Mycosamine orientation of amphotericin B controlling interaction with ergosterol: sterol-dependent activity of conformation-restricted derivatives with an amino-carbonyl bridge

Amphotericin B (AmB 1) is known to assemble together and form an ion channel across biomembranes. The antibiotic consists of mycosamine and macrolactone moieties, whose relative geometry is speculated to be determinant for the drug's channel activity and sterol selectivity. To better understand the relationship between the amino-sugar orientation and drug's activity, we prepared conformation-restricted derivatives 2-4, in which the amino and carboxyl groups were bridged together with various lengths of alkyl chains. K+ influx assays across the lipid-bilayer membrane revealed that ergosterol selectivity was markedly different among derivatives; short-bridged derivative 2 almost lost the selectivity, while 3 showed higher ergosterol preference than AmB itself. Monte Carlo conformational analysis of 2-4 based on NOE-derived distances indicated that the amino-sugar moiety of 2 comes close to C41 because of the short bridge, whereas those of 3 and 4 are pointing outward. The mutual orientation of the amino-sugar moiety and macrolide ring is so rigid in derivatives 2 and 3 that these conformations should be unchanged upon complex formation in lipid membranes. These results strongly suggest that the large difference in sterol preference between derivatives 2 and 3 is ascribed to the different orientation of amino-sugar moieties. These findings allowed us to propose a simple model accounting for AmB-sterol interactions, in which hydrogen bonding between 2'-OH of AmB and 3beta-OH of ergosterol plays an important role.     

Controlling the agglomeration of anisotropic Ru nanoparticles by the microwave-polyol process

A rapid polyol process for the synthesis of ruthenium nanoparticles was developed using microwave irradiation. A colloidal solution of monodispersed anisotropic Ru metal nanoparticles (mean particle size 2-6 nm) with different aspect ratios was obtained first. Particles with different degrees of agglomeration have also been synthesized using monodisperse particles as seeds and PVP (poly-N-vinyl-2-pyrrolidone) as the stabilization reagent. The stabilization mechanisms of different protective reagents were studied by UV-vis spectra. The HRTEM images indicated that dendritic particles formed by controlling agglomeration consisted of single-crystal domains with a random crystalline orientation.     

Catalytic synthesis of benzodithiophenes

Conclusions The reaction of p-diethylbenzene and H₂S on a chromium-containing oxide catalyst gives a thiophene analog of phenanthrene, namely, benzo[2,1-b3,4-b]dithiophene, and a thiophene analog of anthracene, namely, benzo[1,2-b4,5-b]dithiophene.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2857–2859, December, 1988.     

Quinoid pigments of echinodermata III. Minor pigments of the sea urchin Strongylocentrotus nudus

Summary 1. 3-Acetyl-2,7-dihydroxy-6-methylnaphthazarin, not previously described, has been isolated from the test and needles of the sea urchinStronglyocentrotus nudus.2. The pigments of this sea urchin have been shown to include 2,7-dihydroxynaphthazarin and spinochrome E.3. A number of minor pigments forming naphthazarin derivatives has been isolated. One of them is connected with spinochrome C by mutual transformations.The subject matter of the present paper was given in part at the All-Union Conference on Biological Resources of the Seas of the Far East (Vladivostok, 1975).Pacific Ocean Institute of Bioorganic Chemistry, Far Eastern Scientific Center of the Academy of Sciences of the USSR, Vladivostok. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 202–207, March–April, 1977.     

Transients of the Open-Circuit Potential Observed during the Interaction of Formic Acid with Preliminarily Adsorbed Oxygen on a Platinized Platinum Electrode

Transients of the open-circuit potential, which are observed during the interaction of formic acid with preliminarily adsorbed oxygen (O_ads) on a Pt/Pt electrode in 0.5 M H₂SO₄, are measured. It is established, by means of the method of cathodic potentiodynamic pulses, that the slowest interaction of formic acid with O_ads occurs in the region of large coverages of the electrode surface by oxygen (θ_O ∼1–0.8). A presumption is put forward that the process rate in this region is defined by a direct reaction of O_ads with molecules of formic acid from the bulk solution. It is shown that the interaction of formic acid with O_ads in the region of intermediate coverages (θ_O ∼ 0.8–0.2) proceeds via a mechanism of “conjugated reactions.” Transients of the open-circuit potential for formic acid are compared to transients for carbon monoxide obtained in analogous conditions. The substantially shorter overall time of potential decay in the case of CO (at the same concentrations) is caused by a faster reaction of CO with adsorbed oxygen in the region of large θ_O. The difference is explained by assuming that the HCOOH adsorption as opposed to CO bears a dissociative character.__________Translated from Elektrokhimiya, Vol. 41, No. 8, 2005, pp. 936–942.Original Russian Text Copyright © 2005 by Manzhos, Maksimov, Podlovchenko.     

Age-dependent variations of cell response to oxidative stress: proteomic approach to protein expression and phosphorylation

We investigated the protein profiles of variously aged rat astrocytes in response to oxidative stress. After H2O2-exposure of cells at 100 microM for 30 min, the relative intensity of ten protein spots changed on two-dimensional (2-D) gels compared with control gels after silver staining. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) analysis after in-gel digestion revealed that six of these spots corresponded to three kinds of proteins, each of which was composed of a protein and its modified form with a different isoelectric point (pI). These three proteins were identified as peroxiredoxins (PRDXs) II and III, and calpactin I light chain (p11). H2O2-exposure increased the intensity of the spot with lower pI and simultaneously decreased that of the spot with higher pI for both PRDXs II and III. In addition, the expression of annexin VII, S-adenosyl-L-homocysteine hydrolase, elongation factor II fragment (EF-II), and adenosine deaminase was increased by H2O2-exposure in astrocytes from variously aged rats. Using the Pro-Q Diamond staining, heat shock protein 60 kDa (Hsp 60) and alpha-tubulin were observed to be phosphorylated upon H2O2-exposure. While phosphorylation of alpha-tubulin was correlated positively with age, the changes in abundance of ten protein spots as described above were independent of age. These results suggest that aging does not suppress the responses aimed at limiting injury and promoting repair brought about by severe oxidative stress, and might affect cell dynamics including the formation of microtubules.     

Fluorinated dioxolanes. 3. Nucleophilic reactions of perfluoro-4-methyl-1,3-dioxolanes

Conclusions Perfluoro-2,4-dimethyl-2-fluorocarbonyl-1,3-dioxolane reacts with sodium carbonate to give perfluoro-2-methylene-2-methyl-1,3-dioxolane. Under the reaction conditions, the latter dimerizes to perfluoro-2-(2,4-dimethyl-1,3-dioxolan-2-ylmethylene)-4-methyl-1,3-dioxolane, and on treatment with CsF is converted into perfluoromethyl-(1,3-dioxolany-2-yl)ketone.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 938–942, April, 1989.     

Self-assembly of phosphate fluorosurfactants in carbon dioxide

Anionic phosphodiester surfactants, possessing either two fluorinated chains (F/F) or one hydrocarbon chain and one fluorinated chain (H/F), were synthesized and evaluated for solubility and self-assembly in liquid and supercritical carbon dioxide. Several surfactants, of both F/F and H/F types and having varied counterions, were found to be capable of solubilizing water-in-CO2 (W/C), via the formation of microemulsions, expanding upon the family of phosphate fluorosurfactants already found to stabilize W/C microemulsions. Small-angle neutron scatteringwas used to directly characterize the microemulsion particles at varied temperatures, pressures, and water loadings, revealing behavior consistent with previous results on W/C microemulsions.     

The Hund paradox and stabilization of molecular chiral states

The “paradox of optical isomers” revealed by Hund in 1927 is re-examined taking into account the interaction of a chiral molecule with phonons of optically inactive solids below the Debye temperature θ_D. It has been shown, that in the strong coupling limit, where the dephasing rate is much higher than the energy splitting frequency, the interaction can lead to a complete loss of coherence between mirror-antipodal states of the molecule due to the phonon-induced dephasing. This, in turn, suppresses tunnelling oscillations between them, so that transitions, which are reversible in time for an isolated chiral molecule become irreversible for the same molecule placed in a low-temperature matrix. In order to propose a particular mechanism of such stabilization, contributions of a single- and multi-phonon processes in the dephasing rate have been evaluated. It has been established that only the two-phonon scattering provides the sufficiently strong dephasing in low-temperature solids. Such a two-phonon mechanism is responsible for the stabilization of molecular chiral states as long as the temperature of the medium is lower θ_D, but exceeds a few Kelvin degrees. These findings are discussed in the context of the evolutionary concept known as “the cold prehistory of life”.     

Copolymerization of 1-Vinyl-1,2,4-triazole with 2-Hydroxyethyl Methacrylate

Radical copolymerization of 1-vinyl-1,2,4-triazole with 2-hydroxyethyl methacrylate in dimethylformamide and ethanol, initiated with azobis(isobutyronitrile), was studied. The copolymerization constants of this pair of monomers at low conversions and the microstructure parameters were determined. New highly hydrophilic thinly cross-linked copolymers were prepared from these monomers in the presence of crosslinking agents.