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Structural Studies of Λ- and Δ-[Ru(phen)2dppz]2+ Bound to d(GTCGAC)2:  Characterization of Enantioselective Intercalation

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journal contribution
posted on 01.01.1997, 00:00 authored by Cynthia M. Dupureur, Jacqueline K. Barton
1H and 31P NMR spectroscopies have been applied in the structural characterization of the enantioselective interactions between Λ- and Δ-[Ru(phen)2dppz]2+ (dppz = dipyridophenazine) and the hexamer oligonucleotide d(GTCGAC)2. Issues of intercalation, exchange rate, sequence specificity, enantioselectivity, and the distribution of binding geometries have been explored. Several forms of evidence support intercalation by both isomers:  (i) upfield changes in 1H chemical shift for protons of the dppz ligand; (ii) characteristic downfield changes in 31P chemical shifts for the duplex bound by the metal complex; (iii) increases in duplex melting temperature in the presence of both isomers. Slow exchange is achieved near 0 °C, thus permitting the observation of individual binding events. While both isomers intercalate into the helix, enantioselective differences in intercalation are evident. Differences in intercalative geometries are clearly manifested through chiral shifts in racemic mixtures and distinct resonance patterns for the 4‘,7‘-dppz ligand protons of Λ- and Δ-[Ru(phen-d8)2dppz]2+. Intermolecular NOEs place the Δ-isomer in the major groove. For the Λ-isomer, substantially broader lines are evident, reflecting clear differences in the diastereomeric interactions. The Λ-isomer bound to DNA exhibits behavior consistent with a faster exchange rate compared to the Δ-isomer and/or a low level of sequence selectivity under NMR conditions. Similar characteristics of intercalation for both isomers are evident upon fluorine substitution onto the distal end of the dppz ligand; based upon chemical shift changes, it appears that fluorine substitution leads to a deeper stacking interaction. The movement of dppz ligand proton resonances upon binding DNA also indicates that [Ru(phen)2dppz]2+ isomers bind to the DNA helix with a population of intercalative geometries, some of which provide asymmetric protection of the dppz ligand from aqueous solvent. These results therefore support and extend earlier structural models based upon luminescence studies.