Playing with Structural Parameters in the Design of Ruthenium(II) p-Cymene Complexes as Potential Antibacterial Agents

A series of ruthenium(II) arene complexes of the general formula [(η6-pCymene)Ru(L)Cl]PF6 (hereafter RACs) have been designed, synthesized, and characterized with a view to their possible use as antimicrobial agents. We specifically report on five structurally related RAC complexes, i.e., Ru-pCy1-5, incorporating bidentate polypyridyl ligands of different nature (L1 = benzo[i]dipyrido[3,2-a: 2',3'-c]phenazine, L2 = 4,7-diphenyl-1,10-phenanthroline, L3 = 2,2'-biquinoline, L4 = 2,2'-bipyridine-4,4'-diylbis(morpholinomethanone), L5 = (2,2'-bipyridine-4,4'-diylbis(morpholinomethylene)). The complexes Ru-pCy1-5, which showed substantial inertness when dissolved in aqueous media, were investigated by ESI-MS for their ability to interact with two representative model proteins, i.e., SOD and RNase A. Interestingly, these complexes, with the sole exception of Ru-pCy3, tend to form stable adducts with the two proteins upon release of the chloride ligand, in agreement with previous observations on similar Ru compounds. The antimicrobial properties of these compounds were then tested against Gram-positive bacterium Bacillus subtilis and Gram-negative bacterium Burkholderia cenocepacia. The observed antibacterial effects were then tentatively correlated with the structural features of each complex.