Gaining Access to Bacteria through (Reversible) Control of Lipophilicity

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