Insights into how iron sandwich compounds cleave DNA could help scientists trying to develop anticancer drugs, say researchers from the University of Lódz, Poland and Imperial College London, UK.

Ferrocene compounds consist of two aromatic rings that sandwich a central iron cation. 'There is a general interest in ferrocene-based molecules as anticancer agents,' explained Nicholas Long, who fronted the research with Konrad Kowalski and David Mann. It has been known for some years that ferrocenium salts kill cancer cells by cleaving their DNA. The researchers were interested in discovering the mechanism behind this process, as this would help scientists designing ferrocene-based drugs.

The iron cations in ferrocenes can have either a 2+ or 3+ oxidation state. 'Classically, Fe³⁺ is regarded as triggering the DNA scission,' said Long. The new research has shown that Fe²⁺-containing azaferrocenes, which have a nitrogen atom in one of the aromatic rings, can also cleave DNA. 'This questions the established Fe³⁺ status quo,' Long said. The results suggest that the bonding strength between the metal ion and the aromatic rings is more relevant to DNA cleavage than the ion's oxidation state. 

The group also found that azaferrocenes with positively-charged nitrogen atoms had higher DNA cleavage activity than the neutral compounds tested. According to the researchers, this implies that an electrostatic interaction between the positive azaferrocenes and negatively-charged DNA is important for successful DNA cleavage. 

Long said that his group has plans to test the azaferrocene cytotoxicity further and that he expects to develop anticancer agents in the future. 'Crucially though, the first task is to fully understand the action mechanism of this family of compounds,' he said.

Danièle Gibney