卷 66, 编号 10 (2017)
- 年: 2017
- 文章: 23
- URL: https://journals.rcsi.science/1066-5285/issue/view/14936
Reviews
Unique hyper-kagome atomic order in geometrically frustrated iridium spinel-like structures
摘要
The review briefly outlines the results of authors’ theoretical research into unique hyperkagome atomic and orbital order in geometrically frustrated iridium spinel-like structures. The structural mechanism of formation of the hyper-kagome atomic order is established. It is shown that closed loops of Ir—Ir bonds represent a fundamental feature of the iridium spinel-like structures. Each loop consists of ten atoms, thus being a decagon. We assume that decagons are responsible for abnormal chemical and physical properties of crystals. A prediction is made of structural types of crystals in which the hyper-kagome atomic order can exist.
Active sites on the surface of nanocrystalline semiconductor oxides ZnO and SnO2 and gas sensitivity
摘要
The data on active sites on the surface of nanocrystalline semiconductor oxides ZnO and SnO2 are reviewed. Their interrelation to the gas sensitivity of the materials toward the main air pollutants, viz., CO, NO2, NH3, and H2S, is analyzed. The influence of the synthesis conditions, microstructure parameters, content of dopant impurities, and the presence of catalytic modifiers on the concentration of various active sites on the oxide surface is considered. Relationships between the concentration of the surface sites and sensitivity of the oxides to gases with various chemical properties are revealed. The active sites responsible for the formation of a sensory signal upon the selective interaction with molecules of the detected gases are determined.
Classical and interdisciplinary approaches to the design of organic and hybrid molecular systems
摘要
This review summarizes the recent advances in the construction of organic and hybrid systems having considerable potential for practical applications in pharmacology, medicine, materials science, petrochemistry, and chemistry of high-energy compounds. The methodological classification of the approaches into classical and interdisciplinary is proposed. Examples of the efficient application of these approaches for investigating complex molecular systems, as well as for developing new methods of synthesis are given.
Structure of the receptor layer in electrochemical immunosensors. Modern trends and prospects of development
摘要
Literature data on the modern state and prospects for the development of research in the area of receptor layer immobilization in electrochemical immunosensors were examined and systematized. The first section of the review is devoted to structural features and functions of biological immunoreceptors, viz., antibodies or their fragments. The main methods of antibody immobilization on the working electrode surface are considered in detail in the second section. The prospects for the development of electrochemical immunosensors are discussed in the third section of the review.
Biologically active polymer nanosystems
摘要
The methods of synthesis of biologically active nanostructured systems based on functional and natural polymers are reviewed. The formation of nanosystems in the process of interaction between synthetic water-soluble polyelectrolytes and amphiphilic ionic surfactants is discussed. The influence of structure and stability of these systems on their biological activity is considered. The complexation between DNA and polycations with the formation of compacted DNA molecules, and the transport of resulting complexes into the cells are discussed. The data on nanostructuring of hemoglobin using polyfunctional crosslinkers and the data on the use of the obtained nanoparticles as oxygen-transporting blood substitutes are summarized. Using nanodisperse silver stabilized with poly(vinylpyrrolidone) as an example it was demonstrated, that transferring silver into nanodisperse state results in widening its bioactivity.
Targeted synthesis and biological activity of polypharmacophoric agents for the treatment of neurodegenerative diseases
摘要
Synthetic approaches to the design of new multitarget agents for the treatment of neurodegenerative diseases are surveyed. These approaches are based on the conjugation of the pharmacophoric indole, phenothiazine, and aminoadamantane moieties via 1-oxopropylene and 2-hydroxypropylene spacers using reactions of acrylate- and epoxide-containing pharmacophores with tetrahydro-γ-carbolines, cycloalkaneindoles, carbazoles, and aminoadamantanes. The review considers data on biological activity of the compounds assessed within a complex screening system. This system includes neurotransmitter targets associated with cognitive compensation, such as cholinesterases and glutamate receptors, mitochondria, the influence on which can provide neuroprotective effects, and microtubules, the stabilization of which leads to the improvement of axonal transport. The ability of the compounds to act as free-radical scavengers was evaluated. Types of polypharmacophoric compounds promising for further development are proposed.
Computational platform Way2Drug: from the prediction of biological activity to drug repurposing
摘要
The Way2Drug informational-computational platform (www.way2drug.com/dr) provides access to the data on drugs approved for medicinal use in the USA and Russian Federation, as well as computational possibilities for the prediction of biological activity of drug-like organic compounds. Currently realized computational tools of the platform, which allow one to predict several thousands of biological activity types, including the interaction with molecular targets, pharmacotherapeutic and side effects, metabolism, acute toxicity for rats, cytotoxicity, influence on gene expression, and other properties characterizing the evaluation how promising are particular drug-like compounds as potential pharmaceuticals, are reviewed. Using the Way2Drug platform, one can not only select the most promising "hits" for the synthesis and testing of biological activity but also reveal new indications for the launched drugs.
Full Articles
Quantum chemical modeling of possible reactions of mononuclear iron nitrosyl complex [Fe(SC(NH2)2)2(NO)2]Cl•H2O in an aqueous solution
摘要
Possible reactions of the mononuclear iron nitrosyl complex [Fe(SC(NH2)2)2(NO)2]Сl•H2O in an aqueous solution were studied using quantum chemical modeling. The electronic structures of the possible intermediates were examined by the NBO and AIM methods. The substitution of the thio ligand in the iron—sulfur nitrosyl complex by a water molecule and the formation of dimeric intermediate complexes were found to facilitate the NO-donation process.
IR-study of hydrated surface of oxide photocatalysts
摘要
IR spectroscopy combined with thermogravimetry was used to investigate the effect of the pretreatment temperature on the degree of coverage of the surface of oxide photocatalysts, TiO2, ZnO, CeO2, and Zn2+/TiO2, with water. At room temperature, the amount of adsorbed water per unit area of photocatalysts in the air decreases in the row: ZnO ≥ CeO2 > TiO2, whereas the temperature needed for complete removal of physically adsorbed water from the studied oxides decreases in the reverse order. Water is removed from the ZnO surface by evacuation at room temperature; in the case of CeO2 and TiO2, it desorbs at 200 and 300 °С, respectively. The terminal OH groups on the oxide surface are the most strongly bonded with adsorbed water. In the zinc modified TiO2, the terminal OH groups are firstly replaced by Zn cations, which causes both hydrophobization of the samples under atmospheric conditions and a decrease in the temperature at which physically adsorbed water is released from the surface. Evacuation of ZnO at 350 °C removes the surface oxygen and results in the generation of the surface defect sites. This causes strong absorption in the IR spectra in the region of 1000—4000 cm–1. The formation of surface defects probably causes the appearance of donor levels in the band gap. The energy of the transition of electrons from these levels to the conduction band corresponds to the energy of the IR radiation. After oxidation of such samples in O2 at 350 °C, strong absorption in the IR spectra disappears.
Sorption of nicotinic and isonicotinic acids by the strongly basic anion exchanger АВ-17-8
摘要
Thermodynamics and kinetics of sorption with the participation of nicotinic and isonicotinic acids on the strongly basic anion exchanger АВ-17-8 were studied. According to calorimetric measurements, partial (differential) heat of sorption was estimated for anions and zwitterions of pyridinecarboxylic acids upon sorption by the OH-form of the anion exchanger AB-17-8 at 298K. Sorption of zwitterions of pyridinecarboxylic acids by the OH-form of the strongly basic anion exchanger can be presented as the process that involves independent reactions of ion exchange, dissociation of pyridinecarboxylic acid, and neutralization. The kinetics of sorption on the strongly basic anion exchanger with the participation of nicotinic and isonicotinic acids is shown to be controlled by the slow diffusion of the components in the polymer phase. For the organic anion in the phase of the anion exchanger АВ-17-8, the diffusion coefficient is equal to (1.3±0.4)•10–12 m2 s–1.
Zinc-containing derivatives of 2-aminopyrimidine
摘要
A platform containing three anticancer components is proposed. The components are a radioactive 69mZn isotope and zinc complexes, where both zinc and ligand exhibit anticancer properties. Two zinc-containing complexes, namely (2-AP)2ZnCl2 and (2-AP)2Zn(Sal)2 (AP is 2-aminopyrimidine, Sal is salicylate) were synthesized and characterized. Their cytotoxicity with respect to some leukemia cell lines is demonstrated. Their stability in physiological solution and percentage of apoptosis (by flow cytometry) are investigated. Stable complexes of compounds with the isotope 69mZn were characterized by TLC and autoradiography.
Antitumor activity of carboplatin in the composition of a copolymer of lactic and glycolic acids
摘要
Polymer particles containing carboplatin (CPt) were developed by the inclusion of this antitumor agent in a copolymer of lactic and glycolic acids (PLGA-COOH 50/50). The polymer particles were found to have a spherical form with an average diameter not exceeding 200 nm, the ζ-potential is equal to–32.2±1 mV. The CPt-loaded polymer particles possess a cytotoxic activity against human small cell and non-small cell lung carcinoma (lines H69 and A549), as well as against mouse mammary adenocarcinoma (line Ca755). The results of the in vivo studies carried out on female mice of line C57Bl/6 with inoculated mouse melanoma of line B16 showed increasing of lifespan of the animals and inhibition of tumor growth for groups treated with the polymer particles, as compared to the animals treated with the drug substance CPt.
Structure—activity relationship in the series of 1,3,4-6Н-thiadiazines correcting metabolic disorders in experimental diabetes mellitus
摘要
The corrective action of 1,3,4-6Н-thiadiazines in experimental diabetes mellitus was studied. The structure—activity relationship model for this series of compounds was proposed using the multiple linear regression method.
Synthesis and properties of 1-(R-adamant-1-yl)-3-(1-propionylpiperidin-4-yl)ureas and 4-({4-[3-(R-adamant-1-yl)ureido]cyclohexyl}oxy)benzoic acids, efficient target-oriented human soluble epoxide hydrolase inhibitors
摘要
A reaction of R-adamant-1-yl isocyanates with 4-[(4-aminocyclohexyl)oxy]benzoic acid and 1-(4-aminopiperidin-1-yl)propan-1-one in DMF afforded corresponding ureas in 90—95% yield, the target-oriented inhibitors of epoxide hydrolase sEH. The ureas are characterized by reduced melting points and increased solubility in water, as well as by inhibitory activity in the range of 0.5—4.0 nmol L–1.
Structure—hemolytic activity relationship in isobornylphenol derivatives
摘要
A structure — hemolytic activity relationship in isobornylphenol derivatives was analysed. The morphological transformation of erythrocytes under the influence of some representatives of this class of compounds was demonstrated by scanning electron microscopy. The hemolytic activity of the test compounds can vary within wide limits, depending on the structure and position of substituents determining the nature of the interaction of the compound with the cell membrane.
Increasing selective bilirubin removal by hypercross-linked polystyrene hemosorbents
摘要
A high efficiency of indirect bilirubin removal from systems modelling blood plasma by polymers of various structures and, most importantly, by hemocompatible hypercross-linked polystyrenes such as Styrosorb is demonstrated. Approaches to increasing the selectivity of hypercross-linked polystyrenes for the removal of bilirubin from biological fluids with a high serum albumin content were found, making them promising materials for the manufacture of hemosorption columns effective for hepatitis therapy and other conditions caused by a high bilirubin content in the blood plasma.
Synthesis of new N-(pyridin-3-ylmethyl)-2-aminothiazoline derivatives possessing anticholinesterase and antiradical activity as potential multifunctional agents for the treatment of neurodegenerative diseases
摘要
New N-(pyridin-3-ylmethyl)-2-aminothiazolines containing various substituents at the 5 position of the thiazoline ring and the 4-tert-butylbenzyl, 4-isopropylbenzyl, or 4-fluorobenzyl moiety at the nitrogen atom of the amino group were synthesized. The inhibitory activity of the synthesized compounds against human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7), equine serum butyrylcholinesterase (BChE, EC 3.1.1.8), and porcine liver carboxylesterase (CaE, EC 3.1.1.1) was evaluated and their antioxidant properties were studied by ABTS assay. N-(Pyridin-3-ylmethyl)-2-aminothiazolines proveded to be very weak AChE inhibitors, while their inhibitory activity against BChE and CaE was structure-dependent. 2-Aminothiazolines containing the 4-tert-butylbenzyl moiety are more efficient BChE inhibitors compared to the derivatives containing the 4-isopropylbenzyl or 4-fluorobenzyl substituent. An analysis of the dependence of the esterase profile of N-(pyridin-3-ylmethyl)-2-aminothiazolines on the structure of the substituent at the 5 position of the thiazoline ring of these compounds demonstrated that the derivatives containing the iodomethyl substituent possess the highest anti-BChE activity, the compounds with R2 = H and R3 = CH2I have the optimal esterase profile. Regardless of the structure of the substituents in the benzyl moiety, all N-(pyridin-3-ylmethyl)-2-aminothiazolines containing the iodomethyl substituent at the 5 position of the thiazoline ring exhibited high radical scavenging activity comparable with that of the standard antioxidant Trolox. N-(Pyridin-3-ylmethyl)-2-aminothiazolines were shown to be a new promising class of compounds for the design of multifunctional agents for the treatment of neurodegenerative diseases.
Synthesis and pharmacological activity of 2-(biphenyl-4-yl)imidazo[1,2-a]benzimidazoles
摘要
An efficient method for the synthesis of novel 9H-imidazo[1,2-a]benzimidazole derivatives containing a biphenyl substituent at position 2 was developed. These compounds, belonging to the privileged substructures, have been tested for a wide range of pharmacological activities in the in vitro test panel. It was shown that the synthesized derivatives demonstrated high antioxidant activity, some of them inhibit type 1B protein tyrosine phosphatase, activate AMP-activated protein kinase, possess antiplatelet properties, and a rare and very interesting kind of activity, the ability to break cross-links of glycated proteins. The most active compounds can be suggested for further optimization.
Search for approaches to improving the calculation accuracy of the protein—ligand binding energy by docking
摘要
The following reasons limiting the accuracy of calculations of the protein—ligand binding energy by the molecular docking programs are considered: the limited facilities of algorithms of finding a global minimum on a complicated multi-dimensional protein—ligand energy surface, restrictions on the degrees of freedom of a protein—ligand system including docking into a rigid protein, inadequacy of the existing force fields, a lack of taking into account the solvent or too rough allowance for the solvent in the docking procedure, a lack of the local energy optimization in the docking process, an inaccuracy of the construction of models of a target protein and a ligand, simplification of the calculation method of the Gibbs free energy of a molecular system, and limited computer resources for docking of one ligand. A new approach to the development of the new generation of docking programs is proposed. The approach allows one to remove step-by-step the existing simplifications and to increase considerably the accuracy of the whole docking process, including the calculation accuracy of the protein—ligand binding energy. The results of the study are presented and demonstrate the computational feasibility of the assigned docking problem.
Synthetic immunogen for the anti-relapse treatment of opioid dependence
摘要
A synthetic immunogen representing a complex of a conjugate of a macromolecular carrier (natural protein) and a hapten (morphine drug) covalently bound to poly(4-nitrophenyl acrylate) (PNPA) has been developed. The macromolecular carrier in the conjugate is a human serum protein (human gamma-globulin, HGG, or human serum albumin, HSA). The optimal design of the synthetic immunogen was developed. The epitope accessibility and specificity of the immunogen complexes were investigated by ELISA. It was established that antigenic determinants are not shielded upon binding to antibodies for complexes with the optimal (1: 10) ratio of the conjugate to the synthetic polymer. The accute toxicity of PNPA was estimated. The immunogenicity of synthetic complexes was studied in rat immunization models. An influence of the immunogen structure and vaccination dose on the ability to produce specific antibodies to morphine was found.
Brief Communications
Biological activity of some sulfur- and selenium-containing spiro compounds
摘要
Cytotoxicity to K-562 leukemia cell line of two spiro compounds containing selenium or sulfur atom in their structure were compared. 4-Fluorophenyl-(1-thia-3-azaspiro[5.5]undec-2-en-2-yl]amine hydrobromide was synthesized and characterized for the first time. It was found that the introduction of a sulfur atom is more promising for this biological model, since it leads to a 3-fold increase in the therapeutic index in the case of the sulfur-containing compound.