NMR Evidence for Major Groove Binding of Both Λ‐ and Δ‐[Ru(bpy)₂(pqx)](PF₆)₂ to the Oligonucleotide d(CGCGAATTCGCG)₂

Abstract

The enantiomeric complexes Λ-and ∆-[Ru(bpy) 2 (pqx)](PF 6 ) 2 [pqx = 2-(2Ј-pyridyl)quinoxaline] were synthesized and characterized by various spectroscopic techniques. Their binding properties to the oligonucleotide duplex d(CGCGAATTCGCG) 2 were subsequently studied by NMR spectroscopy. 1D and 2D NMR techniques provided evidence for major-groove binding of both enantiomers with the oligonucleotide. The ∆-[Ru(bpy) 2 (pqx)](PF 6 ) 2 enantiomer binds IndroductionThe binding properties of transition metal tris-chelate complexes with DNA have been extensively studied in recent years. [1,2] One of the pioneering works was the report by Barton et al. pointing out the remarkable difference in the binding strength of the enantiomers of [Zn(phen) 3 ] 2ϩ with DNA.[3] The interactions between CT-DNA and the enantiomeric ruthenium complexes Λ-and ∆-[Ru(phen) 3 ] 2ϩ have been studied by several methods, with controversial conclusions. Several studies led to the conclusion that the ∆-isomer either intercalates between the base pairs, [4Ϫ7] or is partially inserted, [8Ϫ10] or it binds to DNA in various ways [11,12] (e.g. in the major [8,10] or in the minor groove [13,14] ). On the other hand Λ-[Ru(phen) 3 ] 2ϩ binds to DNA either by electrostatic forces, [4,5] or surface-bound interactions, [6,12] and with weak binding in the minor [13,14] or the major groove. [8,10] 2,2Ј-Bipyridine has been used as a ligand less often than 1,10-phenanthroline in tris-chelate complexes of Ru II in studies of interactions with DNA due to the lower affinity of this ligand to bind to the DNA helix. Based on photophysical results, it has been suggested that ation or electrostatic interactions. [4,5,15] It has also been reported that no enantiomeric discrimination is apparent between the binding of Λ-and ∆-[Ru(bpy) 3 ] 2ϩ with DNA.[16]The interaction of the mixed-ligand complex [Ru(bpy) 2 (phen)] 2ϩ with DNA has been studied by linear dichroism spectroscopy with the aim of investigating the role of each ligand involved in the complex. The results indicate that the complex shows a similar binding geometry to [Ru(phen) 3 ] 2ϩ in which one phen ligand faces the DNA base pairs, almost as if it were intercalated nearly parallel to them.[9] A similar mixed-ligand complex, [Ru(bpy) 2 (ppz)] 2ϩ (ppz ϭ 4,7-phenanthrolino [6,5-b]pyrazine, a non-classical intercalative ligand), which is longer than phen by a sixmembered fused ring, shows that both Λ-and ∆-enantiomers bind in the major groove of DNA by partial intercalation of the ppz ligand. The bpy ligands are not capable of inducing intercalation and the enantioselectivity is maintained by the different interactions of the ∆-and Λ-enantiomers with the DNA major groove. [17] In an attempt to contribute to the better understanding of how these mixedligand complexes bind to DNA, we have synthesized, characterized and studied the binding properties of the enantiomeric complexes Λ-and ∆-[Ru(bpy) 2 (pqx)] 2ϩ [pqx ϭ 2-(2Ј-pyridyl)quinoxaline], to the oligonucleotide duplex d(5Ј-CGCGAATTCGCG-3Ј) 2 mainly by NMR...

Interaction of Λ- and Δ-[Ru(bpy)2(pbmz)](PF6)2 with the oligonucleotide duplex d(CGCGAATTCGCG)2

“…2) are unaffected by the interaction with the enantiomers, indicating that the base-pair stacking is maintained. Similar results have been obtained in the NMR studies of [Ru(bpy) 2 (pqx)] 2+ with the same sequence [17] and [Ru(phen) 3 ] 2+ with d(CGCGATCGCG) 2 [14]. In the first case both enantiomers were found to bind weakly into the major groove, while in the case of [Ru(phen) 3 ] 2+ a preferential binding in the minor groove of the oligonucleotide was observed.…”

“…Moreover, the binding geometry of the [Ru(bpy) 2 (phen)] 2+ is similar to that of [Ru(phen) 3 ] 2+ [11]. In our previous work we have investigated the interactions between the enantiomeric complexes K-and D-[Ru-(bpy) 2 (pqx)] 2+ , where pqx = 2-(2 0 -pyridyl)quinoxaline, and the oligonucleotide duplex d(CGCGAATTCGCG) 2 by means of NMR techniques [17,18]. The ligand pqx is similar to 2,2 0 -bipyridine, but it involves an additional fused aromatic ring system in its one side.…”

DNA binding selectivity of oligopyridine-ruthenium(ii)-lysine conjugate

“…The slow reaction kinetics between complex (2) and the oligonucleotide on the NMR time scale, observed for both sequences, clearly lead to the conclusion that (2) binds coordinatively to the oligonucleotide, since groove interaction and simple electrostatic interactions are usually in fast exchange. 63 Moreover, intercalation binding of aromatic ligands between the DNA bases is, in the most cases, of intermediate exchange kinetics on the NMR time scale and at ambient temperature. 64…”

15 Noble metals

“…79 Through NMR spectroscopic studies with short chain oligonucletiodes, the complex [Ru(bpy)(L)] 2+ [L = 2-(29-pyridyl)quinoxaline] has been shown to interact with DNA in the major groove, with the usual preference for the D-enantiomer. 80 A detailed electronic investigation of the dinuclear complex [{Ru(bpy) 2 } 2 (L)] 2+ [L = bis(2-oxophenyl)-2,5-dihydropyrazine] has been reported indicating that the bisphenolate bridge results in a weakly coupled Robin-Day class-II mixed-valence state. 81 The asymmetric bridging ligand 3-(2-phenol)-5-(pyridine-2yl)-1,2,4-triazole, with N,O and N,N-chelating sites, also affords weakly-coupled (class II) mixed-valence state in its dinuclear {Ru(bpy) 2 } 2 complex; The Ru(II)-Ru(III) form is, unusually, luminescent but the Ru(II)-Ru(II) form is not.…”