J. Am. Chem. Soc. 134, 10214–10221 (2012)

Metal complexes that combine photosensitivity with the ability to bind to DNA have attracted much attention in the biomedical field. The fact that their fluorescence changes in the presence of DNA may prove useful for sensing applications. Moreover, their DNA-binding ability — which, in turn, can affect biological processes — can be switched on or off in a controlled manner through light irradiation at specific locations. Using scanning force microscopy, a team of researchers in Belgium led by Moucheron, Kirsch-De Mesmaeker and De Feyter have now described the mechanical and structural effects of the binding and photoreaction of a ruthenium complex on long DNA duplexes.

Credit: © 2012 ACS

The ruthenium complex in question comprised two tetraaza-phenanthrene (TAP) moieties — phenanthroline (phen) derivatives in which two carbon atoms are substituted by nitrogen — and a third ligand, a phenanthrolino-hexaaza-triphenylene polyaromatic group, known to intercalate in DNA by sliding between two base pairs. Comparisons between the behaviour of the TAP-based complex and its phen-based analogue, along with studies in the presence of strong hydrogen-bond donor urea, suggest that — as well as the expected intercalation — hydrogen bonding takes place between the uncoordinated nitrogen atoms of TAP and distant DNA segments. This effectively leads to intra- and inter-strand crosslinking, causing the DNA to fold and form large aggregates.

When irradiated, electronically excited TAP-based ruthenium complexes bound to DNA are known to undergo photoelectron transfer with neighbouring guanine residues. This process is followed by back electron transfer or the formation of a complex–duplex adduct, or — in the case of long strands of DNA — cleavage of the sugar-phosphate backbone. The Belgium-based team found that visible-light irradiation of a supercoiled DNA strand (pictured left) in the presence of the TAP-based complex induced the cleavage of some single strands — which releases some structural strain — as well as the formation of adducts. These adducts can result in increased rigidity of the DNA and crosslinking between different segments. Such mechanical and topological changes may impact the biomedical applications of these ruthenium-TAP complexes.