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Coronavirus disease 2019 is a serious disease that causes acute respiratory syndrome and negatively affects the central nervous system. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) crosses the blood-brain barrier due to the S protein on the surface of the viral particles. Thus, it is important to develop compounds that not only have an inhibitory effect but are also capable of completely deactivating the S-protein function. This study describes the purposeful modification of porphyrins and proposes compounds, asymmetrically hetaryl-substituted porphyrins with benzothiazole, benzoxazole, and N-methylbenzimidazole residues, to deactivate the S-protein functions. Molecular docking of SARS-CoV-2 proteins with hetaryl-substituted porphyrins showed that the viral proteins S-, N-, and nsp13 exhibited the highest binding affinity. Hetaryl-substituted porphyrins form strong complexes (13–14 kcal/mol) with the receptor-binding domain of the S protein, while the distance from the porphyrins to the receptor-binding motif (RBM) does not exceed 20 Å; therefore, RBM can be oxidized by 1O2, which is generated by porphyrin. Hetaryl-substituted porphyrins interact with the nucleocapsid protein in the serine/arginine-rich region, and a number of vulnerable amino acid residues are located in the photooxidation zone. This damage complicates the packaging of viral RNA into new virions. High-energy binding of hetaryl-substituted porphyrins with the N- and C-terminal domains of nsp13 was observed. This binding blocks the action of nsp13 as an enzyme of exoribonuclease and methyltransferase, thereby preventing RNA replication and processing. A procedure for the synthesis of hetaryl-substituted porphyrins was developed, new compounds were obtained, their structures were identified, and their photocatalytic properties were studied., Graphical abstract Image 1

In water–DMF at DMF content less than 2.6 mol dm−3, deuteroporphyrin IX dimethyl ester forms both H- and J-aggregates. The J-aggregates are detected as a single type of associated species after binding of the porphyrin with BSA on the surface of the protein IB subdomain.

Protoporphyrin upon its binding with serum albumin changes its secondary structure due to the conversion of part of α helices into β-folding. This process results in the association of albumin globules in vitro.

Glycosized porphyrins are promising compounds for using in PDT, since they combine the ability to act as a photosensitizer, and their saccharide residues provide an increased tumorotropicity of this compound in the affected cells. In this work, the modified 5,10,15,20-tetrakis [4-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl) phenyl] porphine (HOGalPor) synthesis procedure providing an increased yield of the desired product is described. The affinity of natural biopolymers with reference to synthesized porphyrin has been studied. It was found that synthesized porphyrin is associated in aqueous media. There were proposed some mixed solvents and water-solvent concentration ratios were established to ensure the monomerization of porphyrin and the preservation of the native conformation of biopolymers (BSA and DNA). The affinity constants of BSA and DNA were determined with reference to the synthesized porphyrin, as well as localization of porphyrin in biopolymers was established. As part of the protein complex, porphyrin fluoresces very intensively, and this feature makes it possible to use BSA as a transport system for HOGalPor, and HOGalPor itself can act as a fluorescent marker. The interaction of HOGalPor with the intercalation complex of DNA-EtBr leads to the destruction of the latter, while porphyrin does not intercalate in DNA, but forms external complexes with a change in the zeta potential of the surface.

The influence of irradiation on protein- porphyrin complexes at various spectral ranges was studied. Limited applicability of evaluating protein damage degree in terms of fluorescence quenching of the tryptophan protein residues was shown. Depending on the conditions of photoirradiation and the way of porphyrins interaction with bovine serum albumin (BSA), photoirradiation of the porphyrin-protein complexes may result in proteolysis or photolinking inside the protein globule, and in some cases, in destruction of the complex itself. P1 5-(4′-N-tertbutyloxycarbonylglicinaminophenyl)-10,15,20-triphenylporphine, unlike 5,10,15,20-tetraphenylporphin (TPP), has fixed localization in the protein due to “anchor” group providing the stability of the photoinduced transformations of a protein globule. For all porphyrin-protein systems studied, irradiation by light at the Soret band range for P1-protein systems leads to proteolysis of BSA globule, while the irradiation by light with the wavelength more than 500 nm, does not result in total protein damage, but causes oxidation of susceptible amino acid residues. The measurement of the hydrodynamic radii of a protein globule before and after irradiation provided objective information on the proceeding photoinduced processes (proteolysis and crosslinking) which can be used for predicting the mechanism of the cell damage (necrosis, autophagy, apoptosis).

This study was focused on obtaining polymer complex of 5-(4′-N-tert-butyloxycarbonylglicinaminophenyl)-10,15,20-triphenylporphine and 5-(4′-amonophenyl)-10,15,20-triphenylporphine with chitosan. The polymer complexes were characterized spectrally and calorimetrically. The existence of a substituent capable of forming hydrogenic complexes with proteins and other biopolymers in porphyrins provides an effective immobilization of a photosensitizer. Binding with porphyrins was found to result in twisting the chitosan globule and encapsulation of porphyrins. Coating of polymer complex with bovine serum albumin promotes neutralization of zeta potential and formation of 180-nm capsules. As the result of the study, a new universal strategy of water insoluble preparation encapsulation in biopolymers for targeted delivery of drugs and their further release was suggested.

The interaction of water-soluble porphyrins with the bovine serum albumin in borate buffer at pH 8.6 has been studied. The localization of porphyrins in the protein globule has been determined. It was established that the native conformation of albumin upon binding with the porphyrins is preserved, however, the anionic porphyrins are exhibit wedging effect on the albumin domains. The binding constants were obtained from fluorescence spectroscopy data.

New copolymers of acrylamide with zinc 5,10,15,20-tetrakis-(4-allyloxyphenyl)porphyrinate were synthesized and tested as cysteine and histidine sensors.

The complexation processes of chitosan with cobalt(II)tetrasulfophthalocyanine (CoPc) and copper(II)tetrasulfophthalocyanine (CuPc) were studied calorimetrically in solution. It was established that CoPc forms two types of complexes with chitosan, while CuPc forms a single type of complex with chitosan, in which copper(II)tetrasulfophthalocyanine is in dimerized form. The complexes are thermodynamically stable, which was allowed to study them in a solid form by different methods. Joint application of DSC and TG/DTG methods allowed us to identify the temperature intervals for evaporation of physically and chemically bounded water and thermal decomposition of chitosan and its complexes. The glass transition temperature of chitosan (110.8 °C) is greater than the glass transition temperature of the complexes with CuPc (74.7 °C) and CoPc (71.2 °C). Using SEM images and X-ray data of heated, unheated chitosan and its complexes, it was shown that the complexes are predominantly amorphous. Heating of chitosan and its leads to increasing of amorphous phase. Modification of chitosan by phthalocyanines leads to decreasing of thermal stability of complexes insignificantly.

Spectral, hydrodynamic and thermochemical studies have been demonstrated that tetraalkoxy substituted zinc(II)phthalocyanines form stable complexes with defatted and nondefatted bovine serum albumin. The phthalocyanines interact with BSA through heteroatoms of their peripheral substitutes. It was found that ZnPc(4-NH-CO-C6H4-OC3H7)4 is located in the protein subdomains IB and IIA whereas ZnPc(4-NHCO-C6H4-OC6H13)4 and ZnPc(4-NH-CO-C6H4-OC8H17)4 are immobilized on surface of the protein globule at a distance of not greater than 10 nm from the tryptophan residues in the positions 135 and 214 of the protein polypeptide chain. Zinc(II)phthalocyanines (ZnPc(4-NH-CO-C6H4-OC6H13)4 and ZnPc(4-NH-CO-C6H4-OC8H17)4) increase thermal stability of BSA.

The possibility of creating a pH-controllable protein container for the delivery of hydrophobic porphyrins as photosensitizers in cancer cells has been demonstrated.

Recently, a new type of spin labels based on photoexcited triplet molecules was proposed for nanometer scale distance measurements by pulsed dipolar electron paramagnetic resonance (PD EPR). However, such molecules are also actively used within biological complexes as photosensitizers for photodynamic therapy (PDT) of cancer. Up to date, the idea of using the photoexcited triplets simultaneously as PDT agents and as spin labels for PD EPR has never been employed. In this work, we demonstrate that PD EPR in conjunction with other methods provides valuable information on the structure and function of PDT candidate complexes, exemplified here with porphyrins bound to human serum albumin (HSA). Two distinct porphyrins with different properties were used: amphiphilic meso-tetrakis(4-hydroxyphenyl)porphyrin (mTHPP) and water soluble cationic meso-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4); HSA was singly nitroxide-labeled to provide a second tag for PD EPR measurements. We found that TMPyP4 locates in a cavity at the center of the four-helix bundle of HSA subdomain IB, close to the interface with solvent, thus being readily accessible to oxygen. As a result, the photolysis of the complex leads to photooxidation of HSA by generated singlet oxygen and causes structural perturbation of the protein. Contrary, in case of mTHPP porphyrin, the binding occurs at the proton-rich pocket of HSA subdomain IIIA, where the access of oxygen to a photosensitizer is hindered. Structural data of PD EPR were supported by other EPR techniques, laser flash photolysis and protein photocleavage studies. Therefore, pulsed EPR on complexes of proteins with photoexcited triplets is a promising approach for gaining structural and functional insights into such PDT agents.

In this paper, the results of a spectral and thermochemical study of the DNA polyplex formation with chitosan and the effect of ethidium bromide polyplexes, sodium dodecyl sulfate, n-octyltrimethyl ammonium bromide, poly(4-styrenesulfonic acid), and heparin on the stability of the complexes are considered. It has been established that chitosan forms thermodynamically stable complexes with ethidium bromide (EtBr), in which there exists one monomer unit of chitosan for two ethidium bromide ones. The interaction of ethidium bromide with chitosan leads to a charge exchange of the polymer surface. The impact of chitosan on the intercalated DNA-EtBr complex conditions a release of EtBr with a polyplex formation. The process of polyplex formation in the presence of ethidium bromide proceeds endothermically, and in its absence the reaction is exothermic. The polyplex particles formed from DNA after release of EtBr are larger and have a smaller charge, as compared to the polyplex particles obtained without ethidium bromide. It has been found that anionic compounds cause the degradation of polyplexes, and it can prove to be a significant obstacle for using chitosan polyplexes in transfection, since in the presence of heparin in the bloodstream, the complexes will break down before reaching the target.

Molecular complex formation of zinc(II)tetraphenylporphyrin with the ligands—diamino compounds in toluene was studied using calorimetric and spectroscopy titration. The structure of the complexes has been confirmed using 1H NMR and fluorescence spectroscopy. Nature of the interaction between the ligand and the solvent was established using TGA of solvates.

Interaction between bovine serum albumin and alkoxy substituted phthalocyanines was studied by means of electron absorption spectroscopy, fluorescence spectroscopy and viscosimetry. The binding constants and binding distance were calculated. It was found that ZnPc(4-NH-CO-C6H4-OC10H21)4 prevents twisting of BSA molecule and localizes between subdomains IB and IIA in protein globule. ZnPc(4-NH-CO-C6H4-OC6H13)4 and ZnPc(4-NH-CO-C6H4-OC8H17)4 are located on the outer surface of the protein globule. In the case of ZnPc(4-NH-CO-C6H4-OC3H7)4 it can be assumed that the phthalocyanine molecule is in the immediate vicinity of the subdomains IB and IIA.

The interaction of tetracationic porphyrins with DNA was studied using UV-Vis absorption, fluorescence spectroscopy and viscometry, and the particle sizes were determined. Аs cationic porphyrins, two isomer porphyrins, 3,3',3″,3‴-(5,10,15,20-Porphyrintetrayl)tetrakis(1-methylpyridinium) (TMPyP3) and 4,4',4″,4‴-(5,10,15,20-Porphyrintetrayl)tetrakis(1-methylpyridinium) (TMPyP4), were studied. They differ in the position of NCH3+ group in phenyl ring of the porphyrins and hence, in degree of freedom of rotation of the phenyl rings about the central macrocycle. It was found that intercalated complexes are formed at DNA/porphyrin molar ratios (R) of 2.2 and 3.9 for TMPyP3 и TMPyP4, respectively. Decreasing R up to 0.4 and 0.8 for TMPyP3 и TMPyP4, respectively, leads mainly to formation of outside complexes due to π-π stacking between the porphyrin chromophores interacting electrostatically with phosphate framework of DNA. Each type of the obtained complexes was characterized using Scatchard approach. It was ascertained that the affinity of TMPyP4 to DNA is stronger than TMPyP3, meanwhile the wedge effect of the latter is higher. The differences between the porphyrin isomers become more evident at irradiation of their complexes with DNA. It was established that irradiation of the intercalated complexes results in DNA fragmentation. In the case of TMPyP4, DNA fragments of different size are formed. The irradiation of the outside DNA/porphyrin complexes leads to cleavage of DNA (TMPyP3 and TMPyP4) and partial destruction of the complex due to photolysis of the porphyrin (TMPyP3).

Three-component systems consisting of a metalloporphyrin, a bidentate ligand and a solvent were studied by titration calorimetry. The thermodynamic characteristics of the interaction of zinc (II) porphyrins with diamines in DMF were determined, and the composition of the complexes formed was identified.

Physical-chemical characteristics of molecular complexes of Zn(II)tetra-tert-butylphthalocyanine (Zn(tert-Bu)4Pc) with aromatic solvents were obtained. The results show that polarization parameters of the interacting molecules play an important role in stabilization of the phthalocyanine π–π complexes. Dispersion forces are the major factor governing the π–π complex formation of Zn(tert-Bu)4Pc with aromatic molecules. The metallophthalocyanine may be applicable as efficient analytical reagent for separation of isomeric forms of aromatic molecules.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a promising target for antitumor therapy based on Top1 poison-mediated DNA damage. Several novel benzopentathiepines were synthesized and tested as inhibitors of TDP1 using a new oligonucleotide-based fluorescence assay. The benzopentathiepines have IC50 values in the range of 0.2–6.0 μM. According to the molecular modeling, the conformational flexibility of the dibutylamine group of the most effective inhibitor (3d) allows it to occupy an advantageous position for effective binding compared to its cyclic counterparts. The study of cytotoxicity of these compounds revealed that all compounds cause an apoptotic cell death in MCF-7 and Hep G2 cells. Therefore the new class of very effective inhibitors of TDP1 was elaborated.

Physico-chemical characteristics of molecular complexes for water-soluble metallophthalocyanines with alcohol were obtained by the method of thermogravimetric analysis. The change of aggregation state of metallophthalocyanines in aqueous alkaline solutions which is due to the ethanol additions was explained taking into consideration the results of thermogravimetric analysis of metallophthalocyanines crystallosolvates with ethanol.

Education is viewed as not merely a particular domain of social life. It is more a universal process than a mere learning of sciences and arts; it is richer than an individual's socialization. The educational democratization turns out to be a prerequisite of humanization of the entire social life. The orientation at the supreme humane values as a strategic direction of democratic evolution of education is opposed to the authoritarian tendencies as an “antivalue” of pedagogical relations. Being a significant step towards a genuinely humane society, democratization is unable, however, to resolve the fundamental problem of human formation: that of alienation. The opportunity to resolve it is dependent upon proper conditions for a free self-determination of a personality in culture.