Use of electrochemical impedance spectroscopy to assess the stability of the anion exchange membrane MA-41, modified by poly-N,N-diallylmorpholine bromide in overlimiting current modes

The paper presents the results of studying the electrochemical characteristics and long-term stability of MA-41 membranes on the surface of which poly-N,N-diallylmorpholinium bromide was applied. The deposition of a polyelectrolyte on the membrane surface leads to an increase in the limiting current from 0.8 to 1.1 mA/cm2. The comparison of the experimental and theoretically calculated values of the limiting current density allows us to conclude that the modification of the membrane surface by poly-N,N-diallylmorpholinium bromide does not lead to the formation of a continuous polyelectrolyte film on the surface, but its fixation occurs due to the sorption of macromolecules on the surface of the ion-exchanger particles. To quantify the rate of the water dissociation reaction at the membrane/solution interface, the method of electrochemical impedance was used, which makes it possible to compare the rate constants of the water dissociation reaction for different membranes, assuming that the reaction is described by the Gericher impedance. It is shown that modification of the MA-41 membrane surface leads to a decrease in the rate of the water dissociation reaction in the current range i = 1.5–4ilim by a factor of 2–6. The reduction in water dissociation reaction rate is attributed to the substitution of catalytically active secondary and tertiary amino groups in the surface layer of the pristine membrane by stable heterocyclic ammonium bases of poly-N,N-diallylmorpholinium. The study of the long-term stability of the resulting membrane showed that when the membrane is polarized with a current equal to  twice the limiting current, the desorption of the modifier occurs within 25 h, and the properties of the membrane become close to those of the unmodified MA-41 membrane. It was shown that the electrochemical impedance method can be used as a very sensitive method for studying the long-term stability of ion-exchange membranes

Mathematical model of stacked one-sided arrangement of the burners

Paper is aimed at computer simulation of the turbulent methane-air combustion in upgraded U-shaped boiler unit. To reduce the temperature in the flame and hence NOx release every burner output was reduced, but the number of the burners was increased. The subject of studying: complex of characteristics with space-time fields in the upgraded steam boiler E-370 with natural circulation. The flare structure, temperature and concentrations were determined computationally

The Medicinal Chemistry of 5-HT6 Receptor Ligands with a Focus on Arylsulfonyltryptamine Analogs

Arylsulfonyl analogs of aminopyrimidines (e.g. Ro 04-6790; 2), aminopyridines (e.g. Ro 63-0563; 3), 1-phenylpiperazines (e.g. SB-271046; 4), and tryptamines (e.g. MS-245; 5) were described as the first examples of selective 5-HT6 receptor antagonists only ten years ago. Today, hundreds of compounds of seemingly diverse structure have been reported. The early antagonists featured an arylsulfonyl group leading to the widespread assumption that an arylsulfonyl moiety might be critical for binding and antagonist action. With respect to the arylsulfonyltryptamines, it seems that neither the “arylsulfonyl” nor the “tryptamine” portion of these compounds is essential for binding or for antagonist action, and some such derivatives even display agonist action. The present review describes many of the currently available 5-HT6 receptor ligands and, unlike prior reviews, provides a narrative of the thinking (where possible) that led to their design, synthesis, and evaluation. The arylsulfonyltryptamines are also used as the structural basis of attempts to relate various structure-types to one another to afford a better understanding of the overall structural requirements for 5-HT6 receptor binding

Point mutations affecting yeast prion propagation change the structure of its amyloid fibrils

We investigated the effect of the point substitutions in the N-terminal domain of the yeast prion protein Sup35 (Sup35NMp) on the structure of its amyloid fibrils. As the objects of the study, proteins with mutations that have different influence on the [PSI+] prion propagation, but do not prevent the aggregation of Sup35NMp in vitro were chosen. The use of the wide range of physico-chemical methods allowed us to show significant differences in the structure of these aggregates, their physical size, clumping tendency. Also we demonstrated that the fluorescent probe thioflavin T (ThT) can be successfully used for investigation of subtle changes in the structural organization of fibrils formed from various Sup35NMp. The obtained results and our theoretical predictions allowed us to conclude that some of selected amino acid substitutions delimit the region of the protein that forms the core of amyloid fibrils, and change the fibrils structure. The relationship of structural features of in vitro Sup35NMp amyloid aggregates with the stability of the [PSI+] prion in vivo allowed us to suggest that oligopeptide repeats (R) of the amyloidogenic N-terminal domain of Sup35NMp from R0 to R2 play a key role in protein aggregation. Their arrangement rather than just presence is critical for propagation of the strong [PSI+] prion variants. The results confirm the suitability of the proposed combination of theoretical and empirical approaches for identifying changes in the amyloid fibrils structure, which, in turn, can significantly affect both the functional stability of amyloid fibrils and their pathogenicity.Laboratorio de Investigación y Desarrollo de Bioactivo

New PNM Mutation in SUP35

A number of [PSI+]-no-more (PNM) mutations, eliminating [PSI+] prion, were previously described in SUP35. In this study, we designed and analyzed a new PNM mutation based on the parallel in-register β-structure of Sup35 prion fibrils suggested by the known experimental data. In such an arrangement, substitution of non-charged residues by charged ones may destabilize the fibril structure. We introduced Q33K/A34K amino acid substitutions into the Sup35 protein, corresponding allele was called sup35-M0. The mutagenized residues were chosen based on ArchCandy in silico prediction of high inhibitory effect on the amyloidogenic potential of Sup35. The experiments confirmed that Sup35-M0 leads to the elimination of [PSI+] with high efficiency. Our data suggested that the elimination of the [PSI+] prion is associated with the decreased aggregation properties of the protein. The new mutation can induce the prion with very low efficiency and is able to propagate only weak [PSI+] prion variants. We also showed that Sup35-M0 protein co-aggregates with the wild-type Sup35 in vivo. Moreover, our data confirmed the utility of the strategy of substitution of non-charged residues by charged ones to design new mutations to inhibit a prion formationRFBR grant 19-04-00173, RFBR grant 17-54-150002, and PRC CNRS grant PRC1524,18-34-00536, RSF grant 18-14-0005

Stoichiometry and Affinity of Thioflavin T Binding to Sup35p Amyloid Fibrils.

In this work two modes of binding of the fluorescent probe thioflavin T to yeast prion protein Sup35p amyloid fibrils were revealed by absorption spectrometry of solutions prepared by equilibrium microdialysis. These binding modes exhibited significant differences in binding affinity and stoichiometry. Moreover, the absorption spectrum and the molar extinction coefficient of the dye bound in each mode were determined. The fluorescence quantum yield of the dye bound in each mode was determined via a spectrofluorimetric study of the same solutions in which the recorded fluorescence intensity was corrected for the primary inner filter effect. As previously predicted, the existence of one of the detected binding modes may be due to the incorporation of the dye into the grooves along the fiber axis perpendicular to the β-sheets of the fibrils. It was assumed that the second type of binding with higher affinity may be due to the existence of ThT binding sites that are localized to areas where amyloid fibrils are clustered

Characteristics of thioflavin t bound to amyloid fibrils and free dye in aqueous solution.

<p>Characteristics of thioflavin t bound to amyloid fibrils and free dye in aqueous solution.</p

Scatchard plot for the ThT interaction with Sup35p amyloid fibrils.

<p>The experimental data (circles) and best fit curve with the binding constants (<i>K</i>_<i>bi</i>) and the number of binding sites (<i>n</i>_<i>i</i>) are shown.</p