Stacking Interactions in Oligonucleotides by Differential Pulse Voltammetry and Spectroelectrochemistry Measurements

Oxidative DNA damage is a consequence of cellular metabolism, with a propensity for increased levels following exposure to UV and ionizing radiation, and toxic insults. One electron oxidation of DNA generates a radical cation, an electron hole, which is able to migrate along the strand and to irreversibly react leading to strand breaks and nucleobase modifications, with loss or corruption of genetic information, possibly resulting in cellular aging or disease. Differential pulse voltammetry and spectroelectrochemistry proved to be very effective techniques to investigate the oxidation properties of isolated nucleosides and nucleotides in solution. [1-3] Here we present the results concerning the extension of our previous works to oligonucleotides, systems which are better biomimetic DNA models than single nucleosides, allowing molecular processes of free radical reactions to be examined in a less complex environment than DNA, but respectful of its biological characteristics. Short sequences (hexamers), which possess coiled conformations in water solution, have been considered. The higher order structures of the oligonucleotides have been studied by one- and two-dimensional NMR spectroscopy, circular dichroism, and molecular mechanics. Differential pulse voltammetry and spectroelectrochemistry have allowed to characterize the distribution of low lying energy states of one electron oxidized oligonucleotides, giving access to a series of important information about the chemico-physical effects which controls the long range charge transfer in DNA and determines the sites where oxidative DNA damages occur.