There is a dire need for new compounds to combat antibiotic resistance: metal complexes might provide the solution. 906 metal complexes were evaluated against dangerous ESKAPE pathogens and found to have a higher hit-rate than organic molecules.

Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)](2+) (2) (DIP = 4,7-diphenyl-1,10-phenanthroline, bdt = 1,2-benzenedithiolate, dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine), ptpy = 4'-phenyl-2,2':6',2 -terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and phototoxic index (PI) of 2 (IC50(light): 25.3 M, 420 nm, 6.95 J/cm(2); PI >4) and particularly of 1 (IC50(light): 0.62 M, 420 nm, 6.95 J/cm(2); PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic acid. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (1) and by inductively coupled plasma mass spectrometry (1 and 2). Their phototoxicity was also determined against the Gram-(+) Staphylococcus aureus and Gram-(-) Escherichia coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm(2)) against Gram-(+) (S. aureus; >6 log10 CFU reduction) and, for 2, also against Gram-(-) E. coli (>4 log10 CFU reduction). Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)] 2+ (2) (DIP = 4,7-diphenyl-1,10-phenanthroline; bdt = 1,2-benzenedithiolate; dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine); ptpy = 4'-phenyl-2,2':6',2''-terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and photo-index (PI) of 2 (IC50(light): 25.3 μM, 420 nm, 6.95 J/cm 2 ; PI: >4) and particularly of 1 (IC50(light): 0.62 μM, 420 nm, 6.95 J/cm 2 ; PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (1) and by inductively coupled plasma-mass spectrometry (1 and 2). Their phototoxicity was also determined against the Gram-(+) S. aureus and Gram-(−) E. coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm 2 ) against Gram-(+) (S. aureus; >6 log10 CFU reduction) and, for 2, also against Gram-(−) E. coli (>4 log10 CFU reduction). 3Introduction.

Bacteria, similar to most organisms, have a love–hate relationship with metals: a specific metal may be essential for survival yet toxic in certain forms and concentrations. Metal ions have a long history of antimicrobial activity and have received increasing attention in recent years owing to the rise of antimicrobial resistance. The search for antibacterial agents now encompasses metal ions, nanoparticles and metal complexes with antimicrobial activity (‘metalloantibiotics’). Although yet to be advanced to the clinic, metalloantibiotics are a vast and underexplored group of compounds that could lead to a much-needed new class of antibiotics. This Review summarizes recent developments in this growing field, focusing on advances in the development of metalloantibiotics, in particular, those for which the mechanism of action has been investigated. We also provide an overview of alternative uses of metal complexes to combat bacterial infections, including antimicrobial photodynamic therapy and radionuclide diagnosis of bacterial infections.