Synthesis and evaluation of multi-quaternary ammonium cation-functionalized BODIPYs with photodynamic antibacterial effects

As an alternative of antibiotic therapy against drug-resistance or even multi-drug-resistant bacteria, antimicrobial photodynamic therapy (aPDT) is a promising therapeutic approach for cutaneous/oral localized infections as well as an efficient protocol for disinfection of blood products. In this study, a series of BODIPY derivatives modified with multi-quaternary ammonium cations were designed and synthesized. Density functional theory (DFT) showed that the ΔE values of new compounds were significantly reduced compared to the reference compound BDP-1. All new compounds exhibited intense absorption at 650 nm with high molar extinction coefficients for deeper tissue penetration, and obvious singlet oxygen generation ability. They had remarkable photodynamic activity against Staphylococcus aureus, particularly compounds I₁ and II₁ with the lowest minimum inhibitory concentrations (MIC). In vitro aPDT experiments showed that compounds I₁ and II₁ could disrupt the integrity of bacterial cell membranes, causing the leakage of cytoplasmic contents, and eradicate the mature biofilms of S. aureus. Notably, compound I₁ exhibited minimal toxicity toward human hepatocyte cell HL-7702. Since I₁ possessed significant photodynamic inactivation efficacy against S. aureus, obvious disruption capability to the formed biofilm, and minimal toxicity toward normal human cell, it could be suggested as a promising photosensitizer for aPDT and disinfection of blood products.