DNA interaction with Ru(ii) and Ru(ii)/Cu(ii) complexes containing azamacrocycle and dppz residues. A thermodynamic, kinetic and theoretical study.

Abstract

Ru(II) complexes that bring together the properties of the dppz (dipyrido[3,2-a:2′,3′-c]phenazine) intercalating residue and the properties of metal-coordinating macrocycles (L = 4,4′-(2,5,8,11,14-pentaaza[15])-2,2′-bipyridilophane) have been synthesised and their protonation and affinity for copper(II) was analysed. Ru(bpy)(dppz)L²⁺ (D2²⁺) and Ru(dppz)₂L²⁺ (D3²⁺) were found to interact with DNA but the binding mode is not simple and its features strongly depend both on the ligand structure and on the [DNA]/[complex] ratio. Equilibrium measurements (spectrophotometric and spectrofluorometric titrations), kinetics (stopped-flow technique) and theoretical calculations all concur in suggesting that for the less hindered D2²⁺ an important contribution of external binding, driven by dye–dye interactions, is operative, as revealed by the onset of positive cooperativity. On the contrary, for the bulkier D3²⁺ complex dye–dye interactions are less effective, resulting in an intercalation process with lower dppz penetration within DNA slots. The Ru(bipy)₂L²⁺(D1²⁺)/DNA system was also analysed for comparison and helped in showing the non negligible contribution of the macrocycle to the binding process. The binding affinities of the macrocycle copper complexes for DNA are lower than those of their copper-free analogues only in the case of D1²⁺, whereas an affinity enhancement in agreement with the charge increase upon copper coordination is observed for D2²⁺ and D3²⁺. Copper coordination produces complete loss of the cooperative behaviour in the case of D2²⁺. Further mechanistic details are discussed.