Theoretical and experimental study of interaction of macroheterocyclic compounds with ORF3a of SARS-CoV-2

The pandemic infectious disease (Covid-19) caused by the coronavirus (SARS-CoV2) is spreading rapidly around the world. Covid-19 does an irreparable harm to the health and life of people. It also has a negative financial impact on the economies of most countries of the world. In this regard, the issue of creating drugs aimed at combating this disease is especially acute. In this work, molecular docking was used to study the docking of 23 compounds with QRF3a SARS-CoV2. The performed in silico modeling made it possible to identify leading compounds capable of exerting a potential inhibitory and virucidal effect. The leading compounds include chlorin (a drug used in PDT), iron(III)protoporphyrin (endogenous porphyrin), and tetraanthraquinone porphyrazine (an exogenous substance). Having taken into consideration the localization of ligands in the QRF3a SARS-CoV2, we have made an assumption about their influence on the pathogenesis of Covid-19. The interaction of chlorin, iron(III)protoporphyrin and protoporphyrin with the viral protein ORF3a were studied by fluorescence and UV–Vis spectroscopy. The obtained experimental results confirm the data of molecular docking. The results showed that a viral protein binds to endogenous porphyrins and chlorins, moreover, chlorin is a competitive ligand for endogenous porphyrins. Chlorin should be considered as a promising drug for repurposing.

Destruction of Chitosan and Its Complexes with Cobalt(II) and Copper(II) Tetrasulphophthalocyanines

Chitosan is a naturally occurring polysaccharide derived from chitin with a wide range of uses. Phthalocyanines are macroheterocyclic compounds that have a number of useful properties such as coloring and catalytic and antioxidant activity. Phthalocyanines are able to immobilize on chitosan, forming complexes with new useful properties. In this work, we evaluated the ability of phthalocyanines to increase the thermal stability of chitosan. Chitosan (CS) forms complexes with copper(II)-(CuPc) and cobalt(II)-(CoPc) tetrasulphophthalocyanines. The processes of destruction of chitosan (CS) and its complexes with sulphophthalocyanines CuPc and CoPc in oxidizing and inert atmospheres have been studied. It was established that, regardless of the atmosphere composition, the first chemical reactions taking place in the studied systems are elimination reactions. The latter ones in the case of chitosan and complex CS-CuPc lead to the formation of spatially crosslinked polymer structures, and it causes the release of CuPc from the polymer complex. It was found that in the case of CS-CoPc elimination reactions did not lead to the formation of crosslinked polymer structures but caused the destruction of the pyranose rings with a partial release of CoPc. Metallophthalocyanines showed antioxidant properties in the composition of complexes with chitosan, increasing the temperature of the beginning of glycosidic bond cleavage reaction by 30–35 °C in comparison with the similar characteristics for chitosan.

Synthesis and Properties of Bisthiadiazoles with Ethyl and Butyl Spacers

This article is devoted to a selection of the most effective preparative method for the synthesis of bis(5-amino-1,3,4-thiadiazole-2-yl)alkanes. These compounds are binuclear diamines consisting of symmetrical 1,3,4-thiadiazole fragments connected by alkyl spacers of various lengths. The structures of the obtained compounds were determined by IR spectroscopy, mass-spectrometry and elemental analysis. The possibility of using these molecules as precursors for the synthesis of macroheterocyclic compounds with expended coordination cavity consisting of six small cycles was demonstrated. Optimal synthesis conditions of bis(5-amino-1,3,4-thiadiazole-2-yl)ethane and bis(5-amino-1,3,4-thiadiazole-2-yl)butane were found by variation of reaction time and temperature. Virtual screening of the obtained compounds was carried out in order to predict antibacterial and biological activities as well as toxic properties of the targeted products. On the basis of the known literature data on polynuclear diamines, the exhibition of the liquid crystal properties of the synthesized molecules is supposed.

SYNTHESIS AND INVESTIGATION OF COPOLYMERS OF GLYCIDYLMETHACRYLATE AND COPPER COMPLEX METHYL PHEOPHORBIDE “A” IN SOLUTION

The actual direction in the field of creating new functional materials is a complex study of the influence of tetrapyrrole macroheterocyclic compounds on the processes of radical (co)polymerization with widely used monomers, as well as the development of a general approach to the synthesis and study of the properties of such polymer materials. Promising macroheterocyclic compounds are chlorophyll derivatives of various structures. For this purpose, by the method of solution radical copolymerization in toluene and tetrahydrofuran the copolymers of glycidylmethacrylate and copper complex of methylpheophorbide “a” of various compositions were obtained. Identification of the obtained copolymers and investigation of their structure and properties were performed using data from IR, NMR spectroscopy of compounds, elemental and chemical analysis methods. The synthesized copolymers are characterized by molecular-weight characteristics which were determined by gel-permeation chromatography. It was found that the introduction of a copper complex of methylpheophorbide “a” into the copolymer leads to a decrease in the copolymerization rate, the values of the molecular masses of copolymers and an increase in their polydispersity. The effect of solvents on the time of the copolymerization process and the molecular weight characteristics of copolymers is shown. The composition of the obtained copolymers was determined spectrophotometrically by the optical density of their solutions at the maximum of the first absorption band of the copper complex of methylfeoforbide “a”. Comparison of the intensity of bands in the IR spectra of copolymers of different compositions showed that the content of methylpheophorbid links in the polymer chain increases with the increase in the content of porphyrin in the polymerized mixture. The study of the influence of the nature of the solvent and its structural features on chemical reactions involving porphyrin derivatives allowed us to establish that from a thermodynamic point of view, the best solvent for porphyrinpolymers is toluene.

BGR MACROHETEROCYCLIC COMPOUNDS OF ASYMMETRIC STRUCTURE WITH THIADIAZOL FRAGMENTS. SYNTHESIS AND PROPERTIES

This communication is a continuation of the systematic research of the authors in the field of synthesis and study of the properties of macroheterocyclic compounds. The great potential for structural modification allows us to synthesize macroheterocyclic compounds that differ in composition and the nature of the heteroatoms that make up them and make this class of compounds promising from the point of view of the design for the preparation of substances with valuable practical properties. The interaction of N,N/-bis-(1-imino-2-phenyl-1H-indene-3-iliden)-1,4-phenylenediamine with 2,5-dimiano-1,3,4-thiadiazole and 3,5-diamino-1,2,4-thiadiazole the macroheterocyclic compounds of asymmetric structure were synthesized in the molar ratio of the initial substances. Macroheterocycles are powdered substances with different shades of red color, having melting and crystallization temperatures (investigated in the argon current), soluble in chloroform, DMF, acetone, ethanol. Purification was carried out by column chromatography on aluminum oxide of II degree of activity on Brockman (eluent acetone - chloroform, 1:9 by volume). Identification of synthesis products was performed by thin-layer chromatography on Silufol UV-254 plates (eluent – acetone - chloroform, 1:1 by volume). The obtained compounds were characterized by infrared and electron spectroscopy. The electronic absorption spectra were measured on a Hitachi U-2010 instrument in quartz cuvettes at 20 °C. IR spectra were obtained on the Avatar 360 FT-IR ESP device in KVG. Elemental analysis data were obtained using the CHNS-O Analyzer FlashEA of 1112 Series. A bathochromic shift of the absorption bands was noted when the compound with 1,3,4-thiadiazole was closed in a cycle. The spectral characteristics indicate that the molecules of the synthesized compounds do not have a flat structure and the absorption is due to individual fragments that are part of the molecules of the synthesized structures.

COMPLEXES OF IZOTHIADIAZOLE-CONTAINING BROMONITROSUBSTITUTED THREE UNITS PRODUCT WITH D-METALS (NI, CO, ZN)

This work is continuation of synthesis researches of substituted macroheterocyclic compounds with 1,2,4-thiadiazole fragments. Data of synthesis of complexes with divalent d-metals (Ni, Co, Zn) on the basis of received earlier brominenitrosubstituted isothiadiazole three-unit product are presented. Complexes of BAB-type product consisting 1,2,4-thiadiazole and bromine-nitro-isoindole fragments were received by interaction 3,5-bis-[5(6)-bromine-6(5)-nitro-3-iminoizoindolin-1-ilidenamiino]-1,2,4-thiadiazol with acetates of d-metals in 2-ethoxyethanol at 100 ºC for 2 h. After the reaction the mixture was poured into water and precipitate was filtered and washed with 5 % ammonia, water and hot organic solvents (acetone, methanol, dimethylformamide, pyridine). Yield of target products was 18 – 28 %. The resulting complexes are dark brown powders with high solubility in alcohols, DMF, insoluble in water, dichloromethane and hexane. The structures of products were established by data of mass spectrometry, elemental analysis, UV-vis and IR spectroscopy. Data of MALDI-TOF mass spectrometry showed that complexes with metal of three-unit product with 1,2,4-thiadiazole fragment were isolated as monohydrate by analogy with literary for 1,3,4-thiadiazole. Data of atomic absorption analysis with good convergence of the experimental and calculated values confirmed monohydrate structure these products. These complexes of three-unit products will be used for synthesis of new various substituted macroheterocycles with 1,2,4-thiadiazole fragments. <span style="opacity: 0;"> . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . </span>