Developments and applications of separation and microfluidics methods coupled to electrospray mass spectrometry in glycomics of nervous system gangliosides

Gangliosides are particularly abundant in the nervous system (NS) where their pattern and structure in a certain milieu or a defined region exhibit a pronounced specificity. Since gangliosides are useful biomarkers for diagnosis of NS ailments, a clear-cut mapping of individual components represents a prerequisite for designing ganglioside-based diagnostic procedures, treatments, or vaccines. These bioclinical aspects and the high diversity of ganglioside species claim for development of specific analytical strategies. This review summarizes the state-of-the-art in the implementation of separation techniques and microfluidics coupled to MS, which have contributed significantly to the advancement of the field. In the first part, the review discusses relevant approaches based on HPLC MS and CE coupled to ESI MS and their applications in the characterization of gangliosides expressed in healthy and diseased NS. A considerable section is dedicated to microfluidics MS and ion mobility separation MS, developed for the study of brain gangliosidome and its changes triggered by various factors, as well as for ganglioside biomarker discovery in neurodegenerative diseases and brain cancer. In the last part of the review, the benefits and perspectives in ganglioside research of these high-performance techniques are presented.     

Can 2‐acylpyrroles form an intramolecular hydrogen bond?

The formation of intramolecular hydrogen bonding by certain N‐substituted 2‐acylpyrroles has been demonstrated by B3LYP/aug‐cc‐pVDZ calculations, the quantum theory of atoms in molecules, and the natural bond orbital method. Total electron energy densities H_BCP at the bond critical point of the H?O bond were applied to analyze the strength of these interactions. The relations between quantum theory of atoms in molecules, carbonyl stretching vibrational modes ν_{C = O}, and natural bond orbital parameters associated with the formation of the C–H?O interaction have been established. The short contacts were found experimentally in the crystal structure of a new 2‐acylpyrrole derivative 5‐chloro‐2‐oxopentyl‐1‐(5‐chloro‐2‐oxopentyl)pyrrolo‐2‐carboxylate. The influence of 2‐ and N‐substitution of 2‐acylpyrroles on C‐H?O interaction energy is discussed. It was found that the methylene group may act as a proton donor leading to a red‐shift or blue‐shift phenomenon of the ν_C–H stretching mode. Copyright © 2015 John Wiley & Sons, Ltd.     

Arene–perfluoroarene interactions confer enhanced mechanical properties to synthetic nanotubes

Supramolecular nanotubes prepared through macrocycle assembly offer unique properties that stem from their long-range order, structural predictability, and tunable microenvironments. However, assemblies that rely on weak non-covalent interactions often have limited aspect ratios and poor mechanical integrity, which diminish their utility. Here pentagonal imine-linked macrocycles are prepared by condensing a pyridine-containing diamine and either terephthalaldehyde or 2,3,5,6-tetrafluoroterephthalaldehyde. Atomic force microscopy and synchrotron in solvo X-ray diffraction demonstrate that protonation of the pyridine groups drives assembly into high-aspect ratio nanotube assemblies. A 1 : 1 mixture of each macrocycle yielded nanotubes with enhanced crystallinity upon protonation. UV-Vis and fluorescence spectroscopy indicate that nanotubes containing both arene and perfluoroarene subunits display spectroscopic signatures of arene–perfluoroarene interactions. Touch-spun polymeric fibers containing assembled nanotubes prepared from the perhydro- or perfluorinated macrocycles exhibited Young''s moduli of 1.09 and 0.49 GPa, respectively. Fibers containing nanotube assemblies reinforced by arene–perfluoroarene interactions yielded a 93% increase in the Young''s modulus over the perhydro derivative, up to 2.1 GPa. These findings demonstrate that tuning the chemical composition of the monomeric macrocycles can have profound effects on the mechanical strength of the resulting assemblies. More broadly, these results will inspire future studies into tuning orthogonal non-covalent interactions between macrocycles to yield nanotubes with emergent functions and technological potential.

Arene–perfluoroarene interactions resulted in enhanced crystallinity between analogous perhydro- and perfluoro macrocycles in a supramolecular nanotube assembly.     

Use of TLC-Densitometric Method for Determination of Valproic Acid in Capsules

Determination of valproic acid in the drug was carried out on the aluminum silica gel 60F₂₅₄ plates and using acetone–water–chloroform–ethanol–ammonia at a volume ratio of 30:1:8:5:11 as the mobile phase, respectively. Two methods of detection of valproic acid were used. The first was a 2% aqueous CuSO₄×5H₂O solution, and the second was a 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system. The applied TLC-densitometric method is selective, linear, accurate, precise, and robust, regardless of the visualizing reagent used for the determination of valproic acid in Convulex capsules. It has low limits of detection (LOD) and limits of quantification (LOQ), which are equal to 5.8 μg/spot and 17.4 μg/spot using a 2% aqueous CuSO₄×5H₂O solution as visualizing agent and also 0.32 μg/spot and 0.97 μg/spot using a 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system as visualizing reagent, respectively. The described analytical method can additionally be used to study the identity of valproic acid in a pharmaceutical preparation. The linearity range was found to be 20.00–80.00 μg/spot and 1.00–2.00 μg/spot for valproic acid detected on chromatographic plates using a 2% aqueous CuSO₄×5H₂O solution and the 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system, respectively. A coefficient of variation that was less than 3% confirms the satisfactory accuracy and precision of the proposed method. The results of the assay of valproic acid equal 96.2% and 97.0% in relation to the label claim that valproic acid fulfill pharmacopoeial requirements. The developed TLC-densitometric method can be suitable for the routine analysis of valproic acid in pharmaceutical formulations. The proposed TLC-densitometry may be an alternative method to the modern high-performance liquid chromatography and square wave voltammetry in the control of above-mentioned substances, and it can be applied when other analytical techniques is not affordable in the laboratory.     

Structural and Thermodynamic Peculiarities of Core-Shell Particles at Fluid Interfaces from Triangular Lattice Models

A triangular lattice model for pattern formation by core-shell particles at fluid interfaces is introduced and studied for the particle to core diameter ratio equal to 3. Repulsion for overlapping shells and attraction at larger distances due to capillary forces are assumed. Ground states and thermodynamic properties are determined analytically and by Monte Carlo simulations for soft outer- and stiffer inner shells, with different decay rates of the interparticle repulsion. We find that thermodynamic properties are qualitatively the same for slow and for fast decay of the repulsive potential, but the ordered phases are stable for temperature ranges, depending strongly on the shape of the repulsive potential. More importantly, there are two types of patterns formed for fixed chemical potential—one for a slow and another one for a fast decay of the repulsion at small distances. In the first case, two different patterns—for example clusters or stripes—occur with the same probability for some range of the chemical potential. For a fixed concentration, an interface is formed between two ordered phases with the closest concentration, and the surface tension takes the same value for all stable interfaces. In the case of degeneracy, a stable interface cannot be formed for one out of four combinations of the coexisting phases, because of a larger surface tension. Our results show that by tuning the architecture of a thick polymeric shell, many different patterns can be obtained for a sufficiently low temperature.     

Identification of pyrrolo-pyridine derivatives as novel class of antibacterials

Molecular Diversity - A series of 5-oxo-4H-pyrrolo[3,2-b]pyridine derivatives was identified as novel class of highly potent antibacterial agents during an extensive large-scale high-throughput...     

Simultaneous determination of mitotane,its metabolite,and five steroid hormones in urine samples by capillary electrophoresis using β-CD2SDS1 complexes as hydrophobic compounds solubilizers

Mitotane is a cytotoxic drug used in the treatment of inoperable adrenocortical carcinoma, it inhibits steroidogenesis as well, and therefore monitoring the level of steroid hormones in patients treated with mitotane is a crucial point of therapy. Hence, we have developed a simple, fast, and efficient electrophoretic method combined with reverse polarity sweeping as online preconcentration technique and dispersive liquid–liquid microextraction for the simultaneous determination of mitotane, its main metabolite DDA, and five steroid hormones (progesterone, testosterone, epitestosterone, cortisol, and corticosterone) in urine samples. In addition, a new sample matrix consisting of β-CD₂SDS₁ complexes for a high hydrophobic compounds solubilization was developed. Approach based on the application of β-cyclodextrin and SDS complex of a ratio 2:1 allowed for hydrodynamic injection into the capillary of a solution containing both mitotane and other analytes. The detection limits of the analytes for the reverse polarity sweeping-dispersive liquid–liquid microextraction method were found to be in the range of 1.5–3 ng/mL, which were approximately 1000 times lower than in the conventional hydrodynamic injection (5 s, 0.5 psi) without any preconcentration procedure. All analytes were completely resolved in less than 13 min by uncoated silica capillary with an inner diameter of 75 μm (ID) × 60 cm. Electrophoretic separation was performed in reverse polarity with a voltage of –25 kV with a background electrolyte (BGE) consisting of 100 mM SDS, 25% ACN, 25 mM phosphate buffer (pH 2.5), and 7 mM β-cyclodextrin.     

Antimicrobial Activities of Plant Extracts against Solanum tuberosum L. Phytopathogens

The purpose of the study was to select an environmentally friendly plant biopesticide to protect seed potatoes against phytopathogens. The scope included the evaluation of the antimicrobial activities of 22 plant water extracts, 22 water-glycol extracts, and 3 subcritical carbon dioxide extracts using the agar diffusion method against 10 potato phytopathogens. For the most effective extracts, minimal inhibitory concentration (MIC), chemical composition analysis by gas chromatography–mass spectrometry and in situ assays on seed potatoes were performed. Garlic water extract was finally selected as the most effective in phytopathogen growth inhibition, both in vitro and in situ, with MIC values ranging between 6.3–25 mg/mL. 5-Hydroxymethylfurfural was determined to be the main component of this extract (33.24%). Garlic water extract was proposed as a potential biopesticide against potato phytopathogens.