Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors

Acetylcholinesterase (AChE) is one of the classical targets in the treatment of Alzheimer’s disease (AD). Inhibition of AChE slows down the hydrolysis of acetycholine and increases choline levels, improving the cognitive function. The achieved success of plant-based natural drugs acting as AChE inhibitors, such as galantamine (GAL) from Galanthus genus and huperzine A from Huperzia serrate (approved drug in China), in the treatment of AD, and the fact that natural compounds (NCs) are considered as safer and less toxic compared to synthetic drugs, led us to screen the available NCs (almost 150,000) in the ZINC12 database for AChE inhibitory activity. The compounds were screened virtually by molecular docking, filtered for suitable ADME properties, and 32 ligands from 23 structural groups were selected. The stability of the complexes was estimated via 1 μs molecular dynamics simulation. Ten compounds formed stable complexes with the enzyme and had a vendor and a reasonable price per mg. They were tested for AChE inhibitory and antioxidant activity. Five compounds showed weak AChE inhibition and three of them exhibited high antioxidant activity.     

Exploration of the Crystal Structure and Thermal and Spectroscopic Properties of Monoclinic Praseodymium Sulfate Pr2(SO4)3

Praseodymium sulfate was obtained by the precipitation method and the crystal structure was determined by Rietveld analysis. Pr₂(SO₄)₃ is crystallized in the monoclinic structure, space group C2/c, with cell parameters a = 21.6052 (4), b = 6.7237 (1) and c = 6.9777 (1) Å, β = 107.9148 (7)°, Z = 4, V = 964.48 (3) ų (T = 150 °C). The thermal expansion of Pr₂(SO₄)₃ is strongly anisotropic. As was obtained by XRD measurements, all cell parameters are increased on heating. However, due to a strong increase of the monoclinic angle β, there is a direction of negative thermal expansion. In the argon atmosphere, Pr₂(SO₄)₃ is stable in the temperature range of T = 30–870 °C. The kinetics of the thermal decomposition process of praseodymium sulfate octahydrate Pr₂(SO₄)₃·8H₂O was studied as well. The vibrational properties of Pr₂(SO₄)₃ were examined by Raman and Fourier-transform infrared absorption spectroscopy methods. The band gap structure of Pr₂(SO₄)₃ was evaluated by ab initio calculations, and it was found that the valence band top is dominated by the p electrons of oxygen ions, while the conduction band bottom is formed by the d electrons of Pr³⁺ ions. The exact position of ZPL is determined via PL and PLE spectra at 77 K to be at 481 nm, and that enabled a correct assignment of luminescent bands. The maximum luminescent band in Pr₂(SO₄)₃ belongs to the ³P₀ → ³F₂ transition at 640 nm.     

Physical Treatment Reduces Trypsin Inhibitor Activity and Modifies Chemical Composition of Marama Bean (Tylosema esculentum)

The utility of the marama bean (MB) as an alternative protein source to soybean (SB) can be limited by the high concentration of trypsin inhibitors (TI). The physical treatment of MB has the potential to ameliorate the antinutritional activities of TI and modify other chemical components. Thus, this study investigated the effects of physical treatments on the chemical components and trypsin inhibitor activity (TIA) of raw MB and SB. The bean substrates were subjected to each of the following treatment methods: (1) room temperature (20–22 °C) soaking for 24 h; (2) electric stove cooking at 100 °C for 10, 20, and 30 min; (3) steam autoclaving at a temperature of 110 °C and pressure of 7 pounds per square inch (psi), as well as a temperature of 121 °C and 7 psi for 5, 15, and 30 min; (4) pre-soaked autoclaving at 110 °C (7 psi) and 121 °C (17 psi) for 5, 15, and 30 min. Treated MB and SB had greater (p < 0.05) crude protein content than untreated samples. All the treatments (except 24 h soaking of MB) reduced (p < 0.05) the TIA and ash content. Marama and SB are similar in protein content, but their amino acids profile and TIA are quite different. Soaking for 24 h was less effective in reducing TIA in MB and SB, compared to the thermal methods, and it was detrimental to the ash and amino acids profile of the two beans. Soaking prior to autoclaving yielded beans with the lowest TI concentrations. In conclusion, thermal methods reduced the TI contents and modified the level of proximate components and amino acids profile of the beans.     

Stability of the single-domain state in single crystals of triglycine sulphate

The stability of the single-domain state in single crystals of triglycine sulfate is investigated using the Barkhausen effect. Barkhausen jumps are detected upon invariable macroscopic polarization. The parameters of the observed Barkhausen jumps are estimated and compared.     

“Trapped fraction” effect in microfuel with plutonium fuel

Results of the investigation into the thermodynamics of two types of microfuel (with oxygen getter and without it) with plutonium fuel for various degrees of burnup are presented. The behavior of the trapped fraction of Ag, Ce, Cd, Cs, La, Mo, Pu, Pd, Ru, Sr, Te, and Y is investigated. The fraction of any fission product bound into stable chemical compounds with other components of the system and excluded from the diffusion process is called the trapped fraction. An abrupt increase in the trapped fraction of cesium and, correspondingly, a decrease in free cesium during the burnup of ～26% FIMA (fissions per initial metal atom) or more are found for the microfuel containing no oxygen getter. This leads to a substantial nonlinear burnup dependence of the trapped fraction and should be the cause of an abrupt decrease in the Cs output from the microfuel. It seems likely that the found effect is associated with the formation of carbonate Cs₂CO₃ in the plutonium fuel. In the case of microfuel containing the oxygen getter, no formation of cesium carbonate occurs and the trapped fraction of cesium is almost independent of the burnup.     

Forward physics of hadronic colliders

These lectures were given at the Baikal Summer School on Physics of Elementary Particles and Astrophysics in July 2012. They can be viewed as a concise introduction to hadronic diffraction, to the physics of the Pomeron and related topics.     

Quantum chemical calculations for the hydration of model silica modified by aliphatic amines

Various basis sets and methods for quantum-chemical calculations are analyzed, and the effect of the number of diffusion and polarization functions on geometry and energy characteristics of systems that simulate the surface of silica modified by aliphatic amines is studied. The contribution from correlation effects and the superposition error of the basis set to the values of the energy characteristics of the hydration of model objects is evaluated. A section of an aminosilica surface was hydrated in simulation. Conclusions as to the existence of arched structures on the surface of aminosilica that include amino and silanol groups are confirmed.