Control of biofilm formation at molecular level by using polyconjugated aromatic ligands

In this study, four different polyconjugated aromatic imines were synthesized using ortho– and para– diamines with and without hydroxyl groups in order to control bacterial biofilm formation at molecular-level through the intercalation of bacterial second messenger, cyclic dimeric guanosine 3′,5′-monophosphate (c-di-GMP). As key regulators of biofilm formation and several vital functions of bacteria, c-di-GMP molecules were extracted and c-di-GMP intercalation capabilities of four different polyconjugated imines were compared by monitoring UV absorbance reductions and fluorescence emission quenching. The results showed that the compounds without hydroxyl groups reached a 66 % UV absorbance reduction. Moreover, aza-BODIPY was tested as a novel c-di-GMP intercalator, showing up to 45 % reduction on UV absorbance and up to 40 % quenching on fluorescence emission suggesting its potential for bacterial control. Biofilm formation/inhibition studies on a 96-well microtiter dish confirmed the obtained results. Intercalation studies revealed that the selected ligands effectively interacted with c-di-GMP, suggesting their potential to modulate bacterial signalling pathways. These findings offer a promising strategy for controlling biofilm forming pathogens by interfering with their biofilm regulatory mechanisms.