Biofilm Demolition by [Au^III(N N)Cl(NHC)][PF₆]₂ Complexes Fastened with Bipyridine and Phenanthroline Ligands; Potent Antibacterial Agents Targeting Membrane Lipid

Abstract

The development of new antibacterial drugs is essential for staying ahead of evolving antibiotic resistant bacterial (ARB) threats, ensuring effective treatment options for bacterial infections, and protecting public health. Herein, we successfully designed and synthesized two novel gold(III)‐ NHC complexes, [Au(1)(bpy)Cl][PF6]2 (2) and [Au(1)(phen)Cl][PF6]2 (3) based on the proligand pyridyl[1,2‐a]{2‐pyridylimidazol}‐3‐ylidene hexafluorophosphate (1•HPF6) [bpy= 2,2’‐bipyridine; phen= 1,10‐phenanthroline]. The synthesized complexes were characterized spectroscopically; their geometries and structural arrangements were confirmed by single crystal XRD analysis. Complexes 2 and 3 showed photoluminescence properties at room temperature and the time‐resolved fluorescence decay confirmed the fluorescence lifetimes of 0.54 and 0.62 ns respectively; which were used to demonstrate their direct interaction with bacterial cells. Among the two complexes, complex 3 was found to be more potent against the bacterial strains (Staphylococcus aureus, Gram‐positive and Pseudomonas aeruginosa, Gram‐negative bacteria) with the MIC values of 8 µg.mL‐1 and 16 µg.mL‐1 respectively. Studies revealed the binding of the complexes with the fundamental phospholipids present in the cell membrane of bacteria, which was found to be the leading cause of bacterial cell death. Cytotoxicity was evaluated using an MTT assay on 293T cell lines; emphasizing the potential therapeutic uses of the Au(III)‐NHC complexes to control bacterial infections.