Evaluation of Ruthenium(II) N-Heterocyclic Carbene Complexes as Antibacterial Agents and Inhibitors of Bacterial Thioredoxin Reductase.

Hilke Burmeister,Julia E Bandow,Pascal Dietze,Lutz Preu,Ingo Ott

doi:10.3390/molecules26144282

Abstract

A series of ruthenium(II) complexes with N-heterocyclic carbene (NHC) ligands of the general type (arene)(NHC)Ru(II)X2 (where X = halide) was prepared, characterized, and evaluated as antibacterial agents in comparison to the respective metal free benzimidazolium cations. The ruthenium(II) NHC complexes generally triggered stronger bacterial growth inhibition than the metal free benzimidazolium cations. The effects were much stronger against Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) than against Gram-negative bacteria (Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa), and all complexes were inactive against the fungus Candida albicans. Moderate inhibition of bacterial thioredoxin reductase was confirmed for selected complexes, indicating that inhibition of this enzyme might be a contributing factor to the antibacterial effects.

Highlights

Metal complexes with N-heterocyclic carbene (NHC) ligands represent an important type of catalysts, in addition to their application in chemistry, the biomedical properties have been evaluated intensively
The design of drug candidates based on metal NHC complexes has been dominated by gold and silver as metals, more recently, an increasing number of metals has demonstrated very promising results, including, for example, rhodium [8,9,10,11,12] and iridium [12,13] species
We and others have recently reported on ruthenium(II) NHC complexes of the general type (p-cymene)(NHC)Ru(II)X2 and structurally related complexes as novel anticancer drug candidates [14,15,16,17,18,19,20]

Summary

Introduction

Metal complexes with N-heterocyclic carbene (NHC) ligands represent an important type of catalysts, in addition to their application in chemistry, the biomedical properties have been evaluated intensively. We and others have recently reported on ruthenium(II) NHC complexes of the general type (p-cymene)(NHC)Ru(II)X2 (where X = halide) and structurally related complexes as novel anticancer drug candidates [14,15,16,17,18,19,20]. Hartinger et al demonstrated by means of X-ray crystallography with the model protein hen egg white lysozyme that, upon binding, the p-cymene ligand of the complexes was replaced, while the NHC ligand remained coordinated in this case [21]

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Conclusion