Porfirinas e porfirazinas de zinco hidrossolúveis: síntese e atividade fotodinâmica

Abstract

Photodynamic therapy is a therapeutic procedure that has gained a lot of attention in recent years, due to the great potential presented for the treatment of various types of cancer, with low operating costs and milder adverse effects. This procedure involves a photosensitizer, which when exposed to electromagnetic radiation, can result in phenomena that cause the death of cancer cells. Some porphyrins and porphyrazines have characteristics desired for a photosensitizer, such as high absorption in the region of 600 to 800 nm, amphiphilic character, production of reactive oxygen species, such as singlet oxygen, among others. Thus, studying the photophysical and biological properties of these compounds is essential for the development of new drugs. In this way, cationic zinc(II) porphyrins and porphyrazines with the 3-ethylpyridyl substituent were synthesized, with the intermediates and compounds of interest being (H2T3EPyPCl4, [Zn(T3EPyP)]Cl4, H2(3EPy)8PzCl8 e [Zn(3EPy)8Pz]Cl8), characterized by absorption spectroscopy in the ultraviolet and visible region and by hydrogen nuclear magnetic resonance. [Zn(T3EPyP)]Cl4, H2(3EPy)8PzCl, e [Zn(3EPy)8Pz]Cl8 and the intermediate H2(3Py)8Pz are unpublished compounds. Porphyrins were also characterized by elemental, thermal and mass spectrometry analysis (MALDI-TOF MS). The photophysical studies of the compounds of interest involved the quantification of the quantum yield of fluorescence in water, all of which presented values below 0.1. The quantification of the singlet oxygen quantum yield was performed through the development of an irradiation system and a methodology for application in the compounds, which was validated using rose bengal and methylene blue as standards. Porphyrins presented singlet oxygen production in water of 0.16 for H2T3EPyPCl4 and 0.41 for [Zn(T3EPyP)]Cl4, in acetonitrile of 0.85 for H2T3EPyPCl4 and 0.90 for [Zn( T3EPyP)]Cl4. Porphyrazines present values <0.01 in water and in acetonitrile it presented values of 0.16 for H2(3EPy)8PzCl8 and 0.20 for [Zn(3EPy)8Pz]Cl8. Therefore, it was found that porphyrins have a higher production of singlet oxygen than porphyrazines and that compounds containing zinc have a higher production than their respective free base. Biological studies showed that the compounds show low cellular incorporation in non-metastatic melanoma cells (B16F1), do not show toxicity in the dark, and only [Zn(3EPyP)]Cl4 showed phototoxicity with an IC50 of 7.8 µM when irradiated in the range from 620 to 630 nm.