Interaction of Calf Thymus DNA with the Ni(II) Complex of Sodium 1,4-Dihydroxy-9,10-Anthraquinone-2-Sulphonate: A Novel Method of Analysis Using Cyclic Voltammetry

Abstract

Hydroxy-9,10-anthraquinones are cheaper alternatives to anthracycline drugs. They closely resemble anthracycline drugs both from a structural and functional viewpoint. Electrochemical behavior of the Ni(II) complex (Na 2 [Ni(NaLH) 2 Cl 2 ]·2H 2 O) of sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate (NaLH 2 ), analogue of the core unit of anthracycline anticancer drugs, was studied at physiological pH using cyclic voltammetry. The Ni(II) complex of sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulphonate undergoes diffusion-controlled one-electron reduction that enables performing an electrochemical study on the interaction of the complex with calf thymus DNA. The complex was titrated with increasing concentrations of DNA, and the reduction peak for the unbound complex helped in evaluating binding parameters. Analysis of binding data using nonlinear curve fit in a cyclic voltammetry experiment is the first such attempt. The paper evaluates site size of interaction that also serves as a means to determine stoichiometry of complex formation, between a metal ion and ligand from a DNA interaction study, probably a first of its kind.

Exploration of Electrochemical Intermediates of the Anticancer Drug Doxorubicin Hydrochloride Using Cyclic Voltammetry and Simulation Studies with an Evaluation for Its Interaction with DNA

“…Under the same experimental conditions, cyclic voltammetry of pure DNA showed that there was neither any cathodic nor anodic peak in the potential range 0.0 to −0.85 V, clearly indicating that pure DNA was electrochemically inert in the potential range on a glassy carbon electrode. Previous studies [25,26,34,35] also showed that CT DNA was electrochemically inactive at a glassy carbon electrode surface. To find the reversibility of the reduction of doxorubicin hydrochloride in the presence of DNA, a plot of the ratio of the anodic to cathodic peak current ( pa / pc ) versus the logarithm of scan rate (log v) (Figure 3) is considered which shows that the pa / pc ratio is less than unity for lower scan rates and it is almost unity at higher scan rates [32] clearly suggesting that the reduction is quasireversible at lower scan rates and it is reversible at higher scan rates.…”

“…In a previous DNA interaction study, Radi et al [35] carried out a similar ferricyanide experiment to establish that cyclic voltammetric behavior of their studied compound was not affected by addition of a very large excess of DNA and that decrease in peak current of the compound was due to interaction of the compound with DNA and not owing to adsorption. Results of DNA titration using cyclic voltammetry were analyzed by the method of nonlinear fitting [25,26]. To do so, the following compound-DNA equilibrium was considered [36][37][38][39]:…”

“…Determination of using (5) requires the value of Δ max which was determined by double reciprocal plot ( Figure 5) using [25,26] …”

“…CT DNA concentration was 10-fold greater than doxorubicin hydrochloride. Binding stoichiometry or binding site size was determined from the point of intersection of two straight lines obtained from the least-square fit plot of normalized increase of Δ /Δ max against ratio of concentrations of CT DNA (in base) to doxorubicin hydrochloride [25,26] that was drawn considering points before and after saturation, respectively [25,26]. The point of intersection of the two straight lines indicates a ratio of the moles of DNA (in bases) to the mole of doxorubicin hydrochloride in which the saturation is just reached, that is, the number of DNA bases bound per doxorubicin hydrochloride.…”

“…Therefore the study of the redox behavior of anthracyclines is an important aspect as it helps in the understanding of toxicities and therapeutic efficiencies. There are many reports on the redox behavior of these drugs correlated with biological findings [25,26]. The present study is an attempt to revisit the redox behavior of doxorubicin hydrochloride in aqueous media at physiological pH (7.4) using cyclic voltammetry trying to understand the mechanism by which the molecule copes with reduction.…”