Structures and Energetics of the Deprotonated Adenine−Uracil Base

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J. Phys. Chem. B 2008, 112, 3545-3551

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Structures and Energetics of the Deprotonated Adenine-Uracil Base Pair, Including Proton-Transferred Systems Sunghwan Kim, Maria C. Lind, and Henry F. Schaefer III* Center for Computational Chemistry, UniVersity of Georgia, Athens, Georgia 30602 ReceiVed: December 6, 2007

The B3LYP/DZP++ level of theory has been employed to investigate the structures and energetics of the deprotonated adenine-uracil base pairs, (AU-H)-. Formation of the lowest-energy structure, [A(N9)-U](which corresponds to deprotonation at the N9 atom of adenine), through electron attachment to the corresponding neutral is accompanied by proton transfer from the uracil N3 atom to the adenine N1 atom. The driving force for this proton transfer is a significant stabilization from the base pairing in the proton transferred form. Such proton transfer upon electron attachment is also observed for the [A(N6b)-U]- and [A(C2)-U]- anions. Electron attachment to the A-U(N3) radical causes strong lone pair repulsion between the adenine N1 and the uracil N3 atoms, driving the two bases apart. Similarly, lone pair repulsion in the anion A(N6a)-U causes the loss of coplanarity of the two base units. The computed adiabatic electron attachment energies for nine AU-H radicals range from 1.86 to 3.75 eV, implying that the corresponding (AU-H)- anions are strongly bound. Because of the large AEAs of the (AU-H) radicals, the C-H and N-H bond dissociation in the AU- base pair anions requires less energy than the neutral AU base pair. The computed C-H and N-H bond dissociation energies for the AU- anion (i.e., the AU base pair plus one electron) are in the range 1.0-3.2 eV, while those for neutral AU are 4.08 eV or higher.

Introduction Ionizing radiation brings about deleterious biological effects such as mutations, cancer, and apoptosis by altering the DNA sequence in living organisms.1-19 Low-energy electrons with energies below 20 eV, generated by ionizing high-energy radiation, are thought to play an important role in radiationinduced DNA damage, by initiating the formation of various intermediates that can give rise to lethal lesions within DNA strands.1,2,20-34 Boudaiffa, Cloutier, Hunting, Huels, and Sanche1 demonstrated in 2000 that low-energy electrons can generate single- and double-strand breaks in DNA, even if their energies are significantly lower than the ionization threshold of DNA (typically ∼7.5 eV). Recent experimental and theoretical studies28-35 have shown that electrons even with energies of zero or near-zero eV can cause DNA strand breaks. Thus, the interactions of low-energy electrons with DNA components are of great interest. Among the DNA components, the nucleic acid bases (NABs) are thought to be the target of low-energy electrons at an initial step of the radiation-induced DNA damage process.27,36 Thus, many experimental and theoretical attempts have been made to determine the electron affinities of the nucleobases in the gas phase37-46 as well as in aqueous solution.47-58 Although hydration effects in aqueous solution increase the electron affinities of the nucleobases, the corresponding values for the isolated NABs in the gas phase are negative or near zero eV, implying that the low-energy electrons cannot be bound strongly to the NABs in the gas phase. Although the electron affinities of the nucleobases themselves are very small, it is thought that negative charges can be readily developed on the nucleobases within the DNA strands through * To whom correspondence should be addressed. E-mail: [email protected].

dissociative electron attachment (DEA) processes, which give rise to the anions of dehydrogenated nucleobases (that is, the deprotonated nucleobases) as well as other fragment ions. The deprotonated nucleobases have been observed experimentally for all five DNA/RNA bases, namely guanine,59 adenine,59-62 cytosine,62,63 thymine,62-67 and uracil,68-77 and their generation through the DEA process has been shown to be bond- and siteselective.65,66,71 For example, attachment of electrons with energies between 0 and 3 eV to the gas-phase molecules thymine and uracil causes the loss of hydrogen through cleavage of N-H bonds, preferentially over C-H bonds.71 In addition, while 1-eV electrons result in the N1-H bond cleavage of thymine and uracil, the N3-H bond breaking can be induced if the energy of electrons is tuned to 1.8 eV.71 The energetic driving force for formation of the deprotonated nucleobases through the DEA process is thought to be the electron affinities of the dehydrogenated nucleobases, typically larger than 3 eV.61,63,72 Many theoretical studies have been reported on the deprotonated anions of the DNA and RNA bases78-83 as well as those of the DNA base pairs.84,85 In this study, we investigated the structures and energetics of the deprotonated adenine-uracil (AU) base pair (See Figure 1 for the structure of the AU base pair). Although uracil is usually found in RNA, the AU base pair is also of great importance because of the structural similarity of the AU base pair to the adenine-thymine (AT) base pair in DNA. Computational Methods All computations were performed using the Q-Chem 3.0 suite of programs.86 The molecular structures of the deprotonated anions of the AU base pair were optimized using the B3LYP density functional, which is composed of Becke’s threeparameter hybrid exchange functional87 in conjunction with the

10.1021/jp711518n CCC: $40.75 © 2008 American Chemical Society Published on Web 02/28/2008

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Figure 1. Molecular structure of the Watson-Crick adenine-uracil base pair (AU) with atom-numbering scheme.

correlation functional of Lee, Yang, and Parr.88 Double-ζ quality basis sets with polarization and diffuse functions (DZP++) were employed.89-92 An Euler-Maclaurin-Lebedev (75,302) grid, consisting of 75 radial shells and 302 angular points/shell, was employed for the necessary numerical integrations.93 The B3LYP functional with the DZP++ basis sets has been previously reported to yield excellent predictions of the electron affinities of various chemical species.92 The average absolute error for the computed electron affinities, compared to 91 experimentally known electron affinities, was 0.14 eV (0.16 eV after ZPVE corrections). The recently reported structures of the hydrogen-abstracted neutral radical of the AU base pair were used as the starting geometries for the geometry optimizations for the deprotonated anions.94 All optimized structures were confirmed to be true local minima with no imaginary frequencies through vibrational frequency analyses. Results and Discussion The structures of the nine deprotonated AU base pairs have been fully optimized using the geometries of the dehydrogenated AU base pairs as initial geometries. For convenience, the dehydrogenated adenine and uracil radicals are denoted as A-H and U-H, respectively, and the dehydrogenated AU base pair radical is abbreviated as AU-H. The corresponding deprotonated anions are indicated with a negative superscript [i.e., (AH)-, (U-H)-, and (AU-H)-]. The position of dehydrogenation or deprotonation for a given structure is indicated in the parentheses (e.g., A(C2), U(N3), [A(N6a)-U]-, etc.). A. Molecular Structures and Relative Energies. The molecular structures of the nine (AU-H)- anions are displayed in Figures 2 and 3. Their relative energies (Erel) are summarized in Table 1, along with those of the corresponding neutral AU-H radicals.94 Important interatomic distances for (AU-H)- are compared in Table 1 of the Supporting Information with those for the corresponding neutrals. In the DFT study of the neutral AU-H radicals, removal of a hydrogen atom from the adenine N9 and the uracil N1 positions of the AU base pair was predicted to give the two lowest-energy structures [i.e., A(N9)-U and A-U(N1)]. Perhaps surprisingly, the corresponding anions, [A(N9)-U]- and [A-U(N1)]-, are found to be the two lowestlying (AU-H)- anions. The predicted energy difference between these two anions is 2.5 kcal mol-1 after the zero-point vibrational energy (ZPVE) correction. Interestingly, formation of [A(N9)-U]- through electron attachment to A(N9)-U results in proton transfer from the uracil N3 to the adenine N1 atom, whereas such proton transfer does not occur in the formation of [A-U(N1)]-, the second lowest deprotonated structure. As will be discussed later, the driving force for this proton transfer is the strong intermolecular hydrogen bonding in the protontransferred form. Such proton transfer upon electron attachment is also observed for the [A(N6b)-U]- and [A(C2)-U]- anions. Although the A-U(N3) radical is the highest-energy structure among the nine AU-H neutrals, the corresponding anion, [A-U(N3)]-, is the third-lowest-energy structure among the

-

Figure 2. Structures of the (AU-H) anions generated by depro-

tonation from the adenine moiety of the AU base pair. The positions of deprotonation are indicated with red arrows. (AU-H)- anions. The deprotonation from the atom N3 of the uracil moiety causes strong repulsion between the lone pairs on the adenine N1 and uracil N3 atoms and moves the two nitrogen atoms apart from each other (the distance between them is 5.007 Å). Similarly, removal of the H6a atom of adenine causes strong repulsion between the adenine N6 and the uracil O4 atoms, and the coplanarity of the two base units is broken in the resulting anion [A(N6a)-U]-. This anion may be converted into [A(N6b)-U]- through C6-N6 bond rotation, and the lost hydrogen bond between the adenine N-H and uracil CdO groups can be recovered. The molecular structure of the transition state between the [A(N6a)-U]- and [A(N6b)-U]anions for this rotational isomerism is shown in Figure 4, and the rotational barrier is compared with the base pair dissociation energy (DE) of the two anions in Figure 5. While the rotational barrier from [A(N6a)-U]- to [A(N6b)-U]- is predicted to be 19.6 kcal mol-1, the dissociation energy of [A(N6a)-U]- is computed to be 14.3 kcal mol-1, implying that generation of [A(N6a)-U]- is likely to cause dissociation of the base pair rather than recovering the lost hydrogen bond between the bases through the C6-N6 bond rotation. However, the [A(N6a)-U]results in the two bases twisting apart while maintaining the

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Figure 4. Molecular structure of the transition state for rotational isomerism between the [A(N6a)-U]- and [A(N6b)-U]- anions.

Figure 5. Comparison of the rotational barrier between the [A(N6a)U]- and [A(N6b)-U]- anions and their dissociation energies. All energies values are in kcal mol-1, and results in parentheses are ZPVEcorrected.

Figure 3. Structures of the (AU-H)- anions generated by deprotonation from the uracil moiety of the AU base pair. The positions of deprotonation are indicated with red arrows.

TABLE 1: Relative Energies (in kcal mol-1) of the Dehydrogenated AU-H Radicals and Their Respective Anionsa Erel species

neutralsb

anions

A(N9)-U A-U(N1) A-U(N3) A(N6b)-U A(N6a)-U A-U(C6) A(C8)-U A-U(C5) A(C2)-U

0.0 (0.0) 3.2 (2.5) 22.4 (22.3) 7.9 (7.5) 12.2 (11.5) 15.0 (14.8) 18.3 (18.6) 21.4 (21.6) 12.3 (12.6)

0.0 (0.0) 3.6 (3.5) 17.8 (17.0) 18.7 (18.5) 26.6 (24.9) 33.7 (33.8) 44.3 (43.0) 48.6 (48.2) 52.0 (50.8)

a Predictions in parentheses have been corrected for zero-point vibrational energies. Results are presented following the order of the anion energies. b Reference 94.

A(N1)‚‚‚U(H-N3) hydrogen bond, which has shortened by about 0.5 Å, although the N3-H bond of uracil has only lengthened by about 0.1 Å (to 1.133 Å). Comparatively, in the transition state structure, hydrogen transfer is already evident, with the A(N1)‚‚‚U(H-N3) distance being only 1.054 Å and the N3-H bond of uracil having lengthened to 1.869 Å. B. Electron Affinities. Table 2 shows the computed adiabatic electron affinities (AEA), vertical electron affinities (VEA), and vertical detachment energies (VDE) for the AU-H radicals

along with those for the corresponding A-H and U-H radicals, evaluated using the following definitions:

AEA ) E(optimized neutral) - E(optimized anion) VDE ) E(neutral at anion geometry) - E(optimized anion) VEA ) E(optimized neutral) E(anion at neutral geometry) The ZPVE-corrected AEAs for adenine and uracil are -0.30 and 0.24 eV, respectively, implying that while the anion of adenine is not bound, that of uracil is slightly bound. The base pairing of uracil with adenine increases the AEA of the AU base pair to 0.40 eV. Removal of a hydrogen atom from the AU pair makes the AEAs of the resulting radicals much greater, compared to that of the AU pair, indicating that the (AU-H)anions are very strongly bound. The lowest AEA was predicted for the A(C2)-U radical (1.86 eV), and the highest, for the A(N3)-U radical (3.75 eV). All nitrogen-centered radicals show higher AEAs, compared to the carbon-centered radicals. This of course is consistent with greater electronegativity of nitrogen. For all nine radicals, positive values of the VEAs and VDEs were predicted. The VEAs were predicted to range from 0.31 to 3.21 eV, and the VDEs were computed to be in the range between 2.89 and 4.37 eV. Figure 6 shows two possible pathways for generating the AU-H radical from the A-H radical. The change in the AEA upon formation of the AU-H radical (from the A-H radical through base pairing with uracil) is equivalent to the difference in the base pair dissociation energy between the AU-H radical and its corresponding anion, (AU-H)-. As will be discussed later in more detail, the changes in base pair dissociation energies upon electron attachment to the AU-H radicals range

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TABLE 2: Adiabatic Electron Affinity (AEA), Vertical Electron Affinity (VEA), and Vertical Detachment Energy (VDE) for the Dehydrogenated AU-H Radicals and the Corresponding A-H or U-H Radicals, in eVa

a

structure

AEA

VEA

VDE

structure

AEA

VEA

VDE

adenine (A) uracil (U) A-U A(N9)-U A-U(N1) A-U(N3) A(N6b)-U A(N6a)-U A-U(C6) A(C8)-U A-U(C5) A(C2)-U

-0.39 (-0.30) 0.12 (0.24) 0.25 (0.40) 3.50 (3.52) 3.49 (3.47) 3.70 (3.75) 3.04 (3.04) 2.88 (2.94) 2.69 (2.69) 2.38 (2.46) 2.32 (2.36) 1.78 (1.86)

-0.43 -0.28 -0.05 2.86 3.21 2.30 2.46 2.54 2.05 1.84 1.79 0.31

-0.30 0.76 0.96 4.37 3.74 4.20 3.99 3.21 3.35 2.97 2.89 3.44

A(N9) U(N1) U(N3) A(N6b) A(N6a) U(C6) A(C8) U(C5) A(C2)

3.26 (3.23) 3.48 (3.46) 3.80 (3.76) 2.55 (2.55) 2.58 (2.57) 2.68 (2.67) 2.38 (2.40) 2.31 (2.34) 0.90 (0.97)

2.96 3.32 3.26 2.45 2.48 2.15 1.88 1.90 0.16

3.61 3.61 3.99 2.64 2.67 3.22 2.89 2.74 1.73

Numbers in parentheses are ZPVE-corrected values.

TABLE 3: Sum of Natural Atomic Charges (NPAs) (in e-) of the Adenine and Uracil Moieties (qA and qU) in the Dehydrogenated AU-H Base Pairs and the Corresponding Anions, (AU-H)- a (AU-H)*-

AU-H neutral/anion pair A(N9)-U/[A(N9)-U]-

A-U(N1)/[A-U(N1)]A-U(N3)/[A-U(N3)]A(N6b)-U/[A(N6b)-U]A(N6a)-U/[A(N6a)-U]A-U(C6)/[A-U(C6)]A(C8)-U/[A(C8)-U]A-U(C5)/[A-U(C5)]A(C2)-U/[A(C2)-U]-

(AU-H)-

qA

qU

qA

qU

qA

qU

0.0116 0.0488 0.3601 0.0385 0.0240 0.0468 0.0336 0.0496 0.0113

-0.0116 -0.0488 -0.3601 -0.0385 -0.0240 -0.0468 -0.0336 -0.0496 -0.0113

-0.9487 (-0.9603) 0.0094 (-0.0394) -0.0914 (-0.4515) -0.9279 (-0.9664) -0.9535 (-0.9775) 0.0065 (-0.0403) -0.9372 (-0.9708) 0.0078 (-0.0418) -0.7713 (-0.7826)

-0.0513 (-0.0397) -1.0094 (-0.9606) -0.9086 (-0.5485) -0.0721 (-0.0336) -0.0465 (-0.0225) -1.0065 (-0.9597) -0.0628 (-0.0292) -1.0078 (-0.9582) -0.2287 (-0.2174)

-0.6092 (-0.6208) -0.0561 (-0.1049) -0.0571 (-0.4172) -0.5676 (-0.6061) -0.8384 (-0.8624) -0.0537 (-0.1005) -0.8740 (-0.9076) -0.0574 (-0.1070) -0.5826 (-0.5939)

-0.3908 (-0.3792) -0.9439 (-0.8951) -0.9429 (-0.5828) -0.4324 (-0.3939) -0.1616 (-0.1376) -0.9463 (-0.8995) -0.1260 (-0.0924) -0.9426 (-0.8930) -0.4174 (-0.4061)

a Note that (AU-H)*- represents the transient anionic state generated upon the vertical electron attachment to the corresponding neutral (that is, at the optimized geometry of the neutral). Results in parentheses are the changes in qA or qU upon electron attachment, compared to the corresponding neutrals.

Figure 6. Two possible pathways for generating the [(A-H):U]radical from the dehydrogenated adenine (A-H) radical.

from 0 to 11 kcal mol-1 (that is, from 0 to 0.5 eV) in general, while the AEAs of the A-H and U-H are typically in the range between 2.3 and 3.8 eV. Therefore, it is the AEAs of the isolated A-H and U-H radicals that mainly contribute to the large AEAs of the AU-H radicals, and effects of base pairing on the AEAs of the AU-H radical can be considered as minor. The only exception is the A(C2)-U radical, in which the base pairing almost doubles the AEA of A(C2)-U [from 0.97 to 1.86 eV, compared to the A(C2) radical]. Another important observation is that the base pairing in the AU-H radicals almost always increases their AEAs, compared to the corresponding A-H or U-H radicals, because the (AU-H)- anions have larger dissociation energies than the corresponding neutrals in general [except for the A-U(N3) radical]. C. Natural Population Analyses. Table 3 shows the summary of natural population analysis (NPA) charges95 of the AU-H radicals and the corresponding anions, (AU-H)-. Note that the species designated as (AU-H)*- in Table 3 correspond to transient anion structures generated from the vertical electron

Figure 7. Two potential pathways to generate proton-transferred (AUH)- anions. A and U denote the canonical structures of adenine and uracil, respectively, while A′ and U′ indicate their noncanonical tautomeric forms found in the proton-transferred (AU-H)- anions. Note that the base pair dissociation energy can be defined in two ways (DE and DE′).

attachment process to the neutral AU-H radicals. That is, the atomic charges of (AU-H)*- were evaluated from the singlepoint energy computation at the corresponding neutral AU-H geometries. As one can see in Table 3, for all neutral AU-H radicals, the uracil moiety is slightly negatively charged and the adenine moiety is slightly positively charged. For example, the sum of the NPA charges on the uracil moiety (qU) of the A(N9)-U radical is -0.012 e- while that for the adenine moiety (qA) is 0.012 e- (see Figure 1 in Supporting Information). The A-U(N3) radical shows the biggest charge separation (e.g., qU ) -0.360 e-), indicating significant transfer of electron density from the adenine to uracil moiety, as pointed out in an earlier study on the AU-H radical. As implied in the qA and qU values for (AU-H)*-, the excess electron upon vertical electron attachment to the AU-H radical is trapped on the base unit where the hydrogen atom is removed. This is because that the A-H and U-H radicals have much larger vertical electron affinities than the intact adenine and

Structures/Energetics of the A-U Base Pair

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TABLE 4: Base Pair Dissociation Energies (in kcal mol-1) for the AU-H Radicals and the Corresponding (AU-H)Anions and the Alternative Dissociation Energies (DE′) and Proton-Transfer Energies (EPT) for the Hydrogen-Transferred AU-H Anions neutrals

anions

species

DEa

DE

A-U A(N9)-U A-U(N1) A-U(N3) A(N6b)-U A(N6a)-U A-U(C6) A(C8)-U A-U(C5) A(C2)-U

13.8 (12.7) 15.0 (13.7) 13.4 (12.3) 15.4 (12.9) 9.8 (8.9) 6.5 (5.9) 14.2 (13.1) 13.8 (12.6) 14.1 (13.0) 12.3 (11.0)

16.9 (16.4) 21.9 (20.8) 13.6 (12.7) 13.1 (12.5) 21.0 (20.2) 13.4 (14.3) 14.5 (13.5) 13.8 (14.0) 14.5 (13.4) 32.5 (31.7)

a

DE′

EPT

49.3 (47.7)

27.4 (26.9)

30.9 (29.6)

9.9 (9.4)

30.0 (29.0)

-2.5 (-2.7)

Reference 91.

uracil bases, as shown in Table 2. However, in the (AU-H)anions at the potential energy minima, the excess electron is not necessarily localized on the same unit as in the corresponding (AU-H)*- structure. As mentioned above, for [A(N9)U]-, [A(N6b)-U]-, and [A(C2)-U]-, geometrical relaxation from (AU-H)*- to (AU-H)- along the potential energy surfaces causes proton transfer from the uracil to adenine unit. Figure 1 of the Supporting Information depicts the two-step process of electron attachment to A(N9)-U to form [A(N9)U]- through [A(N9)-U]*-. Vertical electron attachment to A(N9)-U results in the transient species, [A(N9)-U]*-, where the excess electron is captured on the adenine part (qA ) -0.9487 e-). Subsequent geometrical relaxation from [A(N9)U]*- to [A(N9)-U]- causes proton transfer from the uracil to adenine, accompanied with negative charge transfer from adenine to uracil. The qA and qU values of [A(N9)-U]- are -0.621 and -0.379 e-, respectively, implying that the excess electron is delocalized on both base units. For the other two proton-transferred anions, [A(N6b)-U]- and [A(C2)-U]-, the excess electron is delocalized on the two base units. D. Base Pair Dissociation Energies (DE). Due to the electron affinities of the A-H and U-H radicals, which are much larger than those of the intact adenine and uracil, the excess electron upon electron attachment to AU-H is mainly captured on the base unit where a hydrogen atom is removed, unless proton transfer has occurred. Therefore, the base pair dissociation energies (DE) (i.e., the deprotonated base pair dissociating into one unaltered base and one deprotonated base by breaking the hydrogen bonds) for nonproton-transferred systems can be evaluated using the following definitions:

DE ) E[(A-H)-] + E(U) E[(AU-H)-] deprotonation from adenine and

DE ) E(A) + E[(U-H)-] E[(AU-H)-] deprotonation from uracil Table 4 lists the computed values of DE for the nine (AUH)- anions. The smallest DE (12.5 kcal mol-1) is predicted for the [A-U(N3)]- anion, and the largest (31.7 kcal mol-1), for [A(C2)-U]-. As mentioned previously, the changes in DE between AU-H and (AU-H)- are relatively smaller than the AEAs of the A-H and U-H radicals. However, the DE of

[A(C2)-U]- is much larger than that of A(C2)-U, by 20.7 kcal mol-1, and this amount is almost comparable to the AEA of the A(C2) radical. Therefore, the contribution of the base pairing to the AEA of the A(C2)-U radical is substantial. In general, the DEs for the (AU-H) radicals are larger than those for the corresponding neutrals, resulting in the increased AEA of the AU-H radicals (compared to the isolated A-H and U-H radicals). In other words, the (A-H)- and (U-H)- anions can interact with the neutral base counterparts (U and A, respectively) more strongly than do the corresponding neutrals (A-H and U-H). Note that electron attachment to the AU-H radical may cause proton transfer from the uracil N3 atom to the adenine N1 atom, resulting in negative charge transfer from the adenine to the uracil units (e.g., [A(N9)-U]-, [A(N6b)-U]-, and [A(C2)U]-). Therefore, for these proton-transferred (AU-H)- anions, we may define two different dissociation energies as depicted in Figure 7. The DE is the energy required for dissociation into the same species as does the corresponding neutral (AU-H) radical. On the other hand, the alternative dissociation energy (DE′) is the energy required for dissociation into their protontransferred components. For example

DE ) E[A(N9)]- + E(U) - E[(A(N9)-U]whereas

DE′ ) E[A′] + E[U(N3)]- - E[A(N9)-U]where A′ is an adenine tautomer that lost a proton at the N9 site but gained the N3 proton of uracil. The predicted values of DE′ for the three proton-transferred anions are compared with the analogous DE values in Table 4, along with the energies of proton transfer between the isolated base components (EPT), evaluated using the following equations:

(A-H)- + U f A′ + (U′-H)EPT ) E(A′) + E[(U′-H)-] - E[(A-H)-] - E(U) where A and U indicate the canonical tautomers for the adenine and uracil bases, respectively, and A′ and U′ denote their noncanonical tautomers found in the proton-transferred (AUH)- anion, respectively. While the ZPVE-corrected DE value for the [A(N9)-U]anion is 20.8 kcal mol-1, its DE′ value is 47.7 kcal mol-1. It should be noted that the EPT (PT ) proton transferred) between the isolated base components of the [A(N9)-U]- base pair is 26.9 kcal mol-1, implying that this proton transfer is not favorable without the energy lowering due to the base pairing. In other words, the base pairing provides sufficient stabilization to compensate for the energy increase due to the proton transfer. Such stabilization arises from the fact that both N6-H6a and N1-H hydrogen atoms of the proton-transferred adenine unit in the [A(N9)-U]- anion act as hydrogen bond donors, which withdraw negative charge density developed on the uracil moiety. Similarly, the proton transfer in the [A(N6b)-U]- anion is also facilitated by strong stabilization of the base pairing. E. Proton Affinities and Bond Dissociation Energies. The proton affinity (PA) for a given (AU-H)- anion was estimated using the following equation:

PA ) E[(AU-H)-] + E(H+) - E(AU) ) E[(AU-H)-] - E(AU)

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TABLE 5: Proton Affinities in eV for the Different (AU-H)- Anion Structures species

proton affinity

A(N9)-U A-U(N1) A-U(N3) A(N6b)-U A(N6a)-U A-U(C6) A(C8)-U A-U(C5) A(C2)-U

14.6 (14.2) 14.8 (14.4) 15.4 (15.0) 15.4 (15.0) 15.8 (15.3) 16.1 (15.7) 16.5 (16.1) 16.7 (16.3) 16.9 (16.4)

TABLE 6: C-H and N-H Bond Dissociation Energies (BDE) in eV for the AU-H Radicals and the (AU-H)Anions (ZPVE-Corrected Values in Parentheses) radicals A(N9)-U A-U(N1) A-U(N3) A(N6b)-U A(N6a)-U A-U(C6) A(C8)-U A-U(C5) A(C2)-U

BDE

anions

BDE

4.44 (4.08) 4.58 (4.19) 5.42 (5.04) 4.79 (4.40) 4.97 (4.58) 5.09 (4.72) 5.24 (4.88) 5.37 (5.01) 4.98 (4.62)

[A(N9)-U]-

1.2 (1.0) 1.4 (1.1) 2.0 (1.7) 2.0 (1.8) 2.4 (2.0) 2.7 (2.4) 3.1 (2.8) 3.3 (3.1) 3.5 (3.2)

[A-U(N1)][A-U(N3)][A(N6b)-U][A(N6a)-U][A-U(C6)][A(C8)-U][A-U(C5)][A(C2)-U]-

Because the E(AU) term in the above equation is common for all nine (AU-H)- anions, the relative energies of the (AUH)- anions determine the relative order of their PAs. Therefore, as listed in Table 5, the smallest PA (14.2 eV) was predicted for the lowest-energy anion structure, [A(N9)-U]-, and the largest (16.4 eV) for [A(C2)-U]-. The computed PAs for the (AU-H)- anions are consistent with the fact that an N-H hydrogen is generally more acidic than a C-H hydrogen. The bond dissociation energy (BDE), required to generate a specific (AU-H)- anion from the AU- base pair anion through homolytic breakage of the corresponding N-H or C-H bond, was defined as

BDE ) E[(AU-H)-] + E(H•) - E(AU-) Again, it is the relative energy of the resulting (AU-H)- anion that determines the relative order of the BDE of the N-H or C-H bond in the AU- base pair. The computed BDEs are listed in Table 6, along with those for the corresponding neutrals. The values of the BDEs for the anions, which are smaller than those for the neutrals, imply that the cleavage of N-H and C-H bonds in the AU- anion is much easier than in the neutral AU base pair. Figure 8 shows three potential pathways for generating the (AU-H)- radical from the AU- base pair: (1) direct deprotonation from the AU base pair; (2) generation of the AU-H radical through hydrogen abstraction, followed by electron attachment; (3) electron attachment to AU and subsequent loss of a hydrogen atom. The direct deprotonation pathway requires the largest energy among the three pathways because the proton affinity of the (AU-H)- anion is larger than 14 eV, as shown in Table 5. For the second pathway, while the initial N-H or C-H bond dissociation requires energies ranging between 4.0 and 5.0 eV (which correspond to the BDEs for the neutral AU base pair), the subsequent electron attachment is energetically favorable because both the VEA and AEA are positive for the resulting (AU-H) radicals. On the other hand, the third pathway does not require much energy (compared to the other two pathways) because the formation of the AU- anion from the AU base pair is energetically favorable (due to the positive EAs)

Figure 8. Three possible pathways for generating (AU-H)- radicals from the AU base pair.

and because the BDEs for the N-H and C-H bonds in the AU- anion are smaller than those for the neutral AU base pair. Concluding Remarks The molecular structures and properties of the deprotonated (AU-H)- anions of the AU base pair have been investigated at the B3LYP/DZP++ level of theory. For the lowest-energy anion, [A(N9)-U]-, proton transfer occurs from the uracil N3 atom to the adenine N1 atom, accompanied by negative charge transfer from the adenine to the uracil unit. This proton transfer was also observed for the [A(N6b)-U]- and [A(C2)-U]anions. The driving force for this proton transfer is the strong base pairing interaction in the proton-transferred forms. Electron attachment to the A(N6a)-U radical causes strong lone pair repulsion between the adenine N1 atom and the uracil N3 atom, driving the two bases apart. Similarly, lone pair repulsion in the A-U(N3)- anion causes the loss of coplanarity of the two base unit. The electron affinities of the AU-H radicals were predicted to be much higher than that of the intact AU base pair. While the predicted AEA of the intact AU base pair is only 0.40 eV, those of the AU-H radicals range from 1.86 to 3.75 eV, implying that the deprotonated anions (AU-H)- are strongly bound. The VEAs of the various AU-H radicals range from 0.31 to 3.21 eV, and the VDEs, from 2.89 and 4.37 eV. The higher VDEs of the (AU-H)- anions result in the decrease in the N-H and C-H bond dissociation energies of the anionic AU- base pair, compared to the neutral AU base pair. This indicates that low-energy electron attachment to the AU base pair can easily cause the loss of a hydrogen atom. In particular, formation of nonplanar-type anions, such as [A(N6a)-U]- and [A-U(N3)]-, may cause significant torsion in double-stranded DNA helical structures. Acknowledgment. This work was supported by National Science Foundation Grant CHE-0451445. Supporting Information Available: A table of interatomic distances for the AU base pair anion and its deprotonated radicals, a figure showing changes in atomic charges upon formation of [A(N9)-U]- through electron attachment to A(N9)-U, and a full author list for ref 86. This material is available free of charge via the Internet at http://pubs.acs.org. References and Notes (1) Boudaiffa, B.; Cloutier, P.; Hunting, D.; Huels, M. A.; Sanche, L. Science 2000, 287, 1658. (2) Michael, B. D.; O’Neill, P. Science 2000, 287, 1603. (3) Carter, K. N.; Greenberg, M. M. J. Am. Chem. Soc. 2003, 125, 13376.

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