Synthesis of ruthenium polypyridine complexes with benzyloxyl groups and their antibacterial activities against Staphylococcus aureus.

Four new ruthenium polypyridyl complexes, [Ru(bpy)(BPIP)](PF) (Ru(II)-1), [Ru(dtb)(BPIP)](PF) (Ru(II)-2), [Ru(dmb)(BPIP)](PF) (Ru(II)-3) and [Ru(dmob)(BPIP)](PF) (Ru(II)-4) (bpy = 2,2'-bipyridine, dtb = 4,4'-di-tert-butyl-2,2'-bipyridine, dmb = 4,4'-dimethyl-2,2'-bipyridine, dmob = 4,4'-dimethoxy-2,2'-bipyridine and BPIP = 2-(3,5-bis(benzyloxyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) had been synthesized and characterized. Their antimicrobial activities were investigated against Staphylococcus aureus (S. aureus) and four complexes showed obvious antibacterial effect, especially the minimum inhibition concentration (MIC) value of Ru(II)-3 was only 4 μg/mL. In addition, Ru(II)-3 was able to kill bacteria quickly and inhibit the formation of biofilm. Meanwhile, the cooperative effect between Ru(II)-3 and general antibiotics were tested and the results showed that Ru(II)-3 could enhance the susceptibility of S. aureus to different types of antibiotics. Most importantly, Ru(II)-3 hardly showed cytotoxicity to mammalian erythrocytes both in homelysis experiment and G. mellonella model. After being injected with high doses of the Ru(II)-3in vivo, the G. mellonella worms still exhibited high survival rates. Finally, a mouse skin infection model and G. mellonella infection model was built to determine the antibacterial activity of Ru(II)-3in vivo. The antibacterial mechanism of Ru(II)-3 was probably related to the membrane-disruption. Taken together, ruthenium polypyridine complexes with benzyloxyl groups had the potential to develop an attractive and untraditional antibacterial agent with new mode of action.