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Novel magnesium(II) porphyrazine with peripheral methyl(3,5-dibromophenylmethyl)amine groups was synthesized in a multi-step procedure starting from commercially available diaminomaleonitrile. All intermediates and the final macrocycle were characterized using UV–Vis, FT-IR, MS and various NMR techniques. The absorption and emission properties of the macrocycle were evaluated in N,N-dimethylformamide, dimethyl sulfoxide, and dichloromethane. The potential photosensitizing activity was evaluated by assessing the ability of the macrocycle to generate singlet oxygen in dimethyl sulfoxide and N,N-dimethylformamide.

5,7-Diaryl-substituted symmetrical diazepinoporphyrazine and tribenzodiazepinoporphyrazine were synthesized and characterized using UV–Vis, MS MALDI, and various NMR techniques. The expected photosensitizing potentials of these porphyrazines were evaluated by measuring their abilities to generate singlet oxygen in organic solvents and by comparing them with that of the recently obtained dendrimeric G1-type diazepinoporhyrazine. Absorbance and fluorescence measurements were performed to study the aggregation properties of the novel macrocycles. The photocytotoxicity of tribenzodiazepinoporphyrazine towards LNCaP cells in its free form and after its incorporation into liposomes was examined using MTT assay under normoxic and hypoxic conditions. It is interesting that all tested liposome formulations maintained their phototoxic activity in hypoxia. Also, tribenzodiazepinoporphyrazine incorporated into liposomes revealed better photocytotoxic effect (IC50 values of 0.600 ± 0.357 μM and 0.378 ± 0.002 μM) than its free form (IC50 values of 3.135 ± 0.156 μM). Following the in vitro experiments, the most promising liposomal formulation containing l -α-phosphatidyl-DL-glycerol for tribenzodiazepinoporphyrazine was found. Moreover, tribenzodiazepinoporphyrazine incorporated into liposomes containing 1,2-dioleoyl-3-trimethylammonium-propane (chloride salt) revealed moderate phototoxicity at 5 × 10−5 μM for antibacterial photodynamic therapy. It was established that an irradiation of planktonic bacterial strains significantly reduced CFUs of Staphylococcus aureus ATCC 25923 in comparison to tribenzodiazepinoporphyrazine containing l -α-phosphatidyl-DL-glycerol liposomes.

The synthesis and physicochemical properties of a novel diazepinoporphyrazine possessing G1-dendrimeric substituents are presented. Initially, diaminomaleonitrile was condensed with 1,3-bis-(4-hydroxyphenyl)-1,3-propanedione to give a novel 1,4-diazepine-2,3-dicarbonitrile derivative which was subjected to an alkylation reaction with 3,5-bis(benzyloxy)benzylbromide furnishing a 1,4-diazepine-2,3-dicarbonitrile derivative with bulky substituents. Subsequent macrocyclization led to the desired diazepinoporphyrazine with conjugated, hyperbranched G1-dendrimeric substituents, which was characterized by MS MALDI and NMR. The potential photosensitizing activity of the novel porphyrazine was evaluated by measuring its ability to generate singlet oxygen. This measurement was performed with and without addition of the anti-aggregation agent tetramethylamonium fluoride to determine the role of the monomeric form in singlet oxygen generation.

Three 5,7-disubstituted-1,4-diazepine-2,3-dicarbonitriles with bulky 2-(3,5-dibromophenyl)ethenyl, 2-(4- tert -butylphenyl)ethenyl and 2-(3,5-dibenzyloxyphenyl)ethenyl substituents were synthesized and characterized using UV–Vis, MS ES, elemental analysis and NMR spectroscopy. NMR data indicated that diazepine rings of all obtained compounds adopted 6 H -tautomeric form. In addition, trans -isomerism within styryl substituents was observed. Experimental data for diazepine derivative containing 2-(4- tert -butylphenyl)ethenyl substituents were verified by X-ray crystallography. The obtained compounds were subjected to photophysical studies. In the UV–Vis absorption spectra two characteristic bands were found. In the solvatochromic study, the first band maxima were located in the range of 384–418 nm, whereas second band maxima in the range of 313–345 nm. Fluorescence intensity of novel diazepine derivatives was rather low in all solvents used with the values of fluorescence quantum yield Ф F = 10 −4 for 2-(3,5-dibromophenyl)ethenyl, and 10 −5 for 2-(4- tert -butylphenyl)ethenyl and 3,5-(dibenzyloxyphenyl)ethenyl 1,4-diazepine-2,3-dicarbonitriles.

Alkylation reaction of dimercaptomaleonitrile disodium salt with N-(2-bromoethyl)phthalimide in N,N-dimethylformamide, and potassium carbonate led to novel maleonitrile derivative. This compound was used in the Linstead tetramerization reaction in n-butanol in the presence of magnesium n-butoxide towards magnesium(II) sulfanyl porphyrazine with phthalimide peripheral substituents. Its demetallation and subsequent zinc(II) ion insertion led to zinc(II) sulfanyl porphyrazine derivative. All obtained compounds were thoroughly characterized using UV–vis, MS, and 1H and 13C NMR spectroscopy. The purity of macrocycles was assessed using HPLC. Novel symmetrical porphyrazines were found to generate singlet oxygen in N,N-dimethylformamide and dimethyl sulfoxide in low yields. The highest, over 4% yield of singlet oxygen generation, was noted for zinc(II) porphyrazine derivative in DMSO. In the biological study, the cytotoxicities and photocytotoxicities of symmetrical sulfanyl porphyrazines with phthalimide peripheral substituents were compared with lately obtained unsymmetrical sulfanyl tribenzoporphyrazine, 22,23-bis[3,5-bis(3,5- dimethoxybenzyloxy)benzylsulfanyl]tribenzo[b,g,l]porphyrazinato magnesium(II). The in vitro study was performed on androgen-sensitive human prostate adenocarcinoma (LNCaP) and human prostate cancer (PC3) cell lines using MTT assay. The data obtained for liposomal formulations containing sulfanyl porphyrazines with phthalimide substituents indicated their low and light-independent cytotoxicity against cancer cells. On the contrary, the sulfanyl tribenzoporphyrazine was studied in its free form and after incorporation in liposomes. In the free form it revealed moderate photocytotoxicity against both cancer cell lines with IC50 values of 7.71 μM and 8.82 μM for LNCaP and PC3 cells, respectively. Moreover, the liposomal DOTAP : POPC formulation containing sulfanyl tribenzoporphyrazine revealed over 10-fold higher effectiveness reaching the IC50 up to 0.52 μM against LNCaP cancer cells in comparison to its free form. On the contrary, liposomal PG formulation of sulfanyl tribenzoporphyrazine was found to be inactive on the human cancer cells.