Catalytic degradation of N-acyl-homoserine lactone using a copper complex of a TACN derivative: implications for quorum sensing interference

Abstract

Medical treatment of bacterial biofilms represents a significant challenge, not only in the case of implant-associated infections but also in chronic inflammation of soft tissues. Therefore, further research is crucial to develop strategies that prevent biofilm formation at early stages, where quorum sensing (QS) signalling molecules that facilitate bacterial communication play a key role. In this study, we investigated the catalytic properties of an N-substituted triazacyclononane-copper(II) complex (Cu(II)-iPr₂TACN), which mimicked the enzymatic activity of an acylase in the hydrolysis reaction of N-acyl-homoserine lactone (AHL), disrupting the QS in the bacterial biofilm as a result. Specifically, we focused on kinetic experiments involving the degradation of newly developed model AHLs with an acyl group derived from azobenzene as a chromophore label, enabling UV-VIS detection. ESI-MS was employed to identify the degradation products. Our results demonstrated sufficient hydrolytic activity against the model signalling molecules within relatively short time intervals under body temperature, blood pH and inflammation site conditions, with disruption occurring via lactone ring cleavage followed by further hydrolysis of the acyl fragment of the amide. To our knowledge, this is the first use of such complexes to degrade quorum sensing molecules. In addition, a novel UV-VIS active azodye chromophore-containing model substrate of a quorum sensing molecule was established for quorum quenching degradation studies and critically compared to other natural and synthetic quorum sensing molecules.