The prасtiсаl useful prоperties оf sulfо derivаtives оf pоrphyrins depend signifiсаntly оn pH. Fоr exаmple, саnсer сells hаve а mоre асidiс envirоnment (pH = 5.5) соmpаred tо nоrmаl сells (pH = 7.2). The effeсt оf pH (5.5 ≤ pH ≤ 6.5 аnd 7.4) оn the соmplexing аbility tоwаrds BSА аnd the phоtосаtаlytiс асtivity оf sulfо-substituted pоrphyrins соntаining а hydrоphоbiс peripherаl substituent (а residue оf benzоthiаzоle, benzimidаzоle аnd benzоxаzоle) wаs studied.Ассоrding tо аbsоrptiоn аnd fluоresсenсe speсtrоsсоpy, it wаs fоund thаt аt pH = 7.4, pоrphyrins in mоnоmeriс fоrm bind tо prоtein. The lосаlizаtiоn оf pоrphyrins inside the prоtein glоbule wаs prоven by IR speсtrоsсоpy, thermосhemiсаl аnаlysis, stаtiоnаry аnd time-resоlved fluоrimetry. It wаs fоund thаt the соmplexаtiоn оf pоrphyrins with BSА leаds tо аn inсreаse in the prоpоrtiоn оf disоrdered struсtures аnd β-sheets аnd а deсreаse in the thermаl resistаnсe оf prоtein. Phоtоirrаdiаtiоn оf соmplexes оf BSА with pоrphyrins led tо оxidаtiоn оf prоtein struсtures.In the rаnge оf 5.5 ≤ pH ≤ 6.5 pоrphyrins exist in the fоrm оf H-self-аssосiаtes thаt аre nоt destrоyed when interасting with BSА; pоrphyrins dо nоt саuse сhаnges in the seсоndаry struсture оf the prоtein, but inсreаse its thermаl resistаnсe by 10°С. Аnаlysis оf phоtосаtаlytiс асtivity shоwed thаt pоrphyrin lоses its аbility tо phоtо-оxidize prоteins in weаkly асidiс envirоnments.

Directed synthesis of novel water-soluble asymmetric porphyrins containing in a molecule three cationic fragments and residues of adenine (PorAD) was performed, using metal-complex catalysis method. The interaction of the synthesized porphyrin with the oligonucleotides poly[d(AT)2] and poly[d(GC)2] and double-stranded deoxyribonucleic acid of the calf thymus (ctDNA) was studied by means of spectral and hydrodynamic methods. It was established that PorAD intercalated not only into GC-enriched regions, but also into AT regions. It was revealed that a distinctive feature of PorAD complexes with nucleic acids was a weak shielding from water molecules, and it implies significant disturbances in the conformation of the nucleic acid; the disturbances being especially pronounced for poly[d(AT)2].

The novel data on the fluorescence behavior of bovine serum albumin and human serum albumin under 375 nm excitation are presented, introducing a distinctive fluorescence phenomenon that holds promising implications for protein research. Extensive studies of these proteins are conducted to understand their intrinsic fluorescence properties, typically observed upon excitation with light in the range of 280-300 nm, resulting in fluorescence emission around 345 nm.

Relevance. The development of antimicrobial drugs and alternative methods, technologies and means of prevention, diagnosis and treatment of human infectious diseases caused by antibiotic-resistant microorganisms is one of the priorities of ensuring the biological safety of the country. Aims. To evaluate the bactericidal activity of tetrapyrrole macroheterocycles (porphyrins) at different light irradiation durations in relation to staphylococci, in vitro. Materials and methods. Studied strains of microorganisms: museum strains of microorganisms – S. aureus ATCC 29213, S. epidermidis ATCC 14990 and antibiotic-resistant strains of bacteria of the genus Staphylococcus (n=18) isolated from clinical biomaterial and from environmental objects in a medical organization. The studied chemical compounds are three different compounds of water-soluble asymmetrically substituted porphyrins containing heterocyclic fragments on the periphery of the porphyrin cycle (residues of benzoxazole, N-methylbenzimidazole and benzothiazole). Results. The activity of all three porphyrin compounds in relation to museum strains of staphylococcus and 77.8% of clinical antibiotic-resistant strains (n=14; 95% CI 20.1-97.5) turned out to be maximal (complete lysis) after 10 minutes of irradiation. Conclusions. The tested tetrapyrrole macroheterocycles (porphyrins) exhibit bactericidal activity against museum and clinical strains of staphylococcus, with different levels of antibiotic resistance, which determines Keywords: antibiotic resistance, water-soluble porphyrin, photodynamic inactivation, photosensitizer, photochemistry, staphylococci No conflict of interest to declare.

Palladium-catalyzed heterylation of monobromophenyl-substituted zinc(II) porphyrin with small heterocycles (benzothiazole, benzoxazole, and N-methylbenzimidazole) was carried out. As a result, unsymmetrical heterylphenyl-substituted zinc(II) porphyrins soluble in organic solvents were obtained. The interaction of heteryl-substituted zinc(II) porphyrins with alpha-helical proteins was studied by spectral methods using bovine serum albumin in aqueous organic solvents. It was found that the titration of the zinc(II) porphyrins with albumin in a sodium phosphate buffer involves a number of equilibria including complexation and aggregation. In the case of porphyrins containing N-methylbenzimidazole and benzoxazole residues, self-aggregation processes initiated by absorption of organic solvent molecules by the protein predominate. It was found that more hydrophobic nature of zinc(II) porphyrin with benzothiazole residue promotes the complex formation with the protein. The photochemical properties of zinc(II) porphyrin with a benzothiazole residue, capacity for the photooxidation of the alpha-helical protein, and the high affinity of protein to this porphyrin make it a promising candidate for the potential applicability for photodynamic inactivation.

A water-soluble cationic porphyrin containing N-methyl- pyridinium fragments and an indole residue, namely, 5-[4-(1-methylindol-2-yl)phenyl]-10,15,20-tris(1-methyl- pyridinium-3-yl)porphyrin triiodide, has been synthesized. The porphyrin forms sedimentation unstable complexes with low and high molecular weight nucleic acids. This ability to precipitate nucleic acids can be used in laboratory, clinical and research practice for isolating nucleic acids.

In this work, new free base corroles (sulfophenylcorrole (mixture of tri(4-sulfophenyl)corrole and tetrasulfotriphenylcorrole) and tri(N-methylpyridin-4-yl)corrole triiodide) were synthesized and associative equilibria in aqueous and organic media were studied. Their binding ability to BSA and DNA was studied by various physicochemical methods. It has been established that complexes with DNA are formed only by cationic corrole, which binds to DNA by the intercalation method. Both cationic and anionic corroles bind to bovine serum albumin. It was found that the synthesized corroles are weakly fluorescent fluorophores and practically do not generate singlet oxygen; however, they are capable of generating superoxide anion radicals; can participate in type I photooxidation. The ability to initiate type I photoprocesses was established on the basis of the processes of photooxidation of nitroblue tetrazolium and BSA. The possibility of potentiating the process of protein photooxidation by potassium iodide has been established. Radical and radical ion reactions underlying the potentiation of BSA oxidation upon photoirradiation with PS were studied. It was found that the addition of KI significantly accelerates the photooxidation of BSA. It has been proven that the stage of formation of triiodide ions, which trigger a cascade of radical ion reactions, plays an important role in the potentiation processes.

The study of the interaction of nucleic acids with ligands is relevant both in terms of scientific interest and high potential practical significance. Nucleic acid complex formation with ligands affects the biochemical functions of the most important carrier of genetic information, which opens up opportunities for treating genetic diseases and controlling the aging of both cells and the organism as a whole. Among the huge variety of potential ligands, porphyrins and related compounds occupy a special placedue to their ability to generate reactive oxygen species under irradiation with light. The photocatalytic properties of porphyrins can be used in the creation of molecular tools for genetic engineering and the treatment of viral and bacterial infections at the genetic level. Modification of porphyrin compounds allows targeting of the ligand to a specific biological target.The review summarizes the literature data describing the process of nucleic acid complex formation with aromatic ligands, mainly with porphyrins. The influence of the structure of macroheterocycles on the features of interaction with nucleic acids is analyzed. Promising directions for further research are outlined.

The interaction of cobalt(II) tetrasulfophthalocyanine (CoPc) with the ORF8 accessory protein of SARS-CoV-2 was studied by spectroscopy and calorimetry. The protein was found to shift the aggregation equilibrium in cobalt tetrasulfophthalocyanine solutions towards dimerization. Most probably, the CoPc dimer binds to ORF8 on the greater β-sheet side, thus causing fluorescence quenching. The protein affinity constant to CoPc dimer is 1.5 × 10 5 . Differential scanning calorimetry data indicate that ORF8 undergoes thermally induced denaturation in the temperature range of 38–67°C. Melting of ORF8 includes two stages, which partly overlap. The complex formation of ORF8 with CoPc leads to thermal stabilization of the protein, thus preventing the second stage of protein unfolding. Denaturation of the complex proceeds between 40 and 77°C as two temperature-separated stages. According to gel electrophoresis and immunoblotting data, visible light photoirradiation of the ORF8 complex with CoPc does not induce photooxidation of the protein. It was shown that water-soluble cobalt sulfo-substituted phthalocyanine can be considered as a potential drug inhibiting the ORF8 accessory protein.

Directed synthesis of a new cationic monoheteryl-substituted porphyrin, 5-[4′-(1′′,3′′,7′′-trimethyixanth-2′′-yl]-10,15,20-tris-( N -methylpyridinium-3′-yl) porphyrin triiodide was carried out. This porphyrin is in a partially associated state in Tris-buffer solutions at pH = 7.4, and has a long fluorescence lifetime (~9 ns). It has been found that the synthetic nucleic acid binds the synthesized porphyrin in the groove with an affinity constant of 2.3×10 7 . It has been shown that the porphyrin binding by poly[d(AT) 2 ] leads to a decrease in the particle size. Photoirradiation of the porphyrin complex with poly[d(AT) 2 ] by visible light leads to the destruction of the nucleic acid and enhances the porphyrin photolysis.

Porphyrins, owing to their unique physicochemical properties, hold great potential as candidates for the synthesis of new materials and active pharmaceutical drugs. The introduction of functional groups into porphyrin structures enables the creation of novel compounds with finely tuned structural and optical properties, as well as complex-forming abilities. In this study, spectral and thermochemical investigations were conducted to explore the complex formation of 5-[4′-( N -methyl-1″,3″-benzoimidazol-2″-yl)phenyl]-10,15,20-tris-( N -methyl-3′-pyridyl)porphyrin triiodide with synthetic (poly[d(GC)2], poly[d(AT)2]) and natural (ssDNA, ctDNA) nucleic acids. It was observed that the porphyrin forms complexes with poly[d(AT)2] and ssDNA, localized within the major groove of the biopolymer. Additionally, the porphyrin forms multiple intercalation complexes with varying geometries when interacting with poly[d(GC)2] and ctDNA. These findings demonstrate a new potential for enhancing the selective binding of ligands with nucleic acids (NA). Moreover, the study highlights the methodological aspect that establishing the type of formed complexes based on ligands’ electronic absorption spectra, known as “fingerprints,“ may lead to incorrect conclusions.

The complex formation of monoheteryl-substituted tricationic porphyrins with representative polynucleotides (poly[d(GC)2] and poly[d(AT)2]) was studied. It has been spectrally established that the studied porphyrins form intercalation complexes of different geometry with poly[d(GC)2]: 1) intercalation between the nitrogenous bases of the porphyrin macroring; 2) intercalation between the nitrogenous bases of the monoheteryl substituent. The studied porphyrins form complexes with the poly[d(AT)2] groove. The DSC method was used to analyse the temperature dependences of the specific heat capacities of solutions of the initial reagents and complexes of porphyrins with poly[d(GC)2] and poly[d(AT)2]; it was found that the proportion of structural changes in the analysed solution associated with intercalation significantly exceeds the similar value during the formation of the complex in the groove of the nucleic acid. The results obtained demonstrate a new potential opportunity to increase the selectivity of binding of ligands to nucleic acids.

We studied the influence of the position of the N-methyl group in tetra-(N-methylpyridyl)porphyrin on the features of its interaction with oligonucleotides using experimental physicochemical methods. Spectral methods detecting changes in the photophysical properties of chromophore ligands made it possible to prove the mechanism of binding to poly[d(AT)2] and poly[d(GC)2]. The thermochemical method made it possible to evaluate the structural consequences of ligation of oligonucleotides, and in the case of tetra-(3-N-methyl-pyridyl)porphyrin, to clarify the mechanism of binding to oligonucleotides. The combination of spectral and thermochemical analysis is useful for elucidating the structure of ligand complexes with synthetic and natural DNA.

Complex formation processes of tetrasulfosubstituted cobalt(II) phthalocyanine with ORF3a accessory protein of SARS-CoV-2 coronavirus were studied. The interaction of ORF3a protein with SARS-CoV-2 virus with tetrasulfosubstituted cobalt(II) phthalocyanine affords a stable complex in which metallophthalocyanine exists in the monomeric form. The complex formation induces slight changes in the secondary structure of the protein by increasing the fraction of disordered fragments of the polypeptide chain. The photoirradiation of the complex of ORF3a protein of SARS-CoV-2 virus with tetrasulfosubstituted cobalt(II) phthalocyanine leads to the photooxidation of amino acid residues of the protein.

A theoretical and experimental study of the interaction of the SARS-CoV-2 ORF10 protein with sulfosubstituted cobalt(II) and copper(II) phthalocyanines was carried out. The structures of the most probable complexes of metal phthalocyanines with the ORF10 protein were obtained by molecular docking methods. Cobalt(II) tetrasulfophthal ocyanine binds to the protein in the monomeric state, while the interaction ofORF1 0 with copper(II) tetrasulfophthalocyanine causes aggregation of the formed protein complexes, which was shown by the UV-Vis spectroscopy. Thermal denaturation of the ORF10 protein and its complexes with metal phthalocyanines was studied by differential scanning calorimetry. A joint analysis of the spectral and thermochemical data made it possible to propose a description of the mechanism of thermal denaturation ofthe ORF10 protein.

Directed synthesis of novel water-soluble asymmetric porphyrins containing in a molecule three sulfo-phenyl fragments and residues of small heterocyclic molecules (benzothiazole (S-spor), benzoxazole (O-spor) and benzo-N-methylimidazole (N-spor)) was performed using metal-complex catalysis method. The state of the synthesised porphyrins in water media was examined by spectrophotometric and potentiometric titration. It was shown that in the case of porphyrins with ben-zothiazole and benzoxazole residues two interconnected processes -protonation of the reaction centre and formation of self-associates from protonated O-spor and S-spor forms -occur in water. For the porphyrin with benzo-N-methylimidazole residual, the protonation processes dominate and revealed association was less evident compared to O-spor and S-spor. It was proved that formation of associates from protonated forms of anionic porphyrins does not result from pi-pi-interaction; the porphyrins under study form the H-bonded acid-base type associates' stabilisation of which is due to specific bindings through direct participation of sulfo groups as well as monoheteryl substitutes in the case of O-spor and S-spor. Potentiometric and spectrophotopotentiometric titrations were conducted, the pKa values which reflect the protonation process of the porphyrin reaction centre were determined. Acid strength increased in the order O-spor < N-spor < S-spor and correlated with electronegativity of heteroatom in the peripheral porphyrin's substitute.

Albumin is a globular protein with a number of functions of vital importance. Its aggregation can cause serious problems and cause hypoalbuminemia. Albumin complex formation with endogenous and exogenous porphyrins can lead to aggregation. This work is a study of the localization effect of a number of endogenous porphyrins, such as protoporphyrin, hematoporphyrin, deuteroporphyrin and their metal complexes in an albumin globule on the albumin state in solutions and resistance of protein complexes to thermally induced denaturation. The structure of the obtained complexes was determined by the IR and fluorescence spectroscopy methods in combination with molecular docking. The results obtained show that nature porphyrins form hydrogen bonds with various sections of the albumin polypeptide chain and cause changes in the protein secondary structure associated with the transformation of alpha-helices into beta-folds and subsequent protein aggregation. The DSC studies revealed that complex formation with porphyrins lowered the thermal effect of protein denaturation by 50-67%. The dependence of the structure of the complexes on the denaturation thermal effect was analyzed. It was established that the changes in the protein denaturation thermal effect could be used to determine porphyrin localization in the protein globule and protein ability to form aggregates, following complex formation. (C) 2021 Published by Elsevier B.V.

This review presents a wide range of tetrapyrrole photosensitizers used for photodynamic therapy (PDT), antimicrobial photodynamic therapy, photoinactivation of pathogens. Methods of synthesis and design of new photosensitizers with greater selectivity of accumulation in tumor tissue and increased photoinduced antitumor activity are considered. The issues of studying the properties of new photosensitizers, their photoactivity, the ability to generate singlet oxygen, and the possibility of using targeted photodynamic therapy in clinical practice are discussed. The review examines the work on PDT by national and foreign researchers.

•The effect of the counterions and the macroring nature on the ability of photosensors to ROS under oxygen-enriched and depleted condition was studied.•The photodynamic ability of cationic porphyrin and chlorins was estimated by the photooxidation reaction of albumin.•Potentiation of albumin photooxidation processes with potassium iodide was studied.•Using of chlorins as sensitizers is more effective than porphyrins in oxygen-depleted condition.