Diamine ligands enhance photodynamic inactivation of gram-negative bacteria using 5-aminolevulinic acid

This study investigates the enhanced efficacy of photoinduced microbial inactivation targeting both planktonic and biofilm forms of Gram-negative bacteria, specifically Acinetobacter baumannii and Proteus mirabilis. The approach utilizes diaminocyclohexane (DACH)-based diamines to augment antibacterial photodynamic therapy (aPDT) employing 5-aminolevulinic acid. Results demonstrated that blue light irradiation produced the highest bactericidal effects, achieving mortality rates of 99.9990 ± 0.0008% for P. mirabilis and 99.990 ± 0.001% for A. baumannii at a light dose of 70 J·cm^-2 in the presence of a non-cytotoxic concentration of (1R,2R)-N,N'-bis([1,1'-biphenyl]-4-ylmethyl)cyclohexane-1,2-diamine. The biofilm destruction efficiency was suboptimal, with maximum bactericidal efficiencies of 87.1 ± 0.1% and 73.1 ± 0.2% for P. mirabilis and A. baumannii, respectively, after exposure to blue light at a dose of 93.5 J·cm^-2. Increased accumulation of protoporphyrin IX within bacterial cells was identified as a key factor contributing to the enhanced photobiocidal efficacy. Additionally, molecular docking analysis was employed to explore potential structural insights into the biological activity of this cyclohexane-1,2-diamine-based ligand. Computational simulations suggested that the ligand could plausibly accommodate within the protoporphyrin IX binding pocket of the modeled ferrochelatase, indicating a potential binding mode compatible with the catalytic cavity.