Oxidizing Ru(II) Complexes as Irreversible and Specific Photo-Cross-Linking Agents of Oligonucleotide Duplexes

Oxidizing polyazaaromatic Ru^II complexes containing two TAP ligands (TAP = 1,4,5,8-tetraazaphenanthrene) are able under illumination to cross-link irreversibly the two strands of an oligonucleotide (ODN) duplex by covalent bond formation. The cross-linking proceeds by two successive absorptions of a photon. An adduct of the metallic complex on a guanine (G) base of one ODN strand is first photoproduced, followed by a second photoaddition of the same Ru species to a G base of the complementary strand, provided that the two G moieties are separated by 0 or 1 base pair. These two processes lead to the cross-linking of the two strands. Such a photo-cross-linking is easily detected with [Ru(TAP)₂(phen)]²⁺ (<b>1</b>; phen = 1,10-phenanthroline) and [Ru(HAT)₂(phen)]²⁺ (<b>2</b>; HAT = 1,4,5,8,9,12-hexaazatriphenylene), whereas it is not observed with [Ru(TAP)₂TPAC]²⁺ (<b>3</b>; TPAC = tetrapyridoacridine) at the same level of loading of the duplex by <b>3</b>. With a concentration of <b>3</b> similar to that of <b>1</b> and <b>2</b>, when the loading of the duplex by <b>3</b> is much more important than with <b>1</b> and <b>2</b>, the photo-cross-linking with <b>3</b> can thus also be observed. As <b>3</b> intercalates its TPAC ligand into the base pairs stack, its mobility is restricted in the duplex. In contrast, <b>1</b> and <b>2</b> can adopt different geometries of interaction, which probably facilitate the photo-cross-linking.