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

The new bifunctional molecule 3,6-diamine-9-[6,6-bis(2-amino-ethyl)-1,6-diaminohexyl]acridine (D), which is characterised by both an aromatic moiety and a separate metalcomplexing polyamine centre, has been synthesised. The characteristics of D and its ZnII complex ([ZnD]) (protonation and metal-complexing constants, optical properties and self-aggregation phenomena) have been analysed by means of NMR spectroscopy, potentiometric, spectrophotometric and spectrofluorimetric techniques. The equilibria and kinetics of the binding process of D and [ZnD] to calf thymus DNA have been investigated at I=0.11m (NaCl) and 298.1 K by using spectroscopic methods and the stopped-flow technique. Static measurements show biphasic behaviour for both D–DNA and [ZnD]–DNA systems; this reveals the occurrence of two different binding processes depending on the polymerto- dye molar ratio (P/D). The binding mode that occurs at low P/D values is interpreted in terms of external binding with a notable contribution from the polyamine residue. The binding mode at high P/D values corresponds to intercalation of the proflavine residue. Stopped-flow, circular dichroism and supercoiled-DNA unwinding experiments corroborate the proposed mechanism. Molecular-modelling studies support the intercalative process and evidence the influence of NH+···O interactions between the protonated acridine nitrogen atom and the oxygen atoms of the polyanion; these interactions play a key role in determining the conformation of DNA adducts.