DNA Binding of ∧-and Δ-cis-β-[Ru(RR-picchxn)(phen)]²⁺Studied by NMR and Flow Linear Dichroism Spectroscopy

Abstract

Two novel substitutionally-inert diastereomeric ruthenium(II) cations of the form lambda- and delta-cis-beta-[Ru(RR-picchxn)(phen)]2+, where RR-picchxn is N,N'-dimethyl-N,N'-di(2-picolyl)-1R,2R-diaminocyclohexane and phen is 1,10-phenanthroline, have been studied with respect to their interactions with duplex DNA. NMR investigations show that both diastereomers bind to the oligonucleotide [d(CGCGATCGCG)]2 in the fast exchange regime and that binding predominantly takes place in the minor groove of the oligonucleotide, but that the governing interactions are significantly different for the two delta and lambda forms. Linear dichroism data support the latter interpretation, in that the relative orientations of cis-beta-[Ru(RR-picchxn)(phen)]2+ to calf thymus DNA also are observed to differ for the delta and lambda diastereomers. Interpretation of these data indicates the lambda form to be bound with the planar phen ligand closely parallel to the DNA base-pairs, but the average orientation of the phen ligand in the delta form deviates significantly from a parallel alignment.

Probing Site Specificity of DNA Binding Metallointercalators by NMR Spectroscopy and Molecular Modeling

“…at 40 °C) to the terminal C 1 ‚G 10 base pair are evident. A similar interaction has been noted previously with the binding of [Ru(phen) 3 ] 2+ to [d(CGCGATCGCG)] 2 at R values >1.0 (4) and for Λ-and ∆-cis-β-[Ru(RR-picchxn)(phen)] 2+ (56). The breakdown of this binding is reflected in Figure 8B for R-phen and R-dpq, which shows similar low-temperature events.…”