Cationic porphyrazines with morpholinoethyl substituents – Syntheses, optical properties, and photocytotoxicities

Abstract

Novel cationic water-soluble magnesium(II) and zinc(II) sulfanyl porphyrazines with peripheral N-methylmorpholinoethyl iodide moieties in the form of iodide salts were synthesized and characterized with ESI MS, UV–Vis, and NMR. The subsequent logPo/w values were lower for octaiodide salts than those for their neutral precursors and, therefore the macrocycles were considered hydrophilic. After measuring the binding constants Kb, it becomes clear that the obtained cationic porphyrazines, as well as the neutral porphyrazines, were poor liposome binders. The cationic water-soluble magnesium(II) and zinc(II) sulfanyl porphyrazines revealed moderate singlet oxygen generation yields and higher susceptibility to decomposition after light exposition. In the antimicrobial studies, magnesium(II) porphyrazine with peripheral N-methylmorpholinoethyl groups presented a log reduction up to 6.5 against Gram-positive bacteria. In vitro, photocytotoxic activity assessments of magnesium(II) and zinc(II) porphyrazines with peripheral N-methylmorpholinoethyl, as well as magnesium(II) sulfanyl porphyrazine derivative in the form of iodide salt, were performed on two types of oral cancer cells – SCC-25 and CAL-27. Zinc(II) sulfanyl porphyrazine with peripheral N-methylmorpholinoethyl groups decreased the viability of the SCC-25 cell line after light irradiation with IC50 at 6.46 μM in its free form and at 3.61 μM after encapsulation in liposomal formulation. The opposite phenomenon was observed for magnesium(II) sulfanyl porphyrazine with peripheral N-methylmorpholinoethyl groups. The magnesium(II) sulfanyl porphyrazine derivative in the form of iodide salt did not demonstrate any photocytotoxicity in the studied cell lines.