Diastereomeric oligopyridine-ruthenium(II)-amino acid conjugated complexes of the general formulas Lambda- and Delta-[Ru(bpy)(2)(4,4'(CO(2)Y)(2)-bpy)](2+), where Y = L-AlaCONH(2), L-LysCONH(2), L-HisCONH(2), L-TyrCONH(2)), 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, Delta-diastereomers in a similar manner, while Lambda-diastereomers in dependence of the nature of the amino acid. NMR studies of d(5'CGCGCG-3')(2), and the complexes Delta-1, Delta-2, Lambda-1 and Lambda-2 indicate that Delta-1 and Delta-2 were bound having the ancillary bpy ligands towards the DNA groove, while the corresponding Lambda-1 and Lambda-2 were orientated in a similar way, facing the ligand 4,4'(CO(2)Y)(2)bpy towards the DNA major groove. Photoinduced DNA cleavage was observed in all cases studied, which take place through singlet oxygen production. Delta-4 and Lambda-4 show the lower photoinduced cleavage yield, probably because the singlet oxygen ((1)O(2)) oxidizes not only the DNA phosporodiesteric bonds but the tyrosine's phenolic OH bond as well.

The synthesis, characterization and DNA binding properties of the complex [Ru(terpy)(4,4'-(COLysCONH(2))(2)bpy)Cl](3+) (1) have been studied. Complex (1) hydrolyzes to (2) with a calculated rate constant K(h) = 2.35 ± 0.08 × 10(-4) s(-1) and binds coordinatively to ct-DNA, with a saturation r-value at about 0.1. Stabilization of the ct-DNA helix at low electrolyte (NaClO(4)) concentration (10 mM) and destabilization at higher electrolyte concentrations (50-200 mM) was observed. Circular dichroism studies indicate that the hydrolyzed complex binds to DNA, increasing the unwinding of the DNA helix with an unwinding angle calculated as Φ = 12 ± 2°. The positive LD signal observed at 350 nm indicates some kind of specificity in complex orientation towards the global DNA axis. Complex (2) binds specifically to G4 on the central part of the oligonucleotide duplexes d(CGCGCG)(2) and d(GTCGAC)(2), as evidenced by NMR spectroscopy. Both lysine moieties were found to interact most likely electrostatically with the DNA phosphates, assisting the coordinative binding and increasing the DNA affinity of the complex. Photoinduced DNA cleavage by (2), upon UVA irradiation was observed, but despite its relative high DNA affinity, it was incomplete (~12%).