In VitroAntibacterial Activity of Dinuclear Thiolato-Bridged Ruthenium(II)-Arene Compounds

The antibacterial activity of 22 thiolato-bridged dinuclear ruthenium(II)-arene compounds was assessed in vitro against Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus . None of the compounds efficiently inhibited the growth of the three E. coli strains tested and only compound 5 exhibited a medium activity against this bacterium (MIC (minimum inhibitory concentration) of 25 μM). However, a significant antibacterial activity was observed against S. pneumoniae , with MIC values ranging from 1.3 to 2.6 μM for compounds 1-3 , 5 and 6 . Similarly, compounds 2 , 5-7 and 20-22 had MIC values ranging from 2.5 to 5 μM against S. aureus. The tested diruthenium compounds have a bactericidal effect significantly faster than that of penicillin. Fluorescence microscopy assays performed on S. aureus using the BODIPY-tagged diruthenium complex 15 showed that this type of metal compound enter the bacteria and do not accumulate in the cell wall of gram-positive bacteria. Cellular internalization was further confirmed by inductively coupled plasma mass spectrometry (ICP-MS) experiments. The nature of the substituents anchored on the bridging thiols and the compounds molecular weight appear to significantly influence the antibacterial activity. Thus, if overall a decrease of the bactericidal effect with the increase of compounds’ molecular weight is observed, however the complexes bearing larger benzo-fused lactam substituents had low MIC values. This first antibacterial activity screening demonstrated that the thiolato-diruthenium compounds exhibit promising activity against S. aureus and S. pneumoniae and deserve to be considered for further studies.