The cyclic voltammetry of Ru(bpy)(3)(2+) in the presence of calf thymus DNA has been studied. Theoretical simulations using DigiSim were performed for the voltammetry of the metal complex in the presence of DNA where the only interaction between the metal complex and DNA was electrostatic binding to the polyanion. The expected binding isotherm was obtained from the simulated voltammetry with input affinities similar to that of Ru(bpy)(3)(2+). The expected binding isotherm was not obtained for simulations with high affinities (>10 degrees M(-1)) expected for intercalating complexes that exhibit neighbor exclusion, because the commercially available version of DigiSim treats only simple equilibria and cannot treat exclusion of binding to adjacent sites. Simulations were then performed for the case where the +3 state of the metal complex oxidizes the guanine base in DNA in a catalytic mechanism. The dependence of i(cat)/i(d) on scan rate and the second-order rate constant for the homogeneous chemical step was determined for the conditions where the metal complex does not bind to DNA, such as at high salt concentration. Under these conditions, there is an optimum scan rate where the catalytic current depends steeply on the homogeneous rate constant, allowing for the most accurate determinations in fitting experimental voltammograms. These considerations were applied to fitting cyclic voltammograms for the case of no DNA binding (high salt) and weak, but significant, DNA binding (50 mM salt). The rate of homogeneous electron transfer from the guanine nucleobase to the metal complex was 10 times faster in the low salt case, indicating a shorter electron-transfer distance and a more intimate association of the metal complex with the DNA.