Gaining Access to Bacteria through (Reversible) Control of Lipophilicity

Development of antimicrobial photodynamic therapy (aPDT) is highly dependent on the development of suitable photosensitizers (PS): ideally affinity of PS towards bacterial cells should be much higher than towards mammalian cells. Cationic charge of PS may lead to selective binding of PS to bacteria mediated by electrostatic interaction; however, the photodynamic outcome is highly dependent on the lipophilicity of PS. Herein we report the aPDT effect of silicon(IV)phthalocyanine derivatives bearing four positive charges and methyl, phenyl or naphthyl substituents on the periphery of the macrocycle. We show that via modulation of lipophilicity it is possible to find a therapeutic window where bacteria but not mammalian cells are effectively killed. The photobiological activity of these PSs dropped significantly when host-guest complexes of PSs with cucurbit[7]uril (CB[7]) were used. CB[7] blocks the hydrophobic part of the molecule and reduces lipophilicity of the PS, indicating that a hydrophobic interaction with the outer membrane of bacterial cells is essential for aPDT activity. Efficiencies of obtained PSs were evaluated using different uropathogenic E. coli isolates and human kidney epithelial carcinoma cells.