Chlorins with (trifluoromethyl)phenyl substituents - Synthesis, lipid formulation and photodynamic activity against bacteria

Two chlorin derivatives bearing (trifluoromethyl)phenyl substituents at meso positions were synthesized via 1,3-dipolar cycloaddition. These pyrrolidine-fused chlorins are characterized by H-1, C-13 NMR spectroscopy, mass spectrometry, UV-Vis absorption and fluorescence spectroscopy. The obtained compounds revealed UV-Vis spectra typical of chlorins. Fluorescence quantum yields were calculated to be ca. 0.2 and ca. 0.3 in DMF and DMSO, respectively, for both compounds. The chlorin bearing 3,5-bis(trifluoro-methyl)phenyl substituent in mesa positions (0.69 in DMF, 0.57 in DMSO) revealed a stronger singlet oxygen formation ability than that with 4-(trifluoromethyl)phenyl moieties (0.50 in DMF, 0.45 in DMSO). Both compounds were found to be stable under irradiation in DMF. Nevertheless, irradiation of both compounds in DMSO solution caused their photo-transformation. As the studied compounds are insoluble in aqueous media, they were incorporated in lipid vesicles. Photodynamic bacteria inactivation experiments showed log reduction of bacterial growth for Enterococcus faecalis at 4.84; Staphylococcus aureus at 4.09; Escherichia coli at 2.23. No activity of both macrocycles was noticed against Pseudomonas aeruginosa and fungi: Candida albicans and Trichophyton mentagrophytes.