Download Metal ions in non-complementary DNA base pairs: an ab initio study

JBIC (1999) 4 : 537–545
Q SBIC 1999
ORIGINAL ARTICLE
Jiří Šponer 7 Michal Sabat 7 Jaroslav V. Burda
Jerzy Leszczynski 7 Pavel Hobza 7 Bernhard Lippert
Metal ions in non-complementary DNA base pairs: an ab initio study of
Cu(I), Ag(I), and Au(I) complexes with the cytosine-adenine base pair
Received: 25 March 1999 / Accepted: 10 June 1999
Abstract Ab initio calculations have been carried out
to characterize the structure and energetics of a silver(I) complex with the cytosine-adenine DNA base
pair and an aqua ligand in the coordination sphere of
Ag. In addition, we have also studied analogous complexes with Cu(I) and Au(I), and structures in which
adenine has been replaced by purine in order to investigate the structural role of the adenine amino group.
The calculations revealed that all metal-modified structures are dominated by the metal-base interactions,
while the water-metal ion interaction and many-body
interligand repulsion are less important contributions.
Nevertheless, the structural role of the water molecule
in the complex is quite apparent and in agreement with
an earlier crystallographic study. The metal-modified
base pairs exhibit large conformational flexibility toward out-of-plane motions (propeller twist and buckle),
J. Šponer (Y) 7 P. Hobza
J. Heyrovský Institute of Physical Chemistry
Academy of Sciences of the Czech Republic, Dolejškova 3,
CZ-182 23 Prague, Czech Republic
e-mail: sponer6indy.jh-inst.cas.cz
Tel.: c420-2-66053776
Fax: c420-2-8582307
comparable or, in some cases, even larger than that observed in the base pairs without metal ions. All structures have been optimized within the Hartree-Fock approximation, while interaction energies were evaluated
with the inclusion of electron correlation.
Key words Ab initio 7 Silver 7 Nucleobase 7
Cytosine 7 Adenine
Introduction
Non-complementary DNA base pairs have been encountered in several biological processes [1]. The incorporation of non-Watson-Crick base pairs (mismatches)
in duplex DNA is one of the errors affecting DNA replication [2–4]. It has also been recognized [5] that nonWatson-Crick systems such as the Hoogsteen and reverse Hoogsteen base pairs are essential for the stability of higher order nucleic acid assemblies, including
DNA triplexes.
The adenine-cytosine A c-C mismatch (Scheme 1a)
has been observed in B-DNA [6–7] and RNA [8] du-
M. Sabat
Department of Chemistry, University of Virginia
Charlottesville, VA 22901, USA
J.V. Burda
Department of Chemical Physics, Faculty of Mathematics and
Physics, Charles University, CZ-121 16 Prague, Czech Republic
J. Leszczynski
Department of Chemistry and Computational Center for
Molecular Structure and Interactions, Jackson State University
Jackson, MS 39217, USA
B. Lippert
Department of Chemistry, University of Dortmund
D-44221 Dortmund, Germany
Supplementary material Geometries of metalated base pairs
obtained at the HF/6-31G* level (15 tables) are available in
electronic form on Springer Verlag’s server at
http://link.springer.de/journals/jbic/
Scheme 1.
538
Scheme 2.
plexes by X-ray crystallography. The A c-C pair has
also been found by NMR spectroscopy in the anticodon
stem-loop of tRNA Lys, 3 [9]. The stabilizing role of this
base pair may have profound consequences, taking into
account that human tRNA Lys, 3 is the primer for HIV
reverse transcriptase, active in the HIV virus life cycle
[10]. On the other hand, the cytosine-adenine reverse
Hoogsteen pair (Scheme 1b) is a part of the C-AT base
triplet. DNA triplexes of this kind have been shown to
be relatively stable by affinity cleavage methods [11].
Metal ions may stabilize several of the non-WatsonCrick systems [12]. The stability of the C-A reverse
Hoogsteen base pair can be greatly enhanced by the
formation of a coordinative N3(C)-metal ion-N7(A)
bond system [13]. This, in turn, should make the metalmodified C-AT base triplet more stable, as its Hoogsteen portion would now be held together by a coordinative bridge in addition to the N6(A)-H...O2(C) hydrogen bond (Scheme 2).
The interest in metal-modified C-A base systems
originated from our previous report [14] describing the
structure of an Ag(I) complex, in which the metal ion
formed coordinative bonds with N3 of cytosine and N7
of adenine distributed in an almost linear fashion. An
interesting feature of the complex was the presence of a
water molecule forming a weak coordinative bond with
the Ag(I) ion. Hydration of bases is believed to play an
important role in the stabilization of H bonds in mismatches [15] and base triplets [16]. Thus, one of the
main goals of this ab initio quantum chemical study was
to establish the geometry and energetics of the hydrated C-metal ion-A systems. Of special interest was
the influence exerted on the base system by the interactions between Ag and the water molecule.
Ab initio quantum chemical calculations have been
previously used to characterize several systems containing nucleic acid bases and metal cations [17–25]. Of the
other relevant studies, hydration of the Ag(I) ion has
recently been the subject of an investigation applying a
semicontinuum quantum chemical solvation model
[26].Use of quantum chemistry for complexes with metal cations is of particular importance since these systems are very difficult to characterize by empirical potential methods owing to pronounced polarization and
charge-transfer effects [20, 22, 23, 27–29].
In order to make a comparison with other monovalent transition metal ions and to obtain further insight
into the interactions, we have also performed calculations for the cytosine-adenine base pair complexes with
Cu(I) and Au(I). We are aware that the latter calculations may not be biologically relevant in that a linear
coordination geometry about Cu(I) is rather the exception than the rule and that linear Au(I) complexes
usually require the presence of soft donors such as
phosphines or S-containing ligands, especially when already bonded to a ring N atom of a nucleobase [30–
31].
Methods
The systems used in calculations included the cytosine-M-adenine
complexes [MpCu(I), Ag(I), Au(I)] and the same assemblies interacting with a molecule of water. All systems were optimized
using the gradient technique within the Hartree-Fock (HF) approximation. The initial structures were based on the parent crystal structure containing the Ag(I) cation [14]. No geometrical constraints were applied. The standard split-valence 6-31G* basis set
of atomic orbitals was used for the H, C, N, and O atoms; the
cations were described using the Christiansen relativistic pseudopotentials [32–34]. This provides a balanced description of the cation and of the rest of the system. The interaction energies were
evaluated using the second-order Moeller-Plesset perturbational
method (MP2) with the same basis set and pseudopotentials as
specified above. All orbitals were considered in the electron correlation calculations.
The interaction energy of the C-M c-A (cytosine-metal cationadenine) trimer, DE ACM, can be expressed in two ways [20]:
either as a difference of the electronic energy of the complex and
of the monomers:
DE ACMpE ACMP[E AcE CcE M],
(1)
or as a sum of three pairwise interaction energies and a threebody term:
DE ACMpDE ACcDE AMcDE CMcDE 3pE ACP[E AcE C]cE AM
P[E AcE M]cE CMP[E CcE M]cDE 3 (2)
By extending these equations to a four-particle system we obtain
the expresion for the A...C...M c...W (water) tetramer:
DE ACMWpE ACMWP[E AcE CcE McE W],
(3)
or
DE ACMWpDE ACcDE AMcDE AWcDE CM
cDE CWcDE MWcDE mb
mb
(4)
where the many-body term DE consists of all three-body and
four-body nonadditivities. The symbol E stands for the total electronic energy of a given complex or subsystem; DE means the interaction energy for a given complex.
All interaction energies were calculated using the optimized
geometries of the complex and were corrected for the basis set
superposition error in the basis set of the whole complex. The
deformation energies of monomers were neglected, since the deformation energies are by an order of magnitude smaller than the
interaction energies [21].
539
All calculations were done using the Gaussian94 suite of programs [35]. Tight option has been used for all optimizations [35].
It means 0.000015 and 0.00001 a.u. for maximum and RMS forces,
and 0.00006 and 0.00004 Å for maximum and RMS displacements.
Results
Structures
Structures of Ag(I) complexes
Gradient optimization using the crystal data for
[(1-MeC)Ag(9-MeA)(H2O)] c [14] (Fig. 1) as the initial
structure resulted in a planar geometry for both the cytosine-Ag-adenine, C-Ag-A c, and the cytosine-Ag(water)-adenine, C-Ag(W)-A c, models. The theoretical structure closely resembles the X-ray data (see below). However, subsequent harmonic vibrational analysis (see below) revealed that there is one imaginary frequency for both complexes, corresponding to a propeller-like conformation of the two bases around the metal
ion. Thus, the planar structures do not represent a minimum on the potential energy surface (PES). Applying
this information, we were able to locate the actual minima on the PES which correspond to significantly nonplanar conformations (Fig. 2). However, the energy difference between the planar and nonplanar structures
are exceptionally small, namely 0.46 and 0.18 kcal/mol
for the structures with and without water, respectively.
The calculations indicate a significant flexibility of the
systems. It should be mentioned that the conformational data could not have been identified based merely on
the crystal structure analysis. As such, they deserve a
more detailed analysis, which will be presented in one
of the following sections. On the other hand, there is no
substantial disagreement between the planar structure
in the crystal and the nonplanar one obtained by quanFig. 2 Stereoviews of the nonplanar structures of the C-AgA c (a) and C-Ag(W)-A c (b)
complexes
Fig. 1 Structure and atom numbering in the [(1-MeC)Ag(9MeA)(H2O)] c complex [14]
tum-chemical calculations. They are isoenergetic, so
that the crystal environment can adopt either of them,
or any intermediate.
Table 1 compares the main structural parameters of
the C-Ag-A c and C-Ag(W)-A c complexes. The distance between Ag and N3 of cytosine is longer than
that between Ag and N7 of adenine in all the complexes under investigation. Interestingly, the N3-Ag-N7
bond system is somewhat deviated from perfect linearity (the N3-Ag-N7 angle is 1707) already, in the absence of the water molecule. The most likely reason for
the distortion appears to be the formation of a H-bond
between O2 of cytosine and the adenine amino group.
The N3-M-N7 bending is further enhanced by the presence of the water molecule, which makes the N6-H...O2
H-bond even shorter.
The water molecule forms a H-bond with the amino
group of cytosine. On the other hand, the water oxygen
atom is too far from H8 of adenine to make even a very
540
Table 1 Selected distances (Å) and angles (7) in the optimized (HF/6-31G* level) A-M-C c and A-M(W)-C c complexes
System
N3-M
N7-M
N3-M-N7
C2N3-N7C5
N6-O2
Ow-N4
Ow-H8
Ow-M
CAgA a
CAgA b
CAgAW a
CAgAW b
CCuA
CCuAW
CAuA
CAuAW
2.41
2.40
2.38
2.40
2.02
2.02
2.15
2.15
2.29
2.27
2.32
2.34
1.98
1.98
2.12
2.12
171.4
169.3
162.1
154.8
174.8
173.4
173.0
173.5
0.6
32.8
0.8
42.6
30.0
0.5
0.0
0.0
3.17
3.22
3.07
3.12
3.12
3.06
3.23
3.06
P
P
3.14
3.14
P
3.06
P
3.06
P
P
3.59
4.56
P
2.68
P
3.04
P
P
2.86
2.77
P
3.32
P
3.54
a
b
Planar structure
weak C-H...O contact. Thus, the water molecule is
bound to cytosine and does not interact with the adenine moiety.
Both nonplanar stuctures are characterized by pronounced pyramidalization of the amino group of adenine [36–41], which allows optimization of the (N6)H...O2 interaction.
Table 2 compares the calculated structure (the planar structure) with its experimental counterpart. Apart
from the previously observed [42] differences between
the experimental and HF values of coordinative bond
lengths and angles involving Ag(I), metric features for
these models agree quite well with those obtained by
the X-ray analysis. The HF procedure is known to overTable 2 Selected geometric parameters (Å, 7) for [C-Ag-AH2O] c obtained from ab initio calculations and the crystal structure analysis for [(1-MeC)Ag(9-MeA)(H2O)] c [14]
Parameter
Ab initio
X-ray
Ag-N3C
Ag-N7A
Ag-O1W
O2C-C2C
N1A-C2A
N1A-C6A
N1C-C2C
N1C-C6C
N3C-C2A
N3A-C4A
N3C-C2C
N3C-C4C
N4C-C4C
N6A-C6A
N7A-C5A
N7A-C8A
N9A-C4A
C4C-C5C
C5A-C6A
C5C-C6C
N3C-Ag-N7A
N3C-Ag-O1W
N7A-Ag-O1W
C2A-N1A-C6A
C2C-N1C-C6C
C2A-N3A-C4A
C2C-N3C-C4C
C5A-N7A-C8A
C4A-N9A-C8A
2.384
2.321
2.845
1.209
1.323
1.328
1.375
1.354
1.315
1.320
1.359
1.320
1.325
1.334
1.395
1.291
1.368
1.438
1.411
1.339
162.10
89.52
108.38
119.87
122.40
111.41
120.78
104.93
107.14
2.128(2)
2.120(2)
2.664(2)
1.240(3)
1.339(4)
1.348(3)
1.377(4)
1.377(4)
1.336(4)
1.342(3)
1.366(4)
1.355(3)
1.326(4)
1.338(4)
1.391(3)
1.312(4)
1.373(3)
1.419(4)
1.405(4)
1.332(4)
165.80(8)
101.28(9)
97.73(8)
118.9(2)
120.9(2)
110.6(2)
120.5(2)
105.1(2)
106.3(2)
Nonplanar structure
estimate the intermolecular bond lengths owing to the
neglect of intermolecular electron correlation effects,
which is also observed in our complex. However, it
does not have a significant effect on the calculated energetics of the complexes, since for the interaction energy single point calculations the electron correlation is
included (see below). Further, there is a certain difference in the position of the water molecule. We assume
that it can be due to the lattice effects, since in the crystal this water molecule interacts with nitrate.
Structures of the Cu(I) and Au(I) complexes
We will now describe briefly the complexes involving
Cu(I) and Au(I). The cation-base distances in these
complexes are significantly shorter than those in the
Ag(I) systems (Table 1). The shortening can be attributed to the small ionic radius of Cu(I) and relativistic
effects pronounced for Au(I). Both Au(I) complexes
(with and without water) are planar. In the case of the
Cu(I) complex, the structure without water is nonplanar with a pyramidalization of the adenine amino
group in the (N6)-H...O2 H-bond. However, upon inclusion of the water molecule the structure becomes
planar. It again underlines the large conformational
flexibility of the studied complexes.
On the other hand, the Cu-O (water) and Au-O
(water) distances are much longer than the analogous
separation in the Ag complex. This indicates a weaker
and purely electrostatic interaction between the Cu(I)
and Au(I) cations and water. Also, in contrast to the
Ag structures, the water molecule does not have any
effect on the N3-M-N7 angle, which is close to linearity.
One possible explanation is that the adenine-cytosine
separation is smaller and water could not enter this
area to form a stronger contact with the cation. Another reason could be an increased interligand polarization repulsion for smaller cations (see below). In the
case of the Cu(I) structure, the water-H8 of adenine
distance is very short, which may indicate a certain CH...O stabilizing contribution and a weak water bridge
between adenine and cytosine. We think that the existence of this bridge could help explain why inclusion of
the water molecule makes the whole complex planar.
541
Table 1 clearly shows that the Ag(I) complexes show
the largest propensity to be bent, mainly the hydrated
complex. This can be attributed to three contributions:
1. In the case of the Ag(I) complex the water comes
much closer to the metal and seems to have a stronger effect.
2. The Ag(I) complexes have longer N-metal bonds;
thus a large N3-Ag-N7 bending is required to establish the inter-base H-bond.
3. The Ag(I)-N coordinative bonds are weaker and the
Ag(I) structures are more flexible compared to the
remaining complexes (see below).
Cytosine-M-purine complexes
The results presented above indicate, in agreement
with the earlier crystallographic studies [14], that the
water molecule in the Ag complex can indeed contribute to the bending of the N3-M-N7 bond. However, it
is also quite evident that some bending occurs already
when the water molecule is not present, possibly owing
to the amino group-carbonyl oxygen interaction and
the large flexibility of the Ag(I) complex. In order to
separate these effects, we have reoptimized all six complexes while replacing adenine with purine (Pur), in order to eliminate the amino group-carbonyl group contact (Fig. 3).
All structures with purine were perfectly planar. It
should be mentioned that the amino group nonplanarities represent a very frequent source of intrinsic nonplanarity of many base pair mismatches [40]. Interestingly, each of the cations responded differently to the
removal of the amino group. In the case of Au(I), the
nonhydrated structure showed the same N3-M-N7 angle as in the complex with adenine (175.07). Upon addition of the water molecule this bond system became linear, with the water molecule well separated from the
Fig. 3 Structure of the planar C-Ag(W)-Pur c complex
metal ion. However, the nonhydrated C-Cu-Pur complex exhibited a slightly larger bending angle of 171.97.
We believe that this is caused by a close C6-H6...O2
contact. This interaction is energetically weaker than
that between the amino and carbonyl groups, but it allows a closer approach of both bases, since the bulky
amino group has been removed. It means that in principle a larger bending can occur. This became quite evident when the bending angle adopted a value of 167.07
upon addition of the water molecule to the Cu coordination sphere. The H6-O2 distance in the complex is
2.57 Å, and the C-H bond is longer by 0.003–0.005 Å
than the other C-H bonds in the structure. This indicates that the contact could be interpreted as a weak
H-bond [43]. The shorter Cu-O (water) distance of
2.99 Å (instead of 3.32 Å for the adenine-containing
system) suggests that a closer contact between the water molecule and the cation is now possible. Thus, the
coordination of water gains in significance as one of the
factors affecting the structure of the complex.
All these trends are even more apparent for the CAg(W)-Pur system, as its structure is more flexible and
the longer M-N bonds require larger bending to optimize the C6-H6...O2 bond. In fact, in this structure, the
H6...O2 distance is 2.49 Å and the N3-M-N7 angle is
156.17. The water molecule is at a rather close distance
from the Ag(I) ion (2.81 Å). In summary, all the data
obtained for the C-M-Pur complexes support the idea
that the water molecule in fact plays an important
structural role.
Let us summarize that the removal of the adenine
amino group influences the bending by two opposing
effects. First, there is a replacement of the N-H...O Hbond with a weaker C-H...O interaction. It obviously
can reduce the propensity for bending. However, at the
same time, the removal of the bulky nitrogen atom allows larger bending values to be reached, sterically hindered with the amino group. Which of these two contributions prevails depends on the other contributions,
such as stiffness and length of the metal-base coordinative bonds and coordination of the water molecule.
We did not obtain the expected structure for the CAg-Pur complex without the water molecule. Here the
two bases were rotated by ca. 1407and the Ag atom was
moved from the N3 position of cytosine to the O2 atom
of the same base. Thus, Ag is now involved in a crosslink between N7(A) and O2(C) (see Fig. 4). This is a
rather unexpected structure and we plan a more detailed investigation of this type of bonding in the near
future. We note, however, that in the dimeric 1-methylcytosine complex [AgC(NO3)]2 [44–45] the Ag ions likewise bind to N3 and O2 in a bridging fashion, but in
this case the metal ions adopt distorted tetrahedral
coordination geometries, with nitrate oxygen atoms
completing the coordination sheres (see also following
paragraph).
542
lengths to 2.2 Å. However, the subsequent optimization
produced, somewhat to our surprise, a complex containing the Ag(I) ion bound to O2 of cytosine and N1
of adenine (Fig. 5). The Ag-O2(C) distance of 2.30 Å is
comparable with that found by X-ray crystallography in
dimeric [(1-methylcytosine)Ag(NO3)2] (2.367(2) Å)
[44–45]. The Ag-N1(A) bond length is 2.25 Å and the
O2(C)-Ag-N1(A) angle is 170.27. The complex is not
planar, as the two bases make an angle of 31.87.
Energetics
Fig. 4 Stereoview of the optimized structure of the cytosineAg(I)-purine complex
Structure of the Ag-modified C-A mismatch
Structural data on metal ion involvement in DNA mismatches are very scarce [12]. Therefore, in order to
gain some valuable information about interactions between the C-A mismatch and the Ag(I) ion, we have
also prepared a model in which the metal ion was
bound through covalent bonds to N3 of cytosine and
N1 of adenine. The initial structure was based on our
previously reported HF/6-31G** geometry of a protonated A-C mismatch ([46], fig. 9c) while replacing the
proton by Ag(I) and adjusting initially the Ag-N bond
The interaction energies are summarized in Tables 3
and 4. Table 3 shows the energetics with the inclusion
of electron correlation effects, while Table 4 presents
the HF components of all contributions for comparison.
All complexes are dominated by the pair-additive
metal-nucleobase contributions. Therefore, these complexes can be considered as systems of two bases crosslinked by a metal cation. The interaction of metal cations with cytosine is stronger, because cytosine has a
larger dipole moment than that of adenine. The two
dominating metal-base contributions are basically unchanged by the presence of the water molecule. The
pairwise water-cation interactions are rather weak (ca.
–15 to –20 kcal/mol). The remaining pairwise contributions are much smaller. The adenine-cytosine interac-
Fig. 5 Stereoview of the Agmodified C-A base pair mismatch
Table 3 Interaction energies in selected A-M-C c and A-M(W)-C c complexes, evaluated at the MP2/6-31G*//HF/6-31G* level (kcal/
mol)
A-C-Cu c
A-C-Cu c-W
A-C-Ag c
A-C-Ag c-W
A-C-Au c
A-C-Au c-W
DE AM
DE CM
DE MW
DE AC
DE AW
DE CW
DE mb
DE ACMW
P55.8
P55.0
P36.4
P36.3
P56.7
P56.6
P71.8
P70.9
P57.8
P56.0
P71.7
P71.9
P
P15.3
P
P21.3
P
P14.1
P3.5
P4.0
P3.9
P4.4
P4.2
P4.0
P
c0.1
P
c1.1
P
c0.3
P
P3.0
P
P1.9
P
P3.5
c8.6
c10.3
c8.0
c16.8
c0.7
c7.2
P125.7
P137.7
P90.1
P101.9
P132.0
P142.6
Table 4 Interaction energies in selected A-M-C c and A-M(W)-C c complexes, evaluated at the HF/6-31G* level (kcal/mol)
A-C-Cu c
A-C-Cu c-W
A-C-Ag c
A-C-Ag c-W
A-C-Au c
A-C-Au c-W
DE AM
DE CM
DE MW
DE AC
DE AW
DE CW
DE mb
DE ACMW
P44.1
P43.2
P30.9
P30.9
P41.8
P41.6
P62.9
P62.3
P54.7
P52.7
P58.6
P58.7
P
P14.8
P
P19.8
P
P13.3
P2.5
P3.0
P3.3
P3.8
P3.5
P3.2
P
c0.4
P
c1.2
P
c0.4
P
P2.3
P
P1.1
P
P2.8
c6.7
c11.2
c7.9
c15.1
c0.2
c5.8
P102.7
P114.0
P80.9
P91.8
P103.6
P113.4
543
tion is weakly attractive with a hydrogen bond between
the adenine amino group and the cytosine carbonyl
group. The energy of this H-bond is around –4 kcal/
mol, representing ca. 30% of the stabilization of the
nonmetalated Hoogsteen and reverse Hoogsteen adenine-cytosine base pairs with two hydrogen bonds [47].
The adenine-water interaction energy is close to 0 kcal/
mol. There is, however, a H-bond between the water
molecule and cytosine and the corresponding pairwise
interaction energy is in the range –2 to –3.5 kcal/mol.
Let us now consider the many-body term, which includes all nonadditive contributions. This term, repulsive for all the complexes, is enhanced by the presence
of the water molecule. This finding should not be surprising. Both C-M-A c and C-M(W)-A c systems can
be considered as formed by coordination of several ligands to a metal cation. In such systems, the polarization and charge transfer effects always lead to an increased repulsion among the molecules participating in
the coordination sphere of the cation. This may explain
why the many-body contribution is repulsive and why it
increases on adding the water molecule. As a result, the
actual energy gain associated with addition of the water
molecule is not around 15–20 kcal/mol, as indicated by
the M...W pair interaction energy term, but less than
10 kcal/mol. The reduction is caused by the increase of
the repulsive term DE mb upon hydration. Nevertheless,
the magnitude of nonadditivity is several times smaller
compared to typical hexahydrates of divalent cations
[23–24, 48], which reflects weaker interactions in the
systems with monovalent cations.
Finally, we would like to analyze the difference between various metal cations used in the present study.
The stabilization energy of the Ag(I) complexes is reduced compared to the complexes containing Cu(I). It
is mainly due to the reduction of the cation-base interactions and reflects the increased ionic radius of Ag(I)
compared to Cu(I). However, this trend is completely
reversed when replacing Ag(I) with Au(I), as the Au(I)
complexes are more stable than those with Cu(I). This
is in agreement with the previous studies and can be
attributed to relativistic effects [17]. Also, compared to
the other two systems, the Au(I) complexes have a
smaller many-body term. The electron correlation effects are important and they represent around 10–20%
of the stabilization.
It should be noted that the binding energies in the
present system are much stronger than base pairing in
neutral nonmetalated base pairs, which amounts to ca.
10–25 kcal/mol [47]. Let us mention, however, that the
interaction energy in protonated base pairs is around
40 kcal/mol (depending on the polarity of the neutral
bases) [46], which is closer to the metalated systems.
As explained in the Introduction, all interaction energy calculations have been corrected for the basis set
superposition error (BSSE) using the full counterpoise
correction. The counterpoise correction represents a
rigorous way of eliminating BSSE. It is frequently assumed that this correction is not necessary for ionic sys-
tems since the BSSE artifact is small compared to the
interaction energies. However, this is not true and in
fact the relative magnitude of the artifact increases with
the number of monomers in the complex, which is the
case in studies of coordination spheres of cations [24].
For example, the uncorrected value of the total interaction energy of the adenine-Ag(I)-cytosine-water complexes is –120.6 kcal/mol, being almost 20 kcal/mol
(20%) below the corrected value of –101.9 kcal/mol
given in Table 3. This number convincingly demonstrates that the magnitude of BSSE in our system requires the counterpoise correction. For more details,
see also [24].
Harmonic vibrational analysis
Harmonic vibrational frequencies of all three A-M-C c
systems and the A-Ag(W)-C c complex have been determined at the HF/6-31G* level. They are summarized
in Table 5. The two lowest frequencies correspond to
the buckle and propeller twist vibrational modes. This
is a very interesting result since these vibrational modes
are among the lowest observed in all nonmetalated
base pairs [49]. Furthermore, the buckle and propeller
vibrational frequencies in the present systems have values very similar to those for the base pairs without metal ions [49]. This means that, despite the fact that the
bases are crosslinked through a system of coordinative
bonds, the base pairs do not lose their flexibility. This
complements our finding (see above) that several complexes examined in this study have significantly nonplanar optimal structures, which are almost isoenergetic
with the planar transition state structures. The metalmodified base pairs can actually be even more flexible
toward nonplanarity than those without metal ions,
since the bases are held together by an almost linear
system of covalent bonds rather than by an essentially
planar assembly of two or three H-bonds.
Table 5 shows that also the stretching vibrations
(136–164 cm –1) for the nonhydrated C-M-A c complexes are rather similar to those found in the base
pairs without metal ions [49].
Table 5 Lowest harmonic vibrational modes ni (cm –1) for the optimized structures of selected systems, determined at the HF/631G* level; (p), (b), and (s) mean the propeller twist, buckle, and
stretch intermolecular vibrations, respectively; the frequencies
were not scaled
ni
C-Au(I)-A
C-Cu(I)-A
C-Ag(I)-A
C-Ag(I)-A-W
1
2
3
4
5
6
7
8
9
10(p)
30(b)
44
73
97
103
155
164(s)
181
18(p)
28(b)
50
80
90
101
139
152(s)
184
13(b)
21(p)
32
58
64
77
92
136(s)
185
14(p)
17(b)
28
41
66
71(s)
80
85
89
544
Concluding remarks
References
The present study provides several new observations
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noncomplementary base pair adenine-cytosine.
In the hydrated complexes, all crosslinked structures
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way Ag(I) interacts with DNA would be advantageous,
considering the established mutagenicity of AgNO3 and
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Acknowledgements This study was supported by grant
A4040903 from IGA AS CR (J.S.), by VW-Stiftung I/74657 (B.L.,
J.S.), by NATO Collaborative Linkage Grant LST.CLG 975296
(J.S., M.S.), and partly by grant 203/97/0029 from the GA CR
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