Ab initio calculations for exploring hydration patterns of adenine

Ho-Tae Kim*

Department of Applied Chemistry, Kumoh National Institute of Technology, 188 Shinpyung-Dong, Kumi city Kyungbuk 730-701, South Korea

Received 5 September 2003; revised 5 September 2003; accepted 3 December 2003

Abstract

Density functional theory (DFT) has been used to optimize the hydrated structures of adenine. The systematic investigation in the

hydration process of adenine is performed. The optimized geometries and hydration energies in the adenine–(H2O)1 – 4 have been obtained

by ab initio calculations at B3LYP/6-311þþG(d, p) level. Adenine–(H2O)1 – 2 complexes are mostly optimized to the structure of planar

geometry. The optimized structures of adenine–(H2O)3 – 4 complexes are mixed with planar and non-planar geometries. The hydration

energies of adenine show that the hydration process of adenine is competed by two ways within a 8 kcal/mol energy difference.

q 2004 Elsevier B.V. All rights reserved.

Keywords: Density functional theory; DNA bases; Adenine–water complex; Hydration

1. Introduction

The hydration process of molecules has been studied in

many research groups. Several experimental techniques

have been applied to study the role of hydration in the

hydrogen bonding complexes [1 – 6]. Theoretical

approaches about the hydration process of molecules have

been also performed by semi-empirical and ab initio

calculations with reasonable accuracy [2,4,5,7–10].

The hydrogen-bonded complexes of DNA bases have

been studied both theoretically and experimentally because

DNA is an essential molecule in the organism. The four

bases of DNA are known to play important roles in the

mechanism of the molecular recognition system of living

things [11–13]. In the system of protein–nucleic acid base

recognition, water molecules are indeed nearly always

present and can make effects on that system [14].

In this paper, an adenine–water system is chosen as a

sample system to study water effects in the hydration

process of nucleic acid bases. The adenine–water system

has been studied in the gas-phase experiment at nano-

second and femto-second time scale under molecular beam

conditions [15–17]. The optimized structures about ade-

nine–(H2O)1 – 3 on the neutral and anion clusters were

obtained by means of semi-empirical model calculations

[18]. Ab initio calculations on the neutral and anion

complexes were also performed about adenine–(H2O)1 – 3

at Hartree–Fock (HF) and second-order Moller–Plesset

(MP2) levels of theory [19]. The prototype HF level

calculations for the hydrated clusters of adenine cation

[15] and the optimized structure of adenine–(water)6 with

the small basis sets [20] were also reported.

In the current study, a systematic investigation about the

stepwise hydration of adenine has been carried out by ab

initio calculations. The investigation on structures and

stabilization energies in the adenine–(H2O)2 – 4 are per-

formed to give some clue to the question, which hydration

process is favorable between single bind site hydration and

two or three bind sites hydration in energy viewpoint.

2. Results and discussion

Geometry optimizations are performed for adenine–

(H2O)1 – 4 using DFT theory at the B3LYP/6-311þþG(d, p)

level. The GAUSSIAN 98 package [21] is employed. The

structural features of adenine are shown in Fig. 1.

The adenine is seen to possess three primary binding

sites A, B, and C because a water molecule can form

two hydrogen bonds between a nitrogen atom and the

hydrogen atom connected to another nitrogen atom. For

example, the two hydrogen bonds of site A are formed as

a N1· · ·H–O(H)–H11–N10 structure.

0166-1280/$ - see front matter q 2004 Elsevier B.V. All rights reserved.

doi:10.1016/j.theochem.2003.12.006

Journal of Molecular Structure (Theochem) 673 (2004) 121–126

www.elsevier.com/locate/theochem

* Tel.: þ82-54-467-4372; fax: þ82-54-467-4477.

E-mail address: hotaekim@kumoh.ac.kr (H.-T. Kim).

The adenine molecule has a planar geometry [22]. The

planar geometry is not changed by the single water

molecule which is hydrated in the adenine primary

binding site with the two hydrogen bonds. The plane

geometry is maintained until two water molecules are

hydrated to the A or B site of adenine. However, the

distortion is started when two water molecules are

hydrated cooperatively to the C primary binding site.

In the case of primary binding sites A and B, the

distortion is started when three water molecules are

hydrated cooperatively to a single binding site. The

optimized bond distances, bond angles, and dihedral

angles of the adenine molecule at the DFT level of

theory were reported elsewhere [22].

The optimized geometries of adenine–(H2O)2 – 4 are

reported here with the combination of a number of water

molecules on the primary binding sites. Few selected

structures among the optimized geometries of adenine–

(H2O)1 – 4 are listed in the table and figures. Triangle, square,

and rhombus patterns occur in the structure of hydrated

adenine when three or four water molecules are hydrated

cooperatively at the single binding site of adenine. This

pattern is in conformity with the findings on the hydration of

benzene, phenol, and water [23–26].

2.1. Adenine· · ·H2O complex

In the first series of calculations the adenine complexes

with a single water molecule are performed. Three

structures where a water molecule is connected to adenine

through two hydrogen bonds were reported in the previous

ab initio calculations [19]. One of three structures, adenine–

(H2O)1–B which possesses a water molecule in B primary

binding site, is shown in Fig. 2 as (I). The hydrated

configuration of site A or C is similar to (I) and hence is not

displayed separately.

The hydrogen-bond distances and angles of adenine–

(H2O)1 complexes are listed in Table 1. The hydrogen-bond

distances of the three complexes are at the 2.814–2.835 A

range, and the hydrogen-bond angles are in the 156.4–

163.48 range at the first hydration step. From the

consideration of typical hydrogen bond distance (2.92–

2.94 A) and angle (1808) in water dimmer [27–29], it seems

that there is some geometric constraint in the adenine–

(H2O)1 complex. Table 1 also shows hydrogen bonds and

angles in H3N· · ·HOH, H2C(H3C)N· · ·HOH complexes. The

hydrogen bond configuration of H2C(H3C)N· · ·HOH com-

plex is similar to that of adenine–(H2O)1. The hydrogen

bond distances (2.932 and 2.922 A) and angles (174.4 and

173.48) in the two complexes also support that there is some

geometric constraint in the adenine–(H2O)1 complex.

The stabilization energies in each of the hydration

complexes are listed in Table 2. The energies of the

adenine–(H2O)1 complexes show that B site is the most

energetically favorable binding site in the single water

hydration step of adenine. B site was also the most stable

binding site in the MP2 level calculations [19]. The

hydrogen bond moiety of adenine–(H2O)1–A complex

has a six-membered ring configuration like that of (I).

However, adenine–(H2O)1–B complex is more stable than

adenine – (H2O)1 – A complex by 1.2 kcal/mol at the

B3LYP/6-311þþG(d, p) level. It is regarded that the

electrical environment of B site for hydrogen bonds is better

than that of A site. The stabilization energy of adenine–

(H2O)1–C(210.7 kcal/mol) is almost the same as the

stabilization energy of B site.

2.2. Adenine–2H2O complex

Three structures where two water molecules are

connected cooperatively to the primary binding sites are

also possible in the adenine–2H2O hydration step. The

adenine–(H2O)2–B2 which possesses two water molecules

in B site is shown as (II) in Fig. 2. Two water molecules are

located at the adenine molecular plane when they are

connected cooperatively in the A or B primary binding site.

However, two oxygen atoms are a little bit off from the

adenine molecular plane when the two water molecules are

connected cooperatively in the C primary binding site. The

side view of adenine–(H2O)2–C2 structure is denoted as

(III) in Fig. 2. H12 atom is 9.98 off from the adenine

molecular plane in the adenine–(H2O)2–C2 structure. It

seems that C site does not have enough space for three

hydrogen bonds with two water molecules.

The hydrogen-bond angles in three adenine–(H2O)2

complexes are at the 173.9–178.78 range in Table 1. These

hydrogen-bond angles in the three adenine–(H2O)2 struc-

tures are similar to the typical hydrogen-bond angle in the

water dimmer or in the H3N· · ·HOH, H2C(H3C)N· · ·HOH

complexes. The decrease of geometric constraint (increase

of hydrogen-bond angle) in the second hydration step is

resulted to the bigger stabilization energy at the site A or B

in Table 2. The stabilization energies per water in the

adenine–(H2O)2 turn out to be 210.3, 212.0, and

29.9 kcal/mol, respectively, in the A, B, and C sites. The

stabilization energy per water in adenine–(H2O)2–B2 is

bigger than that of adenine–(H2O)1–B by 1.1 kcal/mol.

However, The stabilization energy per water in adenine–

(H2O)2–C2 is smaller than that of adenine–(H2O)1–C by

Fig. 1. Structure of adenine. A, B, and C indicate the primary water binding

sites in adenine molecule.

H.-T. Kim / Journal of Molecular Structure (Theochem) 673 (2004) 121–126122

Table 1

The optimized geometric parameters of adenine–(H2O)1 – 3 complexes at B3LYP/6-311þþG(d, p) level

Hydrogen bond distance (A) Hydrogen bond angle (8)

A(N1· · ·H–O) B(N3· · ·H–O) C(N7· · ·H–O) A(N1· · ·H–O) B(N3· · ·H–O) C(N7· · ·H–O)

adenine–(H2O)1 2.828a(1.932b) 2.835(1.976) 2.814(1.895) 160.4 156.4 163.4

adenine–(H2O)2 2.812(1.824) 2.803(1.825) 2.816(1.830) 176.7 172.6 178.2

adenine–(H2O)3 2.796(1.810) 2.795(1.803) 2.818(1.839) 174.7 178.7 173.9

H3N-H-OH 2.932(1.962c) 174.4

H2C(H3C)N-H-OH 2.922(1.949) 173.4

a N· · ·O distance.b N· · ·H distance.c N· · ·H–O hydrogen bond.

Fig. 2. The optimized structures of (I) adenine–(H2O)1–B, (II) adenine–(H2O)2–B2, (III) adenine–(H2O)2–C2, (IV) adenine–(H2O)3–B2C1, (V) adenine–

(H2O)3–B3, (VI) adenine–(H2O)3–C3, and (VII) adenine–(H2O)3–B3tri.

H.-T. Kim / Journal of Molecular Structure (Theochem) 673 (2004) 121–126 123

0.8 kcal/mol even though the hydrogen-bond angle is

increase at the adenine–(H2O)2–C2 complex. The opposite

direction of C site in the stabilization energy originates from

the deviation of oxygen atoms from the adenine molecular

plane. The deviation of oxygen atoms is shown at (III).

Adenine–(H2O)2–B1C1 complex is the most stable

complex among the complexes with separated binding sites

in Table 2. The adenine–(H2O)2–B1C1 complex is less

stable than the adenine–(H2O)2–B2 with a single coopera-

tive binding site, but more stable than the adenine–(H2O)2–

A2 or adenine–(H2O)2–C2 complex. The stabilization

energy difference per water between adenine–(H2O)2–B2

and adenine–(H2O)2–B1C1 is 1.0 kcal/mol.

2.3. Adenine· · ·3H2O complex

In the adenine· · ·3H2O hydration step, plane geometry of

the complexes with a single cooperative binding site has

been broken during the hydration process to construct four

hydrogen bonds (V–VII) and five hydrogen bonds (VIII) in

Fig. 2. Three water molecules in a single binding site are

regarded to make a geometric hindrance that could break the

plane geometry. From a consideration of geometric angle

constraint for three water molecules, C site is the worst site

among three primary binding sites like the C site of

adenine–(H2O)2–C2 complex. B site has a relatively

favorable space condition between A and B sites because

the N3–C4–N9 bond angle (128.88) of B site is bigger than

the N1–C6–N10 bond angle (119.08) of A site in the adenine

molecule. Because of the extra angle space of B site, the

adenine–(H2O)3–B3 is the most stable complex among the

three adenine–(H2O)3 complexes with a single cooperative

binding site. Adenine–(H2O)3–B3tri complex hydrated by

three water molecules with a triangle structure is showed as

(VII). The B site is still the most stable site among the three

sites to construct a triangle configuration in the adenine–

(H2O)3 complexes.

Contrary to the adenine· · ·2H2O hydration step, ade-

nine–(H2O)3–B2C1 complex with separated binding sites

is the most stable configuration in adenine· · ·3H2O

hydration step. The stabilization energy of adenine–

(H2O)3–B2C1 is bigger than that of adenine–(H2O)3–B3

Table 2

Stabilization energy of adenine–(H2O)1 – 4 complexes (kcal/mol)

B3LYP/6-31G(d) B3LYP/6-311þþG(d,p)

A site B site C site A site B site C site

adenine–(H2O)1 213.6 214.4 215.0 29.7 210.9 210.7

adenine–(H2O)2 228.2 231.4 227.1 220.7(210.3a) 224.0(212.0) 219.8(29.9)

adenine–(H2O)2–A1B1 227.8 220.4(210.2)

adenine–(H2O)2–A1C1 227.7 219.7(29.9)

adenine–(H2O)2–B1C1 229.9 222.0(211.0)

adenine–(H2O)3 240.0 243.7 237.5 229.9(210.0) 234.0(211.3) 227.8(29.9)

adenine–(H2O)3–triangle 240.1 242.8 239.5 227.4(29.1) 230.2(210.1) 227.1(29.0)

adenine–(H2O)3–A1B1C1 242.5 230.9(210.3)

adenine–(H2O)3–A2B1 242.0 231.4(210.5)

adenine–(H2O)3–A2C1 242.0 230.3(210.1)

adenine–(H2O)3–B2A1 244.7 233.4(211.1)

adenine–(H2O)3–B2C1 247.1 235.3(211.8)

adenine–(H2O)3–C2A1 239.4 228.5(29.5)

adenine–(H2O)3–C2B1 242.1 231.2(210.4)

adenine–(H2O)4–square 255.2 259.2 253.7 240.2(210.0) 244.2(211.1) 238.3(29.6)

adenine–(H2O)4–rhombus 254.0 256.9 253.0 238.8(29.7) 241.6(210.4) 237.9(29.5)

adenine–(H2O)4–B4Y 255.8 239.6(29.9)

adenine–(H2O)4–A3B1 254.2 240.6(210.2)

adenine–(H2O)4–A3C1 253.7 239.5(29.9)

adenine–(H2O)4–B3A1 256.9 243.4(210.8)

adenine–(H2O)4–B3C1 259.4 245.3(211.3)

adenine–(H2O)4–C3A1 249.8 236.4(29.1)

adenine–(H2O)4–C3B1 252.4 239.1(29.8)

adenine–(H2O)4–A2B1C1 256.6 241.5(210.4)

adenine–(H2O)4–B2A1C1 259.5 244.1(211.0)

adenine–(H2O)4–C2A1B1 254.3 239.7(29.9)

adenine–(H2O)4–A2B2 259.2 244.4(211.1)

adenine–(H2O)4–B2C2 259.3 244.4(211.1)

adenine–(H2O)4–A2C2 253.3 238.9(29.7)

a Stabilization energy per water.

H.-T. Kim / Journal of Molecular Structure (Theochem) 673 (2004) 121–126124

by 1.3 kcal/mol in Table 2. The difference of configuration

corresponding to the most stable complex in adenine· · ·3H2-

O hydration step could be explained with the breakdown of

planar geometry in the complexes with a single cooperative

binding site. The broken plane geometry of adenine–

(H2O)3–B3 is showed in Fig. 2 as (VI). H12 atom is 22.58 off

from the adenine molecular plane in the adenine–(H2O)3–

B3 complex. However, the plane geometry is still

maintained in the case of adenine–(H2O)3–B2C1 even

though three water molecules are hydrated to the adenine

molecule.

From a consideration of stabilization energy in adenine–

(H2O)3 complexes, it seems most reasonable to conclude

that the relative stability of the adenine primary binding

sites depends on the number of water molecules on those

sites. Even adenine–(H2O)3–B2C1 is more stable than

adenine–(H2O)3 –B3, other complexes with separated

binding sites in three water hydration step are less stable

than adenine–(H2O)3–B3. The stabilization energy differ-

ence per water between adenine–(H2O)2 – B2C1 and

adenine–(H2O)2–B3 is 0.4 kcal/mol. Adenine–(H2O)3–

B3tri complex is less stable than adenine–(H2O)3–B3

complex. The stabilization energies in adenine–3H2O

hydration step are listed in the Table 2 within a 7 kcal/mol

energy difference.

2.4. Adenine–(H2O)4 complex

Many possible structures in the adenine· · ·4H2O

hydration step have been explored by the DFT method.

However, only a few selected complexes with separated

binding sites and three complexes with a single cooperative

binding site are listed in Table 2. Stabilization energies are

ranged from 236.4(29.1 per water) to 245.3(211.3 per

water) kcal/mol. The optimized structures with separated

binding sites and a single cooperative binding site are

displayed in Fig. 3. (II), (III), and (IV) have square,

rhombus, and Y shape structures, respectively, in each of the

primary binding sites. (II) is the most stable complex among

three complexes with a single cooperative binding site in

adenine· · ·4H2O hydration step. The square pattern was well

studied in the water tetramer [25], benzene–(H2O)4 [24],

and phenol–(H2O)4 hydration complex [26]. The square

plane of four water molecules in adenine–(H2O)4–B4sq has

a 1188 angle to the adenine molecular plane.

The rhombus shape of four water molecules in adenine–

(H2O)4–B4rhom is not a plane geometry contrary to the

plane geometry of a square shaped structure in the adenine–

(H2O)4–B4sq complex. Because two water molecules of

rhombus shape are distorted from the planar geometry of

rhombus, adenine–(H2O)4–B4rhom is less stable than

Fig. 3. The optimized structures of (I) adenine–(H2O)4–B3C1, (II) adenine–(H2O)4–B4sq, (III) adenine–(H2O)4–B4rhom, and (IV) adenine–(H2O)4–B4Y.

H.-T. Kim / Journal of Molecular Structure (Theochem) 673 (2004) 121–126 125

the adenine–(H2O)4–B4sq in Table 2. The geometry frame

of adenine–(H2O)4–B4Y which possesses four water

molecules with Y shaped configuration is the same with

that of adenine–(H2O)3–B3. The fourth water molecule is

added to the hydrogen atom of center water among the three

water molecules of B site. The stabilization energy of (IV)

complex is smaller than those of (II) and (III) because (IV)

has only five hydrogen bonds compared to the six hydrogen

bonds of (II) and (III) complexes.

In the case of adenine· · ·4H2O, the most stable complex

is adenine–(H2O)4–B3C1 with separated binding sites like

as adenine· · ·3H2O hydration step. However, the stabiliz-

ation energy difference per water between adenine–

(H2O)4 – B3C1 and adenine – (H2O)4 – B4sq is just

0.3 kcal/mol. The stabilization energy difference per

water between adenine–(H2O)4–B2A1C1 and adenine–

(H2O)4–B4sq is also negligible. On the basis of the energy

of hydration complexes which have a different number of

binding sites, it seems that there is no particularly

preferable hydration process in the energy viewpoint

between the process with a single binding site and two

or three binding sites at the adenine· · ·4H2O hydration step.

3. Conclusions

Hydration energies per water range from 29.0 to

212.0 kcal/mol in the adenine–(H2O)1 – 4 hydration pro-

cess. Adenine–(H2O)2–B2 with 212.0 kcal/mol hydration

energy per water seems to have the most favorable

configuration in the hydration process of adenine. The

hydration energies of adenine also show that the cooperative

hydration process with a single binding site and the

hydration process with separated binding sites are competing

within a 8 kcal/mol energy difference in each hydration step.

Acknowledgements

This paper was supported by Research Fund, Kumoh

National Institute of Technology.

References

[1] T. Ebata, A. Iwasaki, N. Mikami, J. Phys. Chem. A 104 (2000) 7974.

[2] Ch. Janzen, D. Spangenberg, W. Roth, K. Kleinermanns, J. Chem.

Phys. 110 (1999) 9898.

[3] T. Ebata, A. Fujii, N. Mikami, Intern. J. Mass. Spectrom. Ion

Processes 159 (1996) 111.

[4] C.J. Gruenloh, J.R. Carney, F.C. Hagemeister, C.A. Arrington, T.S.

Zwier, S.Y. Fredericks, J.T. Woods, K.D. Jordan, J. Chem. Phys. 109

(1998) 6601.

[5] P. Ilich, C.F. Hemann, R. Hille, J. Phys. Chem. B 101 (1997) 10923.

[6] S.K. Kim, W. Lee, D.R. Herschbach, J. Phys. Chem. 100 (1996)

7933.

[7] S.R. Gadre, K. Babu, A.P. Rendell, J. Phys. Chem. A 104 (2000) 8976.

[8] H.H.Y. Tsui, T. van Mourik, Chem. Phys. Lett. 350 (2001) 565.

[9] N.A. Besley, J.D. Hirst, J. Am. Chem. Soc. 121 (1999) 8559.

[10] D.M.A. Smith, J. Smets, L. Adamowicz, J. Phys. Chem. A 103 (1999)

4309.

[11] I. Galetich, M. Kosevich, V. Shelkovsky, S.G. Stepanian, Y.P. Blagoi,

L. Adamowicz, J. Mol. Struct. 478 (1999) 155.

[12] Z. Tao, T. Fujiwara, I. Saito, H. Sugiyama, J. Am. Chem. Soc. 121

(1999) 4804.

[13] S. White, J.W. Szewczyk, J.M. Turner, E.E. Baird, P.B. Dervan,

Nature 391 (1998) 468.

[14] P.I. Nagy, G. Alagona, C. Ghio, J. Am. Chem. Soc. 121 (1999) 4804.

[15] N.J. Kim, Y.S. Kim, G. Jeong, T.K. Ahn, S.K. Kim, Int. J. Mass Spec.

219 (2002) 11.

[16] N.J. Kim, H. Kang, G. Jeong, Y.S. Kim, K.T. Lee, S.K. Kim, J. Phys.

Chem. A 104 (2000) 6552.

[17] H. Kang, K.T. Lee, S.K. Kim, Chem. Phys. Lett. 359 (2002) 213.

[18] V. Periquet, A. Moreau, S. Carles, J.P. Schermann, C. Desfrancois, J.

Electron, Spectrosc. Relat. Phenom. 106 (2000) 141.

[19] A.F. Jalbout, L. Adamowicz, J. Phys. Chem. A 105 (2001) 1033.

[20] N.U. Zhanpeisov, J. Leszczynski, Struct. Chem. 12 (2001) 121.

[21] M.J. Frisch, G.W. Tucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb,

J.R. Cheeseman, V.G. Zakrzewski, J.A. Montgometry, R.E. Strat-

mann, J.C. Burant, S. Dapprich, J.M. Millam, A.D. Daniels, K.N.

Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi,

R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J.

Ochterski, G.A. Peterson, P.Y. Ayala, Q. Cui, K. Morokuma, D.K.

Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J. Cioslowski,

J.V. Ortiz, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I.

Komaromi, R. Gomperts, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-

Laham, C.Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe,

P.M.W. Gill, B.G. Johnson, W. Chen, M.W. Wong, J.L. Andres,

M. Head-Gordon, E.S. Replogle, J.A. Pople, Gaussian 98, Gaussian,

Inc., Pittsburgh, PA, 1998.

[22] X. Yan, P. Day, T. Hollis, A. Monzingo, E. Schelp, J.D. Robertus,

G.W.A. Milne, S. Wang, Prot. Struct. Funct. Genet. 31 (1998) 33.

[23] M.R. Viant, J.D. Cruzan, D.D. Lucas, M.G. Brown, K. Liu, R.J.

Saykally, J. Phys. Chem. A 101 (1997) 9032.

[24] R.N. Pribble, T.S. Zwier, Science 265 (1994) 75.

[25] J.D. Cruzan, M.R. Viant, M.G. Brown, R.J. Saykally, J. Phys. Chem.

A 101 (1997) 9022.

[26] Ch. Jacoby, W. Roth, M. Schmitt, Ch. Janzen, D. Spangenberg, K.

Kleinermanns, J. Phys. Chem. A 102 (1998) 4471.

[27] P.L. Silvestrelli, M. Parrinello, J. Chem. Phys. 111 (1999) 3572.

[28] S.J. Grabowski, Chem. Phys. Lett. 338 (2001) 361.

[29] F.H. Stillinger, Science 209 (1980) 451.

H.-T. Kim / Journal of Molecular Structure (Theochem) 673 (2004) 121–126126