STRUCTURAL STUDIES OF LAMBDA-[RU(PHEN)(2)DPPZ](2-[RU(PHEN)(2)DPPZ](2+) BOUND TO D(GTCGAC)(2) - CHARACTERIZATION OF ENANTIOSELECTIVE INTERCALATION() AND DELTA)

H-1 and P-31 NMR spectroscopies have been applied in the structural ch aracterization of the enantioselective interactions between Lambda- an d Delta-[Ru(phen)(2)dppz](2+) (dppz = dipyridophenazine) and the hexam er oligonucleotide d(GTCGAC)(2). Issues of intercalation, exchange rat e, sequence specificity, enantioselectivity, and the distribution of b inding geometries have been explored. Several forms of evidence suppor t intercalation by both isomers: (i) upfield changes in H-1 chemical s hift for protons of the dppz ligand; (ii) characteristic downfield cha nges in P-31 chemical shifts for the duplex bound by the metal complex ; (iii) increases in duplex melting temperature in the presence of bot h isomers. Slow exchange is achieved near 0 degrees C, thus permitting the observation of individual binding events. While both isomers inte rcalate into the helix, enantioselective differences in intercalation are evident. Differences in intercalative geometries are clearly manif ested through chiral shifts in racemic mixtures and distinct resonance patterns for the 4',7'-dppz ligand protons of Lambda- and Delta-[Ru(p hen-d(8))(2)dppz](2+). Intermolecular NOEs place the Delta-isomer in t he major groove. For the Lambda-isomer, substantially broader lines ar e evident, reflecting clear differences in the diastereomeric interact ions. The Lambda-isomer bound to DNA exhibits behavior consistent with a faster exchange rate compared to the Delta-isomer and/or a low leve l of sequence selectivity under NMR conditions. Similar characteristic s of intercalation for both isomers are evident upon fluorine substitu tion onto the distal end of the dppz ligand; based upon chemical shift changes, it appears that fluorine substitution leads to a deeper stac king interaction. The movement of dppz ligand proton resonances upon b inding DNA also indicates that [Ru(phen)(2)dppz](2+) isomers bind to t he DNA helix with a population of intercalative geometries, some of wh ich provide asymmetric protection of the dppz ligand from aqueous solv ent. These results therefore support and extend earlier structural mod els based upon luminescence studies.