Development of a DNA-damaging ferrocene amino acid

The oxygen-sensitive ferrocenylacetic acid moiety was incorporated in a water-soluble DNA-damaging agent via the synthon 1,1′-ferrocenediacetic acid anhydride. The extent of plasmid nicking was pH-dependent, with complete cleavage at pH 5.5. The nicking was indiscriminate and required O2, implicating reduced oxygen species as the actual damaging agent.

The synthesis and properties of a novel DNA-damaging ferrocene amino acid are presented.Figure optionsDownload as PowerPoint slideHighlights
► Ferroceneacetic acids give active oxygen species via proton coupled electron transfer.
► DNA damage takes place in the presence of oxygen and ferrocenylacetic acid anhydride derivatives.
► DNA damage is pH-dependent, insignificant at pH 7; very active at pH 5.2.