Ruthenation of duplex and single-stranded d(CGGCCG) by organometallic anticancer complexes

We have studied the interaction of the organometallic anticancer ruthenium(II) complexes [(η6-p-cymene)Ru(en)Cl][PF6] (1) and [(η6-biphenyl)Ru(en)Cl][PF6] (2) (en=ethylenediamine) with the single-stranded (ss) DNA hexamer d(CGGCCG) (I) and the duplex d(CGGCCG)2 (II) by HPLC, ESI-MS, and one- and two-dimensional 1H and 15N NMR spectroscopy. For ss-DNA, all three G's are readily ruthenated with [(η6-arene)Ru(en)]2+, but for duplex DNA there is preferential ruthenation of G3 and G6, and no binding to G2 was detected. For monoruthenated duplexes, N7 ruthenation of G is accompanied by strong hydrogen bonding between G-O6 and en-NH for the p-cymene adducts. Intercalation of the non-coordinated phenyl ring between G3 and C4 or G6 and C5 was detected in the biphenyl adducts of mono- and diruthenated duplexes, together with weakening of the G-O6⋅⋅⋅NH-en hydrogen bonding. The arene ligand plays a major role in distorting the duplex either through steric interactions (p-cymene) or through intercalation (biphenyl).