Antinociceptive Effects of Aza-Bicyclic Isoxazoline-Acylhydrazone Derivatives in Different Models of Nociception in Mice

Background: In a study recently published by our research group, the compounds isoxazoline-acylhydrazone derivatives R-99 and R-123 presented promising antinociceptive activity. However, the mechanism of action of this compound is still unknown. Objective: This study aimed to assess the mechanisms involved in the antinociceptive activity of these compounds in chemical models of pain. Methods: Animals were orally pretreated and evaluated in the acetic acid-, formalin-, capsaicin-, carrageenan- and Complete Freund's Adjuvant (CFA)-induced pain models in mice. The effects of the compounds after pretreatment with naloxone, prazosin, yohimbine, atropine, L-arginine, or glibenclamide were studied, using the acetic acid-induced writhing test to verify the possible involvement of opioid, α1-adrenergic, α2-adrenergic or cholinergic receptors, and nitric oxide or potassium channels pathways, respectively. Results: R-99 and R-123 compounds showed significant antinociceptive activity on pain models induced by acetic acid, formalin, and capsaicin. Both compounds decreased the mechanical hyperalgesia induced by carrageenan or CFA in mice. The antinociceptive effects of R-99 and R-123 on the acetic acid-induced writhing test were significantly attenuated by pretreatment with naloxone, yohimbine or atropine. R-99 also showed an attenuated response after pretreatment with atropine and glibenclamide. However, on the pretreatment with prazosin, there was no change in the animals' response to both compounds. Conclusion: R-99 and R-123 showed antinociceptive effects related to mechanisms that involve, at least in part, interaction with the opioid and adrenergic systems and TRPV1 pathways. The compound R-99 also interacts with the cholinergic pathways and potassium channels.

PMMA – C60 composite: thermal decomposition experiments in mass spectrometer and quantum chemical modeling

Mass-spectrometric thermal decomposition experiments with submicron films of neat polymethylmethacrylate (PMMA), and PMMA-fullerene composite (PMMA-C60) after UV irradiation are discussed. The experiment registers thermal desorption mass spectra (TDMS), that is the monomer desorption rate versus time upon gradual heating the PMMA films in a given heating regime. The spectra provide information on the amount of the monomer desorbed at different decomposition stages upon heating the given amount of film material as well as on the spectral shape changes. It is shown that both amount of monomer and the TDMS spectral shape are sensitive to the presence of fullerene and UV irradiation. The experimental results are discussed in terms of quantum chemical models of binding. The DFT/B3LYP-D3/def2/J RIJCOSX level of theory was used. The MMA-C60 structures which can yield different amounts of monomer have been compared.

A Revised Description of the Cosmic Ray Induced Desorption of Interstellar Ices

Nonthermal desorption of ices on interstellar grains is required to explain observations of molecules that are not synthesized efficiently in the gas phase in cold dense clouds. Perhaps the most important nonthermal desorption mechanism is one induced by cosmic rays (CRs), which, when passing through a grain, heat it transiently to a high temperature—the grain cools back to its original equilibrium temperature via the (partial) sublimation of the ice. Current cosmic ray induced desorption (CRD) models assume a fixed grain cooling time. In this work, we present a revised description of CRD in which the desorption efficiency depends dynamically on the ice content. We apply the revised desorption scheme to two-phase and three-phase chemical models in physical conditions corresponding to starless and prestellar cores, and to molecular cloud envelopes. We find that, inside starless and prestellar cores, introducing dynamic CRD can decrease gas-phase abundances by up to an order of magnitude in two-phase chemical models. In three-phase chemical models, our model produces results very similar to those of the static cooling scheme—when only one monolayer of ice is considered active. Ice abundances are generally insensitive to variations in the grain cooling time. Further improved CRD models need to take into account additional effects in the transient heating of the grains—introduced, for example, by the adoption of a spectrum of CR energies.

Chemistry of combustible minerals

This textbook is a publication of the latest generation, designed to optimize the national project "Education"; develops theoretical knowledge about the genesis of natural liquid, gaseous and solid combustible minerals, the formation of the composition and properties, the practical significance of fuel and energy natural complexes. It is devoted to the study of the composition, properties and classification of oils, gas condensate, natural gases and solid combustible minerals, studied at the level of modern achievements of instrumental analytical and factory equipment in accordance with existing technologies, theories and hypotheses about the genesis of hydrocarbons and Earth sciences. The publication is supplemented with the main directions of processing of combustible minerals. Digital and graphical types of chemical models of the synergy of components of gas and oil deposits are described, which are necessary for predicting the phase state and composition of hydrocarbons and optimizing the directions of processing of marketable products. To facilitate the process of cognition of the origin and formation of the composition and properties of natural combustible minerals, a glossary, tests, as well as questions for the test and exam are offered. To control the knowledge gained by students while studying textbook materials, each chapter is accompanied by questions and tasks. Meets the requirements of the federal state educational standards of higher education of the latest generation. It is intended for students studying in the fields of 05.04.01, 05.03.01 "Geology", 21.05.02 "Applied Geology", as well as for specialists in the field of geology, geochemistry, extraction and processing of oil, gas, gas condensate, solid fuels.

Electrometric Investigation of the Nature and Stability of Mixed Ligand Complexes of L-Ornithine and 1,10-Phenanthroline with Some Essential Metal Ions in Aqua-TBAB or PEG-400 Surfactant

Background Despite the availability of information about the effect of aqua-surfactants media on the stability of binary complexes, data related to mixed ligand complexes of Phen and Orn with essential metals in aqua-surfactant medium is scarce. The aim of this study was, to determine the stabilities of the mixed ligand complexes of essential metal ions (Co2+, Ni2+, Cu2+) with Phen and Orn in aqua-TBAB and PEG-400 surfactants with an eye on the prediction of the bioavailability of the metal complexes. Results Complexes of some essential metal (M) ions (Co2+, Ni2+, Cu2+) of L-ornithine (L) and 1,10-phenanthroline (X) ligands in various concentrations (0.0–2.5% v/v) of aqueous tetrabutylammonium bromide (TBAB) or polyethylene glycol-400 (PEG-400) surfactant were synthesized pH-metrically at 298 K and 0.16 mol L− 1 ionic strength. The relative amounts of L:M:X were 2.5:1.0:2.5; 5.0:1.0:2.5; 2.5:1.0:5.0. The data acquisition of acid-base equilibria and determination of stability constants were performed using MINIQUAD75 algorithm. The distribution patterns of the complexes with varying pH and compositions of surfactants were presented from the plots of SIM run data. Conclusions The best fit chemical models were found to be MLXH, MLX2H in the lower pH, and MLX, ML2X in the higher pH ranges for all the metals. The logged values of stability constants decreased linearly with increasing concentrations of surfactants, indicating the dominance of electrostatic factors. The log of the disproportionation constant and the change in log values of the mixed ligand constant indicated additional stability of the mixed ligand complexes, compared to the parent binary complexes due to interactions outside the coordination sphere. This makes the mixed ligand complexes more amenable to metal ion storage and transport and threw light to have information on the less stable binary complexes easily bioavailability while the mixed ligand complexes could be stored and transported in the bio-fluids. Significant change on the magnitudes of the stability constants, high values of standard deviation and rejection of some of the proposed chemical models were observed due to pessimistic error, indicating the sufficiency of the models to represent the data and accuracy of the method employed.

Neptune's Atmospheric Structure from the Spitzer Infrared Spectrometer

<p><strong>Introduction:</strong> NASA’s Spitzer Infrared Spectrometer (IRS) acquired mid-infrared (5 - 37 micron) disc-averaged spectra of Neptune in May 2004, November 2004, November 2005, and May 2006. Meadows et al., (2008, doi: 10.1016/j.icarus.2008.05.023) discovered Neptune's complex hydrocarbons methylacetylene and diacetylene and derived their abundances using the May 2004 data. The rest of the Neptune data has yet to be published. The data have all been reduced using the same methodology as Rowe-Gurney et al., (2021, doi: 10.1016/j.icarus.2021.114506) used for Uranus, so that each year can be reliably compared.</p> <p>We detect the same hydrocarbons seen in Meadows et al., (2008). This includes the strongest bands of methane (CH<sub>4</sub>), acetylene (C<sub>2</sub>H<sub>2</sub>) and ethane (C<sub>2</sub>H<sub>6</sub>) as-well-as weaker but still clearly recognisable features of ethylene (C<sub>2</sub>H<sub>4</sub>), carbon dioxide, methyl (CH<sub>3</sub>), methylacetylene (C<sub>3</sub>H<sub>4</sub>) and diacetylene (C<sub>4</sub>H<sub>2</sub>).</p> <p>At Uranus, there was a considerable longitudinal variation in stratospheric emission detected in the Spitzer data for multiple epochs (Rowe-Gurney et al., 2021). A variation is not present at Neptune in 2005 or late 2004, when all the separate longitudes displayed the same brightness temperature. In May 2004 a stratospheric variation is present, although it is tentative due to the deviation only appearing at a single longitude and because there are larger uncertainties on this early dataset. If the variation is real then it could be caused by stratospheric methane injection associated with convective clouds or perturbations to the location of the south polar warm vortex (Orton et al., 2012, doi: 10.1016/j.pss.2011.06.013).</p> <p><strong>Optimal Estimation Retrievals: </strong>The data from 2005 have optimised exposure times, multiple observed longitudes, and therefore the lowest noise. It is this data we are using to derive the vertical structure of the temperature and composition in the stratosphere and upper troposphere (between around 1 nanobar and 2 bars of pressure). We present full optimal estimation inversions (using the NEMESIS retrieval algorithm, Irwin et al., 2008, doi: 10.1016/j.jqsrt.2007.11.006) of the globally averaged November 2005 data with the aim of constraining the temperature profile and the abundances of the stratospheric hydrocarbons. We fit both the low-resolution (R~120) and high-resolution (R~600) module data, testing multiple temperature priors derived from chemical models (Moses et al., 2018, doi: 10.1016/j.icarus.2018.02.004) and observations from AKARI (Fletcher et al., 2010, doi: 10.1051/0004-6361/200913358). Initial findings show that we are sensitive to stratospheric D/H ratio (derived from the relative abundances of CH<sub>4</sub> and CH<sub>3</sub>D) and therefore we will attempt to constrain this value by finding the best fit for our model.</p> <p><strong>Conclusion:</strong> Full spectrum mid-infrared data from Neptune in 2005 taken by the Spitzer Infrared Spectrometer is to be analysed using optimal estimation retrievals for the first time. The globally-averaged stratospheric temperature structure and the abundances of stratospheric hydrocarbons will be determined along with the ratio of D/H. The disc-averaged thermal and chemical structure from Spitzer will likely be our best characterisation of Neptune’s thermal structure until JWST/MIRI acquired spatially-resolved mid-infrared spectroscopy in 2022.</p>

Geoid and topography on Venus: Isostatic or dynamic?

<p>Venus is commonly described as Earth’s slightly smaller twin planet. However, the dynamics of plate tectonics present at Earth are not observed at Venus.  Gravity and topography are key observations to help understand the interior dynamics of a planet. On Earth, the long-wavelength geoid and total surface topography are not well correlated, with the interpretation that total surface topography is mainly due to the ocean-continent dichotomy whereas geoid reflects density anomalies deep in the mantle, mainly caused by subducted slabs. Dynamic surface topography is small compared to the total surface topography. On Venus, in contrast, the geoid and topography are well correlated, indicating a more direct connection between convection and the lithosphere and crust.</p> <p>For Venus, two end-member origins of geoid and topography variations have been proposed: 1) Deep-seated (i.e. below the lithosphere) density anomalies associated with mantle convection, which may require a recent global lithospheric overturn to be significant [1][2][3]. 2) Variations in lithosphere and crustal thickness that are isostatically compensated - the so-called "isostatic stagnant lid approximation" [4][5], which appears consistent with simple stagnant-lid convection experiments.</p> <p>Here we analyse 2-D and 3-D dynamical thermo-chemical models of Venus' mantle and crust that include melting and crustal production, multiple composition-dependent phase transitions and strongly variable viscosities to test whether variations in crust and lithosphere thickness explain most of the geoid signal [4][5], or whether it is caused mostly by density variations below the lithosphere, and thus, what we can learn about the crust, lithosphere and deeper interior of Venus from observations, as well as which tectonic mode is most likely to explain the observed geoid signal. Multiple input parameter sets are used to recreate the end-member scenarios of stagnant-lid and episodic-lid tectonics and to investigate the influence of the different rheological parameters. Characteristic snapshots of simulations showing end-member tectonic behaviour are analysed to determine the depth ranges of heterogeneities that are the predominant influence on topography and geoid variations. Findings will also guide future efforts to combine gravity and topography observations to infer lithosphere and crustal thickness and their variations (e.g. [6][7]).</p> <p><strong>References</strong></p> <p>[1] Armann, M., and P. J. Tackley (2012), Simulating the thermo-chemical magmatic and tectonic evolution of Venus' mantle and lithosphere: two-dimensional models, <em>J. Geophys. Res.</em>, <em>117</em>, E12003, doi:12010.11029/12012JE004231</p> <p>[2] King, S. D. (2018), Venus resurfacing constrained by geoid and topography, <em>J. Geophys. Res.</em>, <em>123</em>, doi:10.1002/2017JE005475.</p> <p>[3] Rolf, T., B. Steinberger, U. Sruthi, and S. C. Werner (2018), Inferences on the mantle viscosity structure and the post-overturn evolutionary state of Venus, <em>Icarus</em>, <em>313</em>, 107-123, doi:10.1016/j.icarus.2018.05.014.</p> <p>[4] Orth, C. P., and V. S. Solomatov (2011), The isostatic stagnant lid approximation and global variations in the Venusian lithospheric thickness, <em>Geochem. Geophys. Geosyst.</em>, <em>12</em>(7), Q07018, doi:10.1029/2011gc003582.</p> <p>[5] Orth, C. P., and V. S. Solomatov (2012), Constraints on the Venusian crustal thickness variations in the isostatic stagnant lid approximation, <em>Geochemistry, Geophysics, Geosystems</em>, <em>13</em>(11), n/a-n/a, doi:10.1029/2012gc004377</p> <p>[6] Jiménez-Díaz, A., J. Ruiz, J. F. Kirby, I. Romeo, R. Tejero, and R. Capote (2015), Lithospheric structure of Venus from gravity and topography, <em>Icarus</em>, <em>260</em>, 215-231, doi:10.1016/j.icarus.2015.07.020.</p> <p>[7] Yang, A., J. Huang, and D. Wei (2016), Separation of dynamic and isostatic components of the Venusian gravity and topography and determination of the crustal thickness of Venus, <em>Planetary and Space Science</em>, <em>129</em>, 24-31, doi:10.1016/j.pss.2016.06.001.</p>

Effect of Solvent on Protonation Equilibria of L-Serine and L-Tryptophan in Ethylene Glycol-Water Mixtures

Protonation equilibria of L-serine and L-tryptophan in varying compositions (0.0-50.0 % v/v) of ethylene glycol-water mixtures were investigated pH-metrically. Titrations were performed at 303.0 K and the ionic strength of the medium was maintained at 0.16 mol L-1 using sodium chloride. The protonation constants have been calculated with the computer program MINIQUAD 75 and are selected based on statistical parameters. The best fit chemical models of the protonation equilibria were based on crystallographic R-factor, χ2, skewness and kurtosis. The protonation constants of L-serine and L-tryptophan change linearly with increasing ethylene glycol content. This is attributed to the dielectric constant of the medium.