Light-mediated killing of pathogens by cationic photosensitizers (PS) is a promising antimicrobial approach avoiding resistance as being present upon the use of antibiotics. In this study we focused on the impact of the substituents in phenalen-1-one PS. Photodynamic efficacy depending on positively charged moieties including a primary aliphatic, quaternary aliphatic, aromatic ammonium and a guanidinium cation was investigated against Gram-positive and Gram-negative pathogens. Considering the altered steric demand and lipophilicity of these functional groups we deduced a structure-activity relationship. SAGUA was the most potent PS in this series reaching a maximum efficacy of ≥6log10 steps of bacteria killing at a concentration of 10 μM upon irradiation with blue light (20 mW cm-2) for 60 s (1.2 J cm-2) without exhibiting inherent dark toxicity. Its guanidinium moiety may be able to form strong bidentate and directional hydrogen bonds to carboxylate groups of bacterial surfaces in addition to ionic charge attraction. This may supplement fast and effective antimicrobial activity.
Tabenski, I., Cieplik, F., Tabenski, L., Regensburger, J., Hiller, K. A., Buchalla, W., … Späth, A. (2016). The impact of cationic substituents in phenalen-1-one photosensitizers on antimicrobial photodynamic efficacy. Photochemical and Photobiological Sciences, 15(1), 57–68. https://doi.org/10.1039/c5pp00262a