Exploring the potential of highly charged Ru(II)- and heteronuclear Ru(II)/Cu(II)-polypyridyl complexes as antimicrobial agents.

The antimicrobial potential of two ruthenium(II) polypyridyl complexes, [Ru(phen)L1] and [Ru(phen)L2] (phen = 1,10-phenanthroline) containing the 4,4'-(2,5,8,11,14-pentaaza[15])-2,2'-bipyridilophane (L1) and the 4,4'-bis-[methylen-(1,4,7,10-tetraazacyclododecane)]-2,2' bipyridine (L2) units, is herein investigated. These peculiar polyamine frameworks afford the formation of highly charged species in solution, influence the DNA-binding and cleavage properties of compounds, but they do not undermine their singlet oxygen sensitizing capacities, thus making these complexes attractive O generators in aqueous solution. L1 and L2 also permit to stably host Fenton -active Cu ion/s, leading to the formation of mixed Ru/Cu forms capable to further strengthen the oxidative damages to biological targets. Herein, following a characterization of the Cu binding ability by [Ru(phen)L2], the water-octanol distribution coefficients, the DNA binding, cleavage and O sensitizing properties of [Ru(phen)L2] and [CuRu(phen)L2] were analysed and compared with those of [Ru(phen)L1] and [CuRu(phen)L1]. The antimicrobial activity of all compounds was evaluated against B. subtilis, chosen as a model for gram-positive bacteria, both under dark and upon light-activation. Our results unveil a notable phototoxicity of [Ru(phen)L2] and [CuRu(phen)L2], with MIC (minimal inhibitory concentrations) values of 3.12 μM. This study highlights that the structural characteristics of polyamine ligands gathered on highly charged Ru(II)-polypyridyl complexes are versatile tools that can be exploited to achieve enhanced antibacterial strategies.