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

Abstract

The synthesis, characterization and DNA binding properties of the complex [Ru(terpy)(4,4′-(COLysCONH₂)₂bpy)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 (NaClO₄) 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%).