Discovery of Potential,Dual-Active Histamine H3 Receptor Ligands with Combined Antioxidant Properties

In an attempt to find new dual acting histamine H₃ receptor (H₃R) ligands, we designed a series of compounds, structurally based on previously described in our group, a highly active and selective human histamine H₃ receptor (hH₃R) ligand KSK63. As a result, 15 obtained compounds show moderate hH₃R affinity, the best being the compound 17 (hH₃R K_i = 518 nM). Docking to the histamine H₃R homology model revealed two possible binding modes, with key interactions retained in both cases. In an attempt to find possible dual acting ligands, selected compounds were tested for antioxidant properties. Compound 16 (hH₃R K_i = 592 nM) showed the strongest antioxidant properties at the concentration of 10⁻⁴ mol/L. It significantly reduced the amount of free radicals presenting 50–60% of ascorbic acid activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, as well as showed antioxidative properties in the ferric reducing antioxidant power (FRAP) assay. Despite the yet unknown antioxidation mechanism and moderate hH₃R affinity, 16 (QD13) constitutes a starting point for the search of potential dual acting H₃R ligands-promising tools for the treatment of neurological disorders associated with increased neuronal oxidative stress.     

Ten-π - electron nitrogen heterocyclic compounds. VIII. Semi-empirical calculations of chemical-shifts of ring-protons and of methyl-protons

The chemical-shifts of the ring protons and of the methyl protons of some unsub-stituted and some methylpolyazanidenes have been calculated by a semi-empirical method utilizing charge-densities obtained from HMO calculations. The success of this method lies in the choice of the reference compound, pyrrocoline.     

HMO consideration of factors affecting tautomerism in hydroxyarylazo compounds

The factors affecting tautomeric equilibrium of hydroxyarylazo compounds have been treated by the HMO method using difference in bonding energy as criterion of tautomeric stability. The larger the ring bearing the oxygen atom, the more stable is the hydrazone tautomer. By the same approach, it is further shown that intermolecular and intramolecular hydrogen bonding, electron withdrawing substituents, and the formation of hydrogen-bonded dimers favor the hydrazone tautomer.     

A Taxicab geometry quantification system to evaluate the performance of in silico methods: a case study on adenosine receptors ligands

Journal of Computer-Aided Molecular Design - Among still comparatively few G protein-coupled receptors, the adenosine A2A receptor has been co-crystallized with several ligands, agonists as well as...     

Polarographic reduction of benzylidenemalononitrile

The mechanism of reduction of benzylidenemalononitrile (1), C₆H₅CH=C(CN)₂, at the dropping mercury electrode in aqueous solutions containing 50% methanol changes with pH. In acidic solutions the reduction proceeds by a four-electron transfer to the monoprotonated species, yielding an aminomethyl derivative. In alkaline solutions two one-electron steps involving the vinyl double bond reduction are observed. Hydrolysis of dinitrile 1 to form benzaldehyde complicates the study at high pH values. The system is unique in that at pH 5–6 the unprotonated form is reduced at more positive potentials than the protonated form, reflecting a change in the mechanism of the reduction process.     

IR laser-induced decomposition of dialkoxyalkanes

Infrared multiphoton excitation of dimethoxymethane and related compounds results in initially very high conversions with subsequent failure of the reaction to go to completion. This behavior is attributed to a free radical chain decomposition with inhibition of further reaction by collisional deactivation or trapping of intermediates by reaction products.     

Diffusion pore imaging with generalized temporal gradient profiles

In porous material research, one main interest of nuclear magnetic resonance diffusion (NMR) experiments is the determination of the shape of pores. While it has been a longstanding question if this is in principle achievable, it has been shown recently that it is indeed possible to perform NMR-based diffusion pore imaging. In this work we present a generalization of these previous results. We show that the specific temporal gradient profiles that were used so far are not unique as more general temporal diffusion gradient profiles may be used. These temporal gradient profiles may consist of any number of “short” gradient pulses, which fulfil the short-gradient approximation. Additionally, “long” gradient pulses of small amplitude may be present, which can be used to fulfil the rephasing condition for the complete profile. Some exceptions exist. For example, classical q-space gradients consisting of two short gradient pulses of opposite sign cannot be used as the phase information is lost due to the temporal antisymmetry of this profile.     

Autonomous gauge for blast impulse determination close to explosive charges

This paper reports on a new gauge for blast impulse determination close to explosive charges. The gauge is based on the autonomous data recorder g-rec developed at the Ernst-Mach-Institute for data acquisition in harsh environments. Combined with an acceleration sensor these data recorders allow for the direct determination of the momentum transferred to an object by a blast wave even in the immediate vicinity of the explosive charge. From this the blast impulse can be determined. Using autonomous electronics distinct advantages are gained compared to classical passive momentum traps. The paper summarizes the properties of the g-rec recorder and describes the setup of the autonomous momentum trap in detail. Numerical simulations are presented which illustrate the gauge performance and its limitations. Tests with 1 kg charges demonstrate the feasibility of the approach. Good agreement was found between simulations and tests. The application range of the gauges is determined by the measurement range of the built-in acceleration sensor and its overall dimensions and weight. The present configuration is designed for distances between \(\sim \)0.3 and 1 m from charges between several 100 g and several kilograms. Data were successfully collected down to reduced distances of 0.25 m/kg\(^{1/3}\). Minor changes in gauge dimensions, weight, or measurement range enable the gauges to be deployed at even closer distances.