Experimental and theoretical approaches to interactions between DNA and purine metabolism products.

Deoxyribonucleic acid (DNA) is a significant target for small organic and inorganic drug molecules. Understanding the DNA interaction mechanism of these molecules is vital for new drug designs. In this work, interactions between xanthine (XT), theophylline (TP), and theobromine (TB) with calf-thymus double-strained DNA (dsDNA) were monitored via an experimental and theoretical approach. Experimentally, cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques were used on the surface of the NiO/MWCNT/NNaM/PGE electrochemical platform in vitro. Kinetic parameters, including diffusion coefficients, surface concentrations, and standard heterogeneous rate constants, were measured in the absence and presence of DNA using scan rate studies. In the presence of DNA, kinetic parameters were observed to be reduced significantly. Thermodynamic parameters, such as DNA binding constants and standard free Gibbs energies, were calculated for each molecule using the CV and DPV techniques. Both techniques suggested a binding affinity order of XT > TB > TP. Theoretically, density functional theory was applied for geometry optimization, natural bond orbital analyses, and molecular orbital energies of XT, TP, and TB. Experimental and theoretical binding affinities confirm each other. The most energetically stable ligand-DNA complexes expressed that XT, TP, and TB interact with dsDNA via minor groove binding mode, using mostly hydrogen bonds.