Theoretical studies of the electronic and structural features of the fragments of dihydropholate reductase inhibitors

The effects of the structural characteristics of dihydrofolate reductase (DHFR) inhibitors on their tuberculostatic activity have been analyzed. It was shown that an increase in the electron density on bonds and atoms in the ring led to an increase in the biological activity of the compounds. A correlation was found between the biological activity and the characteristics of the critical points of electron density of bonds. The 3D- and 4D-QSAR studies with the CiS algorithm revealed the pharmacophore and antipharmacophore fragments of DHFR inhibitors, and regions of the receptor that are responsible for the biological action of dihydropyrimidines were found. Receptor ligand complexes were modeled. For a series of drugs containing a podand chain, it was found that the chain performed only the transport membranotropic function because the increase in the size of molecules due to the podand chain gives rise to steric hindrances when the chain is built in the receptor cavity.     

Modeling of Supersonic Turbulent Flows in the Vicinity of Axisymmetric Configurations

Calculation results of turbulent flows in the vicinity of axisymmetric configurations of the cylinderflare type for Mach numbers M = 3, 5, and 7 are presented. The calculations are performed for conditions of real physical experiments. The mathematical model is based on the averaged Navier–Stokes equations supplemented by the Wilcox turbulence model. The calculated and experimental distributions of pressure on the body surface, velocity fields, and heattransfer coefficients are compared.     

Mathematical Simulation of Dust Lifting from the Surface

Results of numerical simulation of the shock wave passing along a dusty layer are presented; the simulation was performed under the onetemperature, onevelocity assumption. It is shown that a system of compression and expansion waves is formed inside the layer, and these waves are successively reflected from the external boundary and solid wall. Regular and irregular reflections of the leading shock wave from the solid wall with different scenarios of instability evolution on the layer edge are described. Possible mechanisms of particle lifting from the surface are described.     

Analysis of flow in an annular duct with large injection at the walls

Viscous heat-conducting compressible fluid flow in an annular duct formed by two coaxial cylinders with large injection at the walls is investigated. An asymptotic solution exhibiting the influence of the axial symmetry of the duct is obtained in the vicinity of the y axis and is compared with the results of exact numerical calculations. Asymptotic solutions of the Navier-Stokes equations have been obtained earlier for flows in a plane channel with various rates of wall injection in the case of an incompressible gas [1, 2] and a compressible gas [3].Translated from Izvestiya Akademii Nauk SSSR, Mekhanika Zhidkosti i Gaza, No. 3, pp. 135–139, May–June, 1976.     

Separation and characterization of oxidized isomeric lipid–peptide adducts by ion mobility mass spectrometry

Phospholipids are major components of cell membranes and lipoprotein complexes. They are prone to oxidation by endogenous and exogenous reactive oxygen species yielding a large variety of modified lipids including small aliphatic and phospholipid bound aldehydes and ketones. These carbonyls are strong electrophiles that can modify proteins and, thereby, alter their structures and functions triggering various pathophysiological conditions. The analysis of lipid–protein adducts by liquid chromatography‐MS is challenged by their mixed chemical nature (polar peptide and hydrophobic lipid), low abundance in biological samples, and formation of multiple isomers. Thus, we investigated traveling wave ion mobility mass spectrometry (TWIMS) to analyze lipid–peptide adducts generated by incubating model peptides corresponding to the amphipathic β₁ sheet sequence of apolipoprotein B‐100 with 1‐palmitoyl‐2‐(oxo‐nonanoyl)‐sn‐glycerophosphatidylcholine (PONPC). The complex mixture of peptides, lipids, and peptide–lipid adducts was separated by TWIMS, which was especially important for the identification of two mono‐PONPC‐peptide isomers containing Schiff bases at different lysine residues. Moreover, TWIMS separated structural conformers of one peptide–lipid adduct possessing most likely different orientations of the hydrophobic sn‐1 fatty acyl residue and head group of PONPC, relative to the peptide backbone. Copyright © 2015 John Wiley & Sons, Ltd.     

Interaction of Crown Ether‐Annelated Styryl Dyes with Double‐Stranded DNA

DNA‐binding properties of 15‐crown‐5‐derived mono‐ and bis‐styryl dyes were investigated in the presence of calf thymus DNA. To access the factors that influence the DNA association in the series of these ligands, the structure of the molecules was varied by either changing size of the heterocyclic moiety or altering the position of the styryl substituents. The major binding mode for the monostyryl dyes is intercalation. Notably, binding of the dyes to the nucleic acids leads to a fluorescence enhancement by a factor of up to 54. Therefore, these cationic styryl derivatives may be applied as fluorescent “light‐up” probes for DNA detection.     

Separation of β-blocker and amino acid enantiomers on a mixed chiral sorbent modified with macrocyclic antibiotics eremomycin and vancomycin

A mixed chiral sorbent based on silica with immobilized macrocyclic antibiotics eremomycin and vancomycin was synthesized. A possibility of the separation of enantiomers of β-blockers (metoprolol, pindolol, alprenolol, oxprenolol, labetalol, and atenolol) and amino acids (tryptophan, phenylalanine, DOPA, methionine, and acetyl glutamic acid) on this chiral sorbent by HPLC was studied. The influence of the composition of the mobile phase (pH of buffer solution, its concentration, content of organic modifier, and its nature) on the retention times of β-blocker and amino acid enantiomers, selectivity, and resolution of peaks was studied. It was shown that the mixed chiral sorbent has enantioselectivity to both classes of compounds, while silica modified with vancomycin has no ability to the separation of enantiomers of non-derivatized amino acids, and silica modified with eremomycin has no ability to the separation of β-blocker enantiomers. High values of resolution for amino acids (max Rs > 4) and β-blockers (max Rs > 1) were obtained.     

Structure,magnetic, and electrical properties of bismuth niobates doped with <Emphasis Type="Italic">d</Emphasis>-elements: XVI. Magnetic properties of manganese-containing solid solutions of bismuth orthoniobate BiNiO<Subscript>4</Subscript>

Magnetic susceptibility and ESR properties of manganese-containing solid solutions of bismuth orthoniobate BiNb_1–x Mn_xO_4–δ have been studied. Mn(II), Mn(III), and Mn(IV) atoms as well as their dimers exhibiting antiferro- and ferromagnetic types of exchange have been found in the solid solutions. Parameters of the exchange interactions in the clusters and the distribution of monomers and dimers of manganese atoms in the solid solutions have been calculated as functions of the paramagnetic atom fraction.     

Structure and Thermal Stability of Nanostructured Precursor Powders of Copper(I) Sulfide and Selenide

The hydrochemical precipitation method at 298 and 333 K with, respectively, thiocarbamide and sodium selenosulfate was used to obtain nanostructured powders of copper sulfide with formula composition Cu₂S, which are composed of globules 200–500 nm in diameter, formed by 70–100-nm particles, and copper(I) selenide, composed of crystallites with polyhedral shape, sizes of 80 to 500 nm, and a formula composition Cu_1.84Se. An X-ray diffraction analysis revealed the orthorhombic Cu₂S structure (space group no. 39-Abm2) with unit cell parameters a = 1.182 nm, b = 2.705 nm, and c = 1.343 nm. Powders of Cu_1.84Se copper selenide have a cubic structure (space group Fm3m) with lattice constant a = 0.5693 nm. A thermal analysis demonstrated that the chemically precipitated Cu₂S and Cu_1.84Se powders have a stable elemental composition up to 200–240°C. An intense oxidation of the samples begins at a temperature exceeding 250°C and is accompanied by a sharp decrease in their content of sulfur (selenium) and by an increase in the content of oxygen.