Water in Biology | DNA Electron Transport Dynamics |
Macromolecular RecognitionDNA Electron Transport Dynamics*
Charge transfer in supramolecular assemblies of DNA is unique because of the notion that the π-stacked bases within the duplex may mediate the transport, possibly leading to damage and/or repair. The phenomenon of transport through π-stacked arrays over a long distance has an analogy to conduction in molecular electronics, but the mechanism still needs to be determined. To decipher the elementary steps and the mechanism, one has to directly measure the dynamics in real time and in suitably designed, structurally well-characterized DNA assemblies. Since the first report on conductive one-dimensional DNA crystals more than 30 years ago, different methods have been used for the study of conductivity, the latest of which is the measurement of conductance on the mesoscopic scale, which suggests a large band-gap semiconductor behavior. Charge transfer by photoinduced reactions between donors and acceptors has provided a useful methodology for exploring the mechanism in DNA; the donor and acceptor were either noncovalently or covalently bound to DNA. Evidence for long-range oxidative damage was also demonstrated. However, results for different systems have shown different values for the distance range over which the transfer is efficient, in part because of measurements of the yield in most cases.
Although many studies have focused on systems with a tethered hole donor, a careful study of the effects of stacking and distance on charge transfer requires DNA assemblies unperturbed by donor/acceptor probes. At LMS, we study DNA assemblies with the donor and acceptor being nucleic acid bases. These systems are unique because (i) there are only minor structural perturbations arising; (ii) no ambiguities occur with respect to distance separating donors and acceptors; (iii) the assemblies are structurally well defined and well characterized; and (iv) much is known about the steady-state quenching of fluorescence.
The role of dynamic base motions in DNA ET is not fully understood, as it involves a range of timescales and different motions. At LMS, our approach has been to measure the femtosecond dynamics of charge transport processes occurring between bases within duplex DNA. By monitoring the population of an initially excited 2-aminopurine, an isomer of adenine, we can follow the charge transfer process and measure its rate. We then study the effect of different bases next to the donor (acceptor), the base sequence, and the distance dependence between the donor and acceptor. We find that the charge injection to a nearest neighbor base is crucial and the time scale is vastly different: 10 ps for guanine and up to 512 ps for inosine. Depending on the base sequence the transfer can be slowed down or inhibited, and the distance dependence is dramatic over the range of 14 Å. These observations provide the time scale, and the range and efficiency of the transfer.
The time scales show the distinct local and base-mediated dynamics over three bridge bases, and the dependence on the nature of the bases involved. Based on the facts that the rates are on the picosecond time scale, the base-mediated (superexchange-type) process significantly slows down with distance (≈14 Å), the overall rate is controlled by the initial charge injection (even if the transfer between bases is faster), and the efficiency decreases for each step because of dynamical disorder, we conclude that DNA does not exhibit an efficient molecular wire behavior. Long-range transport must occur on a longer time scale and with a different mechanism, possibly by hopping migration.
To further explore the effects of base dynamics, we have examined ET between DNA bases directly as a function of temperature through femtosecond transient absorption spectroscopy. Our investigations employ photoexcited 2-aminopurine (Ap*) as a dual reporter of DNA base dynamics and DNA-mediated ET. Ap undergoes normal Watson-Crick pairing with T and is well stacked. ET reactions between Ap* and nucleotides, as well as Ap* and bases in DNA have been extensively characterized. In DNA, ET between Ap* and G can be distinguished from other modes of quenching by comparing redox-active G-containing duplexes to otherwise identical duplexes in which the G is replaced by inosine (I), an analogue of G that is essentially inactive towards ET with Ap*.
These results show that ultrafast DNA dynamics play a defining role in DNA-mediated ET. This role originates from the fact that base motions occur on the ET timescale. As ET occurs only through DNA assemblies that have a specific, well-coupled alignment of the DNA bases, motions of the DNA bases that lead to these ET-active conformations can serve as a gate for ET reactions, and thus modulate the rate constants and yields of ET.
These results provide compelling experimental evidence that DNA ET cannot be approximated by models designed for more static donor-acceptor assemblies. Fluctuations of DNA bases must be a part of the descriptions of ET dynamics, especially because conformational gating necessarily becomes more important as the DNA bridge is lengthened.
*The text above has been adapted from the following publications.Selected Publications
Ultrafast Unequilibrated Charge Transfer: A New Channel in the Quenching of Fluorescent Biological Probes, C. Wan, T. Xia, H.-C. Becker, A. H. Zewail, Chem. Phys. Lett. 2005, 412, 158.
Ultrafast Dynamics in DNA-Mediated Electron Transfer: Base Gating and the Role of Temperature, M. A. O'Neill, H.-C. Becker, C. Wan, J. K. Barton, A. H. Zewail, Angew. Chem., Int. Ed. 2003, 42, 5896.
Femtosecond Charge Transfer Dynamics of a Modified DNA Base: 2-Aminopurine in Complexes with Nucleotides, T. Fiebig, C. Wan, A. H. Zewail, Chem. Phys. Chem. 2002, 3, 781.
Femtosecond Direct Observation of Charge Transfer between Bases in DNA, C. Wan, T. Fiebig, O. Schiemann, J. K. Barton, A. H. Zewail, Proc. Natl. Acad. Sci. USA 2000, 97, 14052.
