21010
J. Phys. Chem. B 2006, 110, 21010-21013
Electronic Coupling Mediated by Stacked [Thymine-Hg-Thymine] Base Pairs
Alexander A. Voityuk†
Institució Catalana de Recerca i Estudis AVançats, Institute of Computational Chemistry,
UniVersitat de Girona, 17071 Girona, Spain
ReceiVed: May 6, 2006; In Final Form: August 14, 2006
Very recently it has been shown that stable metal-mediated base pairs [Thymine-Hg-Thymine] can form in
DNA. To estimate the effect of such pairs on the efficiency of charge transfer through DNA, we carry out
quantum mechanical calculations of double-stranded π-stacks GXG, GXXG, and GXXXG, where X )
[Thymine-Hg-Thymine] and stacks GTnG of canonical base pairs. The charge-transfer efficiency in short
duplexes GXG and GTG is found to be similar. However, the donor-acceptor coupling in GXXG and GXXXG
is stronger by a factor of 2.5-3.0 than that in GTnG (n ) 2 and 3), respectively. It is shown that the valence
orbitals of Hg atoms do not essentially participate in mediating the electronic coupling for hole transfer;
however, they may play an important role in excess electron transfer.
Introduction
Recently, it has been found that in DNA duplexes T-T
(thymine-thymine) mispairs capture Hg2+ ions and form stable
neutral base pairs [T-Hg-T].1 The formation of such complexes
results in stabilization of the duplex depending on the number
of consecutive [T-Hg-T] pairs.1 Among various interesting
effects caused by the stacked T-Hg-T pairs, one may expect
remarkable modulation of the charge transfer (CT) efficiency
through DNA. Electron hole transfer mediated by DNA π-stacks
has received remarkable attention over last 15 years.2 A number
of experimental and theoretical studies have been performed to
understand mechanisms of charge migration in the double
helix.3-21
It has become clear that natural DNA is a rather poor electrical
conductor and the DNA conductivity must be essentially
improved to be sufficient for various applications in nanoelectronics. One of the most promising approaches is the development of M-DNA, which contains the metal ions in the middle
of base pairs in the duplex.22-28 It has been shown that M-DNA
may operate as a better conductor than B-DNA.29-31 In such
metal-mediated base pairs, the hydrogen bonds between bases
are replaced by metal-nucleobase coordination bonds. The
interaction of neighboring metal atoms is assumed to provide a
pathway for charge conductivity. However, the change in the
surface charge of DNA caused by the binding of metal ions
may also play an important role in the enhancement of current
with M-DNA.32
The formation of stable DNA π-stacks containing mercurymediated thymine-thymine pairs, in which imino protons of the
bases are replaced by Hg2+, suggests a new approach to the
development of M-DNA.1 Still there have been no experiments
on charge transfer through such π-stacks. Therefore, it is worthy
to compare hole transfer in the modified and natural DNA
π-stacks on the basis of computational models. Because the
efficiency of nonadiabatic charge transfer is directly related to
electronic coupling Vda of diabatic donor and acceptor states
(the CT rate is proportional to Vda2),33,34 the calculation of Vda
in short DNA stacks of similar structure provides reasonable
† Address correspondence to the author at e-mail alexander.voityuk@
icrea.es.
information about the electronic effects in the charge-transfer
process.9,14-16,21 Computational aspects of estimating Vda matrix
elements were considered in detail.35-40
In this paper we compare the results of quantum mechanical calculations of DNA stacks containing metal-mediated
[T-Hg-T] pairs and canonical AT pairs and show that the
interaction of neighboring [T-Hg-T] base pairs should considerably (an order of magnitude) increase the hole transfer efficiency
in a DNA π-stack.
Computational Details
The structures of the neutral [T-Hg-T] pair as well as
canonical GC and AT pairs were optimized by using B3LYP
calculations. The 6-31G* basis sets were used for H, C, N, and
O, while for Hg we employed the LanL2DZ basis set with inner
electrons substituted by effective core potentials and double-ζ
quality valence functions.41 The program Gaussian03 was used.42
The calculated geometries of X, GC, and AT pairs were
employed for generating a number of stacks where the hole
donor and acceptor (GC) pairs are connected with one or two
X and AT bridges. The mutual position of base pairs in a stack
was defined by using six base-step parameters.43
For calculating electronic couplings Vda a multistate Generalized Mulliken-Hush (GMH) approach was employed. A twostate model, commonly used for estimating electronic couplings,
cannot provide accurate Vda values for the DNA π-stacks
because of the multistate effects.44 Recently, the dependence
of the calculated couplings for hole transfer in π-stacks on the
number of adiabatic states treated simultaneously within the
GMH approach has been analyzed.45 It was shown that reliable
estimates of Vda for thermal CT may be obtained by removing
excited states of donor and acceptor from the list of adiabatic
states treated within GMH and a simple scheme was suggested
to select the appropriate states.45 Alternatively, the results
derived within a two-state model can be considerably improved
when the superexchange correction is taken into account.46
The electronic couplings were calculated within the oneelectron approach based on Koopmans’ theorem. The HartreeFock method was used to generate molecular orbitals of the
systems. This approach has recently been justified by comparison of the estimated hole-transfer couplings between stacked
10.1021/jp062776d CCC: $33.50 © 2006 American Chemical Society
Published on Web 09/19/2006
Formation of [Thymine-Hg-Thymine] Base Pairs
J. Phys. Chem. B, Vol. 110, No. 42, 2006 21011
TABLE 1: Electronic Coupling Vda (in meV) of GC Donor and Acceptor Sites in the DNA Stacks GXnG Containing
Metal-Mediated Base Pairs X ) [T-Hg-T] and the Natural GTnG Sequences, Using the Multistate GMH Methoda
GX2G
stack
GXG
GX2G
GX3G
GT2G
multistate model
2-state model
stack
multistate model
2-state model
10.7 (4), 10.5 (6), 10.4 (8)
5.2 (6), 5.1 (8), 5.5 (10)
1.11 (8), 1.07 (10), 1.08(11)
[2.2]b
GTG
GT2G
GT3G
13.7 (4), 11.7 (6), 11.2 (8)
2.0 (6), 2.0 (8), 2.2 (10)
0.29 (8), 0.35 (10), 0.31 (11)
[5.4]b
[0.84]b
[0.08]b
[2.0]b
[0.13]b
a The number of states is given in parentheses. b The estimates obtained within the 2-state model [in brackets] are not accurate and are given only
for comparison.
Figure 1. The structure of the [Thymine-Hg-Thymine] base pair
calculated within B3LYP.
nucleobases with results of CASSCF and CAS-PT2 calculations.47
Results and Discussion
Thymine-Hg-Thymine Pair. Although the energy minimum
of X corresponds to a nonplanar conformation with the
nucleobase planes perpendicular to each other, the planar
structure is found to be only 1.9 kcal/mol higher in energy.
Because the stacking interaction between nucleobases is stronger
than 10 kcal/mol (the reliable values of stacking interaction
energies were obtained by Hobza and Sponer48), a planar
structure of X is expected to be found in π-stacks. The structure
of the planar conformation of [T-Hg-T] is shown in Figure 1.
The distance of 8.59 Å between the N1 atoms bound to the
sugar-phosphate backbone in a DNA stack is found to be
similar to N9-N1 distances in canonical AT and GC pairs. Thus,
no essential structural defects are expected because of the
formation of [T-Hg-T] pairs. Hg atoms lying almost in the
middle of the mispairs will be near the axis of π-stacks. Different
from canonical pairs, both nucleobases of the X pair are
equivalent. As expected, the two first ionization potentials of
an isolated [T-Hg-T] pair are very close to each other; their
difference is about 0.02 eV. However, in the GXG stack, their
splitting is ∼0.83 eV. This remarkable difference is due to the
electrostatic interaction of the thymine bases with neighboring
guanine and cytosine bases. The effect of adjacent nucleobases
on the stability of radical cation states in DNA stacks has already
been examined in detail.49
GXG and GTG. First, we consider the short stacks consisting
of three base pairs. In these systems, the guanine donor and
acceptor sites are in the same strand. Due to the interaction with
bridging bases, the diabatic states are not equivalent and have
slightly different energies. In the ground state of both G1XG3
and G1TG3 radical cations, the hole is mainly localized on G1.
The CT states in both stacks lie only ∼0.05 eV higher than the
ground states, and therefore are thermally accessible. Electronic
couplings between G1 and G3 calculated within two-state and
multistate approaches are presented in Table 1. As can be seen,
the values found within the two-state model are considerably
underestimated and cannot be used for estimating the CT
efficiency. It was shown that in DNA π-stacks where donor
and acceptor are separated by a bridge consisting of P base pairs,
the GMH calculations, which employ (2+2P) adiabatic states,
give quite reliable results.45 In GXG and GTG, very similar
values of Vda are obtained (Table 1): the 4-state model predicts
10.7 and 13.7 meV; respectively; the values of 10.5 and 11.7
meV for GXG and GTG are calculated when taking into account
6 adiabatic states. The estimates derived within 4- and 6-state
models are in good agreement. Also, further extension of the
number of states leads to similar values of Vda. Thus, the
couplings calculated for the GXG and GTG stacks of the regular
structure are quite similar. This result is not unexpected because
in both cases the donor-acceptor coupling is mainly mediated
by the intrastrand interaction guanine-thymine-guanine. In GTG
there are two superexchange pathways: the intrastrand coupling
mediated by thymine (the energy gap is 1.30 eV) and interstrand
coupling mediated by adenine (the energy gap is 0.78 eV). The
corresponding contributions are about 7 and 2 meV, though the
second path is energetically more feasible. In the GXG, the Vda
is almost completely mediated by intrastrand thymine (the
contribution of the alternative pathway is only about 1%). In
this case, the intrastrand superexchange interaction is favored
by both the orbital overlap and the energy gap (the tunneling
gap is 1.17 and 2.00 eV for intra- and interstrand pathways,
respectively).
GXXG and GTTG. In these stacks the distance between the
hole donor and acceptor (GC pairs) is 10.14 Å. The coupling is
mediated by the bridges consisting of two base pairs. The
structure of the GXXG stack is shown in Figure 2. While the
Vda values in GXG and GTG are found to be similar, the
couplings in GXXG and GTTG are remarkably different. As
seen from Table 2, the estimates obtained within the two-state
approach are rather unreliable. However, one arrives at consistent Vda values when taking into account 6, 8, or 10 adiabatic
states. The calculated values of Vda are 5.2 and 2.0 meV in
GXXG and GTTG, respectively. Thus, the efficiency for hole
transfer between the guanine sites in [GXXG] should be larger
than that in [GTTG] by a factor of 6.
Within the superexchange model the donor acceptor coupling
in GBG and GBBG can be approximately estimated as:
VSE
da (GBG) ) VG-BVB-G/∆
2
SE
VSE
da (GBBG) ) VG-BVB-BVB-G/∆ ) Vda (GBG)VB-B/∆
where ∆ is a tunneling gap (energy difference of states with a
hole localized on the bridge and donor sites); only the intrastrand
superexchange pathway is accounted for. Then
SE
VSE
da (GXXG)/Vda (GTTG)
[
]
VSE
da (GXG) VX-X/∆X
) SE
V (GTG) VT-T/∆T
da
SE
Because ∆X ≈ ∆T and VSE
da (GXG) ≈ Vda (GTG), a stronger
21012 J. Phys. Chem. B, Vol. 110, No. 42, 2006
Voityuk
Figure 3. Electronic couplings V between [T-Hg-T] pairs (closed bulks)
and AT base pairs (open bulks) calculated for various conformations
in the corresponding dimers. In the reference conformation rise ) 3.38
Å, twist ) 36°, and all other bese-step parameters are zero. Shift, slide,
and rise are in Å, tilt, roll, and twist are in deg.
Figure 2. Structure of the duplex [GXXG]. The distance between base
pairs is 3.38 Å.
interaction between [T-Hg-T] pairs, VX-X, as compared with
that of AT pairs, VT-T, is responsible for more efficient hole
transfer in the GXXG stack.
GXXXG and GTTTG. Let us consider systems where the
donor and acceptor sites are linked with a bridge consisting of
three pairs. Table 1 lists Vda values for XXX and TTT bridges
estimated by using the multistate GMH models. The Vda value
derived for GX3G with use of the two-state model is an order
of magnitude smaller than the couplings calculated with the
number of state g8. In the case of GT3G the couplings found
within the multistate and two-state models differ by a factor of
about 4. When comparing the Vda values for GX3G and GT3G
one may suggest that the hole transfer through the modified
stack should be an order of magnitude faster than that through
the normal DNA stack. Thus, the X-X interaction provides a
more efficient supererexchange path than T-T.
On the basis of the theoretical model for hole transfer through
DNA it was shown that switching from the superexchange to
an alternative mechanism occurs when three or more bridging
base pairs separate the d-a sites.50 A similar conclusion was
also derived from comparison of the calculated and observed
hole transfer rates in several π-stacks.16 Therefore, we do not
consider bridges containing more than 3 base pairs.
Conformational Dependence of VX-X and VT-T. Recently,
it has been shown that electronic couplings in DNA strongly
depend on the position of nucleobases and are very sensitive to
structural fluctuations.51,52 Therefore, the relation |VX-X/VT-T|
> 1 calculated for a selected stack structure may change when
other conformations are considered. Let us compare the
couplings in dimers [X, X] and [(TA), (TA)] with different
mutual positions of the base pairs. Figure 3 demonstrates a rather
dissimilar behavior of the couplings VX-X and VT-T by
conformational changes in the dimers. A mutual position of two
base pairs is defined by 6 base-step parameters, three translations
(slide, shift, and rise) and three rotation angles (tilt, roll, and
twist). As can be seen, in several [(TA), (TA)] conformations
(shift -0.5 Å, roll -5°, twist 31°) the coupling is negative.
This means that in the vicinity of the reference structure of
the dimer there should be many configurations where the
coupling is close to zero. On the contrary, the coupling of X
pairs in the dimer [X, X] retains its sign in all 13 considered
conformations. Also, the VX-X values are found to be essentially
larger than the corresponding VT-T values. This means that both
the mean value of VX-X and its quadratic average calculated
along an MD trajectory are expected to be larger than the
corresponding values for VT-T. Thus, our conclusion that the
stacked [T-Hg-T] pairs facilitate the hole transfer through DNA,
which was derived for ideal π stacks, should also hold when
structural fluctuations are accounted for.
Role of Hg-Hg Orbital Overlap. Better conductivity of
M-DNA as compared with B-DNA is often attributed to the
overlap of metal orbitals. One can explore the role of the Hg
orbitals in mediating the electronic coupling for hole transfer
by inspecting HOMO and HOMO-1 of the [X, X] dimer. Within
the one-electron approximation these orbitals describe adiabatic
states of the radical cation and can be employed to calculate
the electronic coupling matrix elements. The orbitals are shown
in Figure 4. As can be seen, there is no essential contribution
of Hg orbitals to HOMO and HOMO-1, and therefore, the metal
atoms do not participate directly in the superexchange interaction. Also, other lower lying occupied MO, HOMO-I with I )
2-6, which describe excited states of the XX bridge do not
contain any remarkable contribution of the metal orbitals. Thus,
larger values of the hole-transfer coupling VX-X as compared
with VT-T cannot be attributed to the metal-metal interaction,
and the difference in the VT-T and VX-X magnitudes should be
assigned to the changes in π-electron density caused by
replacement of adenine by thymine and deprotonation of the
thymine bases. However, it should be emphasized that although
the metal orbitals play a minor role in mediating the hole transfer
coupling, the situation will probably change in the case of excess
electron transfer through π-stacks containing the XX sequence
because of considerable contribution of the metal orbitals in
LUMO of [T-Hg-T] (Figure 3).
Conclusions
On the basis of quantum mechanical calculations of double
stranded π-stacks GXnG, X ) [Thymine-Hg-Thymine], and
GTnG, n ) 1-3, we studied the effects of substitution of X for
the canonical AT pair on the hole transfer efficiency in DNA
stacks. The multistate GMH method was employed to estimate
the coupling matrix elements.
1. While the donor-acceptor couplings are calculated to be
similar in GTG and GXG, the Vda in GXnG is found to be
remarkably stronger (by a factor of 2.5-3.0) than that in GTnG
(n ) 2 and 3) because of the bridge-bridge interaction.
Formation of [Thymine-Hg-Thymine] Base Pairs
Figure 4. LUMO, HOMO and HOMO-1 of [X, X] dimer. The metal
orbitals do not contribute to HOMO, HOMO-1, and several lower states,
and therefore cannot essentially participate in hole transfer. On the
contrary, LUMO and LUMO-1 consist mainly of the valence orbitals
of mercury and should play an important role in excess electron transfer
through the modified DNA π-stack.
2. Comparison of VX-X and VT-T in a number of conformations of π-stack dimers reveals that in all considered structures
the VX-X values are larger than VT-T. Therefore, one can expect
that accounting for structural dynamics of the stacks will not
change the conclusion about the intrinsic enhancement of the
hole mobility in GXnG stacks as compared with GTnG.
3. No essential contribution of the metal-metal interaction
to the superexchange mediated coupling for hole transfer has
been found. Thus, the difference in the VT-T and VX-X electronic
couplings should be attributed to structural changes in π-electron
density caused by replacement of adenine by thymine and
deprotonation of the thymine bases [T-Hg-T].
Acknowledgment. This work has been supported by the
Spanish Ministerio de Educación y Ciencia, Project No.
CTQ2005-04563.
References and Notes
(1) Miyake, Y.; Togashi, H.; Tashiro, M.; Yamaguchi, H.; Oda, S.;
Kudo, M.; Tanaka, Y.; Kondo, Y.; Sawa, R.; Fujimoto, T.; Machinami, T.;
Ono, A. J. Am. Chem. Soc. 2006, 128, 2172.
(2) Long-Range Charge Transfer in DNA; Shuster, G. B., Ed.; Topics
in Current Chemistry Series; Springer, Berlin, Germany, 2004; Vol. 236, p
237.
J. Phys. Chem. B, Vol. 110, No. 42, 2006 21013
(3) Dandliker, P. J.; Holmlin, R. E.; Barton, J. K. Science 1997, 275,
1465.
(4) Jortner J.; Bixon, M.; Langenbacher T.; Michel-Beyerle, M.-E. Proc.
Natl. Acad. Sci. U.S.A. 1998, 95, 12759.
(5) Bixon, M.; Giese, B.; Wessely, S.; Langenbacher T.; MichelBeyerle, M.-E.; Jortner J. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 11713
(6) Schuster, G. B. Acc. Chem. Res. 2000, 33, 253.
(7) Giese, B. Acc. Chem. Res. 2000, 33, 631.
(8) Lewis, F. D.; Letsinger, R. L.; Wasielewski, M. R. Acc. Chem.
Res. 2001, 34, 159.
(9) Delaney, S. D.; Barton, J. K. J. Org. Chem. 2003, 68, 6475.
(10) Berlin, Y. A.; Kurnikov, I. V.; Beratan, D. N.; Ratner, M. A.; Burin,
A. L. Top. Curr. Chem. 2004, 237, 1-36.
(11) Bixon, M.; Jortner, J. J. Am. Chem. Soc. 2001, 123, 12556.
(12) Berlin, Y. A.; Burin, A. L.; Ratner, M. A. J. Phys. Chem. A 2000,
104, 443.
(13) Berlin, Y. A.; Burin, A. L.; Ratner, M. A. J. Am. Chem. Soc. 2001,
123, 260.
(14) Jortner, J.; Bixon, M.; Voityuk, A. A.; Rösch, N. J. Phys. Chem.
A 2002, 106, 7599.
(15) Voityuk, A. A.; Bixon, M.; Jortner, J.; Rösch, N. J. Chem. Phys.
2001, 114, 5614.
(16) Tong, G. S. M.; Kurnikov, I. V.; Beratan, D. N. J. Phys. Chem. B
2002, 106, 2381.
(17) Barnett, R. N.; Cleveland, C. L.; Joy, A.; Landman, U.; Schuster,
G. B. Science 2001, 294, 567.
(18) Liu, C.-S.; Hernandez, R.; Schuster, G. B. J. Am. Chem. Soc. 2004,
126, 2877.
(19) Voityuk, A. A.; Siriwong, K.; Rösch, N. Angew. Chem., Int. Ed.
2004, 43, 624.
(20) Conwell, E. M. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 8795.
(21) Senthilkumar, K.; Grozema, F. C.; Guerra, C. F.; Bickelhaupt, F.
M.; Lewis, F. D.; Berlin, Y. A.; Ratner M. A.; Siebbeles, L. D. A. J. Am.
Chem. Soc. 2005, 127, 14894..
(22) Meggers, E.; Holland, P. L.; Tolman; W. B.; Romesberg, F. E.;
Schultz, P. G. J. Am. Chem. Soc. 2000, 122, 10714.
(23) Atwell, S.; Meggers, E.; Spraggon, G.; Schultz, P. G. J. Am. Chem.
Soc. 2001, 123, 12364.
(24) Carell, T.; Behrens, C.; Gierlich, J. Org. Biomol. Chem. 2003, 1,
2221.
(25) Spring, B. Q.; Clegg, R. M. Biophys. J. 2004, 86, 472A.
(26) Switzer, C.; Sinha, S.; Kim, P. H.; Heuberger, B. D. Angew. Chem.,
Int. Ed. 2005, 44, 1529.
(27) Zhang, L.; Meggers, E. J. Am. Chem. Soc. 2005, 127, 74.
(28) Tanaka, K.; Tengeiji, A.; Kato, T.; Toyama, N.; Shionoya, M.
Science 2003, 299, 1212.
(29) Wettig, S. D.; Wood, D. O.; Aich, P.; Lee, J. S. J. Inorg. Biochem.
2005, 99, 2093.
(30) Wettig, S. D.; Bare, G. A.; Skinner, R. J. S.; Lee, J. S. Nano Lett.
2003, 3, 617.
(31) Long, Y. T.; Li, C. Z.; Kraatz, H. B.; Lee, J. S. Biophys. J. 2003,
84, 3218.
(32) Liu, B.; Bard, A. J.; Li, C. Z.; Kraatz, H. B. J. Phys. Chem. B
2005, 109, 5193.
(33) Marcus, R. A.; Sutin, N. Biochim. Biophys. Acta 1985, 811, 265.
(34) Newton, M. D. Chem. ReV. 1991, 91, 767.
(35) Cave, R. J.; Newton, M. D. J. Chem. Phys. 1997, 106, 92139226.
(36) Cave, R. J.; Newton, M. D. Chem. Phys. Lett. 1996, 249, 15.
(37) Voityuk, A. A.; Rösch, N. J. Chem. Phys. 2002, 117, 5607.
(38) Rösch, N.; Voityuk, A. A. Top. Curr. Chem. 2004, 237, 37-72.
(39) Voityuk, A. A.; Rösch, N. J. Phys. Chem. B 2002, 106, 3013.
(40) Voityuk, A. A. J. Chem. Phys. 2005, 123, 034903.
(41) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299.
(42) Frisch, M. J. et al. Gaussian 03; Gaussian, Inc.: Pittsburgh, PA,
2003.
(43) Bloomfield, V. A.; Crothers, D. M.; Tinoco, I. Nucleic Acids:
Structures, Properties, and Functions; University Science Books: Sausalito,
CA, 1999.
(44) Voityuk, A. A. J. Phys. Chem. B 2005, 109, 17917.
(45) Voityuk, A. A. Chem. Phys. Lett. 2006, 422, 15.
(46) Voityuk, A. A. J. Chem. Phys. 2005, 124, 064505.
(47) Blancafort, L.; Voityuk, A. A. J. Phys. Chem. A, 2006, 110, 6426.
(48) Hobza, P.; Sponer, J. J. Am. Chem. Soc. 2002, 124, 11802.
(49) Voityuk, A. A.; Jortner, J.; Bixon, M.; Rösch, N. Chem. Phys. Lett.
2000, 324, 430.
(50) Berlin, Y. A.; Burin, A. L.; Ratner, M. A. Chem. Phys. 2002, 27,
61.
(51) Voityuk, A. A.; Siriwong, K.; Rösch, N. Phys. Chem. Chem. Phys.
2001, 3, 5421.
(52) Troisi, A.; Orlandi, G. J. Phys. Chem. B 2002, 106, 2093.