Photodynamic inactivation of Staphylococcus aureus by novel fullerene C60 derivatives

AGAZZI, MAXIMILIANO L.GA; GSPONER, NATALIA S.; MILANESIO, M. ELISA; SPESIA, MARIANA B.; DURANTINI, EDGARDO N.

Córdoba

Congreso; 16th International Congress on Photobiology; 2014

International Union of Photobiology

Potential biological activities of fullerenes have been investigated with the aim of using it in the field of medicine [1]. An important inconvenience for this application is the low solubility of fullerenes in polar solvents and the consequent formation of aggregates in aqueous solutions. However, the development of covalent chemistry of C60 has opened the possibility to attach this spherical structure with several groups, which allows increment in the biological activity. The emergence of antibiotic resistance amongst pathogenic bacteria has led to a major research effort to find alternative antibacterial therapies. An alternative method includes a non-oncologic application of photodynamic therapy, named photodynamic inactivation (PDI) of microorganism [1]. In recent years, fullerene C60 derivatives were assessed as potential photosensitizers to inactivate microorganisms [2]. In particular, dicationic fullerenes proved active photosensitizers in PDI [3]. In the present work, we have synthesized a novel N,N-dimethyl-2-[4?-(3-N,N,N-trimethylamino)propoxyphenyl] fulleropyrrolidinium (DC60+2) bearing two cationic groups. Spectroscopic and photodynamic properties of DC602+ and its analogous without intrinsic charges (DC60) were compared in N,N-dimethylformamide. The singlet molecular oxygen, O2(1g), production was evaluated using 1,3-diphenylisobenzofuran and 9,10-dimethylanthracene, giving values of 0.4 and 0.8 for DC602+ and DC60, respectively. Potential biological activities of fullerenes have been investigated with the aim of using it in the field of medicine [1]. An important inconvenience for this application is the low solubility of fullerenes in polar solvents and the consequent formation of aggregates in aqueous solutions. However, the development of covalent chemistry of C60 has opened the possibility to attach this spherical structure with several groups, which allows increment in the biological activity. The emergence of antibiotic resistance amongst pathogenic bacteria has led to a major research effort to find alternative antibacterial therapies. An alternative method includes a non-oncologic application of photodynamic therapy, named photodynamic inactivation (PDI) of microorganism [1]. In recent years, fullerene C60 derivatives were assessed as potential photosensitizers to inactivate microorganisms [2]. In particular, dicationic fullerenes proved active photosensitizers in PDI [3]. In the present work, we have synthesized a novel N,N-dimethyl-2-[4?-(3-N,N,N-trimethylamino)propoxyphenyl] fulleropyrrolidinium (DC60+2) bearing two cationic groups. Spectroscopic and photodynamic properties of DC602+ and its analogous without intrinsic charges (DC60) were compared in N,N-dimethylformamide. The singlet molecular oxygen, O2(1g), production was evaluated using 1,3-diphenylisobenzofuran and 9,10-dimethylanthracene, giving values of 0.4 and 0.8 for DC602+ and DC60, respectively. The photodynamic inactivation produced by these fullerene derivatives was investigated in vitro on a typical Gram-positive bacterium, Staphylococcus aureus. Photosensitized inactivation of S. aureus cell suspensions (106 cell/mL) by DC60+2 exhibits a ~4 log decrease of cell survival (99.99% of cellular inactivation), when the cultures were treated with 1 M photosensitizer and irradiated for 30 min with visible light. In contrast, a low photocytotoxicity was found for DC60. Also, the photodynamic activity of DC60+2 was effective to inactivate S. aureus in a higher cell density of 108 cell/mL. These results indicate that dicationic DC602+ is an interesting photosensitizer with potential applications in the eradication of S. aureus cells. The photodynamic inactivation produced by these fullerene derivatives was investigated in vitro on a typical Gram-positive bacterium, Staphylococcus aureus. Photosensitized inactivation of S. aureus cell suspensions (106 cell/mL) by DC60+2 exhibits a ~4 log decrease of cell survival (99.99% of cellular inactivation), when the cultures were treated with 1 M photosensitizer and irradiated for 30 min with visible light. In contrast, a low photocytotoxicity was found for DC60. Also, the photodynamic activity of DC60+2 was effective to inactivate S. aureus in a higher cell density of 108 cell/mL. These results indicate that dicationic DC602+ is an interesting photosensitizer with potential applications in the eradication of S. aureus cells.