Ruthenium complexes as antimicrobial agents

Abstract

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.

Oxidatively Locked [Co2L3]6+ Cylinders Derived from Bis(bidentate) 2-Pyridyl-1,2,3-triazole “Click” Ligands: Synthesis, Stability, and Antimicrobial Studies

“…With pathogens developing a resistance to beta-lactams and other commonly used antibiotics, the need for new antimicrobial medicines is growing. Metal-containing antibacterial drugs have become a global research focus over the past decade and are showing increasing promise [53][54][55]. As the previously …”

“…Unfortunately, these experiments also indicated that the cobalt(III) cylinders are not active antimicrobial agents, and no inhibition of bacterial growth was observed over a range of concentrations, from 1024 µg·mL −1 to 1 µg·mL −1 . Given the stability of the [Co 2 (L pytrz ) 3 ](OTf) 6 cylinders in aqueous and pseudo-biological conditions and the activity of other triply stranded helicates [13,18], related dinuclear ruthenium(II) compounds [53,57], and cobalt(III) complexes [41,42], the observed lack of activity was initially surprising. However, a series of elegant papers from Keene and co-workers have shown that the charge of the metal complex is an important factor for obtaining active antimicrobial complexes.…”

“…However, a series of elegant papers from Keene and co-workers have shown that the charge of the metal complex is an important factor for obtaining active antimicrobial complexes. They have developed a family of highly active dinuclear ruthenium(II) complexes that are overall 4+ cations [53,57]. Subsequently, they generated the analogous dinuclear iridium(III) complexes that are overall 6+ cations and found that these compounds displayed no antimicrobial activity [58].…”

“…With pathogens developing a resistance to beta-lactams and other commonly used antibiotics, the need for new antimicrobial medicines is growing. Metal-containing antibacterial drugs have become a global research focus over the past decade and are showing increasing promise [53][54][55]. As the previously Additional stability tests, in D 2 O, were also conducted with the [Co 2 L2 3 ](OTf) 6 cylinder against the common biological nucleophiles histidine and chloride ions.…”

“…With pathogens developing a resistance to beta-lactams and other commonly used antibiotics, the need for new antimicrobial medicines is growing. Metal-containing antibacterial drugs have become a global research focus over the past decade and are showing increasing promise [53][54][55]. As the previously investigated, biologically robust, ruthenium(II) triply stranded helicate [Ru 2 (L3) 3 ] 4+ and related dirhenium(I) L pytrz complexes had displayed modest antimicrobial activity [33,56], we screened the new [Co 2 (L pytrz ) 3 ](OTf) 6 cylinders against S. aureus (Gram-positive bacteria) and E. coli (Gram-negative bacteria).…”