Synthesis and Characterization of Bulky Substituted Hemihexaphyrazines Bearing 2,6-Diisopropylphenoxy Groups.

New substituted [30]trithiadodecaazahexaphyrines (hemihexaphyrazines) were synthesized by a crossover condensation of 2,5-diamino-1,3,4-thiadiazole with 4-chloro-5-(2,6-diisopropylphenoxy)- or 4,5-bis-(2,6-diisopropylphenoxy)phthalonitriles. The compounds were characterized by 1H-, 13C-NMR, including COSY, HMBC, and HSQC spectroscopy, MALDI TOF spectrometry, elemental analysis, IR and UV-Vis absorbance and fluorescence techniques.

An Indium Synthetic Etioporphyrin for Organic Electronics: Aggregation and Photoconductivity in Thin Films.

A new complex of indium(III)chloride with etioporphyrin-I was synthesized and characterized. As with naturally occurring extraligated etioporphyrins, the InCl-EtioP-I spectrum in solution has a very strong B-band and a more than an order of magnitude weaker Q-band, but this difference diminishes in solid films of InCl-EtioP-I obtained by thermal evaporation in vacuum. In a solid, molecules have a tight convex-convex arrangement in a 2D double layered structure with interplane distance of 3.066 Å. The conductivity of films can easily be activated by the action of temperature or light. In the cells with symmetrical lateral contacts the photocurrent exceeds the dark current by about three orders of magnitude, with the contribution of photons in the Q-band range being greater than expected from the experimental or calculated absorption spectrum. The Q-bands contribute significantly to the photovoltaic effect in the ITO/InCl-EtioP-I/Al sandwich cells. Such cells show an untypically strong signal in the photodiode regime, which yields the spectral detectivity of 10^12 Jones.

Prospects for the use of macrocyclic photosensitizers for inactivation of SARS-CoV-2: selection of compounds leaders based on the molecular docking data.

The treatment of coronavirus COVID-19, like other viral diseases, is currently underdeveloped. This fact necessitates the search for new drugs and treatment methods that will effectively disrupt the life cycle of the virus. A big problem in the therapy of viral diseases is the ability of viruses to evade the host's immune response. We suppose that the search for drugs that can change the evasiveness of the virus from the immune response of the host is a very promising strategy, as it can help the body to cope with the infection. Protein SARS-CoV-2 ORF8 is one of the key proteins that can suppress antiviral immunity. This paper considers the available information on the structure and functioning of ORF8, as well as the results of molecular docking of ORF8 to a wide range of tetrapyrrole macroheterocyclic compounds capable of generating reactive oxygen species upon photoirradiation. This principle of photoinactivation of biosubstrates underlies the methods of photodynamic therapy of cancer. Application of photoinactivation of drug-resistant forms of bacteria and some viruses can be useful in the fight against COVID-19 and other viral infections. In this work, the structure of ORF8 complexes with macrocyclic compounds is considered in detail, the dependence of their binding affinity on the nature of macrocycles and the nature of peripheral substituents is analyzed and spectral studies of the binding of ORF8 to chlorin is performed. This paper is a part of a large project to investigate the possibility of using macrocyclic compounds for the treatment of viral diseases.Communicated by Ramaswamy H. Sarma.

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.

Dianionic States of Trithiadodecaazahexaphyrin Complexes with Homotrinuclear MII3O Clusters (M = Ni and Cu): Crystal Structures, Metal- Or Macrocycle-Centered Reduction, and Doublet-Quartet Transitions in the Dianions.

Metal complexes of trithiadodecaazahexaphyrin (Hhp) that contain MII3O clusters inside a π-extended trianionic (Hhp3-) macrocycle have been prepared. Studies of the magnetic properties of NiII3O(Hhp) and CuII3O(Hhp) reveal a diamagnetic and EPR-silent trianionic (Hhp3-) macrocycle and diamagnetic NiII3(O2-) or paramagnetic CuII3(O2-) tetracations. The positive charge of MII3O(Hhp) is compensated by one acetate anion {MII3O(Hhp)}+(CH3CO2-). The three-electron reduction of {MII3O(Hhp)}+ yields {cryptand(Cs+)}2{NiII2NiIO(Hhp5-)}2-·2C7H8 (1) and {cryptand(Cs+)}2{CuII3O(Hhp•6-)}2-·C7H8 (2) crystalline salts. The magnetic properties of 1 reveal the formation of Hhp5- and the reduction of nickel(II) to the paramagnetic NiI ion (S = 1/2), which is accompanied by the formation of the {NiII2NiIO(Hhp5-)}2- dianion. As a result, the magnetic moment of 1 is 1.68 µB in the 20-220 K range, and a broad EPR signal of NiI was observed. The Hhp5- macrocycle has a singlet ground state, but the increase in the magnitude of the magnetic moment of 1 above 220 K is attributed to the population of the triplet excited state in Hhp5-. The {NiII2NiIO(Hhp5-)}2- dianion is transferred from the doublet excited state to the quartet excited state with an energy gap of 1420 ± 50 K. Salt 1 also shows an unusually strong low-energy NIR absorption, which was observed at 1000-2200 nm. In 2, a highly reduced Hhp•6- radical hexaanion (S = 1/2) coexists with a CuII3(O2-) cluster (S = 1/2) in the {CuII3O(Hhp•6-)}2- dianions. The dianions have a triplet ground state with antiferromagnetic exchange between two S = 1/2 spins with J = -6.4 cm-1. The reduction of Hhp in both salts equalizes the initially alternated C-N bonds, supporting the increase in the Hhp macrocycle electron delocalization.

Modeling the binding of protoporphyrin IX, verteporfin, and chlorin e6 to SARS-CoV-2 proteins.

In this work, we analyze the latest data on the molecular docking of a range of SARS-CoV-2 proteins to protoporphyrin IX, verteporfin, and chlorin e6, as well as consider the prospects for using chlorins and porphyrins as agents for photoinactivation of the SARS2 virus.

Mechanism of cyanocobalamin chlorination by hypochlorous acid.

Hypochlorous acid (HOCl) is a strong oxidant produced by myeloperoxidase. Previous work suggested that HOCl modifies the corrin ring of cobalamins to yield chlorinated species via mechanisms that are incompletely understood. Herein, we report a mechanistic study on the reaction between cyanocobalamin (CNCbl, vitamin B12) and HOCl. Under weakly acidic, neutral and weakly alkaline conditions, the reaction produces the c-lactone derivative of CNCbl chlorinated at the C10-position of corrin ring (C10-Cl-CNCbl-c-lactone). Formation of C10-Cl-CNCbl-c-lactone was not observed at pH ≥ 9.9. The chlorination of CNCbl by HOCl proceeds via two pathways involving one and two HOCl molecules: the reaction is initiated by the very fast formation of a complex between CNCbl and HOCl, which either undergoes slow transformation to chlorinated species, or rapidly reacts with a second HOCl molecule to produce C10-Cl-CNCbl. Subsequent reaction of C10-Cl-CNCbl with HOCl proceeds rapidly toward lactone ring formation by H-atom abstraction at position C8. This work uncovered mechanisms and products of the reaction of a biologically active and therapeutically used cobalamin, CNCbl and the endogenous oxidant HOCl. Binding and reactivity studies of C10-Cl-CNCbl and C10-Cl-CNCbl-c-lactone with relevant proteins of the cobalamin pathway and with cultured cells are necessary to elucidate the potential physiological effects of these species.

Molecular mechanisms causing albumin aggregation. The main role of the porphyrins of the blood group.

In this paper was studied the interaction of deutero- and hematoporphyrin with bovine serum albumin, using various methods of physico-chemical analysis. It was established that the localization of porphyrins occurred in the IB subdomain, while hematoporphyrin interacted with the protein in a monomeric form, and deuteroporphyrin - as a J-dimer. Based on spectral studies, the affinity constants of binding albumin with porphyrins were determined, and the affinity of the protein for deuteroporphyrin appeared to be higher than for hematoporphyrin. It was shown that the interaction of albumin with the studied porphyrins led to a change in the secondary structure of the protein, it being accompanied by a decrease in the proportion of disordered protein fragments and an increase in ß-folding.

Double-Decker Paramagnetic {(K)(H3 Hhp)2 }⋠2- Radical Dianions Comprising Two [30]Trithia-2,3,5,10,12,13,15,20,22,23,25,30-Dodecaazahexaphyrins and a Potassium Ion.

Reduction of free-base [30]trithia-2,3,5,10,12,13,15,20,22,23,25,30-dodecaazahexaphyrin (H3 Hhp) yields {cryptand[2.2.2](K)}2 {(K)(H3 Hhp)2 }⋅4C6 H4 Cl2 (1) containing double-decker {(K)(H3 Hhp)2 }⋅2- radical dianions, whose structure was elucidated using X-ray diffraction. Potassium ion forms 12 short (K+ )⋅⋅⋅N(H3 Hhp) contacts with two H3 Hhp macrocycles in the 3.048-3.157 Šrange. Dianions have S=1/2 spin state manifesting an effective magnetic moment of 1.64 µB at 300 K and a narrow Lorentzian electron paramagnetic resonance signal. Quantum chemical calculations support the ionic nature of the (K+ )-N(H3 Hhp) interactions and the nearly equal distribution of the -1.5 charge over each macrocycle. H3 Hhp takes the role of an aza-crown ether in free-base reduced state and forms a new type of double-decker complex.

Thermochemical research of chitosan complexes with sulfonated metallophthalocyanines.

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.

Magnesium Porphine Supermolecules and Two-Dimensional Nanoaggregates Formed Using the Langmuir-Schaefer Technique.

Porphyrins are functional elements of important biomolecules, whose assemblies play a central role in fundamental processes such as electron transfer, oxygen transport, enzymatic catalysis, and light harvesting. Here we report an approach to formation of porphyrin supermolecules, a particular type of nanoparticles with unusually strong noncovalent intermolecular interactions. Key differences between the supermolecules and noncovalent nanostructures described earlier are as follows. (1) Supermolecules consist of molecules of the same type without side groups promoting the self-assembly and without any spacers; no surfactant or catalyst to assist the process is needed. (2) They exhibit unusual photophysical properties and remain stable even in organic solvents. Their formation occurs under specially selected conditions at the air-water interface at room temperature. Following this route, we have formed supermolecules of magnesium porphine, a functional element of chlorophyll. The properties of these supermolecules are markedly different from those of the constituent molecules. For example, in contrast to the pink color of the monomer solution, solutions of supermolecules are transparent for visible light and absorb in the ultraviolet and near-infrared regions. We also present atomic force microscopy visualization of the porphyrin two-dimensional nanoaggregates forming at the air-water interface that were predicted in our previous works. This approach offers a guideline for the discovery of new supermolecules, including complex biological ones, and the formation of supermolecular materials with novel properties.

Characterization of the complex between native and reduced bovine serum albumin with aquacobalamin and evidence of dual tetrapyrrole binding.

Serum albumin binds to a variety of endogenous ligands and drugs. Human serum albumin (HSA) binds to heme via hydrophobic interactions and axial coordination of the iron center by protein residue Tyr161. Human serum albumin binds to another tetrapyrrole, cobalamin (Cbl), but the structural and functional properties of this complex are poorly understood. Herein, we investigate the reaction between aquacobalamin (H2OCbl) and bovine serum albumin (BSA, the bovine counterpart of HSA) using Ultraviolet-Visible and fluorescent spectroscopy, and electron paramagnetic resonance. The reaction between H2OCbl and BSA led to the formation of a BSA-Cbl(III) complex consistent with N-axial ligation (amino). Prior to the formation of this complex, the reactants participate in an additional binding event that has been examined by fluorescence spectroscopy. Binding of BSA to Cbl(III) reduced complex formation between the bound cobalamin and free cyanide to form cyanocobalamin (CNCbl), suggesting that the ß-axial position of the cobalamin may be occupied by an amino acid residue from the protein. Reaction of BSA containing reduced disulfide bonds with H2OCbl produces cob(II)alamin and disulfide with intermediate formation of thiolate Cbl(III)-BSA complex and its decomposition. Finally, in vitro studies showed that cobalamin binds to BSA only in the presence of an excess of protein, which is in contrast to heme binding to BSA that involves a 1:1 stoichiometry. In vitro formation of BSA-Cbl(III) complex does not preclude subsequent heme binding, which occurs without displacement of H2OCbl bound to BSA. These data suggest that the two tetrapyrroles interact with BSA in different binding pockets.

Studies on reaction of glutathionylcobalamin with hypochlorite. Evidence of protective action of glutathionyl-ligand against corrin modification by hypochlorite.

Glutathionylcobalamin (GSCbl), a tight complex of glutathione (GSH) with cobalamin(III), is readily oxidized to aquacobalamin by hypochlorite. Corrin macrocycle remains unmodified in the presence of threefold excess of hypochlorite, whereas aqua- and cyanocobalamins are partially transformed to chlorinated species under the same conditions. The suggested mechanism of reaction between GSCbl and hypochlorite involves subsequent oxidation of thiol and amino groups and dissociation of oxidized glutathione from Co(III)-ion.

Kinetics and mechanism of oxidation of super-reduced cobalamin and cobinamide species by thiosulfate, sulfite and dithionite.

We studied the kinetics of reactions of cob(I)alamin and cob(I)inamide with thiosulfate, sulfite, and dithionite by UV-Visible (UV-Vis) and stopped-flow spectroscopy. We found that the two Co(I) species were oxidized by these sulfur-containing compounds to Co(II) forms: oxidation by excess thiosulfate leads to penta-coordinate complexes and oxidation by excess sulfite or dithionite leads to hexa-coordinate Co(II)-SO2(-) complexes. The net scheme involves transfer of three electrons in the case of oxidation by thiosulfate and one electron for oxidation by sulfite and dithionite. On the basis of kinetic data, the nature of the reactive oxidants was suggested, i.e., HS2O3(-) (for oxidation by thiosulfate), S2O5(2-), HSO3(-), and aquated SO2 (for oxidation by sulfite), and S2O4(2-) and SO2(-) (for oxidation by dithionite). No difference was observed in kinetics with cob(i)alamin or cob(i)inamide as reductants.

First tellurium-containing phthalocyanine analogues: strong effect of tellurium on spectral, redox and conductivity properties of porphyrazines with annulated chalcogenodiazole ring(s).

The first tellurium-containing phthalocyanine analogues have been prepared and spectroscopically characterised: the Mg(II) complex of tetra(1,2,5-telluradiazolo)porphyrazine and a low-symmetry tert-butyl substituted Mg(II) tribenzoporphyrazine with one fused 1,2,5-telluradiazole ring. It was observed that the introduction of Te atom(s) reduces the energy of the Q-transition, facilitates the reduction of the macrocycle and strongly increases the conductivity of thin films.

Generation and characterization of high-valent iron oxo phthalocyanines.

The first high-valent iron oxo complex on the phthalocyanine platform has been prepared from iron tetra-tert-butyl-phthalocyanine and m-chloroperbenzoic acid and characterized by low temperature UV-vis, cryospray MS, EPR, X-ray absorption and high resolution X-ray emission methods.