One of the major advances in medical science has been the development of antimicrobials; however, a consequence of their widespread use has been the emergence of drug-resistant populations of microorganisms. There is clearly a need for the development of new antimicrobials--but more importantly, there is the need for the development of new classes of antimicrobials, rather than drugs based upon analogues of known scaffolds. Due to the success of the platinum anticancer agents, there has been considerable interest in the development of therapeutic agents based upon other transition metals--and in particular ruthenium(II/III) complexes, due to their well known interaction with DNA. There have been many studies of the anticancer properties and cellular localisation of a range of ruthenium complexes in eukaryotic cells over the last decade. However, only very recently has there been significant interest in their antimicrobial properties. This review highlights the types of ruthenium complexes that have exhibited significant antimicrobial activity and discusses the relationship between chemical structure and biological processing--including site(s) of intracellular accumulation--of the ruthenium complexes in both bacterial and eukaryotic cells.

1H NMR spectroscopy was used to study the oligonucleotide binding of the Δ enantiomers of [Ru(phen)2L]2+ where the bidentate ligand L is 1,10-phenanthroline (phen), dipyrido[3,2-d:2‘,3‘-f]quinoxaline (dpq) or dipyrido[3,2-a:2‘,3‘-c](6,7,8,9-tetrahydro)phenazine (dpqC). The data from one- and two-dimensional NMR experiments of the oligonucleotide−metal complex binding suggest that all three ruthenium(II) polypyridyl complexes bind in the DNA minor groove. While a minimally intercalated oligonucleotide binding mode may be proposed for Δ-[Ru(phen)3]2+, the NMR data clearly indicate that Δ-[Ru(phen)2dpq]2+ binds the hexanucleotide d(GTCGAC)2 by intercalation, of the dpq ligand, from the minor groove. This demonstrates that metallointercalators can intercalate from the DNA minor groove. Molecular modeling of the metal complex in the intercalation site suggests that Δ-[Ru(phen)2dpq]2+ binds in a “head-on” fashion with the phenanthroline rings in the minor groove and the dpq ligand inserted into the nucleotide base stack. NOESY experiments of the binding of Δ-[Ru(phen)2dpq]2+ with d(GTCGAC)2 and d(TCGGGATCCCGA)2 suggest that intercalation from the minor groove is favored at purine−purine/pyrimidine−pyrimidine sequences for this complex. The syntheses of Δ-[Ru(phen)2dpq]2+ and Δ-[Ru(phen)2dpqC]2+ are reported along with crystal structure of [Ru(phen)2dpq](PF6)2 (monoclinic crystal system, space group P21 /c, Z = 4, a = 9.483(2) Å, b = 33.374(6) Å, c = 12.900(3) Å, β = 110.05(2)°, V = 3835(2) Å3).