A novel set of symmetric methylene blue derivatives exhibits effective bacteria photokilling - a structure-response study

This study focuses on the structure-response relationship of symmetrically substituted phenothiazinium dyes. Four hydrophilic derivatives with the ability of additional hydrogen bonding (, ) or additional electrostatic interaction (, ) were synthesized, photophysically characterized and compared to the parent compound methylene blue (MB, ) and a lipophilic derivative () without additional coordination sites. Derivative was most effective against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli reaching a maximum photodynamic efficacy of >5log10 steps (≥99.999%) of bacteria killing in 10 minutes (5 μM, 30 J cm(-2)) without inherent dark toxicity after one single treatment with the incoherent light source PDT1200 (λmax = 660 nm, 50 mW cm(-2)). Interestingly, one derivative with two additional primary positive charges () showed selective killing of Escherichia coli (5 μM, 30 J cm(-2), 4log10 steps inactivation (≥99.99%)) and no antimicrobial effect on Staphylococcus aureus. This might allow the development of a new generation of photosensitizers with higher antimicrobial efficacy and selectivity for future applications.