The electrochemical response of electrode-attached redox oligo-nucleotides is governed by low activation energy electron transfer kinetics

The mechanism responsible for electron transport within layers of redox DNA anchored to electrodes has been the subject of numerous studies over the last twenty years, but remains a controversial issue. Herein, we thoroughly study the electrochemical behavior of a series of short, model, ferrocene (Fc) end-labeled dT oligonucleotides, terminally attached to gold electrodes, using high scan rate cyclic voltammetry complemented by molecular dynamics simulations reproducing DNA Brownian motion. We evidence that the electrochemical response of both single-stranded and du-plexed oligonucleotides is controlled by the kinetics of electron transfer at the electrode, obeying Marcus theory, but with reorganization energies considerably lowered by the attachment of the ferrocene to the electrode via the flexible DNA chain. This so far unreported effect, that we attribute to a slower relaxation of water around Fc when attached to moving DNA, is shown to uniquely shape the time-dependent electrochemical response of Fc-DNA strands and, being markedly dissimilar for single-stranded and duplexed DNA, likely contributes to the signaling mechanism of E-DNA sensors.