FULL PAPER © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 1 wileyonlinelibrary.com 1. Introduction The use of DNA molecules as scaffolds, supports, and templates has inspired diverse branches of the modern nanobio- science. The current technological appli- cations of DNA span from the use of nucleic acid templates to activate enzyme cascades, [1] and self-assembly of nanoscale nucleic acid building blocks into mes- oscale structures, [2] to self-organization of supramolecular DNA nanostructures acting as molecular nanomachines. [3] DNA has been proposed as biological tem- plate for the assembly of nanoelectronic devices and nanocircuits. [4] Moreover, DNA has been extensively investigated for the development of field-effect transis- tors, [5] chemical and biological sensors, [6] and nanodiodes. [7] From the structural perspective, the DNA molecule can be considered as a nanowire, with diam- eter of 2 nm, featuring long well-defined polymeric sequences decorated by func- tional groups. [8] The understanding of the conducting properties of DNA molecules has been a scientific challenge for more than 50 years. The possible charge transfer between electron donors and acceptors through DNA, obtained from solution chemistry experiments, [9] stimulated a series of direct electron transfer measurements aimed at the develop- ment of high-tech applications, ranging from band-gap insu- lators to effective molecular wires. [10] Yet, understanding the electrical conduction properties of such complicated aperiodic polyelectrolyte system remains a major scientific problem. [11] The prevailing DNA architecture, the double helix, possess well stacked, nearly parallel bases, with overlapping π-electron systems [10] and, thus, can be a good candidate for long-range charge transfer. [12] Notwithstanding experimental findings and theoretical interpretations have spurred intense debate over the electrical properties of DNA, the electronic properties of DNA still remain controversial, and the nature of the carriers respon- sible for DNA electrical conductivity is still under investigation. It has been demonstrated that both vacancies and electrons can migrate through the DNA helix over distances, [13] as well as, results indicate that correlation effects are probably responsible Triggering Mechanism for DNA Electrical Conductivity: Reversible Electron Transfer between DNA and Iron Oxide Nanoparticles Massimiliano Magro, Davide Baratella, Petr Jakubec, Giorgio Zoppellaro, Jiri Tucek, Claudia Aparicio, Rina Venerando, Geppo Sartori, Federica Francescato, Fabio Mion, Nadia Gabellini, Radek Zboril,* and Fabio Vianello* A new category of iron oxide nanoparticles (surface active maghemite nanoparticles (SAMNs, γ-Fe 2 O 3 )) allows the intimate chemical and electrical contact with DNA by direct covalent binding. On these basis, different DNA- nanoparticle architectures are developed and used as platform for studying electrical properties of DNA. The macroscopic 3D nanobioconjugate, consti- tuted of 5% SAMNs, 70% water, and 25% DNA, shows high stability, electro- chemical reversibility and, moreover, electrical conductivity (70–80 Ω cm -1 ). Reversible electron transfer at the interface between nanoparticles and DNA is unequivocally demonstrated by Mössbauer spectroscopy, which shows the appearance of Fe(II) atoms on nanoparticles following nanobioconjugate formation. This represents the first example of permanent electron exchange by DNA, as well as, of DNA conductivity at a macroscopic scale. Finally, the most probable configuration of the binding is tentatively modeled by density functional theory (DFT/UBP86/6-31+G*), showing the occurrence of electron transfer from the organic orbitals of DNA to surface exposed Fe(III) on nano- particles, as well as the generation of defects (holes) on the DNA bases. The unequivocal demonstration of DNA conduction provides a new perspective in the five decades long debate about electrical properties of this biopolymer, further suggesting novel approaches for DNA exploitation in nanoelectronics. DOI: 10.1002/adfm.201404372 Dr. M. Magro, Dr. D. Baratella, Dr. F. Francescato, F. Mion, Prof. F. Vianello Department of Comparative Biomedicine and Food Science University of Padova Legnaro 35044, Italy E-mail: fabio.vianello@unipd.it Dr. P. Jakubec, Dr. G. Zoppellaro, Dr. J. Tucek, Dr. C. Aparicio, Prof. R. Zboril Regional Centre of Advanced Technologies and Materials Department of Physical Chemistry Faculty of Science Palacky University Olomouc 779 00, Czech Republic E-mail: radek.zboril@upol.cz Dr. G. Sartori Department of Biomedical Sciences University of Padova Padova 35131, Italy Dr. R. Venerando, Dr. N. Gabellini Department of Molecular Medicine University of Padova Padova 35131, Italy Adv. Funct. Mater. 2015, DOI: 10.1002/adfm.201404372 www.afm-journal.de www.MaterialsViews.com