Structural fractal analysis of the active sites of acetylcholinesterase from various organisms.

Acetylcholinesterase (AChE) is the object of many studies due to the fact that it plays an important role in the vital activity of organisms. In particular, when new AChE inhibitors are developed, much attention is paid to the specificity of their action. One of the approaches used to study the specificity is to compare AChE taken from various organisms. In this work, crystallographic data are used to investigate the active sites of AChE (ASAs) in the free (uncomplexed) state for the following five organisms: Homo sapiens (HS), Mus musculus (MM), Torpedo californica (TC), Electrophorus electricus (EE), and Drosophila melanogaster (DM). The structural fractal analysis (SFA) proposed by us earlier is used as a research method. This method is based on the calculation and comparison of the fractal dimensions of molecular structures. SFA demonstrates that there are no significant structural differences between the active sites of human AChE and other AChEs. However, differences are found for the MM/EE pair. Further analysis of individual AARs has revealed two different areas of active sites. Ser203, Trp236, Phe338, and Tyr341 are found to belong to a variable region, and the remaining AARs belong to a conservative region of the ASAs. The fraction of "variability" is low, 0.8%.

Structural and Optical Properties of Silicon Carbide Powders Synthesized from Organosilane Using High-Temperature High-Pressure Method.

The development of new strategies for the mass synthesis of SiC nanocrystals with high structure perfection and narrow particle size distribution remains in demand for high-tech applications. In this work, the size-controllable synthesis of the SiC 3C polytype, free of sp2 carbon, with high structure quality nanocrystals, was realized for the first time by the pyrolysis of organosilane C12H36Si6 at 8 GPa and temperatures up to 2000 °C. It is shown that the average particle size can be monotonically changed from ~2 nm to ~500 nm by increasing the synthesis temperature from 800 °C to 1400 °C. At higher temperatures, further enlargement of the crystals is impeded, which is consistent with the recrystallization mechanism driven by a decrease in the surface energy of the particles. The optical properties investigated by IR transmission spectroscopy, Raman scattering, and low-temperature photoluminescence provided information about the concentration and distribution of carriers in nanoparticles, as well as the dominant type of internal point defects. It is shown that changing the growth modes in combination with heat treatment enables control over not only the average crystal size, but also the LO phonon-plasmon coupled modes in the crystals, which is of interest for applications related to IR photonics.

Structural Fractal Analysis of the Active Site of Acetylcholinesterase in Complexes with Huperzine A, Galantamine, and Donepezil.

The fractal dimension (D) of the active site of hAChE in the unliganded state and as part of complexes with hyperzine A, galantamine, and donepezil is calculated using molecular interatomic-distance histograms. Fractal matrices of structural changes (FMSCs) are formed by pairwise comparison of the values of D and by revealing the significance of their differences. FMSCs are found to be used to quantitatively estimate the changes in the structures of the molecules in various states. When analyzing FMSCs, we found that the most significant structural changes are related to the Glu202 amino acid residue. No structural perturbations are revealed in the case of Trp86, Gly122, Ala204, Phe338, Tyr341, Gly448, and Ile451.

The Influence of Structural Patterns on Acute Aquatic Toxicity of Organic Compounds.

Investigation of the influence of molecular structure of different organic compounds on acute toxicity towards Fathead minnow, Daphnia magna, and Tetrahymena pyriformis has been carried out using 2D simplex representation of molecular structure and two modelling methods: Random Forest (RF) and Gradient Boosting Machine (GBM). Suitable QSAR (Quantitative Structure - Activity Relationships) models were obtained. The study was focused on QSAR models interpretation. The aim of the study was to develop a set of structural fragments that simultaneously consistently increase toxicity toward Fathead minnow, Daphnia magna, Tetrahymena pyriformis. The interpretation allowed to gain more details about known toxicophores and to propose new fragments. The results obtained made it possible to rank the contributions of molecular fragments to various types of toxicity to aquatic organisms. This information can be used for molecular optimization of chemicals. According to the results of structural interpretation, the most significant common mechanisms of the toxic effect of organic compounds on Fathead minnow, Daphnia magna and Tetrahymena pyriformis are reactions of nucleophilic substitution and inhibition of oxidative phosphorylation in mitochondria. In addition acetylcholinesterase and voltage-gated ion channel of Fathead minnow and Daphnia magna are important targets for toxicants. The on-line version of the OCHEM expert system (https://ochem.eu) were used for a comparative QSAR investigation. The proposed QSAR models comply with the OECD principles and can be used to reliably predict acute toxicity of organic compounds towards Fathead minnow, Daphnia magna and Tetrahymena pyriformis with allowance for applicability domain estimation.

Memory Effect in the Spatial Series Based on Diamond and Graphite Crystals.

To study the relation between the structure of a compound and its properties is one of the fundamental trends in chemistry and materials science. A classic example is the well-known influence of the structures of diamond and graphite on their physicochemical properties, in particular, hardness. However, some other properties of these allotropic modifications of carbon, e.g., fractal properties, are poorly understood. In this work, the spatial series (interatomic distance histograms) calculated using the crystal structures of diamond and graphite are investigated. Hurst exponents H are estimated using detrended fluctuation analysis and power spectral density. The values of H are found to be 0.27-0.32 and 0.37-0.42 for diamond and graphite, respectively. The calculated data suggest that the spatial series have long memory with a negative correlation between the terms of the series; that is, they are antipersistent.