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+) (1; phen = 1, 10-phenanthroline) and [Ru(HAT)(2)(phen)](2+) (2; HAT = 1,4,5,8,9,12-hexaazatriphenylene), whereas it is not observed with [Ru(TAP)(2)TPAC](2+) (3; TPAC = tetrapyridoacridine) at the same level of loading of the duplex by 3. With a concentration of 3 similar to that of 1 and 2, when the loading of the duplex by 3 is much more important than with 1 and 2, the photo-cross-linking with 3 can thus also be observed. As 3 intercalates its TPAC ligand into the base pairs stack, its mobility is restricted in the duplex. In contrast, 1 and 2 can adopt different geometries of interaction, which probably facilitate the photo-cross-linking.