In this work, screening studies of the cytotoxic effect of chlorins with fragments of di-, tri-, and pentaethylene glycol at the macrocycle periphery in relation to HeLa, A549, and HT29 cells were performed. It is shown that, despite different hydrophobicity, all the compounds studied have a comparable photodynamic effect. The conjugate of chlorin e6 with pentaethylene glycol, which has the lowest tendency to association among the studied compounds with tropism for low density lipoproteins and the best characteristics of the formation of molecular complexes with Tween 80, has a significant difference in dark and photoinduced toxicity (ratio IC50(dark)/IC50(photo) approximately 2 orders of magnitude for all cell lines), which allows to hope for a sufficiently large "therapeutic window". A study of the interaction of this compound with HeLa cells shows that the substance penetrates the cell and, after red light irradiation induces ROS appearance inside the cell, associated, apparently, with the photogeneration of singlet oxygen. These data indicate that photoinduced toxic effects are caused by damage to intracellular structures as a result of oxidative stress. Programmed type of cell death characterized with caspase-3 induction is prevailing. So, the conjugate of chlorin e6 with pentaethylene glycol is a promising antitumor PS that can be successfully solubilized with Tween 80, which makes it suitable for further in vivo studies.

Interactions of cationic and anionic chlorin photosensitizers (PSs) for photodynamic therapy with the potential delivery vehicle, the micellar surfactant Tween 80, were studied by spectrophotometric and fluorescence titration. The formation of PS—Tween 80 complexes in an aqueous solution was demonstrated. Two binding modes of the macrocycles to surfactant micelles, each with its own binding constant and stereochemistry of interactions, are observed in the spectrophotometric titration curves. Regardless of the sign and magnitude of the charge of the PS molecule, water-soluble chlorin macroheterocycles are located in the outer layer of the micelle surrounded by polar oxyethylene groups, into which hydrated iodide ions can penetrate. Cationic PSs were found to be, in general, more accessible to the quencher.

The electronic absorption spectra of cationic forms of porphyrinoids in acetonitrile or benzene with the addition of acetic or trifluoroacetic acid have been studied and the values of the acid-base interaction constants have been calculated. The order of changes in the basicity of the studied compounds obtained from spectrophotometric, quantum-chemical (DFT, B3LYP, and CC-pVDZ using NBO analysis), and thermodynamic data have been consistent.

Electronic absorption spectroscopy and fluorescence spectroscopy were used to study conditions for the formation of associates of amphiphilic phorbins and chlorins in an ethanol–water system. The conditions and degree of disaggregation in the presence of solubilizing additives of nonionic surfactants (Tween 80) and biocompatible polymers (polyethylene glycol and polyvinylpyrrolidone) were also investigated. The propensity of the macroheterocycles based on chlorophyll a to association in water-alcoholic solutions decreases on going from covalently bound dimeric structures to monomeric ones, on going from phorbins to chlorins and on accumulating hydrophilic glycol or positively charged alkylammonium fragments in the molecule. Among the considered solubilizers, the nonionic surfactant Tween 80 emerged as the most efficient means for destroying chlorin associates in water–alcohol solutions with a high content of water.

Spectral characteristics (electronic absorption spectra, fluorescence emission spectra, 1H NMR) of prepared Cu(II) and Zn(II) complexes of 2,7,12,17-tetraphenylporphycene {H2(β-Ph)4Por}, their thermal stability, and persistence toward acids, as well as electrochemical and electrocatalytic properties have been discussed. It has been found by cyclic voltammetry that the electrocatalytic activity of metalloporphycenes M(β-Ph)4Por in the reaction of molecular oxygen reduction is close to that of metalloporphyrins M(ms-Ph)4P. Thermal stability and persistence of M(β-Ph)4Por in acidic medium are considerably lower than those of porphyrin analogs. Thus, the kinetic stability of copper(II) complex of 2,7,12,17-tetraphenylporphycene in HOAc–H2SO4 medium as compared with Cu(ms-Ph)4P is lower by more than an order of magnitude, while its thermal stability is almost 200°С lower, which is caused by sterically unfavorable change in the shape of coordination center of ligand H2(β-Ph)4Por upon complexation.

Porphycene, β-phenyl-substituted analog of tetraphenylporphyrin, and its complexes with Cu(II) and Zn(II) have been prepared. Spectral parameters of the porphycene, its acid-base properties and thermal stability in the solid phase as well as its complexes stability towards dissociation in acidic medium have been studied by means of electronic absorption and NMR spectrometry, mass spectroscopy, thermogravimetry, and quantum chemistry simulation.

Distortion of flat ligand structure in metal complexes of porphyrins caused by N-methyl substitution considerably decreases the kinetic stability of these compounds in DMSO–HOAc proton-releasing medium ((AcO)Zn(N-Me)TPP (Ib) < (AcO)CoII(N-Me)TPP (Ia) < ZnTPP (IIb) < CoIITPP (IIa)) and their resistance to thermal destruction in crystal state {(AcO)CoII(N-Me)TPP (Ia) < (AcO)Zn(N-Me)TPP (Ib) < H(N-Me)TPP (I) < H2TPP (II) < CoIITPP (IIa) < ZnTPP (IIb)}, however, exerts a positive effect on the electrocatalytic activity of the compounds in the electroreduction of molecular oxygen, which changes in the following order: II < I < IIa < Ib « Ia. It was proved by thermogravimetry and electron spectroscopy that N-substituted metal complexes with Zn(II) and Co(II), in contrast to the corresponding ligands, undergo dealkylation to form metal porphyrins (MP) when heated above 200°C under both an inert and air oxygen atmosphere.

Complexes of some meso - and undeca -substituted corroles with manganese, copper, and zinc are synthesized. Their stability in protolytic dissociation processes studied using spectroscopy methods increases for meso -triphenylcorrole ( I ) complexes in the following series of metals: Zn < Mn < Cu. The stability of copper complexes in the HOAc-H 2 SO 4 environment increases after electron-donor substitution of molecules in the series: Cu( ms -Ph) 3 Cor ( Ib ) > Cu( ms -4-OCH 3 Ph) 3 Cor ( IIb ) ≈ Cu(β-Br) 8 ( ms -Ph) 3 Cor ( IVb ) > Cu( ms -4-NO 2 Ph) 3 Cor ( IIIb ). Contrariwise, the dissociation rates of manganese corroles increase with increasing electron-donating properties of the substituents in the macrocycle: IVb < IIIb < Ia < IIa . Dissociation of metallocorroles is accompanied by donor-acceptor and acid-base interactions, as well as by intramolecular redox processes, to result in low selectivity of dissociation and formation of side products. The dissociation scheme of corrole complexes with mixed-valence d metals was proposed for the first time.

Синтезированы комплексы некоторых мезо- и ундека-замещенных корролов с марганцем, медью и цинком, спектрально изучена их устойчивость в процессах протолитической диссоциации, которая для комплексов мезо-трифенилкоррола (I) растет в ряду металлов: Zn2SO4 повышается при электронодонорном замещении молекул в ряду: Cu(ms-Ph)3Cor (Ib)>Cu(ms-4-OCH3Ph)3Cor (IIb) Cu( -Br)8(ms-Ph)3Cor (IVb)>Cu(ms-4-NO2Ph)3Cor (IIIb). Напротив, скорость реакции диссоциации марганец-корролов увеличивается с ростом электронодонорности заместителей в составе макроцикла: IVb

Shielding of coordination centers in metalloporphyrins (MPs, M = Cd) through covering it with a covalently bonded “lid” or by an endocyclic N -substituent results in retardation of metal exchange reaction (Cd/Zn or Cd/Cu) by up to 10 times. A decrease in the metal exchange rate was observed in spite of the fact that the shielding gave rise to a pronounced distortion of the predominately planar structure of aromatic ligands in the MP structure in the studied objects, which was confirmed by electronic and fluorescence spectroscopy as well as by 1 H NMR spectroscopy. It was found that 2,8,12,18-tetramethyl-3,7,13,17-tetrabutyl-10,20-di- ortho -methoxyphenylporphin exists as a mixture of cis - and trans -atropisomers with a ratio of 1: 2.

Transmetalation reactions of cadmium complexes of tetraphenylporphine (CdTPP, I ) and tetrabenzoporphine (CdTBP, II ) in individual and mixed solvents have been investigated. For individual solvents, provided that the reaction proceeds via the same mechanism, its rate generally increases as the donor number increases in the order DMSO < DMF < PrOH-1 < MeCN (CdTPP-Zn(OAc) 2 -Solv system). On passing to the CdTPP-Cu(OAc) 2 -Solv system, the reaction rate order changes to DMSO < PrOH-1 < MeCN < DMF because the transmetalation mechanism changes from mixed to associative, as follows from the reaction order with respect to the salt being zero. The effect of the DMSO-DMF mixed solvent on the transmetalation reaction is limited to changing the reaction rate through alteration of the stability of the [CuX 2 (Solv 1 ) n − m − 2 (Solv 2 ) m ] solvated salts. The trans effect of the ligands in the solvated salts does not increase the transmetalation rate.

The reaction kinetics of the metal exchange Cd(II)-Cu(II) and Cd(II)-Zn(II) in the cadmium complexes (CdP) with porphyrin ligands (H2P) differing by degree of stiffness (tetraphenylporphin, N-methyltetraphenylporphin, and tetraphenyltetrabenzoporphin) in the DMSO medium, was studied using spectrophotometric method. The rate of metal exchange reaction depends on the nature of the non-planatrity of H2P in the structure of CdP complexes, as well as on the additional screening of the reaction center MN4 by the extra-ligands and substituents. The reduction of the coordinating ability of the anion X− in the structure of the solvate-salt of incoming metal M’X2(Solv)n−2 in a series: acetylacetonate > acetate > chloride > nitrate favors the metal exchange. In the most studied cases the reaction of CdP proceeds along a combined associative-dissociative mechanism. The order of the metal exchange reaction is found to be depending on temperature indicating a change in the contributions of associative and combined routes. The “pure” associative reaction mechanism in a medium of DMSO was for the first time found for the labile complex CdTPTBP with the saddle-type nonplanar ligand.

Planarity disturbance in metal porphyrin macrorings produces destabilization of complexes in dimethyl sulfoxide-acetic acid and benzene-acetic acid systems, except for cases where the coordination center is additionally stabilized by endocyclic substituents and/or extra ligands. The first dissociation stage of complexes with N-substituted analogs of porphyrins involves substitution of the acido ligand in the strongly shielded coordination sphere by an electron-donor solvent molecule. The revealed dependences of dissociation rate constants on acid concentration in DMSO, untypical of most metal porphyrins, are explained by a change in the type of the attacking species with changing solvent composition. The dissociation rate constants of complexes in an electron donor solvent can be lower by several orders of magnitude than in a weakly solvating medium.

Kinetics of metal exchange reaction Cd(II) → Zn(II) and Cd(II) → Cu(II) in Cd complexes with tetraphenylporphyrin in DMSO is studied. Reaction with Cu(II) nitrate occurs in both cases more vigorously as compared to that with Zn(II) nitrate. Conditions for metal exchange reactions are studied depending on the nature of metal porphyrinate, a salt (nitrates, acetates, and chlorides of Zn(II), Cu(II), and Co(II), and of organic solvent (DMSO, CH3CN). It is shown that Zn(II) complexes with nonplanar porphyrins do not show metal exchange Zn(II) → Cu(II) or Zn(II) → Co(II) under mild conditions in DMSO and CH3CN.

Kinetic stability of zinc complexes with meso -phenyltetrabenzoporphyrins in DMSO–HOAc mixture and in glacial acetic acid was studied. The stability of complexes was found to decrease with reduction in their macrocyclic effect and with increasing polarization of their macrocycles. The stability of nonplanar and nonsymmetrically substituted complexes was determined to be lower than that of the more planar and symmetrically substituted complexes.

Electronic spectroscopy and chemical kinetics were the tools used to study the dissociation of Mg-tetra(tert-butyl)phthalocyanine in ethanol-acetic acid from 298 to 318 K. The activation energies and entropy changes in the reaction were calculated. The results are discussed in terms of the acidoprotolytic dissociation of the magnesium complex. It was shown that an undissociated acetic acid molecule is the major reactant of the title system. The most likely stoichiometric and activation mechanism of the process is discussed.