A. V. Lobanov

Aggregation state of amphiphilic cationic tetraphenylporphyrin derivatives in aqueous microheterogeneous systems

The conditions for the formation of ionic associates and J- and H-aggregates from amphiphilic cationic tetraphenylporphyrin derivatives in aqueous solutions of anionic surfactants and polyelectrolytes in a wide range of concentrations and pH are considered. The aggregation behaviors of tetraphenylporphyrin and its cationic derivatives in aqueous microheterogeneous systems are compared illustrating the influence of the porphyrin molecular structure on its ability to form supramolecular aggregates of a certain structure. The mechanism of the promoting action of premicellar solutions of anionic surfactants on the formation of J-aggregates of the diprotonated form of cationic porphyrins was proposed. The acid-base properties of a number of new synthetic meso-aryl-substituted porphyrins in aqueous microheterogeneous systems were characterized.

Generation of reactive oxygen species under singlet oxygen photosensitivity by chlorophyll and its analogs

The kinetic and photochemical parameters of the generation of reactive oxygen species, including singlet oxygen photosensitized by chlorophyll and its analogs on the basis of magnesium complexes of tetrapyrroles, are determined. It is shown that the nature of the central metal ion is the determining factor in the deactivation of formed singlet oxygen. The photosensitizing activity of tetrapyrrolic metal complexes is shown to decrease upon their aggregation.

Antitumor activity of carboplatin in the composition of a copolymer of lactic and glycolic acids

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.

Effect of histidine on the sensitized generation of singlet oxygen in the complexes with chlorophyll

The energies of the intermolecular interactions of an O2 molecule in the ground and excited states with the electron-excited and non-excited model complexes of chlorophyll were calculated using the DFT, CASSCF, SA-CASSCF, MCQDPT2, and XMCQDPT2 methods. The activation energies of formation and dissociation of the oxygen complexes were estimated. The radiative electric dipole moments of (0 → 0) spin-allowed S → S, T → T, and spin-forbidden S → T transitions were calculated taking into account the spin-orbit coupling, and rate constants of nonradiative transitions that determine the generation and deactivation of the O2 molecule (1Δg) were evaluated. The effect of histidine on the probability of singlet oxygen generation sensitized by the model chlorophyll complex was considered in detail.

Photocatalysts based on aluminum and zinc phthalocyanines supported on modified montmorillonite

The efficiency of the sensitizing action of photocatalysts prepared from montmorillonite modified by a cationic surfactant and treated with aluminum and zinc phthalocyanines was studied. The rates and quantum yields of acceptor (9,10-diphenylanthracene) consumption upon irradiation with the visible light of poly(methyl methacrylate) films and dispersions in toluene containing the photocatalysts were determined. The quantum yields of singlet oxygen generation were estimated on the basis of these data. The influence of the medium and concentration of phthalocyanines on the spectral characteristics of the photocatalysts was considered.

Spectral-Fluorescent Properties of Supramolecular Systems Based on Chlorin e 6

The spectral-fluorescent properties of various supramolecular systems based on chlorin e6 (Ce6) are determined to facilitate the development of new medicines for photodynamic therapy and diagnostics. The effect of various excipients, such as poly-N-vinylpyrrolidone (PVP), polyethylene glycol (PEG), bovine serum albumin (BSA), chitosan, Triton X-100 (TX-100), sodium hexametaphosphate (SHMP), and poly(dimethyldiallylammonium chloride) chloride (PDDAC), on the optical absorption and fluorescence of Ce6 is demonstrated. In the Ce6−PVP, Ce6−PEG, Ce6−BSA, Ce6−TX-100, Ce6−SHMP, and Ce6−PDDAC systems, Ce6 molecules are disaggregated and complexes thereof with excipients are formed. The quantum yield of Ce6 fluorescence in supramolecular systems is close to that of the free-form photosensitizer, in the absence of excipients. The results suggest that supramolecular complexes of Ce6 are promising for the development of medicines with controllable photodynamic activity.

Polymer nanoparticles loaded with FeCl-tetraphenylporphyrin for binary catalytic therapy of neoplasms

In order to study the possibility of using a metal complex of the porphyrin series, FeIIICl-tetraphenylporphyrin (FeClTPP), and its polymeric form as antitumor agents for binary catalytic therapy, the technology of preparation of polymer particles containing FeClTPP was developed for the first time. The experimental data obtained allow one to conclude that the developed form using a copolymer of lactic and glycolic acids (ratio of monomer units 50: 50), ultrasonic homogenization, D-mannitol (as a cryoprotectant), the active agent to polymer ratio 1: 10, and the organic to aqueous phase ratio 1: 10 and 1: 20, respectively, has the optimal physicochemical parameters. It was found that the free substance of FeClTPP and polymer particles with FeClTPP are active against MCF-7 (human breast adenocarcinoma), HeLa (human cervical carcinoma), and MG-63 (human osteosarcoma) cell lines. The polymer particles containing FeClTFP exhibit the highest cytotoxic effect against MCF-7 lines as compared to the free substance. The results of the study indicate that both the substance of tetraphenylporphyrin and its resulting polymeric form are promising for the treatment of tumor diseases in binary catalytic therapy.

Morphological features of composites prepared from polylactide and iron(III)−tetraphenylporphyrin complex

A material based on polylactide and iron(III)–tetraphenylporphyrin complex is prepared. The UV electronic spectra of the samples indicate the presence of porphyrin microinclusions in the polylactide matrix. According to optical microscopy, these inclusions have a size of 50–200 μm. It is determined that the melting point of the polylactide matrix decreases by 1–3°C with increasing porphyrin content in the composition. An experiment at a temperature of 40 ± 1°C shows that the degree of crystallinity of the polylactide matrix of the compositions varies insignificantly and does not exceed the degree of crystallinity of the original pure polylactide. In this case, the melting point remains almost unchanged.

Immobilized phthalocyanines of magnesium, aluminum, and zinc in photodynamic treatment of mesenchymal stromal cells

Phthalocyanines of magnesium, aluminum, and zinc immobilized on nano-sized silica and poly-N-vinylpyrrolidone in aqueous solutions were synthesized. Photochemical activity of the immobilized metal complexes was assessed by generation of singlet oxygen. Nontoxic concentrations of the new photosensitizers were determined in vitro. A comparative analysis of the efficiency of photodynamic therapy (PDT) was performed for immobilized phthalocyanines using mesenchymal stromal cells as a cell model. Aluminum phthalocyanine immobilized on nano-sized silica displayed the highest cell tropism. Irradiation of phthalocyanine-loaded cells resulted in generation of active singlet oxygen and subsequent apoptotic cell death. The use of immobilized phthalocyanines allowed decreasing the effective concentration (dose) of photosensitizer and enhancing the PDT cytotoxicity.

Aggregation and photophysical properties of phthalocyanines in supramolecular complexes

The concentration dependence of the degree of association of zinc and aluminum phthalocyanines in supramolecular systems is determined. Complexes containing rare photoactive associates with an absorption maximum significantly shifted to longer wavelengths are obtained. The radiative lifetimes, extinction coefficients, and energy of HOMO-LUMO electronic transitions of isolated and associated metal phthalocyanine complexes are determined. It is demonstrated that the existence of the metal phthalocyanine largely in an aggregated state is characteristic of zinc phthalocyanine systems, while aluminum phthalocyanine, having an additional extraligand, chloride ion, is stabilized in the isolated state.