Double Orthogonal Click Reactions for the Development of Antimicrobial Peptide Nanotubes

A new class of amphipathic cyclic peptides, which assemble in bacteria membranes to form polymeric supramolecular nanotubes giving them antimicrobial properties, is described. The method is based on the use of two orthogonal clickable transformations to incorporate different hydrophobic or hydrophilic moieties in a simple, regioselective, and divergent manner. The resulting cationic amphipathic cyclic peptides described in this article exhibit strong antimicrobial properties with a broad therapeutic window. Our studies suggest that the active form is the nanotube resulted from the parallel stacking of the cyclic peptide precursors. Several techniques, CD, FTIR, fluorescence, and STEM, among others, confirm the nanotube formation.     

Crystal habit modifications of imatinib mesylate under various precipitation conditions

Abstract  

Crystals of the α-form of imatinib mesylate with various habits (e.g., polyhedral-like and plate-like) were prepared from various organic solvents (e.g., butyl lactate, 4-methyl-2-pentanone, 2-methyl-2-butanol, 2-isopropoxyethanol, propyl ether) by several precipitation methods. The methods provide imatinib mesylate in a non-needle-shaped crystalline α-form. The crystal modification was identified by hot-stage microscopy, scanning electron microscopy, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and X-ray powder diffraction (XRPD). The analyses by DSC, IR, and XRPD indicate that imatinib mesylate crystals with various habits have the same crystal structure. The plate-like habit has been also observed in the system where the organic solvent acts as a precipitant.     

Synthesis and toxicity assay of ceramic nanophosphors for bioimaging with near-infrared excitation

Yttrium hydroxyl carbonate (Y(OH)CO₃) precursors were synthesized by the homogeneous co-precipitation method in the presence of polyacrylic acid (PAAc). Resultant precursor particle size is about 15–20 nm with narrow size distribution whereas the particle size is smaller than those acquired by the conventional homogeneous precipitation method. Effective decrease of Y(OH)CO₃ particle size was found to be higher for the presence of weak polyanionic ionomer such as PAAc than the presence of strong polyanionic ionomer such as sodium polystyrene sulfonate (PSS). It was observed that the morphology and size of the precursors are almost unchanged after the calcination process. Er³⁺ doped Y₂O₃ nanoparticles were synthesized by PAAc assisted homogeneous co-precipitation method showed bright green (550 nm) and red (660 nm) upconversion (UC) as well as near-infrared (NIR) fluorescence (1550 nm) under 980-nm excitation. UC and NIR fluorescence bioimaging and in-vitro cytotoxicity assay of Er³⁺ doped Y₂O₃ nanoparticles were successfully attempted with commercially available macrophages and B-cell hybridomas. Cellular uptake of nanoparticles is evidenced from bright field, UC and NIR fluorescence images of macrophages.     

XANES speciation of mercury in three mining districts – Almadén,Asturias (Spain), Idria (Slovenia)

The mobility, bioavailability and toxicity of mercury in the environment strongly depend on the chemical species in which it is present in soil, sediments, water or air. In mining districts, differences in mobility and bioavailability of mercury mainly arise from the different type of mineralization and ore processing. In this work, synchrotron‐based X‐ray absorption near‐edge spectroscopy (XANES) has been taken advantage of to study the speciation of mercury in geological samples from three of the largest European mercury mining districts: Almadén (Spain), Idria (Slovenia) and Asturias (Spain). XANES has been complemented with a single extraction protocol for the determination of Hg mobility. Ore, calcines, dump material, soil, sediment and suspended particles from the three sites have been considered in the study. In the three sites, rather insoluble sulfide compounds (cinnabar and metacinnabar) were found to predominate. Minor amounts of more soluble mercury compounds (chlorides and sulfates) were also identified in some samples. Single extraction procedures have put forward a strong dependence of the mobility with the concentration of chlorides and sulfates. Differences in efficiency of roasting furnaces from the three sites have been found.     

Determination of adsorption heats of individual adsorption complex by combination of microcalorimetry and FTIR spectroscopy

Adsorption of CO as a probe molecule on K-FER zeolites differing in Si/Al ratio was investigated. Successful determination of adsorption heats of individual adsorption complexes formed upon adsorption of CO molecules on K-FER zeolites at 300 K by combination of IR spectroscopy with adsorption microcalorimetry is reported. Adsorption heat of bridged carbonyl complexes, where CO molecule interacts with two nearby extraframework K⁺ cations, was experimentally determined for the first time. It was found that bridged complexes on dual cationic sites exhibit adsorption heat of 34.8 kJ mol^?1, whereas monodentate carbonyls on single isolated K⁺ cation exhibit adsorption heat of only 26.2 kJ mol^?1 and adsorption heat of isocarbonyls was 21.5 kJ mol^?1.     

Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States

Parkinson’s disease is the second most common neurodegenerative disorder, in which both alpha-synuclein (α-syn) and dopamine (DA) have a critical role. α-Syn is known to be natively unstructured in equilibrium with subpopulations of more compact structures. It is these compact structures that are thought to be linked to amyloid formation. In the presence of DA, α-syn yields a diverse range of SDS-resistant, non-amyloid oligomers, however the precursor state conformation has not been established. Here, three DA molecules have been observed to bind per α-syn monomer by electrospray-ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS). Each of these DA molecules binds exclusively to the extended conformation of α-syn, and binding is not observed in the compact state of the protein. Measurements of collisional cross sectional areas show that the incremental uptake of DA pushes the protein towards a highly extended population, becoming fully populated upon the binding of three DA ligands. Tyrosine (Tyr) as a closely related structural analog, exhibited limited binding to the protein as compared with DA, with a maximum of two ligands being observed. Those Tyr ligands that do bind were observed as adducts to the extended conformation akin to DA. These findings suggest DA is able to modulate α-syn self-assembly by inducing the population of a highly extended state.

An automated headspace solid-phase microextraction followed by gas chromatography–mass spectrometry method to determine macrocyclic musk fragrances in wastewater samples

A fully automated method has been developed for determining eight macrocyclic musk fragrances in wastewater samples. The method is based on headspace solid-phase microextraction (HS-SPME) followed by gas chromatography–mass spectrometry (GC-MS). Five different fibres (PDMS 7 μm, PDMS 30 μm, PDMS 100 μm, PDMS/DVB 65 μm and PA 85 μm) were tested. The best conditions were achieved when a PDMS/DVB 65 μm fibre was exposed for 45 min in the headspace of 10 mL water samples at 100 °C. Method detection limits were found in the low ng L^?1 range between 0.75 and 5 ng L^?1 depending on the target analytes. Moreover, under optimized conditions, the method gave good levels of intra-day and inter-day repeatabilities in wastewater samples with relative standard deviations (n?=?5, 1,000 ng L^?1) less than 9 and 14 %, respectively. The applicability of the method was tested with influent and effluent urban wastewater samples from different wastewater treatment plants (WWTPs). The analysis of influent urban wastewater revealed the presence of most of the target macrocyclic musks with, most notably, the maximum concentration of ambrettolide being obtained in WWTP A (4.36 μg L^?1) and WWTP B (12.29 μg L^?1), respectively. The analysis of effluent urban wastewater showed a decrease in target analyte concentrations, with exaltone and ambrettolide being the most abundant compounds with concentrations varying between below method quantification limit (<MQL) and 2.46 μg L^?1.