemical characteristics of folpet particles (morphology, granulometry, stability) in its commercial forms under their typical application conditions. Moreover, the cytotoxic effect of these particles and the generation of reactive oxygen species were assessed in vitro on respiratory cells.

Results

Granulometry of two commercial forms of folpet (Folpan 80WG^® and Myco 500^®) under their typical application conditions showed that the majority of the particles (>75%) had a size under 5 μm, and therefore could be inhaled by humans. These particles were relatively stable over time: more than 75% of folpet remained in the particle suspension after 30 days under the typical application conditions. The inhibitory concentration (IC₅₀) on human bronchial epithelial cells (16HBE14o-) was found to be between 2.89 and 5.11 μg/cm² for folpet commercial products after 24 h of exposure. Folpet degradation products and vehicles of Folpan 80 WG^® did not show any cytotoxicity at tested concentrations. At non-cytotoxic and subtoxic concentrations, Folpan 80 WG^® was found to increase DCFH-DA fluorescence.

Conclusion

These results show that the particles of commercial forms of folpet are relatively stable over time. Particles could be easily inhaled by humans, could reach the conducting airways and are cytotoxic to respiratory cells in vitro. Folpet particles may mediate its toxicity directly or indirectly through ROS-mediated alterations. These data constitute the first step towards the risk assessment of folpet particles by inhalation for human health. This work confirms the need for further studies on the effect of environmental pesticides on the respiratory system.     

Structural and molecular recognition studies with acyclic anion receptors

Acyclic molecules containing amides, ureas, and pyrrole groups have proven to be effective and selective anion-binding agents. In this Account, the structural chemistry of isophthalamide anion complexes, ortho-phenylenediamine based bis-ureas, and amidopyrroles, as well as anion-triggered deprotonation processes in neutral anion receptor systems, are discussed.     

REPLACE: a strategy for iterative design of cyclin-binding groove inhibitors

We describe a drug-design strategy termed REPLACE (REplacement with Partial Ligand Alternatives through Computational Enrichment) in which nonpeptidic surrogates for specific determinants of known peptide ligands are identified in silico by using a core peptide-bound protein structure as a design anchor. In the REPLACE application example, we present the effective replacement of two critical binding motifs in a lead protein-protein interaction inhibitor pentapeptide with more druglike phenyltriazole and diphenyl ether groups. These were identified through docking of fragment libraries into the volume of the cyclin-binding groove of CDK2/cyclin A vacated through truncation of the inhibitor peptide-binding determinants. Proof of concept for this strategy was obtained through the generation of potent peptide-small-molecule hybrids and by the confirmation of inhibitor-binding modes in X-ray crystal structures. This method therefore allows nonpeptide fragments to be identified without the requirement for a high-sensitivity binding assay and should be generally applicable in replacing amino acids as individual residues or groups in peptide inhibitors to generate pharmaceutically acceptable lead molecules.     

Laminar mixing of shear thinning fluids in a SMX static mixer

Flow and mixing of power-law fluids in a standard SMX static mixer were simulated using computational fluid dynamics (CFD). Results showed that shear thinning reduces the ratio of pressure drop in the static mixer to pressure drop in empty tube as compared to Newtonian fluids. The correlations for pressure drop and friction factor were obtained at Re_MR?100. The friction factor is a function of both Reynolds number and power-law index. A proper apparent strain rate, area-weighted average strain rate on the solid surface in mixing section, was proposed to calculate pressure drop for a non-Newtonian fluid. Particle tracking showed that shear thinning fluids exhibit better mixing quality, lower pressure drop and higher mixing efficiency as compared to a Newtonian fluid in the SMX static mixer.     

Synthesis and self-association in aqueous media of poly(ethylene oxide)/poly(ethyl glycidyl carbamate) amphiphilic block copolymers

New temperature sensitive AB, ABA, and BAB amphiphilic block copolymers consisting of hydrophilic poly(ethylene oxide) and hydrophobic poly(ethyl glycidyl carbamate) blocks were synthesized by anionic polymerization followed by chemical modification reactions. The self-association of the block copolymers in aqueous media was studied by UV-vis spectroscopy and dynamic and static light scattering. The obtained block copolymers spontaneously form micelles in aqueous media. The critical micellization concentration varied from 0.5 to 4 g/L depending on the copolymer architecture and composition. The influence of the temperature upon the self-association of the block copolymers was investigated. The increase of temperature did not affect the value of the critical micellization concentration, but led to the formation of better defined micelles with narrow size distribution.     

Quantitative31P nuclear magnetic resonance analysis of the phospholipids of erythrocyte membranes using detergent

³¹P Nuclear magnetic resonance (NMR) spectra of human erythrocyte lysates dissolved in sodium cholate were acquired. The narrow resonances of phospholipids were mostly well resolved, allowing identification and accurate quantitative analysis of phospholipid classes of the erythrocyte membranes. The ether-linked phosphatidylethanolamine components of the erythrocyte membranes were identified, based on the removal of plasmalogens by acidolysis and of diacyl phospholipid species by degradation using phospholipase A₁. It was also shown that the introduction of double bonds on the acyl chains of phosphatidylcholine shifted the³¹P NMR resonances to lower frequencies. Quantitative analyses of phospholipids from the spectra were based on their apparent molar concentrations. The recoveries of phospholipids from erythrocytes were significantly higher than those using conventional extraction procedures.     

Antibacterial Property of Cold Sprayed Chitosan-Cu/Al Coating

The antibacterial behavior of CS-Cu (chitosan-copper complex) powder and their composite coatings were investigated against Escherichia coli (DH5α). CS-Cu powder and Al (aluminum) based CS-Cu composite powders were synthesized using in-house powder processing techniques. The results indicated that the antibacterial effect of all the powders increased with the proportion of CS-Cu powder. These composite powders were subsequently used as feedstock to generate antibacterial coatings via cold spray technology. The ratios of CS-Cu to Al in their composite powders were 25:75, 50:50, and 75:25 (wt.%). Microstructural characterization and phase analysis of feedstock powders and as-deposited coatings were carried out using FESEM/EDX and FTIR. Antibacterial composite CS-Cu/Al coatings were successfully deposited using cold spraying parameters of 6-8 bars at preheated helium gas, temperature between 140 and 150 °C. The coatings retained the antibacterial properties of the original feedstock powders.     

Synthesis and nonlinear optical characterization of new poly{2,2′-(3,4-didodecyloxythiophene-2,5-diyl)bis[5-(2-thienyl)-1,3,4-oxadiazole]}

A new donor–acceptor type poly{2,2′-(3,4-didodecyloxythiophene-2,5-diyl)bis[5-(2-thienyl)-1,3,4-oxadiazole]} (P) was synthesized starting from thiodiglycolic acid and diethyl oxalate through multistep reactions. The polymerization was carried out using chemical polymerization technique. The optical and charge-transporting property of the copolymer was investigated by UV–vis, fluorescence emission spectroscopic and cyclic voltammetric studies. The copolymer shows UV absorption maxima at 375 nm and displays bluish-green fluorescence in DMF solution. Its electrochemical band gap was determined to be 2.07 eV. The nonlinear optical (NLO) properties of the copolymer was investigated at 532 nm using single beam Z-scan and degenerate four-wave mixing (DFWM) techniques with nanosecond laser pulses. The copolymer exhibits strong optical limiting behavior due to effective three-photon absorption (3PA). Values of the effective 3PA coefficient (γ), third-order nonlinear susceptibility (χ⁽³⁾) and figure of merit (F) have been calculated.     

Fluorescence studies of electrospun MEH-PPV/PEO nanofibers

We report a study of the fluorescence properties of the conjugated polymer poly [2-methoxy-5-(2′-ethyl hexyloxy)-p-phenylene vinylene] (MEH-PPV) and polyethylene oxide (PEO) nanofibers. MEH-PPV/PEO nanofibers with different compositions have been fabricated by the electrospinning technique. The fluorescence spectra of the nanofibers show that the emission shoulder at ∼630 nm blue-shifts ∼45 nm, whereas the main emission peak around 590 nm blue-shifts ∼15 nm with decreasing concentration of MEH-PPV in the nanofiber. In addition, confocal microscopic studies of a single MEH-PPV/PEO electrospun nanofiber indicate that the fluorescence spectra of the nanofiber do not show any polarization dependence. The results are discussed in terms of the aggregation of MEH-PPV in an inert matrix.     

Hydrogels containing silver nanoparticles for burn wounds show antimicrobial activity without cytotoxicity

This research introduces a novel dressing for burn wounds, containing silver nanoparticles in hydrogels for infected burn care. The 2‐acrylamido‐2‐methylpropane sulfonic acid sodium salt hydrogels containing silver nanoparticles have been prepared via ultraviolet radiation. The formation of silver nanoparticles was monitored by surface plasmon bands and transmission electron microscopy. The concentration of silver nitrate loaded in the solutions slightly affected the physical properties and mechanical properties of the neat hydrogel. An indirect cytotoxicity study found that none of the hydrogels were toxic to tested cell lines. The measurement of cumulative release of silver indicated that 70%–82% of silver was released within 72 hr. The antibacterial activities of the hydrogels against common burn pathogens were studied and the results showed that 5 mM silver hydrogel had the greatest inhibitory activity. The results support its use as a potential burn wound dressing. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40215.