Charge Transfer DOI: 10.1002/anie.200602106 Double Proton Coupled Charge Transfer in DNA** Francesco Luigi Gervasio,* Mauro Boero, and Michele Parrinello Charge transfer processes in DNA play an important role in oxidatively generated damage and possibly in repairing mechanisms. [1–3] Furthermore, if conductive, DNA could be used in nanoelectronic devices. [4–6] Unfortunately, the many experiments conducted have provided contradictory results, with conductivities that cover the entire range from metallic to insulator. [7–11] Such experiments are technically difficult as they require handling of single molecules or small bundles of DNA and fine control of their contact to the metallic leads and to the supporting surfaces. Despite experimental diffi- culties, a general consensus has been reached. [1,12] In partic- ular, experiments on chemically modified or photosensitizer intercalated DNA have demonstrated that wet DNA and DNA bundles can carry charge. [1,13,14] On the other hand, long DNA helices deposited on mica surfaces or in dry conditions were found to be insulators or wide-bandgap semiconduc- tors. [12] These results are not unexpected as the intrinsic randomness of DNA, induced by distortions and defects, can affect its conducting properties. Moreover, oxidation plays an important role as a parasitic event relative to hole (positive radical) migration. [15,16] As discussed in reference [17], charge transportation in duplex DNA takes place when the Fermi energies of the electrodes fall between the HOMO and the LUMO of the constituents and can occur through two possible mechanisms: a) a coherent single-step transportation from donor to acceptor (superexchange limit) [18] or b) multistep charge hopping. [19,20] Both mechanisms have been observed in wet DNA. In these experiments, the charge is injected site selectively by either intercalating an oxidizing agent or introducing some modification into the DNA. Similarly a charge sink can be created by the introduction of a modified base or of a GGG sequence; the effect of such modifications is to lower the ionization potential (IP) with respect to that of an isolated G, thus making the site an effective hole trap. [21] By using this approach, Giese et al. determined the effect of the bridge length on the efficiency of hole transfer by varying the numberof(A:T) n base pairs between the charge injection site and the GGG. [22] An exponential decay of the charge-transfer efficiency was observed as a function of the interposed (A:T) n sequence for n < 4, [23] in agreement with a single-step super- exchange-mediated transfer mechanism. Similar results have been reported by Nakatanu and Saito in reference [1]. In DNA sequences containing isolated G:C sites between the source and sink, the charge was shown to hop reversibly between all guanines. [24] Although the role of fluctuations in modulating DNA conductivity and a possible polaron-like hopping mechanism has been investigated in several experiments, [20,25–28] our knowledge of the microscopic changes induced by the charge defect and its transfer is mostly based on indirect evidence. Different localization mechanisms have been proposed: a change in the tilt angle of the bases, a rearrange- ment of the solvation shell, a fluctuation in the position of counterions, and a change in the protonation state of G. The first was hypothesized on the basis of simplified theoretical models. [29] The importance of the polarization of the solvent shell has been shown to play a role in the charge transfer in poly(A:T). [30] The ion-gated charge-hopping mechanism was proposed from first-principles simulations that showed a correlation between the charge localization and the position [*] Dr. F. L. Gervasio, Prof. M. Parrinello Computational Science Department of Chemistry and Applied Biosciences ETH Zurich USI Campus Via Giuseppe Buffi 13, 6900 Lugano (Switzerland) Fax: (+ 41)586-664-817 E-mail: fgervasi@phys.chem.ethz.ch Homepage: www.rgp.ethz.ch Prof. M. Boero Center for Computational Sciences University of Tsukuba 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8576 (Japan) [**] We acknowledge generous grants from the Earth Simulator Center (ES-JAMSTEC)–Yokohama and from the Swiss National Super- computing Centre(CSCS) which have made this calculation possi- ble. M.B. is grateful to Takashi Ikeda and Masaru Hirata for their valuable help. F.L.G. is grateful to Y. Mantz for his valuable help. Communications 5606 # 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2006, 45, 5606 –5609