Tetracationic tetraaryltetranaphtho[2,3]porphyrins for photodynamic inactivation against Staphylococcus aureus biofilm

Abstract

Antimicrobial photodynamic therapy (aPDT) has emerged as a promising strategy for addressing bacterial infections, particularly those involving biofilm formation. The electrostatic attraction between the negatively charged bacterial cell walls and the cationic charges of photosensitizers facilitates the accumulation of PSs on bacterial surfaces, thereby enhancing aPDT efficacy. In this study, three series of tetracationic tetraaryltetranaphtho[2,3]porphyrins (TNPs), each incorporating different cationic groups with alkyl chains of varying lengths, were designed and synthesized. Their photodynamic inactivation efficacy against S. aureus, E. coli and C. albicans was evaluated, respectively. These TNPs exhibited strong absorption at ∼730 nm with high molar extinction coefficients (>51,500 L·mol⁻¹·cm⁻¹), fluorescence emission at ∼758 nm and efficient singlet oxygen generation capabilities. Among them, TNPs with shorter alkyl chains (I₁, II₁ and Ⅲ₁) exhibited enhanced phototoxicity against planktonic microbes, with I₁ (containing pyridinium substituents) showing the highest activity. These three compounds effectively disrupted mature S. aureus biofilms, with Ⅲ₁ (bearing diethylmethylammonium groups) demonstrating superior biofilm eradication capabilities. These findings highlight the dual antibacterial and biofilm-disrupting potential of these Ar₄TNP derivatives. Furthermore, their selective toxicity toward bacterial cells over mammalian cells at therapeutic doses provides a foundation for developing safer antimicrobial agents, offering promising alternatives to antibiotics for tackling drug-resistant pathogens and persistent biofilm-associated infections.