Synthesis and properties of 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl] chlorin as potential broad-spectrum antimicrobial photosensitizers

• Novel chlorin derivative bearing four basic amine groups was synthetized.
• Amine chlorin produces efficiently singlet molecular oxygen.
• Chlorin photosensitizes the formation of superoxide anion radical in presence of NADH.
• Effective photodynamic inactivation mediated by chlorin was found in microorganisms.

A novel 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl]chlorin (TAPC) was synthesized by reduction of the corresponding porphyrin TAPP with p-toluenesulfonhydrazide, followed by selective oxidation with o-chloranil. Spectroscopic properties and the photodynamic activity of these photosensitizers were compared in N,N-dimethylformamide. An increase in the absorption band at 650 nm was found for the chlorin derivative with respect to TAPP. These photosensitizers emit red fluorescence with quantum yields of 0.15. Both compounds were able to photosensitize singlet molecular oxygen with quantum yields of about 0.5. Also, the formation of superoxide anion radical was detected in the presence of TAPC or TAPP and NADH. Photodynamic inactivation was investigated on a Gram-positive bacterium Staphylococcus aureus, a Gram-negative bacterium Escherichia coli and a fungal yeast Candida albicans cells. In vitro experiments showed that TAPC or TAPP were rapidly bound to microbial cells at short incubation periods. These photosensitizers, without intrinsic positive charges, contain four basic amino groups. These substituents can be protonated at physiological pH, increasing the interaction with the cell envelopment. Photosensitized inactivation improved with an increase of both photosensitizer concentrations and irradiation times. After 15 min irradiation, a 7 log reduction of S. aureus was found for treated with 1 μM photosensitizer. Similar result was obtained with E. coli after using 5 μM photosensitizer and 30 min irradiation. Also, the last conditions produced a decrease of 5 log in C. albicans cells. Therefore, TAPC was highly effective as a broad-spectrum antimicrobial photosensitizer.

Photodynamic inactivation mediated by TAPC was investigated on Staphylococcus aureus, Escherichia coli and Candida albicans.Figure optionsDownload as PowerPoint slide