Coupling characteristics and proton transfer mechanisms

of guanine–NaC monohydrate

Fangfang Liu a, Peng Qian b, Shihai Yan b, Yuxiang Bu a,b,*

a Department of Chemistry, Qufu Normal University, Qufu, 273165, People’s Republic of Chinab Institute of Theoretical Chemistry, Shandong University, Jinan, 250100, People’s Republic of China

Received 4 August 2005; received in revised form 17 November 2005; accepted 30 November 2005

Available online 2 February 2006

Abstract

The coupling characteristics and the proton transfer mechanisms of guanine–NaC monohydrate are determined in this investigation after the

implementation of the geometry optimization and the harmonic vibrational frequency calculations. There are two elementary coupling modes: the

interaction of monohydrated sodium ion with two heteroatoms which form a ringed coupling, and hydrogen-bond involved coupling mode. Two

potential reaction pathways, coupling mode and hydration have been taken into account, and the accurate values of binding energy are corrected

for basis set superposition error (BSSE) and zero-point vibrational energy (ZPVE). Relative energies of the hydrated guanine–sodium ion

complexes indicate that the ringed-coupling complexes are predominant geometries with much lower energies. Monohydrated sodium ion

coupling with O6 and N7 generates the most stable geometry with a five-member cycle. Sodium ion plays an important role in the tautomerization

for guanine–sodium ion complexes. This investigation indicates that the stable cation-p complexes cannot be optimized for guanine–sodium ion

monohydrate. Amino-involved coupling often gives rise to a twisted four-membered cycle with unrealistic distribution of positive charge and

higher energies. The rotation of amino group is likely to lead to the redistribution of the base pair hydration bonding. Effective distribution of the

positive charge is an important factor in the stabilization of biological systems and binding energies for the monohydrated guanine–sodium ion

complexes. The enolic coupling complex has the higher energy than the keto type due to the hindrance for the positive charge.

q 2006 Elsevier B.V. All rights reserved.

Keywords: Guanine–NaC monohydrate; Density functional theory (DFT); Binding energy; Coupling mode; Cation-p complexes; Proton transfer

1. Introduction

The potential of some metals to interrupt DNA replication

processes has been related to the ability of metals to stabilize

tautomers of the DNA bases that are incompatible with the

formation of Watson–Crick [1] base pairs and double helixes

[2–4]. Recently, it has already become the interesting research

topic of the related realms, such as molecular biology, genetics

and the chemistry biology, etc. As the range of research

expanding continuously, the different subject interests us

obviously. The conformational behavior and function of

DNA are often influenced by the presence of metal ions

[5–10]. In fact, cation–base interactions are involved in many

important biophysical processes such as the stabilization of

0166-1280/$ - see front matter q 2006 Elsevier B.V. All rights reserved.

doi:10.1016/j.theochem.2005.11.033

* Corresponding author. Address: Institute of Theoretical Chemistry,

Shandong University, Jinan, Province 250100, China. Tel.: C86 531

8365740; fax: C86 531 8564464.

E-mail address: byx@sdu.edu.cn (Y. Bu).

DNA triple and quadruple, helices and stabilization of the

ribose–base stacking in z-DNA [11,12]. Certain metals or

metal ions could stabilize the tautomerization of base to

obstruct the DNA replication processes. Therefore, the

research of the DNA and metal ions interaction would not

only help understand the essence of its coupling, but also have

certain important meaning for the control and treatment of the

diseases from the molecular level.

The alkali metals (LiC, NaC, KC) are abundant and

important inside the living creature; they have a low tendency

to form covalent bonds, so they should be considered

nonspecific binders. They interact mostly with phosphate

groups, neutralizing the negative charge to stabilize a double

helix structure, but their interactions with bases, rather than

phosphate groups, also neutralize the negative charges on the

phosphate in a zwitterions effect to a certain extent [13].

Additionally, the alkali metal ions have an inhibitory effect on

the chain initiation process by RNA polymerases which may in

turn alter the extent and fidelity of the RNA synthesis [14,15].

Several previous experimental [16,17] and theoretical

[16–28] works are devoting to the gas–phase interaction of

Journal of Molecular Structure: THEOCHEM 760 (2006) 209–217

www.elsevier.com/locate/theochem

F. Liu et al. / Journal of Molecular Structure: THEOCHEM 760 (2006) 209–217210

alkali metals with nucleic acid bases. The interaction of a

specific alkali metal ion with a nucleic acid (NA) is controlled

by the bond strength between the metal ion and the possible

donor centers on the bases. The known sites for cation

coordination are mainly the N7, N9 and O6 atoms of guanine.

The existence of metal-N7 binding in guanine has been

confirmed by various spectroscopic methods [29–35] obtained

by Marzilli [32], Egli [33], Takahara [34], and MC Fail-Isom

[35], etc. and in some cases essentially divalent cations are

involved. Spckava [36,37] researched the same circumstance

using empirical methods. In most recent experimental and

theoretical investigation, Rodgers and Armentrout [16]

reported an exhaustive study on the LiC, NaC and KC

interactions with uracil, thymine, and adenine, and compared

their experimental and MP2 binding enthalpies with those

obtained by Cerda and Wesdemiotis [26], with the adjustment

on the basis of some considerations concerning the limitations

on the absolute accuracy of the metal affinity values. Russo

[38] reported the coupling of five kinds of basic base with

sodium and potassium alkali metal ions, computed the metal

ion affinity, and found the preponderant geometries under their

experimental conditions.

A more thorough theoretical investigation is presented in

this work. Two potential reaction paths, coupling modes, and

hydration have been taken into account, considering the effect

of the participations of the hydrogen bond and amino group.

The proton transfer phenomenon occurs in the process from

keto form to the enolic one, and the preponderant geometries

are also considered.

2. Computational details

The density functional method adopted here is B3LYP, i.e.

Becke’s three-parameter hybrid functional [39] using the Lee–

Yang–Parr [40,41] correlation function. The geometries of the

minima and the transition structures are located using standard

6-311CG* basis set, which includes diffuse and polarization

functions on both heavy and hydrogen atoms.

To evaluate the basis set superposition error (BSSE) [42]

produced in the calculations of the interaction energies; the

Boys-Bernardi’s counterpoise technique has been employed.

The calculations are performed using the following general

scheme.

DEBSSE ZDEcomplexK½EcomplexðAÞ CEcomplexðBÞ�C ðEA CEBÞ

where DEBSSE denotes the interaction energy taking into

consideration BSSE. DEcomplex, the interaction energy value

without consideration of BSSE (calculated as the difference

between the energy of complex and the sum of energies of the

isolated submits A and B). Ecomplex(A) and Ecomplex(B) are the

energy values of the complexes on the assumption that the

orbitals of molecules A and B are the so-called ‘ghost’ orbitals.

EA and EB refer to the energy values of A and B monomers,

respectively.

Two potential reaction pathways have been taken into

account as follows

GCNaCðH2OÞ/G/NaCðH2OÞ (1)

G/NaCCH2O/G/NaCðH2OÞ (2)

where G denotes the guanine molecule. The first process is the

reaction occurring between G and NaC (H2O); EB refers to the

binding energy.

EB ZKðETðG/NaCðH2OÞÞKETðGÞKETðNaCðH2OÞÞÞ

The second process is the hydration reaction of G–NaC, and

EH is the hydration energy.

EH ZKðETðG/NaCðH2OÞÞKETðG/NaCÞKETðH2OÞÞ

To obtain the true energy, a zero-point vibrational energy

correction (ZPVE) was added to the total energy. All of the

computations were performed using the GAUSSIAN 03 program

[43] and the SCF convergence criteria Tight was used

throughout.

3. Results and discussion

3.1. Geometries and stability of guanine and G–NaC

complexes

As displayed in Fig. 1, five kinds of isomer of guanine and

the corresponding guanine–NaC coupling complexes have

been investigated, as well as the tautomerization due to the

resonance of N7 and N9 atoms and the interconversion

between keto and enolic forms. Though G5–NaC bond

would be improbable in DNA for the guanine is binding to

deoxyribose at site N9, we just only consider all the possible

cases theoretically and the practicalities would be verified in

the experiments.

It can be seen from the energies reported in Table 1 that the

most stable tautomeric form of guanine is G1, followed by G2

by 0.4 kcal/mol and G3 by 3.7 kcal/mol. The enolic guanine

tautomers G4 and G5 are higher by 4.61 and 6.4 kcal/mol than

G1, respectively. It is agreement with the results of Russo that

the energy of the enolic form is higher than keto form, though

some differences exist by the reason of different basis sets.

Therefore, these results suggest that it is endothermic for the

reaction proceeding from the keto form to the enolic one, and

according to the base mate principia, the formation of the

enolic form is unfavorable for the combination between

guanine and cytosine.

The binding of metal ions to DNA bases is known to affect

the relative stabilities of keto and enolic isomers, and the

attachment site of NaC ion is also playing an important role. To

determine the position of the NaC ion in the guanine–NaC

complex, several initial geometries were investigated. The

NaC ion bridging the N7 and O6 positions, the NaC ion

bridging the N3 and N9 positions, and the NaC ion bridging the

N1 and O6 positions are considered. Though the situation of

the cation-p coupling complex has been taken into account,

this coupling mode has not been optimized. This proves that

NaC ion cannot form the p coupling complex with guanine,

which is in agreement with the results of Zhu, etc. [44]. It has

Fig. 1. The optimized tautomers of Guanine (a) and Guanine-NaC (b) at B3LYP/6-311CG* level.

F. Liu et al. / Journal of Molecular Structure: THEOCHEM 760 (2006) 209–217 211

been found that only the LiC ion can form a p coupling

complex with guanine according to the B3LYP method with

6-311CCG** basis set because of the small radius of LiC and

its centralized electric charge. But for NaC, whose radius is

bigger and the positive charge is scattered, it is difficult to form

a cation-p coupling complex. The attachment of the metal

cation to the favored sites of each free tautomer gives rise to the

bicoordinated complexes as depicted in Fig. 1(b).

The most stable complex is optimized starting from the G2

tautomer and is characterized by a further five-membered ring

formation involving the metal species. In this species, the

distances of N7–NaC and O6–NaC are 2.394 and 2.281 A,

respectively. Similar to the case of G2, the conjugation of the

Table 1

Calculated absolute, relative and the binding energies of five tautomers of guanine

G1 G2

ET/au K542.583131 K542.582525

DE/(kcal/mol) 0.0 0.4

G1–NaC G2–NaC

ET/au K704.745609 K704.760149

DE/(kcal/mol) 9.1 0.0

BSSE/(kcal/mol) 0.72 0.67

EB/(kcal/mol) 46.29 55.84

ring is weakened because of the coupling of the NaC ion to the

guanine in G3. The sodium positive charge neutralizes the

negative charge on N7 and O6, and the density of the electron

cloud is reduced, so the CaO and C5–N7 bonds are

lengthened. G4–NaC has the highest energy because the

electronegativity of O6 is reduced as compared to G2–NaC,

nitrogen N3 in the pyridine ring lies lower than the N7 atom in

the imidazole ring, and the formation of four-membered ring

blocks the base pairing.

The remaining complexes follow the same stability order

irrespective of the cation considered: G1–NaCOG5–NaCOG3–NaCOG4–NaC at 9.1, 13.0, 13.6 and 19.9 kcal/mol,

respectively. The stability order of the guanine complexes is

obtained at B3LYP/6-311CG* level

G3 G4 G5

K542.577205 K542.575880 K542.572931

3.7 4.6 6.4

G3–NaC G4–NaC G5–NaC

K704.738397 K704.728447 K704.739386

13.6 19.9 13.0

0.90 0.99 0.71

45.30 39.80 48.79

F. Liu et al. / Journal of Molecular Structure: THEOCHEM 760 (2006) 209–217212

consistent with the fact that the formation of a five-membered

cycle is favored with respect to that of a four-membered ring of

the keto form complexes. If a hydroxyl group is involved, the

information from the five-membered cycle is advantageous [13].

3.2. Structures and characters of G–NaC (H2O) complexes

We have optimized five guanine tautomers and considered

several cases when they are coupled with NaC and one water

molecule, simultaneously, including cation-heteroatoms biden-

tate complex, cation-heteroatom unidentate complex, cation-pcomplex, amido-involved complex and complex with different

location sites of NaC and H2O, etc. In these complexes, the

H2O molecule mainly interacts with the NaC ion, and also

participates in the formation of hydrogen bond with the

guanine molecule. The optimized complexes have been

displayed in Figs. 2–4. The IR spectra obtained at B3LYP/

6-311+G* level are shown in Figs. 5–9.

According to the optimized structures, though we have fully

considered the influnce of the cation-p coupling complex, the

Fig. 2. Optimized geometries for Gm- NaC Monohydrate (mZ1, 2, 3, 4

optimized results do not have the cation-p complexes because

the positive charge is more extended after the hydration. On the

other hand, guanine was not twisted because its certain rigidity,

so the destruction of aromaticity would not influence the bases

to pair. It can be inferred that the guanine has the ability to form

a cation-p coupling complex with some other metal ions, such

as the magnesium ion which has more positive charges [44].

Table 2 lists the G–NaC (H2O) absolute energies, relative

energies, and interaction energies which are the binding

energies (EB) for the first process and the hydration energies

(EH) for the second process. All interaction energies are

calculated with BSSE correction.

G1–NaC(H2O). In G1W1 (where, Wn denotes the different

cases when a guanine molecule is coupled with one water

molecule), NaC is coupled with two nitrogen N atoms which

have small electronegativity, with the bond lengths of 2.46 and

2.36 A, respectively. They form a four-membered ring with

slightly great tension. The distance between NaC and O is

about 2.250 A, longer than that of the hydration sodium ion.

The distance of Na and O atom of G1W2 is 2.171 A for the

, 5) complexes. W represents water and distances are in angstroms.

Fig. 2 (continued)

F. Liu et al. / Journal of Molecular Structure: THEOCHEM 760 (2006) 209–217 213

participation of hydrogen bond, and the length of hydrogen

bond is 1.87 A. The six-membered cycle has some tension. As

the coupling of sodium on N3 and N9, the original conjugation

effect has been weakened, the positive charge distributed

effectively, and the density of the electron cloud on the

carbonyl increased relatively, so the length of CaO is

shortened, and the infrared frequency is increasing (see

Fig. 5). It can be inferred that the participation of the metal

ion can hinder or promote the tautomerization of the base,

while the H2O molecule has little effect on this kind of function

as compared to metal ion.

G2–NaC(H2O). The G2W1 is the most stable structure

among all guanine–NaC hydrate complexes. NaC couples with

O6 and N7 to form a bidentate five-membered ring complex

with the bond lengths of 2.313 and 2.433 A, respectively. The

distance between the Na and O atom is 2.250 A, similar to that of

G1. It can be seen from the DNA molecular structure, the

combined location site of G2W1 is in the large groove of the

helix and with a small special block. It is a favorable geometrical

position. G2W2 forms a seven-membered cycle because of the

participation of the hydrogen bond. It is more stable as

compared to the other complexes although with a higher energy.

The energy of G2W3 is the highest among all these

monohydrates. The participation of the hydrogen bond makes

the six-membered ring to twist to a nonplanar structure. The

distance between NaC ion and nitrogen N of guanine molecule

is 2.505 A. Their interaction is very weak, which causes the

rotation of the amino group. The NaC ion takes almost all

positive charges. It indicates that during the coupling process

of metal ions with bases, if the positive charges cannot get

distributed effectively, the interaction energy will be reduced,

and the coupling is disadvantageous for the living system.

The coupling of the sodium ion to O6 and N7 destroys the

conjugation of the ring. The neutralization of sodium positive

charge causes the electron cloud density of O6 and N7 to be

reduced, therefore, the CaO bond length is shortened with

infrared frequency decreases (1793.0, 1729.3, 1735.3, 1732.9,

1838.3 cmK1). For G2W3, the participation of –NH2 group in

the coupling destroys the conjugation of the ring distinctly and

leads to the increasing of the electron cloud density of

carbonyl. Therefore, the bond length of CaO is shortened

and the infrared frequency is increased (see Fig. 6).

G3–NaC(H2O). G3W1 and G3W2 are the enolic forms of

G2W1 and G2W2, respectively. They have higher energies and

some changes occur in the bond lengths. The NaC (H2O) leans

to N7 as a whole, and the negative charges in O6 are reduced.

The base group of G3W3 has already been changed to G4

which can be understood. The NaC ion forms two twisted four-

membered rings with N1 and O6, N1 and N2, respectively,

which leads to the increase of energy. Because of the

destruction of aromaticity by participation of amino group

and the larger tension of the twisty four-membered ring, the

energies of G3W4 and G3W5 are increased.

G4–NaC(H2O). Similar to G3, the rotation of the amino

group, the destruction of the four-membered ring and the

insufficient dispersion of positive charges make the energy to

increase. The structures of G4W3 and G4W4 indicate that the

guanine amino group may be rotated freely within specific

Fig. 3. Optimized geometries for sodium monohydrate. Distance is in angstrom.

F. Liu et al. / Journal of Molecular Structure: THEOCHEM 760 (2006) 209–217214

limits. The conformation change caused by the bond rotation

may often induce the disease and the amino rotation will cause

the failure of the pairing between guanine and cytosine,

influencing the physiological function of DNA.

The bond lengthes of C6–O6 and N1–C6 are lengthened due

to the coupling of NaC on the guanine. The infrared

frequencies are decreased (see Fig. 8), and the bond energies

are reduced. While for G4W3 and G4W4, the atoms coupled

with NaC have little electronegativity, the –NH2 group

participates in the coupling. So, the distance between the

atoms C6 and O6 becomes shorter.

G5–NaC(H2O). G5W1 and G5W2 are the enolic isomers of

G1W1 and G1W2, respectively, and the energies are higher as

compared to the former. G5W3 and G5W2 are similar in

structure, only the positions of H2O and the sodium ion are

exchanged. As compared with the uncoupled configuration, the

coupling of the sodium atom to guanine weakens the

conjugation of the ring, increases the electron cloud density

Fig. 4. Optimized geometries for corresponding transition sta

of the hydroxyl group, and shortens the bond length,

respectively.

No cation-p coupling complex has been found in the first

process. The other way around, they incline to form four or

seven-membered cycle complexes. We can also see that the

energy of the enolic form is higher than the energy of the keto

form.

Compared with the first process, the hydration of guanine–

NaC is different in the second process. Comparing Fig. 3 with

Fig. 1(b), with the consideration of the static coupling effect of

the H2O molecule, the sodium ion is far away from guanine and

the main bond length is increased because the positive charges

are more effectively scattered. As one can see from Table 2

that, the binding energy of the process (1) is about 20 kcal/mol

higher than that of (2), which is the most remarkable difference

between these two processes. Process (2) has lower interaction

energy, so it may be the advantageous reaction path in the

organism.

3.3. Proton transfer mechanism

It is found that the energies of G1, G2, G3, G4, and G5

tautomers change in a small energy range by 6.4 kcal/mol. The

small energy differences of tautomers suggest some inter-

conversion processes during the generation of the sample that

tes. W represents water and distances are in angstroms.

Table 2

Absolute, relative, and binding (or hydration) energies and the BSSE

corrections of guanine–NaC monohydrate complex obtained at

B3LYP/6-311CG* level

ET/au DE//(kcal/

mol)

BSSE/(kcal/

mol)

EB/(kcal/

mol)

EH/(kcal/

mol)

G1W1 K781.200118 8.50 3.16 37.41 16.87

G1W2 K781.196085 11.03 2.90 35.14 14.60

G2W1 K781.213660 0.00 2.97 46.48 16.43

G2W2 K781.211592 1.30 2.93 45.23 15.17

G2W3 K781.158362 34.70 3.20 11.55

G3W1 K781.193492 12.66 3.17 36.97 17.22

G3W2 K781.183612 18.86 2.54 31.40 11.65

G3W3 K781.181682 20.07 3.27 30.29 15.96

G3W4 K781.171017 26.76 3.29 22.74

G3W5 K781.170204 27.27 3.33 22.19

G4W1 K781.184696 18.18 3.44 32.01 17.68

G4W2 K781.190141 22.12 3.33 28.17

G4W3 K781.178390 22.13 3.33 28.16

G4W4 K781.170638 27.00 3.29 23.34

G5W1 K781.193927 12.38 3.05 40.04 17.00

G5W2 K781.190141 14.76 2.91 37.81 14.76

G5W3 K783.187660 16.32 2.82 36.34 13.29

G5W4 K781.179187 21.63 3.25 30.59

G5W5 K781.167282 29.10 3.34 23.03

0 1000 2000 3000 4000wavenumbers(cm–1)

G2

G2Na+

G2W1

G2W2

G2W3

1793.0(C=O)

1729.3(C=O)

1735.3(C=O)

1732.9(C=O)

1838.34(C=O)

3647.8(N9-H)3591.4(N1-H)

3629.8(N9-H)

3579.1(N1-H)

3581.4(N1-H)

3632.4(N9-H)

3324.9(O-H...N7)

3583.8(N1-H)

3633.4(N9-H)

3638.9(N9-H)

(N1-H+HNH)

3573.0 3578.1

Fig. 6. IR spectra of G2, G2NaC and G2Wn(nZ1–3) obtained at B3LYP/6-311C

G* level.

F. Liu et al. / Journal of Molecular Structure: THEOCHEM 760 (2006) 209–217 215

could give rise to a mixture of complexes. It can be seen from

the conclusion aforementioned that G2, G3 and G1, G5 are the

proton transfer (PT) isomers, respectively. G1 and G2 are the

keto forms, and G3 and G5 are the corresponding enolic ones.

It is well known that the enolic coupling complexes have

higher energies than the keto types, that is, the keto complex

would be more stable than the relevant enolic complex. During

the PT process, it is required to overcome higher barrier due to

the hindrance of the positive charge. All the optimized

geometries for corresponding transition states in the PT

processes have been displayed in Fig. 3. The calculated barrier

heights of both directions are summarized in Table 3.

As listed in Table 3, in the PT process G1/G5, the barrier

height in the forward (reverse) direction is 39.60(33.21) kcal/

0 1000 2000 3000 4000

0

500

1000

1500

2000

2500

Wavenumbers(cm–1)

3360.7(O-H)

1768.2(C=O)

1811.0(C=O)

G1

G1Na+

G1W1

G1W2

1806.8(C=O)

1804.6(C=O)

239.5(C-Na+)

325.7(C-Na+-H2O)

353.1(Na+-H2O)208.6(N9-Na+)

Fig. 5. IR spectra of G1, G1NaC and G1Wn(nZ1–2) obtained at B3LYP/6-311C

G* level.

mol, while for the process G2/G3, the value is 36.82(33.49)

kcal/mol. Compared with the direct PT of guanine, when the

sodium ion has been taken into account, the barrier height is

increased to 39.93(36.03) kcal/mol and 45.62(32.00) kcal/mol,

respectively. Therefore, it can be inferred that the coupling of

sodium ion influences the PT process of G2/G3 more

significantly. The transformation of G4/G5 occurs only

through a simple rotation around the O6–H bond and it is not

the case to be considered in the present investigation.

G2–NaC and G3–NaC, G1–NaC and G5–NaC, these two

pairs of PT isomers have some similarities of their bond

lengths. NaC–O6 is 2.281 and 2.363 A, NaC–N9 is 2.394 and

2.325 A for the former, respectively. While for the latter, the

NaC–N3 bond distance are 2.413 and 2.396 A, respectively.

For NaC–N9, it is 2.322 and 2.343 A, respectively. It can be

seen that the sodium ion prefers N7 and N9, respectively, in

these two different PT processes. However, the energy

difference is about 13.6 kcal/mol, higher than the energy

before coupling for the process G2/G3. The latter’s energy

0 1000 2000 3000 4000

0

500

1000

1500

2000

2500

wavenumbers(cm–1)

G3

G3Na+

G3W1

G3W2

G3W3

G3W4

G3W5

3726.9(C-O...H)3653.26(N9-H)

1683.2(C5-C6+C6OH)

1713.5(C5-C6+C6OH) 3719.6(C-O...H)3633.9(N9-H)

1711.5(C5-C6+C6OH) 3721.26(C-O...H)3637.2(N9-H)

1712.2(C5-C6+C6OH) 3677.6(C-O...H)3638.5(N9-H)

1693.19(C5-C6+C6OH)

1662.2(C5-C6+C6OH)

1670.5(C5-C6+C6OH)

3735.8(C-O...H)3633.5(N9-H)

3721.4(C-O...H)3642.8(N9-H)

3746.9(C-O...H)3635.1(N9-H)

Fig. 7. IR spectra of G3, G3NaC and G3Wn(nZ1–5) obtained at B3LYP/6-311C

G* level.

Table 3

The calculated tautomeric energies, DE (in kcal/mol), and the barrier heights,

E* (in kcal/mol) for the forward and reverse reactions (noted with superscript f

and r, respectively)

Reaction process Ef Er DE DH DS DG

G1/G5 39.60 33.21 6.39 6.42 K0.17 6.47

G1–NaC/G5–NaC 39.93 36.03 3.90 3.67 K2.88 4.53

G1W1/G5W1 39.69 35.83 3.86 3.85 0.57 2.87

G1W2/G5W2 39.95 36.23 3.72 3.69 0.26 3.62

G2/G3 36.82 33.49 3.33 3.29 K0.54 3.46

G2–NaC/–G5–NaC 45.62 32.00 13.62 13.48 K1.69 13.99

G2W1/–G3W1 44.79 32.15 12.64 12.52 K1.08 12.84

G2W2/G3W2 42.45 24.92 17.53 17.42 K0.51 17.57

The thermodynamic parameters (the enthalpy (DH, in kcal/mol), entropy (DS,

in cal/mol K), and the Gibbs free energies (DG, in kcal/mol)) of the PT

processes.0 1000 2000 3000 4000

0

500

1000

1500

2000

2500

wavenumbers(cm–1)

G4

G4Na+

G4W1

G4W2

G4W3

G4W4

3652.3(N9-H)

3736.8(C6-O...H)

3634.7(N9-H)3737.3(C6-O...H)

3637.5(N9-H)3740.0(C6-O...H)

3632.6(N9-H)

3724.6(C6-O...H)

3634.2(N9-H)

3722.2(C6-O...H)

3642.0(N9-H)3720.1(C6-O...H)

1684.0(C5-C6+C6OH)

1710.8(C5-C6+C6OH)

1706.9(C5-C6+C6OH)

1674.0(C5-C6+C6OH)

1666.1(C5-C6+C6OH)

1652.0(C5-C6+C6OH)

Fig. 8. IR spectra of G4, G4NaC and G4Wn(nZ1–4) obtained at B3LYP/6-311C

G* level.

F. Liu et al. / Journal of Molecular Structure: THEOCHEM 760 (2006) 209–217216

difference is 3.9 kcal/mol, which is lower than that before

coupling. The attachment site of sodium ion has great influence

to the different isomers, which hinders G2 to transform into G3,

and promotes G1 to transform into G5. Accordingly, in the

organism, the metal ion will exert a significant influence on the

base pairing, impelling the transition from a disadvantageous

configuration to an advantageous one, which reflects the

stabilization of metal ion to the active molecule of living

beings.

This phenomenon should contribute to the larger scattering

of the positive charge. After coupling, the positive charge of

G3 is more centralized, thus, the energy difference increases.

While in the case of G5, the situation is reversed. The positive

charge is diminished after coupling, and the energy difference

is reduced, which is consistent with the above conclusion.

Hydration also plays an important role in stabilizing the PT

isomers according to the universal law of hydration inside the

organism, but the effect on relative stability is inconspicuous.

Hydration reduces the stability of these two pairs of PT isomers

by 0.9 and 0.1 kcal/mol, respectively. It indicates that the PT

tautomerism of guanine is mainly influenced by the dispersion

0 1000 2000 3000 4000

0

500

1000

1500

2000

2500

wavenumbers(cm–1)

G5

G5Na+

G5W1

G5W2

G5W3

G5W4

G5W5

3730.0(C6-O...H)

3718.5(C6-O...H)

3720.8(C6-O...H)

3720.6(C6-O...H)

3719.7(C6-O...H)

3723.1(C6-O...H)

3750.0(C6-O...H)

3307.7(O18H-N3)

3479.0(O18H-N3)

1703.0(C5-C6+C6O-H)

1671.1(C5-C6+C6O-H)

1683.0(C5-C6+C6O-H)

1683.0(C5-C6+C6O-H)

1677.2(C5-C6+C6O-H)

1683.4(C5-C6+C6O-H)

1705.4(C5-C6+C6O-H)

Fig. 9. IR spectra of G5, G5NaC and G5Wn(nZ1–5) obtained at B3LYP/6-311C

G* level.

of the positive charge. Metal ion can promote this tautomerism

distinctly but hydration has only a little effect on.

As shown in Table 3, all the positive values of DH, ranging

from 3.29 to 17.42 kcal/mol, indicate that all the tautomeric

processes should be exothermic reactions. The small values of

DS (below 3 kcal/mol K) show that the DG should be

essentially governed by DH.

4. Conclusions

In present paper, full geometry optimizations and harmonic

vibrational frequency calculations for guanine–sodium ion

monohydrate complex are implemented with the help of the

density functional theory (DFT) method at the B3LYP/6-311CG* level. Thermodynamic and kinetic parameters, such as

tautomeric energies and barrier heights during the proton

transfer process from keto type to enolic type have been

discussed, respectively. The following primary conclusions are

drawn from this investigation.

(1) The binding of NaC to guanine is favored at the N7 and O6

positions for the keto isomer. It is found that the

preponderant geometry in organism is G2–W1 with the

Na–O bond length of 2.250 A, which is slightly longer than

that of the uncoupled monohydrate sodium ion. The

participation of the metal ion may hinder or promote the

tautomerization of the base, and a water molecule has little

effect on this kind of function as compared to the metal ion.

(2) The enolic coupling complex has higher energy than the

keto form, namely, during the PT process from the keto

form to the enolic one, it needs to overcome higher barrier

caused by the hindrance of the positive charge. Among the

guanine–NaC (H2O) isomers, the planar ring complex has

the lower energy than the others. The cation-p complexes

cannot be formed because of the participation of the

hydrogen bond and the twist of the ring. The guanine

molecule has certain rigidity and would form cation-pcoupling complexes with some metal ions, such as the

magnesium ion which has more positive charge.

(3) The monohydrated sodium ion would effectively couple to

bases if the positive charge gets effective distribution. It

F. Liu et al. / Journal of Molecular Structure: THEOCHEM 760 (2006) 209–217 217

can be seen that the effective distribution of positive charge

is an influential factor in the stabilization of biological

systems and in the binding energies of the monohydrated

guanine–sodium ion complex.

(4) Amino-involved coupling often gives rise to a twisted four

or six-membered ring with ineffective distribution of the

positive charge and higher energies. So the amino group of

guanine is not the best attachment site for a metal ion. The

rotation of the amino group may lead to the disruption of

the base pair hydrogen bonding.

(5) The interaction energy in the formation of monohydrated

guanine–NaC is lower, therefore it may be more

advantageous in the organism.

Acknowledgements

This work is supported by NSFC (20273040, 20573063),

NCET and the Natural Science Foundation of Shandong

Province (Z2003B01). Supports from SRFDP and SCF for

ROCS, SEM are also acknowledged. A part of calculations

were performed at the Virtual Laboratory of Computational

Chemistry, CNIC, CAS and the High-performance Compu-

tational Center in Shandong University.

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