The work is devoted to study of new nanostructural photosensitizer Octasens based on micellar form of Zinc 4,5-octakis(decylthio)-3,6-octachlorphthalocyanine with absorption maximum at 728 nm. Photosensitizer shows selective accumulation in tumors and provides efficient (more than 83%) inhibition of growth of model tumor.

The aim of the research was to develop dosage form of 5-aminolevulinic acid (ALA) as a hydrogel composition based on chitosan, carbopol, or hydroxyethylcellulose (HEC). Distribution of protoporphyrine IX (PPIX) in animal tissues was studied by using local fluorescence spectroscopy in mice bearing Ehrlich tumour and healthy rabbits. We have shown that ALA when included in hydrogel compositions induced PPIX synthesis in the application area tissues. The intensity of PPIX fluorescence in the tumor was time(1-4 h) and dose-dependent (5-20 %). The PPIX distribution in the tumor was more even when DMSO was introduced into gel composition. We observed that ALA as a component of hydrogel penetrated through stratum corneum and appeared in animal blood. Based on data obtained, we conclude that HEC-based gel with ALA and DMSO was most stable gel and might be chosen for the development of ALA dosage form for topical application.

The results ofin vivo biokinetic investigation of the photodynamic activity of a series of new photosensitizers, including a tetraazachlorine derivative (2,3,3a,21а-tetrahydro-2-methyl-3а,8,13,18-tetraphenyl-5,10,15,20-tetraaza-1Н,22Н,24Н-pyrrolo[3, 4-b]porphine), two difluoroboryl-substituted complexes of diphenylazadiisoindolylmethene (N,N-difluoroboryl-N-[3-(4-tert-butylphenyl)-2Н-isoindol-1-yl)]-N-[3-(4-tert-butylphenyl)-1Н-isoindol-1-yliden]amine and N,N-difluoroboryl-1-[3-(4-methoxyphenyl)-2Н-isoindol-1-yl)]-N-[3-(4-methoxyphenyl)-1Н-isoindol-1-yliden]amine), and sulfanyl-substituted phthalocyanine (1,8,15,22-tetrakis(tert-butylsulfanyl)-29Н,31Н-phthalocyanine) are reported. Upon intravenous injection in the form of micellar suspensions in 4% aqueous solutions of Cremophor EL and Proksanol 268, the compounds under consideration exhibit pronounced photodynamic activity in mice bearing solid form of Ehrlich tumor and sarcoma S-37. A comparison of the tumor growth rate and the time to attaining a critical tumor volume in the test and control groups shows evidence for a high photodynamic activity of the new photosensitizers.

A series of zinc and aluminum phthalocyanines containing 3–8 pyridiniomethyl or cholinyl substituents on average were synthesized. As the number of cation substituents increased, in aqueous solutions, the aggregation ability of phthalocyanines decreased, while the quantum yields of fluorescence and singlet oxygen generation increased. The photodynamic inactivation of coliform bacteria sensitized by zinc and aluminum phthalocyanine polycations with an increase in the substitution degree became more effective.

Results of an in vivo biokinetic investigation of the photodynamic activity of a series of new photosensitizers including a tetraazachlorin derivative (2,3,3α,21α-tetrahydro-2-methyl-3α,8,13,18-tetraphenyl-5,10,15,20-tetraaza-1 H ,22 H ,24 H -pyrrolo[3, 4- b ]porphine), two difluoroboryl-substituted complexes of 3,3′-diphenylazadiisoindolylmethene { N , N -difluoroboryl- N -[3-(4- t -butylphenyl)-2 H -isoindol-1-yl)]- N -[3-(4- t -butylphenyl)-1 H -isoindol-1-yliden]amine and N , N -difluoroboryl-1-[3-(4-methoxyphenyl)-2 H -isoindol-1-yl)]- N -[3-(4-methoxyphenyl)-1 H -isoindol-1-yliden]amine}, and a sulfanyl-substituted phthalocyanine [1,8,15,22-tetrakis( t -butylsulfanyl)-29 H , 31 H -phthalocyanine] are reported. These compounds exhibit pronounced photodynamic activity in mice bearing solid Ehrlich ascites carcinoma and sarcoma S-37 upon intravenous injection as micellar suspensions in aqueous solutions (4%) of Cremophor EL and Proxanol 268. Acomparison of the tumor growth rate and the time of attaining a critical tumor volume in the test and control groups shows evidence for high photodynamic activity of the new photosensitizers.

Chlorine-containing products of incomplete nucleophilic substitution in tetrachlorophthalonitrile were subjected to further reaction with nucleophiles. The nature of the nucleophiles and the order of their introduction into stepwise nucleophilic substitution in tetrachlorophthalonitrile were shown to be of principal importance for selective synthesis on this basis of phthalonitrile derivatives with various substituents.

Iron phthalocyanine-catalyzed oxidative chlorination of aromatic hydrocarbons using the H 2 O 2 -HCl system led to the formation of the corresponding chlorine derivatives.

Nucleophilic replacement of chlorine atoms in tetrachlorophthalonitrile by the action of primary and secondary amines was studied. The reactions of tetrachlorophthalonitrile with amines at a ratio of 1: 10 gave with high yields and regioselectivity the corresponding 4,5-diamino-3,6-dichlorophthalonitriles from cyclic secondary amines and 4-amino-3,5,6-trichlorophthalonitriles from primary amines and acyclic secondary amines. 4-Amino-3,5,6-trichlorophthalonitriles were used to synthesize cobalt and zinc phthalocyanine complexes. It was shown that replacement of chlorine atoms in the pyrrolic β-positions of hexadecachlorophthalocyanines by amino groups is not accompanied by red shift of the long-wave absorption band in the electronic spectra.

The paper presents the results of studying the photofungicidal activity of a photosens (octacationic phthalocyanine) in the in vitro and in vivo systems. Cultured Candida guilliermondii were employed in in vitro investigations. The single combined action of octacationic phthalocyanine at a concentration of up to 1 microM and laser irradiation at a wavelength of 675 nm were established to allow the high activation (up to 100%) of yeast fungi to be achieved in the in vitro system. In vivo investigations were performed on 14 rabbits (28 eyes) with induced keratomycosis. In the first series, fluorescent diagnosis of photosens accumulation in the pathological corneal areas was made in 9 (18 eyes). Based on the data obtained in the second series of experiments, the authors examined the feasibilities of photodynamic therapy for corneal mycotic lesions with the above photosensitizer in 5 rabbits (10 eyes).

The electroreduction of methyl 5-nitro-4-oxopentanate was studied by means of a polarographic method and preparative electrolysis in acidic-alcoholic solutions. The effects of the following factors on the yield and quality of 5-amino-4-oxopentanoic acid hydrochloride were studied: the cathode material, amount of electricity, temperature, nature of the solvent, concentrations of the initial nitro compound and hydrochloric acid, and the cell design. It was shown by electrolysis at a controlled potential and in a galvanostatic mode that the products of methyl 5-nitro-4-oxopentanate electroreduction are hydroxyamino and amino compounds, and also ammonium chloride, nitromethane, methylhydroxylamine hydrochloride, and monomethylamine hydrochloride. Their ratio depends on the electrolysis conditions. The highest overall substance yield (61.1–66.0%) and current yield (68.1–68.6%) of 5-amino-4-oxopentanoic acid hydrochloride was achieved at a copper cathode in a filter-press cell. The content of the main substance in the electrochemically obtained samples of 5-amino-4-oxopentanoic acid was 89.5–91.0%.

Nucleophilic substitution of chlorine atoms in tetrachlorophthalonitrile by benzene- and alkanethiols in the presence of a base was studied at different reactant ratios. The substitution is characterized by complete regioselectivity: the chlorine atom in position 4 of tetrachlorophthalonitrile is replaced first; next follows replacement of the 5-chlorine atom. The reactions of tetrachlorophthalonitrile with nucleophiles at ratios of 1:2 and 1:4 lead to the formation of the corresponding 3,6-dichloro-4,5-bis[phenyl(alkyl)sulfanyl]- and tetrakis[phenyl(alkyl)sulfanyl]phthalonitriles. The latter were converted into metal complexes of [phenyl-(alkyl)sulfanyl]-substituted phthalocyanines which absorb in the red and near-IR regions of the electronic spectra.

Nucleophilic substitution of chlorine in tetrachlorophthalonitrile by the reaction with aryloxy anions is studied. Depending on the reactant ratio, the products of substitution of one, two, and/or three chlorine atoms are formed. Their tetramerization gives aryloxychloro-substituted phthalocyanines having the absorption band in the near-IR range.

Photosense has been synthesized at the State Research Center «NIOPIK», it belongs to the second generation of Russian photosensitizers. Photosense is a mixture of sulfated aluminium phthalocyanine sodium salts. The aim of investigation was to develop the quality control strategies of Photosense sterically stabilized liposomal form in order to improve the treatment of malignancies. The spectrophotometric and fluorescence extinguishing methods of quantitative detection of drug inside the liposome are discussed.

Water-soluble anthracene derivatives containing carboxy, dihydroxyphosphinyl, or pyridinium fragments bound via methylene groups to 9- and 10-carbon atoms were prepared, and their spectra, solubility, and reactivity toward singlet oxygen were studied. Using sodium α,α'-(anthracene-9,10-diyl)bis(methyl- malonate) as acceptor, it is possible to determine the quantum efficiency of singlet oxygen generation in aqueous solutions and in microheterogeneous media in the presence of biomacromolecules.

Starting from 1,2-naphthalocyanine lutetium acetate (1,2- NcLuOAc ) the unsymmetrical lutetium phthalo(naphthalo)cyanine (1,2- NcLuPc ) has been synthesized and characterized by optical absorption spectra and fast atom bombardment (FAB) mass spectrometry. 1,2-Naphthalocyanine shows several geometrical isomers, both the mixture (noted Nc ∑ ) and one of them ( Nc Cs ) have been used for forming the corresponding bismacrocycles. As a result the first racemic mixture of a chiral unsubstituted phthalo(naphthalo)cyanine complex has been synthesized and characterized.