Selective Recognition of Conformation-Specific Arylamine–DNA Adduct in Frameshift Model by [Ru(phen)₂(dppz)]²⁺

Arylamine modification of guanine base at the G₃ position in the NarI sequence (−G₁G₂CG₃CC−) causes a frameshift mutation. Polymerase and ¹⁹F NMR studies have shown that the next flanking base at the 3′ position to the G₃ adduct modulates the mutational outcome because of its different conformations. Here, we have studied the interaction of the 16-mer NarI sequence (5′-CTCTCG₁G₂CG₃CXATCAC-3′) (G₃ = N-acetyl-2-aminofluorene (AAF)–dG and X is either C or T) with [Ru­(phen)₂(dppz)]²⁺ (phen = 1,10-phenanthroline and dppz = dipyrido­[3,2-a:2′,3′-c]­phenazine). Interaction studies between isomers of Ru­(II) and two oligonucleotide models, viz., (a) full duplex, and (b) slipped mutagenic intermediate (SMI), have been carried out. Luminescence studies reveal that the sensitivity of Ru­(II) with an adduct increases 2- to 3-fold compared to that of control in full duplex. In SMI, the sensitivity of Ru­(II) varies with the next flanking base and in the order of −G^AAFCC > −G^AAFCT. Microscale thermophoretic data reveal that in full duplex Λ-Ru binds to −G^AAFCT– by 13- and 4-fold stronger than its control and −G^AAFCC–, respectively. In SMI, Δ-Ru binds to −G^AAFCC– (41% stacked (S) conformer) by 3-fold while −G^AAFCT– (86% major groove (B) conformer) weakens the binding of Λ-Ru by 250-fold compared to the control. The results presented here reveal that the binding of Ru­(II) not only depends on conformations of the AAF–dG adduct but also is isomer-centric and might be helpful in determining the conformational heterogeneity of other covalent aryl/heterocyclic amine–DNA adducts.