An electrochemical study of the adsorptive behaviour of varenicline and its interaction with DNA

Abstract

The electrochemical behaviour of a novel nicotinic α 4β2 subtype receptor partial agonist varenicline (VAR), which is used for smoking cessation, was investigated in Britton-Robinson buffers (pH 2.0-12.0) by cyclic, differential pulse and square wave voltammetry at a hanging mercury drop electrode (HMDE). The influence of pH, scan rate, concentration, accumulation potential and time on the peak current and potential suggested that the redox process was adsorption controlled in alkaline media. In addition, the experimental value of the surface coverage, γ = 1.03×10-10 mol cm-2, was used to determine the conditions when VAR was fully adsorbed at the electrode surface. Bearing in mind the potential high toxicity of VAR due to the presence of a quinoxaline structure, its interaction with double stranded-DNA (ds-DNA) was postulated and studied when both compounds were in the adsorbed state at a modified HMDE. Using the adsorptive transfer technique, changes in potential and decreases in the normalized peak currents were observed. The estimated value of the ratio of surface-binding constants indicated that the reduced form of VAR interacted with ds-DNA more strongly than the oxidized form. Subtle DNA damage under conditions of direct DNA-VAR interaction at room temperature was observed. The proposed type of interaction was intercalation. This study employed a simple electroanalytical methodology and showed the potential of a DNA/ /HMDE biosensor for investigation of genotoxic effects. © 2012 Copyright (CC) SCS.