Synthesis of porphyrin-polyethylenimine conjugates as antimicrobial agents

IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta Nacional 36 Km 601, X5804BYA Río Cuarto, Córdoba, Argentina.

Increasing of resistant bacteria to clinical antibiotics has conducted to establish new treatments for infections. One of them includes photodynamic inactivation of microorganisms. In general, the presence of positive charge precursor groups allows improving the photoinactivation due to an increase in interaction with microbial cells. In this context, 5,15-di(4-(N,N-dimethylaminophenyl)-10,20-di(pentafluorophenyl)porphyrin (1) and 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (2) were synthesized from the condensation of 4-pentafluorobenzaldehyde and 5-(pentafluorophenyl)dipyrromethane or pyrrole catalysed by boron diethyl etherate in dichloromethane. After oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and purification using flash chromatography, porphyrin 1 and 2 were isolated in 24% and 36%, respectively. An aromatic nucleophilic substitution reaction was used to obtain conjugated polymers based in these porphyrins covalently linked to polyethylenimine (PEI-1 and PEI-2). The reaction was carried out in N,N-dimethylformamide (DMF) giving 100% conversion. After that, the solvent was removed by distillation under reduce pressure and the solid was washed with petroleum ether and drying in a vacuum oven. These conjugates showed the Soret absorption band and the four characteristic Q bands of porphyrins. Photodynamic studies indicated that PEI-2 is more effective than PEI-1 to produce singlet oxygen and decompose L-tryptophan with a significant contribution of a type II mechanism. In addition, in vitro PDI studies demonstrated that both polymers are effective phototherapeutic agents for the eradication of bacteria.