Equilibria and kinetics of the intercalation of Pt-proflavine and proflavine into calf thymus DNA

Abstract

The interaction of the cis-platinum derivative of proflavine [{PtCl(tmen) 2}{HNC 13H 7(NHCH 2CH 2) 2}] + (PRPt) with CT-DNA is investigated by spectrophotometry and T-jump relaxation in 0.11 M NaCl, pH 7.0, and 25°C. The DNA–proflavine (PR) system is investigated under the same conditions. Static measurements indicate that base-dye interactions prevail and their analysis reveals that the site size for PRPt ( n=2.6) is twice that found for PR ( n=1.3). One relaxation effect is observed for the DNA/PR system and two effects for the DNA/PRPt system, the faster of them being similar to that of DNA/PR. The kinetics of the process are discussed in terms of the three-step sequence D+ S ⇄ DS I ⇄ DS II ⇄ DS III , where PR and the aromatic residues of PRPt intercalate into DNA by the same mechanism. The third step represents the penetration of platinum residues between base-pairs and is associated to remarkable enthalpy and entropy changes. Further mechanistic details are discussed.