Oligopyridine–ruthenium(ii)–amino acid conjugates: synthesis, characterization, DNA binding properties and interactions with the oligonucleotide duplex d(5′-CGCGCG-3′)2

Abstract

Diastereomeric oligopyridine–ruthenium(II)–amino acid conjugated complexes of the general formulas Λ- and Δ-[Ru(bpy)₂(4,4′(CO₂Y)₂-bpy)]²⁺, where Y = L-AlaCONH₂, L-LysCONH₂, L-HisCONH₂, L-TyrCONH₂), were synthesized and characterized. Their binding properties with ct-DNA and the oligonucleotide duplex d(5′CGCGCG-3′)₂, by means of circular dichroism (CD), NMR spectroscopy and DNA thermal denaturation (T_m) curves were studied. CD and T_m data indicate that all diastereomeric complexes bind to the DNA major groove, Δ-diastereomers in a similar manner, while Λ-diastereomers in dependence of the nature of the amino acid. NMR studies of d(5′CGCGCG-3′)₂, and the complexes Δ-1, Δ-2, Λ-1 and Λ-2 indicate that Δ-1 and Δ-2 were bound having the ancillary bpy ligands towards the DNA groove, while the corresponding Λ-1 and Λ-2 were orientated in a similar way, facing the ligand 4,4′(CO₂Y)₂bpy towards the DNA major groove. Photoinduced DNA cleavage was observed in all cases studied, which take place through singlet oxygen production. Δ-4 and Λ-4 show the lower photoinduced cleavage yield, probably because the singlet oxygen (¹O₂) oxidizes not only the DNA phosporodiesteric bonds but the tyrosine's phenolic OH bond as well.