New cationic diketopyrrolopyrrole photosensitizers for the photoinactivation of gram-negative and gram-positive bacteria

Diketopyrrolopyrroles (DPP) are a versatile group of dyes and pigments with a wide range of applications, namely in the biological field. In this paper, we report the synthesis and the photodynamic activity of new cationic DPP derivatives that effectively inactivate Gram-positive and Gram-negative bacteria. These new compounds were synthetized using an easy synthetic procedure to introduce one or two pyridin-4-ylsulfanyl units followed by cationization. The photodynamic effectiveness of these DPP derivatives against Pseudomonas aeruginosa [Gram-negative] and methicillin-resistant Staphylococcus aureus [Gram-positive] strains was studied. Their photodynamic activity was also studied in the presence of potassium iodide (KI). Overall, both neutral and cationic DPP derivatives were highly effective in inactivating S. aureus, while only the cationic compounds were efficient against P. aeruginosa. Our findings suggest that for S. aureus, the production of singlet oxygen and a non-symmetrical structure were key factors in the photodynamic inactivation (PDI) success, whereas, for P. aeruginosa, the presence and number of cationic charges played a more significant role. In all cases, the application of KI reduced both the treatment time and PS concentration required for effective photodynamic inactivation of the studied bacteria. The ability to tailor simple DPP derivatives into effective DPP-based PSs for the inactivation of multidrug-resistant pathogenic bacterial strains, and the synergistic impact produced by the addition of KI, opens new possibilities for focused antimicrobial therapy.