Abstract
The antimicrobial properties of silver and silver complexes have been known in medicine since ancient times. However, limitations in stability and solubility have impaired medicinal chemistry and drug development research. With the advent of N-heterocyclic carbenes (NHC) as ligands, the development of synthesis methods for organometallic silver species of the type (NHC)AgX (where X = halide) has brought significant improvements, and the class of antimicrobial silver NHC complexes has emerged. However, reports studying structure-activity relationships and the mechanism of action of this compound type are still rare. This paper explores the activity of silver NHC complexes with halide (chloride, iodide) ligands and attempts to elucidate their mechanism of antibacterial action in Gram-negative E. coli bacteria in comparison to non-organometallic silver nitrate. In particular, the complexes with an iodide ligand were confirmed to cause stronger antibacterial effects in E. coli than silver nitrate. Moreover, iodide complexes exhibit an enhanced cellular uptake, show signs of DNA condensation, strongly inhibit TrxR in E. coli and cause a strong depolarization of the membrane potential and permeability of the inner cell membrane. In contrast, chloride silver NHC complexes and silver nitrate caused permeability of the outer membranes and also showed a different activity pattern in most of the studied mechanisms. In conclusion, by variation of the halide ligand of silver NHC complexes the mechanism of action and strength of antibacterial activity can be fine-tuned.