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.

We have synthesized novel organoiridium(III) antimicrobial complexes containing a chelated biguanide, including the antidiabetic drug metformin. These 16- and 18-electron complexes were characterized by NMR, ESI-MS, elemental analysis, and X-ray crystallography. Several of these complexes exhibit potent activity against Gram-negative bacteria and Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus (MRSA)) and high antifungal potency toward C. albicans and C. neoformans, with minimum inhibitory concentrations (MICs) in the nanomolar range. Importantly, the complexes exhibit low cytotoxicity toward mammalian cells, indicating high selectivity. They are highly stable in broth medium, with a low tendency to generate resistance mutations. On coadministration, they can restore the activity of vancomycin against vancomycin-resistant Enterococci (VRE). Also the complexes can disrupt and eradicate bacteria in mature biofilms. Investigations of reactions with biomolecules suggest that these organometallic complexes deliver active biguanides into microorganisms, whereas the biguanides themselves are inactive when administered alone.

Half-sandwich RhIII anticancer complexes with activated Cp* rings not only undergo sequential CH3 H–D exchange, but also react with biological dienes, generating RhI Diels–Alder adducts in aqueous media at ambient temperature.