Amphiphilic cationic Zn-porphyrins with high photodynamic antimicrobial activity

Photodynamic inactivation of microbes can efficiently eradicate antibiotic-resistant strains. Systematic structural modification was used to investigate how porphyrin-based photosensitizers (PSs) could be designed for improved antibacterial activity. Zinc(II)5,10,15,20-tetrakis( -alkylpyridinium-2(3,4)-yl)porphyrins presenting systematic modifications at the periphery of the porphyrin ring were evaluated for toxicity and antimicrobial photodynamic activity by measuring metabolic activity, cell membrane integrity and viability using antibiotic-sensitive and resistant strains as model Gram-negative targets. Maximal sensitizer uptake, and, upon illumination, decrease of viable bacteria by >6 log were achieved by positively charged amphiphilic PSs with longer (six to eight carbon) alkyl substituents. Antibacterial photoefficiency (throughout the text photoefficiency has been used as equivalent of photocytotoxic efficacy) can be increased by orders of magnitude by increasing the lipophilicity of cationic alkylmetalloporphyrin PSs.