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Metal-Mediated DNA Base Pairing and Metal Arrays in Artificial DNA Towards New Nanodevices.

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Metal Ions in Artificial DNA
Metal-Mediated DNA Base Pairing and Metal Arrays in
Artificial DNA: Towards New Nanodevices
Hans-Achim Wagenknecht*
base pairing · DNA structures · metal–metal
interactions · nucleoside mimetics · oligonucleotides
Fifty years after the elucidation of the
DNA double-helix structure, the unique
properties of the DNA double helix
continue to fascinate chemists. The
principle of base pairing between two
complementary oligonucleotide strands
is rather uncomplicated. Essentially, two
noncovalent forces mainly stabilize the
double-helical structure of DNA: a) the
arene–arene p stacking of the planar
heterocycles of the DNA bases, and
b) the hydrogen bonding between the
complementary DNA bases.
Besides the biological importance of
DNA as the carrier of genetic information, the regular and canonical structure
of duplex DNA can be regarded as a
template for the bioinspired generation
of new functionalized molecular architectures.[1] Especially the self-assembly
and the highly specific interstrand recognition of two complementary oligonucleotides represent the most promising aspects of the DNA framework on
the way to new inorganic and bioorganic
nanosize devices.[2]
One important strategy for the functionalization of DNA duplexes is the
replacement of the natural bases by
artificial nucleosides or nucleoside mimics.[3] However, this approach is restricted to molecules with a distinct shape and
size that should be comparable to normal base pairs to ensure that the DNA
modifications occur highly specifically
[*] H.-A. Wagenknecht
Institute for Organic Chemistry
and Biochemistry
Technical University of Munich
Lichtenbergstrasse 4
85 747 Garching (Germany)
Fax: (+ 49) 89-289-13210
and site selectively.[3] In the last
2–3 years, a new generation of such
nucleoside mimics were reported in
which the hydrogen-bonding interactions were replaced by a metal-mediated
base pairing.[4–6] The advantage of this
modification strategy is that it allows the
metal ions to be placed in the interior of
the DNA duplex. This represents an
important structural prerequisite for the
development of new molecular devices
based on interacting metal centers. Tor
and Weizman coined the term “ligandosides” for suitable metal ion nucleoside
chelators, which should fulfill the following requirements:[4]
a) The nucleoside mimics should be
compatible with the standard automated DNA synthesis.
b) The chelating part of the nucleoside
mimics should have a higher affinity
than natural DNA bases towards
metal ions.
c) The nucleoside mimics should form
planar complexes with metal ions,
and their dimensions should be comparable with those of a DNA base
The groups of Tor,[4] Schultz and
Meggers,[5] and Shionoya[6] synthesized a
few strong chelators that meet the above
criteria and incorporated them as artificial DNA bases into oligonucleotides
(Figure 1). DNA base pairing resulted
from the addition of metal ions such as
Cuii, PdII, or Agi, which form planar
complexes with the nucleoside chelators. The planarity of these artificial
DNA base pairs ensures their proper
intercalation within the DNA base
stack. A remarkable consequence of
the insertion of just one artificial metal-ion-mediated base pair is that the
thermal stability of the modified DNA
duplex is strongly enhanced relative to
one with normal hydrogen-bond interactions.
The incorporation of metal complexes as artificial base pairs into the
biopolymer DNA represents a third key
motif for interactions between the two
complementary strands of the biopolymeric DNA. Hence, this modification
can be recognized as an extension of the
genetic alphabet and, more importantly,
is also expected to lead to novel DNA
structures and functions. An important
milestone towards such new DNA architectures was recently reported by
Shionoya and co-workers, who incorporated several metal ions adjacent to each
other into an artificial DNA framework.
As a result, a self-assembled metal array
was formed.[7] Examples of one-dimensional arrays in solution are quite limited and they are mainly investigated in
the solid-state.[8] Shionoya and co-workers synthesized a hydroxypyridone nucleobase, which meets all the criteria for
a ligandoside.[4] The deprotonated hydroxypyridone chelator forms stable,
planar, and electrostatically neutral
complexes in the presence of Cuii ions
(Scheme 1).[9]
The hydroxypyridone nucleoside
was synthetically incorporated through
automated phosphoramidite chemistry
into short oligonucleotides that contain
three to seven nucleotide units. The
DNA base sequences were designed in
such a way that between one and five
Cuii-modified nucleosides were placed
adjacent to each other. An important
observation was that the modified oligonucleotides do not form stable duplex
structures in the absence of Cuii ions.
Thus, duplex formation can be attributed solely to the CuII-mediated alterna-
DOI: 10.1002/anie.200301661
Angew. Chem. Int. Ed. 2003, 42, 3204 – 3206
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Figure 1. Metal-ion-mediated base pairs replace natural base pairs in DNA duplexes and, as a result, enhance the thermal stability.[4–6]
The most important
structural feature of this
artificial DNA is the alignment of the Cuii ions along
the axes inside the duplexes.
The canonical helical conformation of these DNAlike duplexes ensure regular
Cuii–Cuii distances. EPR
spectroscopy was employed
to characterize the mode of
interaction between the
stacked Cuii-mediated base
pairs. The EPR spectra
were quite different from
that of a single Cuii-containing base pair and confirmed
a ferromagnetic coupling
Scheme 1. Formation of a metal array of hydroxypyridone–
d electron of each of the
Cuii complexes inside a DNA-like duplex through Cuii-mediated self-assembly of two complementary oligonucleotides.
Cuii ions (S = 1=2 ). Thus the
spectrum of the duplex with
n adjacent Cuii centers
tive base pairing. The successful forma- could be attributed to the spin state
tion of helical DNA-like duplexes was S = n/2 (n = 1–5). Based on the fine
splitting of the EPR signals the Cuii–
confirmed spectroscopically:
a) The UV/Vis spectra showed an addi- Cuii distance in the artificial DNA
tional band at 307 nm as a result of duplexes could be estimated to be
Cuii complexation;
3.7 D, which is remarkably similar to
b) Electrospray ionization mass spec- the distance between two adjacent base
trometry provided the correct mass- pairs in natural DNA duplexes (3.4 D).
In conclusion, the replacement of
es for the intermolecular oligonuhydrogen-bonded base pairs with metal
cleotide complexes.
c) Circular dichroism spectra con- complexes represents a promising modfirmed the right-handed helicity of ification on the way towards new molecular devices based on interacting
the duplexes.
Angew. Chem. Int. Ed. 2003, 42, 3204 – 3206
metal centers. The work of Shionoya
and co-workers clearly describes a remarkable example of how this idea can
be applied to arrange a discrete onedimensional metal array in a predictable
manner. The DNA serves simply as a
structural framework. The formation of
a magnetic chain by the self-assembled
alignment of metal centers within a
DNA-like double helix is of great importance to the field of nanotechnology
as it provides the basis for novel nanodevices such as semiconductors, molecular magnets, and wires.
[1] J.-M. Lehn, Supramolecular Chemistry:
Concepts and Perspectives, Wiley-VCH,
Weinheim, 1995.
[2] a) C. M. Niemeyer, Angew. Chem. 2001,
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[3] a) E. T. Kool, J. C. Morales, K. M. Guckian, Angew. Chem. 2000, 112, 1046 – 1968;
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[4] a) H. Weizman, Y. Tor, Chem. Commun.
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Am. Chem. Soc. 2001, 123, 3375 – 3376.
[5] a) E. Meggers, P. L. Holland, William B.
Tolman, F. E. Romesberg, P. G. Schultz, J.
Am. Chem. Soc. 2000, 122, 10 714 – 10 715;
b) S. Atwell, E. Meggers, G. Spraggon,
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[6] a) M. Tasaka, K. Tanaka, M. Shiro, M.
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[7] K. Tanaka, A. Tengeiji, T. Kato, N.
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108, 2946 – 2948; Angew. Chem. Int. Ed.
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base, towards, pairing, metali, array, nanodevices, dna, new, mediated, artificial
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