Ruthenation of Duplex and Single-Stranded dA by OrganoA Anticancer Complexes

We have studied the interac- tion of the organometallic anticancer ruthenium(II) complexes ((h 6 -p- cymene)Ru(en)Cl)A6 )( 1) and ((h 6 - biphenyl)Ru(en)Cl)A6 )( 2) (en = eth- ylenediamine) with the single-stranded (ss) DNA hexamer dA (I) and the duplex dA2 (II )b y HPLC, ESI-MS, and one- and two-di- mensional 1 Ha nd 15 N NMR spectro- scopy.For ss-DNA, all three G?s are readily ruthenated with ((h 6 -arene)- A 2 + , but for duplex DNA there is preferential ruthenation of G3 and G6, and no binding to G2 was detect- ed.For monoruthenated duplexes, N7 ruthenation of G is accompanied by strong hydrogen bonding between G- O6 and en-NH for the p-cymene ad- ducts.Intercalation of the non-coordi- nated phenyl ring between G3 and C4 or G6 and C5 was detected in the bi- phenyl adducts of mono- and diruthen- ated duplexes, together with weakening of the G-O6···NH-en hydrogen bond- ing.The arene ligand plays a major role in distorting the duplex either through steric interactions (p-cymene) or through intercalation (biphenyl).