pubs.acs.org/JPCL
Proton Transfer in Adenine-Thymine Radical Cation Embedded in B-Form DNA Colin Kinz-Thompson and Esther Conwell* Department of Chemistry, University of Rochester, Rochester, New York 14627
ABSTRACT On the basis of pKa measurements, it has been predicted that proton transfer will not occur in the radical cation of the A/T base pair (A: adenine, T: thymine). Testing this prediction, we have performed simulations as a function of time on an A/Toligomer missing one electron, in solution, using the code CP2K. We find that proton transfer occurs rapidly at temperatures below room temperature. We suggest that the difference in behavior of (A/T) 3 þ from that predicted on the basis of pKa measurements is the effect of hydration. Hydration also appears to have effects not previously considered on hole motion in solution. SECTION Biophysical Chemistry
an (A/T)þ base pair (Scheme 1) was judged to be unfavorable.1,3 There is no doubt that Aþ, adenine cation, is a strong acid, but it has been considered that T, thymine, is too weak a base for much protonation to occur. Pulse radiolysis measurements of the transient spectrum of (A/T)- have shown an absorbance change that is attributed to irreversible protonation on the C6 site of thymine.6 However, this is most likely due to a proton or deuteron picked up from solution by the thymine, changing T- to T (Hþ) or T (Dþ).9 There has been no report of PT being observed in (A/T)þ. We report in this Letter that simulations we have carried out for an A/T radical cation in solution have shown PT in (A/T)þ. We suggest that the difference in the behavior of A/T from that predicted in refs 1 and 3 is due to the effects of hydration. We have carried out QM/MM simulations on a 10-mer, A/T duplex of canonical B-DNA that was generated using the AMBER 9 software suite.10 To prepare the system, 18 Naþ counterions, matching the number of phosphates, were placed along the backbone, and the initial structure was equilibrated. Following this minimization, the system was solvated with a truncated octahedron of ∼2000 TIP3P waters such that the edge of the water box is a minimum of 8 Å from any atom in the system. The system was again minimized, restraining the DNA atoms with a 500 kcal mol-1 Å-2 force constant and then minimized once more without restraints on any of the atoms. Five contiguous A/T base pairs (numbers 4 through 8) and their sugar plus backbone atoms were chosen as the quantum system, with one electron removed to introduce a hole. The code used for the simulations was CP2K, which is freely available. It provides a general framework for DFT using a mixed Gaussian and plane waves approach and classical pair and many-body potentials.11
P
rotonation and deprotonation have been greatly studied, theoretically and experimentally, in DNA in single bases, in Watson-Crick base pairs, and in longer sequences. It has been shown experimentally, in agreement with predictions from pKa measurements, that at room temperature proton transfer (PT) takes place in guanine-cytosine (G/C) base pairs charged positively or negatively. In the cation, a hole is captured by the guanine, which has the lowest oxidation potential of the bases, creating Gþ/C. Creation of the hole causes the base pair to become acidic, resulting in PT: the proton in the central hydrogen bond linking G and C moves from its position close to the N1 nitrogen of G to a position close to the N3 nitrogen in C.1-4 The proton-transferred form of the cation may be written G/(Hþ)C. As a result of proton transfer, the anion goes from G/C- to G(N1 -Hþ)-/C(N3 þHþ). PT is important because the chemical properties of the G/C base pair and the dynamic properties, in particular, the motion of the hole or the excess electron, are different in the protontransferred form from the untransferred form.5 Density functional theory (DFT) calculations were in agreement with experiment for the case of an isolated (G/C)- in showing PT to be exothermic by a few kilocalories per mole and a small energetic barrier for the transfer. For (G/C)þ, however, until recently, DFT calculations were in disagreement with experiment, predicting PT to be endothermic by ∼1 kcal/mol, with a significant barrier for the transfer.6 Quite recently the contradiction between theory and experiment was resolved by Kumar and Sevilla.5 They showed, using DFT, that taking into account the first hydration layer in (G/C)þ leads to agreement with experiment. Whether PT occurs in A/T base pairs is also of interest. Sequences with a number of contiguous A/T pairs have been greatly studied since it was found, ∼10 years ago, that a hole injected into such a sequence travels with relatively little attenuation through as many as 16 A/T's.7,8a,b This suggested that such sequences might be used as conductors in a circuit made up of DNA. On the basis of the pKa measurements, PT in
r 2010 American Chemical Society
Received Date: February 17, 2010 Accepted Date: April 6, 2010 Published on Web Date: April 14, 2010
1403
DOI: 10.1021/jz100214h |J. Phys. Chem. Lett. 2010, 1, 1403–1407
pubs.acs.org/JPCL
Scheme 1. Schematic Diagram Showing Predicted Proton Transfer (PT) Reaction in a One-Electron-Oxidized A/T Base Paira
a
Circle shows the locations of the proton in the base pair.
Following the calculations of Mantz et al.,12 in describing the quantum system, we used the Kohn-Sham energy functional expression at the restricted open shell DFT-BeckeLee-Yang-Parr level, ROBLYP,13,14 corrected by applying an empirical self-energy correction as described in ref 15. The remaining energy terms describing the molecular mechanical systems in CP2K are standard.12 We used a double-ς valence basis set with polarization functions. A later check showed that the error in using double-ς rather than triple-ς gave rise to a difference in the N-H and H-O bond lengths that we calculated to be
