An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA

Abstract

The electrochemical behavior of 9-chloroacridine (9Cl-A), a precursor molecule for synthesis of acridine derivatives with cytostatic activity, is a complex, pH-dependent, diffusion-controlled irreversible process. Oxidation of 9Cl-A initiates with the formation of a cation radical monomer, continues via the formation of a dimer subsequent oxidation to new cation radical. Reduction of 9Cl-A produces radical monomers which are stabilized by dimer formation. The investigation was performed using cyclic, differential pulse and square wave voltammetry at a glassy carbon electrode. The interaction between 9Cl-A and double-stranded DNA (dsDNA) was investigated using a multilayer dsDNA-electrochemical biosensor and 9Cl-A solutions from 1.0×10-7M (the lowest 9Cl-A concentration whose interaction with DNA was possible to detect) up to 1×10-4M. These allowed the binding constant, K=3.45×105M-1 and change in Gibbs free energy of the formed adsorbed complex to be calculated. Complex formation was a spontaneous process proceeding via 9Cl-A intercalation into dsDNA inducing structural changes. The intercalation of 9Cl-A into dsDNA was supported by molecular docking analysis. The combination of simple methodology and the use of biosensors to investigate DNA interactions is a powerful tool to offer insight into aspects of drug design during pharmaceutical development.