Marked Variations of Dissociation Energy and H-Bond Character of

Dec 10, 2004 - oxidation and the coupling of Li+ to the guanine-cytosine base pair can ... The interaction of the cation Li+ with guanine is attractiv...
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J. Phys. Chem. B 2005, 109, 593-600

593

Marked Variations of Dissociation Energy and H-Bond Character of the Guanine-Cytosine Base Pair Induced by One-Electron Oxidation and Li+ Cation Coupling Lixiang Sun† and Yuxiang Bu*,†,‡ Institute of Theoretical Chemistry, Shandong UniVersity, Jinan, 250100, P. R. China, and Department of Chemistry, Qufu Normal UniVersity, Qufu, 273165, P. R. China ReceiVed: September 6, 2004; In Final Form: October 24, 2004

The variation of dissociation energy and H-bond character of the G-C cation and the Li-GC cation have been investigated by employing density functional theory (B3LYP) with the 6-31+G* basis set. The one-electron oxidation and the coupling of Li+ to the guanine-cytosine base pair can strengthen the interaction between guanine and cytosine. The interaction of the cation Li+ with guanine is attractive and is attributed to the polarization of the H-bonds between G-C that enhances G-C interaction. The cooperativity of the three H-bonds in the GC and Li-GC cations is different from that in the neutral GC base pair. The proton-transfer process between N1 of the guanine and N3 of the cytosine can occur in the GC cation and the Li-GC cation. The geometries of the transition state are out of plane, especially for the transition state of the Li-GC cation. The analysis of the activation energy for the proton-transfer process shows that the GC+ before and after proton transfer can exist simultaneously in the gas phase, but for the Li-GC+ system, the Li-GC+ without proton transfer is the dominating species in the gas phase.

1. Introduction One-electron oxidations in DNA have recently received considerable attention due to their connection with DNA damage caused by ionizing radiation1-5 and oxidation agents.6-8 The electron-transfer reactions of guanine (G) are central to understanding both hole transfer along DNA9-12 and biological damage to nucleic acids.13-16 The one-electron oxidation of DNA causes the oxidation of guanine with the lowest oxidation potential among four DNA bases.17-20 Moreover, initially oxidized radical species on other fragments can migrate to the most easily oxidized nucleobase guanine. Thus, the DNA damage is predicted to be produced at this site.4,21 Various studies suggest a lower oxidation potential of guanine in duplex DNA compared to monomer guanine or guanine in single-strand DNA. As for other factors that control the oneelectron oxidation rate of guanine in duplex DNA, a computational experiment has suggested that the base pairing with cytosine lowers the ionization potential of guanine by about 0.75 eV.22 Moreover, proton-transfer reactions between base pair ion radicals or between base pair ion radicals and surrounding hydrogen-bonded water molecules can be important determinants of ion radical stabilization and migration in DNA.7,23 At pH 7 the neutral oxidized radical (G(-H)•) is formed by deprotonation of N1, as determined by both optical and conductance detection.24

G+• h G(-H)• + H+

(1)

When G+• is formed in a double-stranded DNA, the effect of base pairing is to transfer the proton to N3 of cytosine (C) in the base pair. The pKa of N3-protonated C is slightly higher (pKa ) 4.45) than that of reaction 1.13 The theoretical study suggests that the radical cation of the G-C pair (G:C+•) can * Address correspondence to this author. E-mail: [email protected]. † Shandong University. ‡ Qufu Normal University.

undergo a facile proton shift along its central hydrogen bond.22,25 UB3LYP/D95*//UHF/6-31G* calculations show that the shift of the central hydrogen-bonded proton at N1 of guanine to N3 of cytosine is only slightly endothermic (+1.6 kcal/mol).22 The single proton-transferred structure along its central hydrogen bond in the neutral G-C pair is not a minimum on the PES, but rather a saddle point.26 The proton transfer from G+• to C could be very fast, because it involves the movement of a proton along a preexisting hydrogen bond.27-29 Thus, the formation of G+•:C as an initial product would not be observed in double-stranded DNA, and the initial spectrum obtained immediately after the pulse may be a proton-shifted resonance structure (G+•:C T G(-H)•:C(+H+)).30 Some factors must play an important role in modulating such a process, such as the effect of the water molecules and the interaction with the other base pairs. But in the gas phase, the proton of the C(+H+) is not picked up by a water molecule, so the G+•:C can exist for a long time. Li et al. have reported that the total energy of GC+•PT (here PT means the proton transfer) before ZPE and thermodynamic correction is higher (∆E ) 1.25 kcal/mol) than that of GC+•, the initial structure before proton transfer, and taking zero-point energy and thermodynamic energy corrections into account does not make the overall process favorable.31 Metal cations are known to play an important role in both the stabilization and destabilization of DNA.32 It is well-known that the N7 position of guanine, which is ready accessible in the major groove of duplex DNA and is not involved in Watson-Crick base pairing, is the preferred metal binding site.32-34 Many studies have analyzed the interaction of different metal cations to guanine34-42 and their influence on base pairing.39-48 A few theoretical results have shown that the presence of metal cations interacting at the N7 position of guanine promotes the proton transfer from the N1 of guanine to the N3 acceptor site of cytosine.39,41 Most of the theoretical studies performed on the interaction of metal cations with guanine or the guanine-cytosine base pair

10.1021/jp0459817 CCC: $30.25 © 2005 American Chemical Society Published on Web 12/10/2004

594 J. Phys. Chem. B, Vol. 109, No. 1, 2005 have dealt with alkali, alkaline-earth, or close-shell transitionmetal cations. Only a few studies48,49 have analyzed the interaction of Cu2+, a d9 open-shell cation, with guanine, and its influence on the intermolecular proton-transfer processes of the base pairing. Due to the oxidation character of Cu2+, its interaction with the guanine-cytosine base pair leads to the formation of oxidized guanine, which has been previously shown to favor the proton transfer from N1 to N3 of cytosine.48 Asensio et al.50 have evaluated the cooperative hydrogen bonding in adenine-thymine and guanine-cytosine base pairs. In their article, to obtain an estimate of the energies of the individual H-bonds in each pair, they rotated one of the bases with respect to the other about the axis of each hydrogen bond, in turn, so that the planes of the individual bases become perpendicular to each other. They optimized the geometries of these structures with the constraints that (a) the planes of the bases remain perpendicular to each other and (b) that the angle of the hydrogen bond in which the hydrogen atom is central remains fixed. Their results indicated that the counterpoise corrections corrected cooperativity of guanine-cytosine is -4.32 kcal/mol obtained by the B3LYP/D95** method. Li+ is the simplest alkali metal ion among all groups, so the quantities of the calculation can be accepted, and the complex including the Li+ would be a suitable mode both from experimental and theoretical points of view for us to obtain more helpful insights into the the biological processes that involve metal ions. In this work, we employ DFT theory to aid our understanding of the details of the marked variations of dissociation energy and H-bond character of the guaninecytosine base pair induced by one-electron oxidation and Li+ cation coupling. The changes of the guanine-cytosine structures induced by one-electron oxidation and Li+ cation binding are discussed. The IR vibrational frequencies of each structure are calculated and analyzed to illuminate the changes of the geometries of the guanine-cytosine base pair. The cooperative hydrogen bonding of guanine-cytosine in the GC cation radical and Li-GC+ are investigated. In addition, the proton-transfer process in the GC cation radical and the effect of the interaction between Li+ with the GC base pair on the proton-transfer process are studied. 2. Theoretical Methods Molecular geometries and harmonic vibrational frequencies of the considered structures have been obtained by using the nonlocal hybrid three-parameter B3LYP density functional approach51-53 as implemented in the Gaussian 98 program.54 The B3LYP method is used in this work along with the basis set of 6-31+G* because it shows good accuracy55-58 with comparatively low cost in computational time. Single-point calculations at the B3LYP/6-31+G* geometries have been performed with the B3LYP/6-31++G** method. The openedshell systems are calculated at the unrestricted B3LYP (UB3LYP) method by using the same basis set. To determine the cooperative hydrogen bonding in guaninecytosine, we reoptimized the geometries with the following constraints: (1) the dihedral angle of each base was fixed at its value in the optimized planar base pair and (2) in the perpendicular species, each planar base was kept perpendicular to the each other with the X-H‚‚‚Y angle fixed at its value in the optimized planar base pair (X and Y refer to the heavy atoms in the H-bond). We take the difference between the sum of the individual H-bond energies and the total interaction of the base pairs in their normal coplanar geometries as the cooperative part of the H-bonding interactions.

Sun and Bu

Figure 1. Numbering scheme of GC+ and Li-GC+.

Basis set superposition error has been corrected by using the counterpoise correction.59 The zero-point vibrational energy corrections are only applied for the calculations of the relative energies. All computations were performed for the gas-phase structures, without considering solvent effects, because the influence of the surrounding is likely to be energetically small for proton transfer between hydrogen-bonded stacked DNA bases in duplex DNA.31 Within the DNA stacked bases, the solvent is excluded, and the DNA interior has a relatively low dielectric constant.25,60 3. Results and Discussion 3.1. Equilibrium Geometries. The number scheme of GC+ and Li-GC+ is given in Figure 1. Table 1 lists the lengths of hydrogen bonds during proton transfer involved in GC+ and Li-GC+ hydrogen bonding for the initial structure, the transition structure, and the final proton-transferred structure. First of all, it should be mentioned that the GC and GC+ systems have Cs symmetry, the lowest electronic state being 1A′ for the neutral GC and 2A′′ for the GC+, but the Li-GC+ system has C1 symmetry with a 1A state. From Table 1 we can observe that one-electron ionization from the guanine-cytosine base pair results in the changes in the geometry. The changes are located at the guanine fragment. Mulliken charge and spin density also indicate that the ionization of GC is mainly located at the guanine monomer. The Mulliken charge on guanine fragment is 0.90 and the spin density is 1.00. The spin density surface of the GC+ is drawn in Figure 2. This is not surprising considering that guanine has a lower ionization potential than cytosine.17-20 Since guanine is the monomer that loses the electron, and thus becomes more acid, those hydrogen bonds in which this monomer acts as the proton donor become stronger in the ionized system.61 This implies a shortening of the distance between the two heavy atoms and a lengthening of the H-X bond involved. In contrast, those H-bonds in which guanine acts as the acceptor become weaker. These changes can be observed from Table 1. That is, the N1-N3 and N2-O2 H-bond distances of GC decrease after ionization while the O6N4 distance increases. The structures are both the planar geometries before and after the proton transfer, and the skeleton of each fragment only slightly changed. Initially for GC+, the N-N distance (between N1 on guanine and N3 on cytosine) is 2.872 Å. It shortens to 2.648 Å at the transition state, showing that the two DNA base rings move closer together, and then the distance expands to 2.854 Å after proton transfer. For the optimized neutral geometry (GC), this distance is 2.967 Å before the proton transfer. This motion suggests that the oscillatory motions between base pairs in the DNA duplex may greatly promote proton transfer.31 The frequency analysis for GC+ in its initial state suggests a lowfrequency (113.1 cm-1) vibration mode that changes the N-N distance between cytosine and guanine and may couple to the proton-transfer process. One such oscillation that moves the two ring structures toward and away from each other, thus altering the N-N distance, was found at 89.2 cm-1.31 But according to

Variations of Dissociation Energy and H-Bond Character

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TABLE 1: The Lengths of Hydrogen Bonds in Different GC Derivatives GC GC+ GC+(PT) GC+(TS) Li-GC+ Li-GC+(PT) Li-GC+(TS)

RN1-Hb

RN3-Hb

RN4-Ha

RO6-Ha

RN2-Hc

RO2-Hc

RO6-N4

RN1-N3

RN2-O2

RLi-O6

RLi-N7

1.033 1.056 1.793 1.335 1.048 1.760 1.378

1.935 1.816 1.061 1.314 1.866 1.072 1.262

1.036 1.020 1.046 1.032 1.020 1.052 1.037

1.788 1.986 1.693 1.722 2.007 1.671 1.728

1.024 1.051 1.022 1.034 1.032 1.015 1.020

1.920 1.665 1.941 1.707 1.785 1.977 1.830

2.824 2.999 2.738 2.748 3.026 2.723 2.762

2.967 2.872 2.854 2.648 2.912 2.833 2.641

2.943 2.715 2.954 2.734 2.816 2.987 2.843

1.911 1.881 1.889

2.005 1.968 1.980

Figure 2. The spin density surfaces of GC+ and GC+(PT).

TABLE 2: The Charge Distributions of the GC Base Pair and Its Derivatives GC GC+ GC+(PT) Li-GC+ Li-GC+(PT)

G/G+/Li-G+

C

0.080 0.902

-0.080 0.098

0.900

0.100

G(-H)/Li-G(-H)+ C(+H)+

0.008

0.992

0.147

0.853

Li

0.533 0.510

our calculated results, the mode of the frequency at 89.2 cm-1 is the bending vibration out of plane of the two ring structures. Another obvious change in the structure before and after the proton transfer is the variety of the other two hydrogen bonds: the distance of Hc-O2 is changed from 1.665 Å to 1.941 Å, while at the same time, the hydrogen bond of O6-Ha is shortened from 1.986 Å to 1.693 Å. The N1-N3 and O6-N4 H-bond distances of GC+ decrease after the proton transfer while the N2-O2 distance increases. These changes in the strength of the two hydrogen bonds result in a slight rocking of the base pairs in the ring planes during the transfer of proton, but the geometry of this base pair still holds the plane. For the neutral GC, these two distances are 1.920 and 1.788 Å, respectively, showing that GC+(PT) is closer to GC than GC+. For the Li+-GC system, although the geometries are not the Cs symmetry, the structures are almost planar. The Li+ cation interacts with both the N7 and O6 of guanine; that is, the complex shows a bidentate coordination. However, the metal-ligand distances indicate that the Li+ cation has a larger distance with O6 and N7 in Li-GC+ (Li-O6, 1.911 Å; Li-N7, 2.005 Å), whereas in Li-GC+(PT), these distances are slightly shortened (Li-O6, 1.881 Å; Li-N7, 1.968 Å). This is because the repulsive effect between Li and G(-H) in Li-GC+(PT) is smaller than that between Li and G in Li-GC+. From Table 2, we can deduce that the charge on the G in Li-GC+ is 0.367 e, while in LiGC+(PT) the charge on the G(-H) is -0.363 e, so the Li+ligand distance in Li-GC+(PT) is smaller than that in Li-GC+. With respect to the H-bond distance it can be observed from Table 1 that the binding of the lithium cation induces important changes. The O6-N4 hydrogen bond increases whereas the other two, N1-N3 and N2-O2, decrease, especially for the latter one. Such changes follow the same trend observed for the ionized GC+. The metal cation interaction strengthens those hydrogen bonds in which guanine acts as a proton donor and weakens the one in which it acts as a proton acceptor.48 Similar trends have been observed in previous theoretical studies.43,44 Another obvious change in the structure before and after the proton transfer is the variety of the other two hydrogen bonds: the O6-Ha hydrogen bond shortens from 2.007 Å to 1.671 Å, while

at the same time, the distance of Hc-O2 is changed from 1.785 Å to 1.977 Å. These changes in the strength of the two hydrogen bonds result in a slight rocking of the base pairs in the ring planes during the transfer of proton. This trend is the same as that in the GC+ system. After the proton transfer, the O6 and N1 atoms obtained more negative charge than those in Li-GC+, while the N2 atom only obtained a small negative charge. So the O6-N4 and N1-N3 bonds become shorter relative to those in GC, but the N2-O2 bond becomes longer. 3.2. IR Spectroscopic Character. We have calculated the vibrational frequencies of the several structures using the B3LYP/6-31+G* method. The frequency analysis proves the changes of the geometries. The vibrational frequency of the N4Ha in the neutral GC is 3193.0 cm-1 (IR intensity: 541.6), while the corresponding frequency of this H-bond in the GC+ is 3476.4 cm-1 (IR intensity: 650.5). This indicates that the N4-Ha bond has strengthened in the GC+ relative to that in the neutral GC, so the H-bond of O6‚‚‚Ha is weakened and becomes longer than that in the neutral GC. As for the N1-Hb and N2-Hc bonds, the frequencies are 3251.1 (IR intensity: 1763.4) and 3404.3 cm-1 (IR intensity: 1256.1) in the neutral GC, respectively. In GC+, those frequencies have red-shifted as 2848.8 (IR intensity: 522.0) and 2962.5 cm-1 (IR intensity: 3898.0). This proves that the guanine becomes more acid after losing one electron, thus those hydrogen bonds in which this monomer acts as the proton donor become stronger in the ionized system. Frequency comparison between the GC+ and the GC+(PT) indicates that the frequency of the N4-Ha bond has red-shifted from 3476.4 (IR intensity: 650.5) to 3033.5 cm-1 (IR intensity: 2840.8) and the frequency of the N2-Hc bond has blue-shifted from 2962.5 (IR intensity: 3898.0) to 3452.9 cm-1 (IR intensity: 900.1). This explains that the cytosine becomes more acid and the guanine become less acid after the proton transfer. So the N4Ha bond becomes weaker and the distance between O6-N4 becomes shorter in GC+(PT) than those in GC+, while the N2Hc bond becomes stronger and the distance between N2-O6 becomes longer in GC+(PT) than those in GC+. The vibration frequency of the N3-Hb bond in GC+(PT) is smaller than that in GC+ by 71.7 cm-1, thus the distance of the N1-N3 bond in GC+(PT) is shorter than that in GC+ by 0.02 Å. These analyses have proved the changes of geometry mentioned above. The vibrational frequency of the N4-Ha in Li-GC+ is 3466.1 cm-1 (IR intensity: 742.3), which has been blue-shifted by 273.1 cm-1 relative to that in the neutral GC and is very close to the corresponding frequency (3476.4 cm-1) of this H-bond in the GC+. As the N4-Ha bond has strengthened in Li-GC+ relative to that in neutral GC and is very close to that in GC+, the H-bond of O6‚‚‚Ha is weakened and becomes longer than that in the neutral GC and close to that in the GC+. As for the N1Hb and N2-Hc bonds, in Li-GC+, the frequencies are 3001.7 (IR intensity: 1537.4) and 3265.6 cm-1 (IR intensity: 1656.4), which have been red-shifted by 249.4 and 138.7 cm-1, respectively. This proves that the guanine becomes more acid after binding the Li+ cation, thus those hydrogen bonds in which this monomer acts as the proton donor become stronger.

596 J. Phys. Chem. B, Vol. 109, No. 1, 2005

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Figure 3. The dissociation schemes for several species.

Comparison of the frequencies between Li-GC+ and Li-GC+(PT) indicates that the frequency of the N4-Ha bond has redshifted from 3466.1 (IR intensity: 742.3) to 2926.1 cm-1 (IR intensity: 3197.1) and the frequency of the N2-Hc bond has blue-shifted from 3265.6 (IR intensity: 1656.4) to 3543.1 cm-1 (IR intensity: 533.0). This explains that the cytosine becomes more acid and the guanine becomes less acid after the proton transfer. So the N4-Ha bond becomes weaker and the distance between O6-N4 becomes shorter in Li-GC+(PT) than those in Li-GC+, while the N2-Hc bond becomes stronger and the distance between N2-O6 becomes longer in Li-GC+(PT) than those in Li-GC+. The vibration frequency of the N3-Hb bond in Li-GC+(PT) is 2587.7 cm-1 (IR intensity: 2168.2), which is smaller than (3001.7 cm-1, IR intensity: 1537.4) in Li-GC+ by 414.0 cm-1, thus the distance of the N1-N3 bond in LiGC+(PT) is shorter than that in Li-GC+ by 0.08 Å. These analyses have also proved the changes of geometry mentioned above.

TABLE 3: The Dissociation Energies (kcal/mol) of the GC Base Pair and Its Derivatives GC

GC+

∆E(6-31+G*) 24.75 42.02 ∆E(6-31++G**) 25.21 42.66

GC+(PT) Li-GC+ Li-GC+(PT) 42.05 42.62

31.62 32.02

44.20 45.02

3.3. Ionization Potential and Li+ Binding Energy. Mulliken charges and spin densities indicate that the ionization of GC is mainly localized at the guanine monomer. The spin density surface of GC+ is drawn in Figure 2. The interaction of the guanine with the cytosine decreases the adiabatic ionization potential. Namely, the adiabatic ionization potential of GC is 158.77 kcal/mol obtained by the 6-31++G** basis set, while that of guanine is 176.38 kcal/mol at the same theoretical level. It is not surprised that the formation of three H-bonds between guanine and cytosine makes the geometry of the guanine similar to that of the ionized guanine especially for the part associated with the N2 atom, so the deformation of the guanine resulted

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TABLE 4: Mulliken Atomic Net Charges at O6, N1, and N2 of Guanine and Ha, Hb, Hc, N4, N3, and O2 of Cytosine GC GC+ GC+(PT) Li-GC+ Li-GC+(PT)

O6

N1

N2

Ha

Hb

Hc

N4

N3

O2

-0.57 -0.43 -0.50 -0.61 -0.66

-0.47 -0.42 -0.53 -0.49 -0.58

-0.45 -0.38 -0.40 -0.42 -0.46

0.46 0.51 0.55 0.41 0.49

0.69 0.51 0.52 0.74 0.78

0.47 0.55 0.51 0.49 0.44

-0.51 -0.91 -0.88 -0.47 -0.45

-0.54 -0.59 -0.69 -0.54 -0.44

-0.53 -0.61 -0.54 -0.52 -0.44

from the ionization decreases. A simple thermodynamic cycle shows that the decrease of the ionization potentials of the dimers compared to that of the free monomers is just the increase of the binding energy produced by ionization.61 That is, the lowering of the adiabatic ionization potential of GC compared to G is 17.61 kcal/mol. The binding energy of the Li+ cation to GC is -80.76 kcal/ mol, while the binding energy of the Li atom to GC is -22.84 kcal/mol. The simple thermodynamic cycle shows that the increase of the binding energy produced by ionization is just the decrease of the ionization potential of the dimer compared to that of the free monomer with the lower ionization energy. The adiabatic ionization potential of the Li atom is 129.65 kcal/ mol, while that of Li-GC is 72.46 kcal/mol. That is, the lowering of the adiabatic ionization potential of Li-GC compared to Li is 57.19 kcal/mol. This observation also implies that the local Li ionization is not dominant. 3.4. Dissociation Energy. According to the Mulliken charge population in Table 2, the dissociation schemes for several H-bond complexes are given in Figure 3. GC is dissociated as the neutral guanine and the neutral cytosine, while GC+ is dissociated as the guanine cation and the neutral cytosine, GC+(PT) is dissociated as the guanine(-H) and the cytosine(+H) cation. Similarly, Li-GC+ is dissociated as the Li-G+ cation and the neutral cytosine, and Li-GC+(PT) is dissociated as the neutral Li-G(-H) and the C+(+H) cation. It can be observed from Table 3 that ionization and the binding of Li+ produce a significant increase of the dissociation energy of GC. In addition, a slightly large basis set (6-31++G**) is also employed to calibrate this energy quantity. The results obtained at the B3LYP/6-31++G** level are slightly larger by 0.4-0.8 kcal/ mol than those calculated at the B3LYP/6-31+G* level for the same geometry, indicating a good agreement between them. From Table 3, it can be seen that the one-electron oxidation and the binding of Li+ can increase the interaction between the guanine and the cytosine. The dissociation energies of GC+ and Li-GC+ are larger than that of GC by 17.45 and 6.81 kcal/mol, respectively. Several factors contribute to modify the strength of hydrogen bonds when the metal cation interacts at the N7 and O6 positions of guanine.48 On one hand, the interaction of the cation Li+ with guanine is attractive and originates from the polarization of the H-bonds between G-C that enhances G-C interaction. On the other hand, the charge transfer from guanine to the lithium cation also contributes to the observed changes. To analyze the effect of the electron density of guanine on the interaction changes produced upon lithium cationization and the H-bond character, we present in Table 4 the Mulliken net atomic charge of O6, N1, and N2 of guanine and Ha, Hb, Hc, N4, N3, and O2 of cytosine in GC, GC+, GC+(PT), Li-GC+, and Li-GC+(PT). Comparing the net atomic charges between the neutral GC and Li-GC+, it can be deduced that the polarization of the H-bonds between G-C induced by binding the lithium cation to the GC base pair enhances the G-C interaction. It is not surprised that the injection of one positive charge can strengthen the hydrogen bonds. Maybe we can deduce that the

TABLE 5: The H-Bond Energies in Various Base Pairsa GC+

GC 6-31+G* interaction O‚‚‚Ha-N N‚‚‚Hb-N N-Hc‚‚‚O cooperetivity 6-31++G** interaction O‚‚‚Ha-N N‚‚‚Hb-N N-Hc‚‚‚O cooperetivity

GC+(PT) Li-GC+ Li-GC+(PT)

-24.75 -42.02 -3.52 -8.41 -6.22 -24.85 -11.16 -31.91 -3.85 23.15

-42.05 -31.04 -25.34 -4.97 19.30

-31.62 -5.29 -20.14 -24.17 17.98

-44.20 -32.71 -31.49 -10.15 30.15

-25.21 -42.66 -3.74 -8.48 -6.52 -25.10 -11.36 -32.31 -3.59 23.23

-42.62 -31.30 -25.58 -5.01 19.27

-32.02 -5.38 -20.33 -24.32 18.01

-45.02 -33.15 -32.21 -10.46 30.80

a The interaction energy (kcal/mol) followed by the energies of each H-bond individually and the cooperativity (deviation between the total H-bond energy of the triple H-bond of the species and the sum of three individual H-bond energies).

TABLE 6: H-Bond Distances (Å) for the Planar and Twisted Base Pairs GC

GC+

GC+(PT) Li-GC+ Li-GC+(PT)

O‚‚‚Ha-N planar 1.788 1.986 1.693 twisted 1.926 2.039 1.657 difference 0.138 0.053 -0.036 N‚‚‚Hb-N planar 1.935 1.816 1.793 twisted 2.028 1.895 1.863 difference 0.093 0.079 0.070 N-Hc‚‚‚O planar 1.920 1.665 1.941 twisted 1.883 1.624 2.138 difference -0.037 -0.041 0.197

2.007 2.082 0.075 1.866 1.942 0.076 1.785 1.748 -0.037

1.671 1.640 -0.031 1.760 1.671 -0.089 1.977 2.105 0.128

binding of guanine-cytosine can be strengthened as long as one cation bonds to guanine-cytosine. The energies for H-bonds in base pairs are listed in Table 5, and the H-bond distances (Å) for the planar and twisted base pairs are shown in Table 6. From Table 5, we can see clearly that the cooperativity of the neutral GC is negative, but those of other GC base pair derivatives are positive. Namely, the cooperative effect of three H-bonds is larger than the sum of the three individual bonds in the neutral GC, while in other geometries the cooperative effect of three H-bonds is smaller than the sum of the three individual bonds. Comparing the energies of three H-bonds between the neutral GC and other geometries, respectively, we can deduce that the electron oxidation and the bonding of Li+ can strengthen the H-bonds, especially two of the three bonds. A system with three H-bonds between rigid monomers cannot adjust its intermolecular geometry to simultaneously optimize all three interactions.50 So the molecular geometries do not allow all three H-bonds to simultaneously achieve their optimal interactions. This can be seen from Table 6. Thus, some interactions are sacrificed especially in the GC cation and the GC bounded by Li+, because the difference of the individual H-bond energies is much larger than that in GC. A more detailed comparison of the energies of H-bonds in the base pairs indicates that the interaction of the O‚‚‚Ha-N bond and the N-Hb‚‚‚N bond is a significant contribution to the stability of GC+, while the contribution to the stability of GC+(PT) mainly originates from the interaction of the

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SCHEME 1

TABLE 7: The Energies (kcal/mol) of GC+(TS), GC+(PT), Li-GC+(TS), and Li-GC+(PT) Relative to GC+ and Li-GC+ 6-31+G* 6-31++G**

a

GC+(TS)

GC+(PT)

Li-GC+(TS)

Li-GC+(PT)

5.90 3.20 4.70 2.00

1.25 1.40 1.32 1.47

8.65 6.02 7.39 4.76

6.22 6.12 5.92 5.82

a The data in the second row for each basis set are referred to the ones corrected with zero-point vibration energies.

N-Hb‚‚‚N bond and the N-Hc‚‚‚O bond. This is similar to that in Li-GC+ and Li-GC+(PT). Comparison between the H-bond distance for the neutral GC and GC+ and Li-GC+ shows that the largest difference between the planar H-bond and the twisted H-bond is in the O‚‚‚Ha-N bond in the neutral GC, while in GC+ and Li-GC+, the difference of N-Hb‚‚‚N is the largest. This implies that the N‚‚‚Hb-N bond is significantly compressed in the planar base pair, so the proton-transfer process can occur, while in the neutral GC this process does not take place. 3.5. Proton Transfer. The one-electron oxidation and the binding of Li+ to guanine-cytosine both induce the proton transfer. Scheme 1 shows the single- and double-transfer processes studied in the present work. As already stated, the positively charged monomers have an increased acid character. This implies that those H-bonds in which the charged monomer acts as donor are strengthened, while those in which it acts as acceptor are weakened. This has been indicated with the letters s (strong) and w (weak) in Scheme 1. The GC bonded with the Li+ cation is similar. For the structure before the proton transfer, we have one weak and two neighbor strong H-bonds; that is, a (w-s-s) situation. The proton transfer from N1 to N3 leads to a (s-s-w) situation with two neighbor strong H-bonds, while the others produce the alternated (s-w-s) pattern. It is not surprising that any attempt to localize the energy minimum with the (s-w-s) pattern collapsed to the other structures.61 The geometry optimizations and the calculations of the vibration frequencies are carried out with the B3LYP/6-31+G* method. The geometries of GC+(TS) and Li-GC+(TS) are listed in Table 1. The relative energies of two cation systems are given in Table 7. From Table 1 we can observe that the GC+ and the Li-GC+ structures undergo similar changes during the proton-transfer processes: the G and C rings draw closer together in the transition state and then relax to ring separation distances similar to the starting

configuration. A slight in-plane rocking of the structure during the proton-transfer process is also predicted. It must be mentioned that the stable geometries of the GC cation and GC bounded by Li+ are planar or nearly planar, but the geometries of TS are not in plane, especially for Li-GC+(TS). The side views of Li-GC+(TS) and GC+(TS) are drawn in Figure 4. The dihedral angle N3C2N2Hc of GC+(TS) is 179.9°, which is very close to that of the guanine cation, but has an obvious difference with that (148.7°) in the neutral guanine. In Li-GC+(TS), the dihedral angle N3C2N2Hc (164.0°) is much larger than those in GC+(TS) and in the guanine cation. Different from the situation in GC+(TS), the dihedral angle N3C2N2H2 is 6.8° in Li-GC+(TS), which indicates a considerable pyramidalization of the part centered at N2. The dihedral angle N3C4N4Ha is 8.2° in Li-GC+(TS) and is similar to that (9.3°) in the neutral cytosine. This is because the charge located on the proton Hb is 0.901 positive charge, and the proton Hb does not belong to each of the bases, so the guanine and the cytosine have the characters of their neutral geometries. This phenomenon exists in the GC cation, but is less obvious than that in the Li-GC+ cation. The positive charge on the proton Hb in GC+(TS) is only 0.494 e, very much smaller than that in Li-GC+(TS). Thus, in GC+(TS), the guanine and the cytosine hold the character of the guanine cation and the cytosine cation. From Table 7, we can observe that the shift of the central hydrogen-bonded proton at N1 of guanine to N3 of cytosine is only slightly endothermic (+1.32 kcal/mol) in the GC cation, but in Li+-GC, this process is endothermic by +5.92 kcal/mol. Taking zero-point vibration energy correction into account does not make the overall process favorable, but it can decrease the activation energy for the proton-transfer process. The imaginary negative frequency of GC+(TS) is 1347.7i cm-1, which corre-

Figure 4. Side view of Li-GC+(TS) and GC+(TS).

Variations of Dissociation Energy and H-Bond Character sponds to the vibration mode of the Hb between the N1 of the guanine and the N3 of the cytosine. From GC+ to GC+(PT), it must only surmount the 5.90 kcal/mol calculated at the 6-31+G* basis set level, and in the results obtained with the 6-31++G** basis set it decreases to 4.70 kcal/mol. Since GC+(PT) is higher than GC+ by 1.25 kcal/mol, the transform from GC+(PT) to GC+ has a barrier of 4.65 kcal/mol, and it is only 1.80 kcal/ mol after considering the zero-point vibration energy correction. For the Li-GC cation, the activation energy of the proton-transfer process from Li-GC+ to Li-GC+(PT) is 8.65 kcal/mol, even though considering the correction of the zero-point vibration energy it is also 6.02 kcal/mol, which is larger than that in the GC cation. Thus it is to be expected that the proton dissociation energy (252.8 kcal/mol) of the Li-G+ cation is larger than that (235.1 kcal/mol) of the G+ cation. The results show that the energy barrier of the reverse process is 2.43 (6-31+G*) and 1.47 kcal/mol (6-31++G**). If we consider the effect of the zero-point vibration energy, the barrier decreases to -0.10 kcal/ mol at the B3LYP/6-31+G* level, and it decreases further to -1.06 kcal/mol at the B3LYP/6-31++G** level of theory. Negative activation energy implies the reverse PT is spontaneous. In addition, the reaction is controlled by the zero-point vibration energy. In a word, the GC+ and GC+(PT) can exist a long time in the gas phase, but Li-GC+(PT) can easily transform to Li-GC+ by surmounting a very small barrier, so it does not exist stably in the gas phase. In addition, from Tables 2 and 7 we can deduce that the more positive the charge on the GC base pair, the easier the proton transfer from N1 of the guanine to the N3 of the cytosine and the more stable the structure after proton transfer. So the charge density redistribution induced by the different magnitude of the charge on the GC base pair is the dominant factor on the proton transfer. The formation of GC+ as an initial product would not be observed in doublestranded DNA.30 This is due to the effect of the water molecules. So the bonding of the water molecules can change the stability of the system, and the Li-GC+(PT) may exist stably in the solution. The effect of the bonding of the water molecules should be worthy of further investigation in the future. 4. Conclusion In this article, employing density functional theory with the B3LYP functional and the 6-31+G* basis set, we have successfully optimized the stable structures and have located the transition structures for the proton-transfer processes in the GC cation and the Li-GC cation. The frequencies are calculated to confirm the stable structure and the transition state. The oneelectron oxidation and the binding of Li+ to the guanine-cytosine base pair can strengthen the interaction between guanine and cytosine. The enhanced electrostatic ion-dipole interaction between the Li cation and the dipole moment in C is the dominant factor on the enhancement of the interaction between guanine and cytosine. Maybe we can deduce that the binding of guanine-cytosine can be strengthened as long as one cation bonds to guanine-cytosine. The frequency analyses show that the changes are in accord with the changes of the geometries. The cooperativity of the three H-bonds in the GC and Li-GC cations is different from that in the neutral GC base pair. The proton-transfer process of between N1 of the guanine and N3 of the cytosine can occur in the GC cation and the Li-GC cation. The geometries of the transition state are out-of-plane, especially for the transition state of the Li-GC cation. The reason is that the transferred proton has a large positive charge and does not belong to any of the base moieties, so the guanine and the cytosine have the character of their neutral structures in

J. Phys. Chem. B, Vol. 109, No. 1, 2005 599 geometry. The activation energy for the proton transfer of the guanine-cytosine cation is 2.0-3.2 kcal/mol, while the reverse activation energy is 0.53-1.80 kcal/mol. So the proton transfer process in the guanine-cytosine cation species can occur easily and both geometries can simultaneously exist in the gas phase. For the Li-GC cation, the transformation from Li-GC+ to LiGC+(PT) must surmount a barrier of 4.76-6.02 kcal/mol, while the reverse activation barrier is not positive at the B3LYP level. So for the Li-GC cation, the Li-GC+ is the dominating species in the gas phase. This phenomenon may change in solution. The coupling effect of the water molecules or the other solvent molecules needs further investigation. Acknowledgment. This work is supported by the National Natural Science Foundation of China (20273040), NCET, and the Natural Science Foundation of Shandong Province (Key project). Support from SRFDP and SCF for ROCS and SEM is also acknowledged. References and Notes (1) Sevilla, M. D.; Becker, D.; Yan, M.; Summerfield, S. R J. Phys. Chem. 1991, 95, 3410. (2) Yan, M.; Becker, D.; Summerfield, S. R.; Renke, P.; Sevilla, M. D. J. Phys. Chem. 1992, 96, 1983. (3) Cullis, P. M.; Malone, M. E.; Merson-Davies, L. A. J. Am. Chem. Soc. 1996, 118, 2775. (4) Melvin, T.; Botchway, S. W.; Parker, A. W.; O’Neill, P. O. J. Am. Chem. Soc. 1996, 118, 10031. (5) Angelov, D.; Spassky, A.; Berger, M.; Cadet, J. J. Am. Chem. Soc. 1997, 119, 11373. (6) Johnston, D. H.; Glasgow, K. C.; Thorp, H. H. J. Am. Chem. Soc. 1995, 117, 8933. (7) Steenken, S. Chem. ReV. 1989, 89, 503. (8) Candeias, L. P.; Steenken, S. J. Am. Chem. Soc. 1992, 114, 699. (9) Hall, D. B.; Holmlin, R. E.; Barton, J. K. Nature 1996, 382, 731. (10) Schuster, G. B. Acc. Chem. Res. 2000, 33, 253. (11) Meggers, E.; Michel-Beyerle, M. E.; Giese, B. J. Am. Chem. Soc. 1998, 120, 12950. (12) Lewis, F. D.; Wu, T.; Zhang, Y.; Letsinger, R. L.; Greenfield, S. R.; Wasielewski, M. R. Science 1997, 277, 673. (13) Burrows, C. J.; Muller, J. G. Chem. ReV. 1998, 98, 1109. (14) Steenken, S. Chem. ReV. 1989, 89, 503. (15) Angelov, D.; Spassky, A.; Berger, M.; Cadet, J. J. Am. Chem. Soc. 1997, 119, 11373. (16) Cullis, P. M.; Malone, M. E.; Merson-Davies, L. A. J. Am. Chem. Soc. 1996, 118, 2775. (17) Colson, A. O.; Besler, B.; Sevilla, M. D. J. Phys. Chem. 1993, 97, 8092. (18) Sevilla, M. D.; Besler, B.; Colson, A. O. J. Phys. Chem. 1995, 99, 1060. (19) Seidel, C. A. M.; Snulz, A.; Sauer, H. M. J. Phys. Chem. 1996, 100, 5541. (20) Steenken, S.; Javanovic, S. V. J. Am. Chem. Soc. 1997, 119, 617. (21) Melvin, T.; Botchway, S.; Parker, A. W.; O’Neill, P. J. Chem. Soc., Chem. Commun. 1995, 653. (22) Hutter, M.; Clark, T. J. Am. Chem. Soc. 1996, 118, 7574. (23) Steenken, S.; Telo, J. P.; Novais, H. M.; Caudeias, L. P. J. Am. Chem. Soc. 1992, 114, 4701. (24) Candeias, L. P.; Steenken, S. J. Am. Chem. Soc. 1989, 111, 1094. (25) Colson, A. O.; Besler, B.; Sevilla, M. D. J. Phys. Chem. 1992, 96, 9787. (26) Florian, J.; Leszczynski, J. J. Am. Chem. Soc. 1996, 118, 3010. (27) Steenken, S. Biol. Chem. 1997, 378, 1293. (28) Douhal, A.; Kim, S. K.; Zewail, A. H. Nature 1995, 378, 260. (29) Zewail, A. H. J. Phys. Chem. 1996, 100, 12701. (30) Kobayashi, K.; Tagawa, S. J. Am. Chem. Soc. 2003, 125, 10213. (31) Li, X.; Cai, Z.; Sevilla, M. D. J. Phys. Chem. B 2001, 105, 10115. (32) Lippert, B. Coord. Chem. ReV. 2000, 200-202, 487-516. (33) Martin, R. B. Acc. Chem. ReV. 2000, 200-202, 487. (34) Burda, J. V.; Sponer, J.; Hobza, P. J. Phys. Chem. 1996, 100, 7250. (35) Fonseca Guerra, C.; Bickelhaupt, F. M.; Snijders, J. G.; Baerends, E. J. J. Am. Chem. Soc. 2000, 122, 4117. (36) Russo, N.; Toscano, M.; Grand, A. J. Am. Chem. Soc. 2001, 123, 10272. (37) Petrov, A. S.; Lamm, G.; Pack, G. R. J. Phys. Chem. B 2002, 106, 3294. (38) Cerda, B. A.; Wesdemiotis, C. J. Am. Chem. Soc. 1996, 118, 11884.

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