TTF-modified DNA

Article abstract of DOI:10.1002/chem.200800505

A study was conducted to demonstrate tetrathiafulvalene (TTF)-modified DNA. The effect of TTF incorporation on duplex stability was analyzed by thermal denaturation investigations. It was observed that incorporation of TTF moiety in each strand led to a a considerable increase instability of DNA in comparison with its unmodified form. Investigations revealed that the increase in stability can be due to stacking interactions between the TTF units, with the neighboring nucleobases and to hydrophobic interactions of the pentyl chains. Cooperativity of the melting process in the natural and modified part of the DNA duplex, was shown by monitoring the denaturation process at 290 nm and 330 nm. The study also demonstrated that TTF-modified DNA strands form stable hybrids with all other modified strands.

Full text of DOI:10.1002/chem.200800505

DOI: 10.1002/chem.200800505
TTF-Modified DNA
Nicolas Bouquin, Vladimir L. Malinovskii, Xavier GuØgano, Shi-Xia Liu,
Silvio Decurtins, and Robert Häner*[a]
Ever since its first description,[1] tetrathiafulvalene (TTF)
has taken an eminent role in the field of materials sciences.
Due to their specific p-donor properties, TTFs have been in-
corporated into a number of macrocyclic, molecular, and
supramolecular systems to create multifunctional materials
introduction of pyrimido-TTF nucleosides into a phosphoro-
thioate oligoribonucleotide.[52] Due to the interesting elec-
tronic properties of TTF and its excellent stacking proper-
ties, we have explored the generation of TTF-modified
DNA. Here, we present the synthesis of a non-nucleosidic
TTF building block (F, see Table 1), its incorporation into
oligonucleotides, as well as the properties of several modi-
fied hybrids.
[2–8]
with desired structure, stability, and physical properties.
As a consequence, theyare frequentlyused as donor units
in donor–acceptor (D–A) ensembles that are of prime inter-
est due to their potential applications in molecular electron-
ics and optoelectronics.[9–13] In addition, their tendencyto
form p-stacked aggregates renders them attractive objects
for the construction of supramolecular assemblies with ap-
plications in liquid-crystalline materials and organogels.[14,15]
DNA represents a highlydeveloped, yet verypractical scaf-
fold for the construction of complex assemblies.[16] Due to
the existence of well-developed and versatile methods for
oligonucleotide synthesis, the use of modified nucleic acids
has become an attractive wayfor the generation of function-
alized nanostructures.[17] During the past decade, non-nucle-
osidic aromatic hydrocarbons, such as phenanthrene,[18–20]
pyrene,[21–28] and perylene,[29–33] have been developed as
building blocks for modified nucleic acids.[34–37] Theywere
explored as hairpin replacements,[38–44] as units for conforma-
tional control in DNA,[45–47] or as replacements of the natu-
ral nucleotides maintaining helical organization.[48–50] Further
efforts are aimed at the development of advanced functional
building blocks with a high level of structural organization.
Interest in TTF–oligonucleotide conjugates is documented
in patents describing the use of redox-active labels for the
development of oligonucleotide-based sensors.[51] So far,
however, a single report on the preparation of such a con-
struct exists, in which Neilands and co-workers describe the
Table 1. Hybridization data of TTF-modified DNA duplex.[a]
Hybrid
Tm [8C] DTm [8C]
5
6
(5’) AGC TCG GTC ATC GAG AGT GCA
(3’) TCG AGC CAG TAG CTC TCA CGT
72.5
–
7
8
(5’) AGC TCG GTC AFC GAG AGT GCA
(3’) TCG AGC CAG TFG CTC TCA CGT
77.4
+4.9
[a] Conditions: 1.0 mm oligonucleotide concentration (each strand), 10 mm
phosphate buffer (pH 7.4) and 100 mm NaCl.
The synthesis of the tetrathiafulvalene phosphoramidite
building block is shown in Scheme 1. Starting from the
known 2,3-bis(2-cyanoethylthio)-6,7-bis(pentylthio)tetrathia-
fulvalene (1),[53] bis-diol 2 was prepared bytreatment with
sodium in ethanol followed byalkylation with 2-chloroetha-
nol. Reaction with 4,4’-dimethoxytrityl chloride gave the
mono-protected intermediate 3, which was subsequently
converted into the phosphoramidite derivative 4.
Building block 4 was used for the synthesis of modified
oligonucleotides. Despite the known susceptibilityof TTF
towards strong acids and oxidants, the standard phosphora-
midite protocol[54] was successfullyapplied. Although some
fragmentation of the TTF-modified oligonucleotides was ob-
served during ammonia deprotection, oligomers 7–9 were
[a] N. Bouquin, Dr. V. L. Malinovskii, X. GuØgano, Dr. S.-X. Liu,
Prof. Dr. S. Decurtins, Prof. Dr. R. Häner
Department of Chemistryand Biochemistry
Universityof Bern
Freiestrasse 3, 3012 Bern (Switzerland)
E-mail: robert.haener@ioc.unibe.ch
[55]
easilypurified byreverse phase HPLC.
Supporting information for this article is available on the WWW
under http://www.chemistry.org or from the author.
5732
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Chem. Eur. J. 2008, 14, 5732 – 5736

COMMUNICATION
bychiral induction bythe nu-
cleic acid environment. This
signal disappears upon duplex
melting (Figure 1, inset).
The structural and electronic
effects resulting from TTF
modification were further stud-
ied in mixed DNA hybrids
(Table 2). Non-nucleosidic per-
ylene diimide (PDI, building
block E) or pyrene (S) units
were placed opposite TTF. PDI
was selected due to its high sen-
Scheme 1. Synthesis of TTF phosphoramidite 4; DMT=4,4’-dimethoxytrityl; PAM=2-cyanoethyl N,N-diiso-
propyl-phosphoramidite.
sitivitytowards conformational
Table 2. Hybridization data of mixed DNA hybrids.[a]
The effect of TTF incorporation on duplex stabilitywas
analyzed by thermal denaturation experiments (Table 1). In-
corporation of one TTF moietyin each strand (duplex 7*8)
Hybrid
Tm [8C]
9
10
(5’) AGC TCG GTC FFC GAG AGT GCA
(3’) TCG AGC CAG EEG CTC TCA CGT
72.1
results in
a considerable increase in stability( DTm =
+4.98C) in comparison to the unmodified duplex 5*6. The
increase in stabilitycan be due to stacking interactions be-
tween the TTF units with the neighboring nucleobases as
well as to hydrophobic interactions of the pentyl chains. Co-
operativityof the melting process in the natural and the
modified part of duplex 7*8 was shown bymonitoring the
denaturation process at 290 as well as at 330 nm (hyperchro-
micityof TTF absorption, see the Supporting Information).
The circular dichroism (CD) spectrum of the duplex 7*8
(Figure 1) is consistent with an overall B-conformation with
a maximum at 280 nm and a minimum at 251 nm, indicating
that the TTF units are structurallywell integrated into a B-
type DNA. Despite the high duplex stability, no signs of ex-
citon coupling were detected in the TTF region from 300 to
400 nm. A weak CD signal was observed, which is explained
9
11
(5’) AGC TCG GTC FFC GAG AGT GCA
(3’) TCG AGC CAG SSG CTC TCA CGT
67.5
69.3
66.7
12
8
(5’) AGC TCG GTC ASC GAG AGT GCA
(3’) TCG AGC CAG TFG CTC TCA CGT
13
8
(5’) AGC TCG GTC SSC GAG AGT GCA
(3’) TCG AGC CAG TFG CTC TCA CGT
[a] Conditions: 1.0 mm oligonucleotide concentration (each strand), 10 mm
phosphate buffer (pH 7.4) and 100 mm NaCl.
[29]
changes in CD spectroscopy, and pyrene for its diverse
fluorescence properties.[56] TTF-modified strands form stable
hybrids with all other modified strands. The Tm values are
generallysomewhat lower than the one of the reference
duplex 5*6 (72.58C, Table 1), except for the PDI/TTF-mixed
hybrid 9*10, which has a comparable Tm value (72.18C). In
the same duplex, CD spectroscopy(Figure 2) revealed
strong exciton coupling of the PDI chromophores. This
shows that the PDI units are oriented in a twisted conforma-
tion and that a well-ordered helical structure is maintained
in the modified region of the duplex.[57]
As expected for
a neutral form of tetrathiafulva-
lene,[3,53,58,59] no fluorescence was observed for single-strand-
ed TTF-modified oligonucleotides (7, 8) nor duplex 7*8. On
the other hand, the low oxidation potential of TTF may, in
principle, favor fluorescence quenching via photo-induced
electron transfer, as recentlyapplied in the construction of
Figure 1. Temperature-dependent CD spectrum of TTF-modified duplex
7*8. Conditions: 5.0 mm oligo concentration (each strand), 10 mm phos-
phate buffer (pH 7.4) and 100 mm NaCl; inset shows enlarged view of the
region from 300–400 nm.
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5733

R. Häner et al.
Table 3. Quenching properties of TTF-modified oligonucleotide
pyrene containing hybrids.[a]
8 in
Oligonucleotides
f
Quenching
in %
12
13
(5’) AGC TCG GTC ASC GAG AGT GCA
(5’) AGC TCG GTC SSC GAG AGT GCA
0.014
0.094
0.008
–
–
12
6
(5’) AGC TCG GTC ASC GAG AGT GCA
(3’) TCG AGC CAG TAG CTC TCA CGT
35.6
12
8
(5’) AGC TCG GTC ASC GAG AGT GCA
(3’) TCG AGC CAG TFG CTC TCA CGT
0.004
0.062
0.014
70.5
46.0
85.1
13
6
(5’) AGC TCG GTC SSC GAG AGT GCA
(3’) TCG AGC CAG TAG CTC TCA CGT
13
8
(5’) AGC TCG GTC SSC GAG AGT GCA
(3’) TCG AGC CAG TFG CTC TCA CGT
Figure 2. Temperature-dependent CD spectra of duplex 9*10. Conditions:
2.5 mm oligonucleotide concentration (each strand), 10 mm phosphate
buffer (pH 7.4) and 100 mm NaCl; De (molÀ1 dm3 cmÀ1).
[a] Conditions: see Table 1; quinine sulfate was used as standard for
quantum yield (f) determination.
switchable fluorescent systems.[53,58,59] Indeed, quenching of
pyrene fluorescence by TTF was observed in hybrids 12*8
and 13*8 containing one and two pyrenes, respectively
(Figure 3, Table 3, and the Supporting Information). The
In conclusion, a non-nucleosidic tetrathiafulvalene build-
ing block suitable for incorporation into DNA has been de-
scribed. TTF-modified oligonucleotides form stable hybrids,
which were characterized bythermal denaturation, fluores-
cence, and CD spectroscopy. Exciton coupling revealed a
high degree of structural organization in the modified
region of a hetero-duplex formed byTTF and perylene dii-
mide-containing strands. Furthermore, fluorescence quench-
ing in TTF/pyrene modified hetero-hybrids was demonstrat-
ed. The finding presented here mayhelp in the development
of optical sensors or redox-active, oligonucleotide-based di-
agnostics.
Experimental Section
General: Reactions were carried out under N2 atmosphere using distilled,
anhydrous solvents. Flash column chromatography (CC) was performed
byusing silica gel 60 (63–32 mM, Chemie Brunschwig AG). If compounds
were sensitive to acid, the silica was pre-treated with solvent containing
1% Et3N. All NMR spectra were measured at room temperature on a
Bruker AC-300 spectrometer. 1H NMR spectra were recorded at
300 MHz. Chemical shifts (d) are reported in ppm relative to the residual
undeuterated solvent (CDCl3: 7.27 ppm). 13C NMR spectra were record-
ed at 75 MHz. Chemical shifts are reported in ppm relative to the residu-
al non-deuterated solvent (CDCl3: 77.00 ppm). 31P NMR spectra were re-
corded at 162 MHz. Chemical shifts are reported in ppm relative to 85%
H3PO4 as an external standard. Electron ionization mass spectra (EI-MS)
were recorded on an AutospecQ (Waters Micromass) instrument.
Figure 3. Normalized fluorescence spectra of pyrene modified single
strands 12 and 13 and the respective hybrids formed with an unmodified
single strand (6) and a TTF-containing strand (8). Conditions: 1.0 mm oli-
gonucleotide concentration (each strand), 10 mm phosphate buffer
(pH 7.4) and 100 mm NaCl; lex at 354 nm.
Synthesis of 2,3-bis(2-hydroxyethylthio)-6,7-bis(pentylthio)tetrathiafulva-
lene (2): A solution of sodium (0.17 g, 7.35 mmol) in ethanol (20 mL)
was added to a suspension of the cyanoethyl-protected compound 1
(0.85 g, 1.47 mmol) in anhydrous degassed ethanol (80 mL) under nitro-
gen. After being stirred at room temperature for 4 h, the red-brown mix-
ture was treated with 2-chloroethanol (1.78 g, 22.05 mmol). After a few
minutes, the solution turned orange and a precipitate started to form.
The mixture was then stirred overnight after which it was treated with
water (50 mL) and extracted with dichloromethane. The extract was
washed with water, dried with magnesium sulfate, and concentrated. The
resulting solid was purified bychromatography(silica gel: CH 2Cl2/EtOAc
8:2) to give compound 2 in 73% yield (0.60 g, 1.08 mmol). 1H NMR
fluorescence spectrum of 13 shows pyrene excimer emission
with a maximum at 505 nm. This signal was decreased by
85% in duplex 13*8, which is considerablymore than ob-
served bya non-modified complementarystrand (duplex
13*6). A slightlylower—but still significant—quenching
effect (~70%) was observed in the case of monomer fluo-
rescence (duplex 12*8). These data show that TTF can act
as a quencher within a DNA duplex.
5734
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Chem. Eur. J. 2008, 14, 5732 – 5736

TTF-Modified DNA
COMMUNICATION
(CDCl3, 300 MHz): d=0.90 (t, 6H), 1.36 (m, 8H), 1.65 (m, 4H), 2.81 (t,
4H), 3.01 (t, 4H), 3.76 ppm (t, 4H); EI-MS: m/z: 560 [M+], C20H32O2S8,
MW=560.02; Rf (CH2Cl2/EtOAc 4:1)=0.15.
[2] J. Yamada, T. Sugimoto, TTF Chemistry. Fundamentals and Applica-
tions of Tetrathiafulvalene, Springer, Berlin, 2004.
[3] J. L. Segura, N. Martin, Angew. Chem. 2001, 113, 1416–1455;
Angew. Chem. Int. Ed. 2001, 40, 1372–1409.
[4] See also the special issue on molecular conductors in Chem. Rev.
2004, 104, 4887–5056.
Synthesis
of
2-{2-[(4,4’-dimethoxytrityl)oxy]ethylthio}-3-(2-hydroxy-
(0.50 g,
A
0.89 mmol) was dissolved in drypyridine (7.5 mL), and 4,4 ’-dimethoxytri-
tyl chloride (0.30 g, 0.89 mmol) in dry pyridine (2.5 mL) was added drop-
wise. After the mixture had been stirred at room temperature for 6 h, a
solution of sodium bicarbonate (25 mL) was added. The crude product
was isolated byextraction with dichloromethane and dried with magnesi-
um sulfate and concentrated. To avoid decomposition of the product on
silica gel, the column was prepared with solvent containing 1% triethyla-
mine. The crude was purified bychromatography(silica gel: hexane/
EtOAc 2:1) to give compound 3 in 35% yield (0.27 g, 0.31 mmol).
1H NMR (CDCl3, 300 MHz): d=0.87 (t, 3H), 0.90 (t, 3H), 1.30 (m, 8H),
1.63 (m, 4H), 2.76 (t, 2H), 2.82 (t, 2H), 2.87 (t, 2H), 3.02 (t, 2H), 3.34 (t,
2H), 3.62 (t, 2H), 3.79 (s, 6H), 6.83 (m, 4H), 7.19 (m, 1H), 7.28 (m, 2H),
7.31 (m, 4H), 7.43 ppm (m, 2H); EI-MS: m/z: 862 [M+]; C41H50O4S8,
MW=862.15; Rf (hexane/EtOAc 2:1)=0.4.
[5] M. B. Nielsen, C. Lomholt, J. Becher, Chem. Soc. Rev. 2000, 29,
153–164.
[6] C. Goze, C. Leiggener, S. X. Liu, L. Sanguinet, E. Levillain, A.
Hauser, S. Decurtins, ChemPhysChem 2007, 8, 1504–1512.
[7] F. Dumur, N. Gautier, N. Gallego-Planas, Y. Sahin, E. Levillain, N.
Mercier, P. Hudhomme, M. Masino, A. Girlando, V. Lloveras, J.
Vidal-Gancedo, J. Veciana, C. Rovira, J. Org. Chem. 2004, 69, 2164–
2177.
[8] M. R. Bryce, J. Mater. Chem. 2000, 10, 589–598.
[9] C. Y. Jia, S. X. Liu, C. Tanner, C. Leiggener, L. Sanguinet, E. Levil-
lain, S. Leutwyler, A. Hauser, S. Decurtins, Chem. Commun. 2006,
1878–1880.
[10] G. Ho, J. R. Heath, M. Kondratenko, D. F. Perepichka, K. Arsen-
eault, M. Pezolet, M. R. Bryce, Chem. Eur. J. 2005, 11, 2914–2922.
[11] E. Tsiperman, J. Y. Becker, V. Khodorkovsky, A. Shames, L. Sha-
piro, Angew. Chem. 2005, 117, 4083–4086; Angew. Chem. Int. Ed.
2005, 44, 4015–4018.
[12] J. Wu, S. X. Liu, A. Neels, F. Le Derf, M. Salle, S. Decurtins, Tetra-
hedron 2007, 63, 11282–11286.
[13] N. Martin, L. Sanchez, M. A. Herranz, B. Illescas, D. M. Guldi, Acc.
Chem. Res. 2007, 40, 1015–1024.
[14] J. Puigmarti-Luis, V. Laukhin, A. P. del Pino, J. Vidal-Gancedo, C.
Rovira, E. Laukhina, D. B. Amabilino, Angew. Chem. 2007, 119,
242–245; Angew. Chem. Int. Ed. 2007, 46, 238–241.
[15] C. Wang, D. Q. Zhang, D. B. Zhu, J. Am. Chem. Soc. 2005, 127,
16372–16373.
[16] N. C. Seeman, Mol. Biotechnol. 2007, 37, 246–257.
[17] U. Feldkamp, C. M. Niemeyer, Angew. Chem. 2006, 118, 1888–1910;
Angew. Chem. Int. Ed. 2006, 45, 1856–1876.
[18] F. D. Lewis, E. L. Burch, J. Photochem. Photobiol. A 1996, 96, 19–
23.
[19] S. M. Langenegger, R. Häner, Bioorg. Med. Chem. Lett. 2006, 16,
5062–5065.
[20] S. M. Langenegger, R. Häner, Helv. Chim. Acta 2002, 85, 3414–
3421.
[21] M. Nakamura, Y. Ohtoshi, K. Yamana, Chem. Commun. 2005,
5163–5165.
[22] F. Samain, V. L. Malinovskii, S. M. Langenegger, R. Häner, Bioorg.
Med. Chem. 2008, 16, 27–33.
[23] S. M. Langenegger, R. Häner, Chem. Commun. 2004, 2792–2793.
[24] U. B. Christensen, E. B. Pedersen, Helv. Chim. Acta 2003, 86, 2090–
2097.
[25] I. Trkulja, R. Häner, Bioconjugate Chem. 2007, 18, 289–292.
[26] I. Trkulja, R. Häner, J. Am. Chem. Soc. 2007, 129, 7982–7989.
[27] A. Okamoto, T. Ichiba, I. Saito, J. Am. Chem. Soc. 2004, 126, 8364–
8365.
Synthesis of 2-{2-[(diisopropylamino)(2-cyanoethyl)phosphinoxy]ethyl-
ACHTREUNG
ACHTREUNG
amine (0.096 g, 0.75 mmol) were dissolved in drydichloromethane
(7.5 mL). 2-Cyanoethyl N,N-diisopropylchlorophosphoramidite (0.078 g,
0.33 mmol) dissolved in drydichloromethane (2.5 mL) was added drop-
wise. The reaction mixture was stirred at room temperature for 2 h. The
crude product was directlypurified bychromatography(silica gel:
hexane/EtOAc 2:1 +1% triethylamine). The fractions were combined
and evaporated under high vacuum to furnish compound 4 in 85% yield
1
(0.27 g, 0.25 mmol). H NMR (CDCl3 300 MHz): d=0.88 (t, 3H), 0.90 (t,
3H), 1.16 (m, 12H), 1.33 (m, 8H), 1.64 (m, 4H), 2.59 (m, 2H), 2.79 (t,
2H), 2.82 (t, 2H), 2.96 (t, 2H), 2.99 (t, 2H), 3.32 (t, 2H), 3.61 (m, 4H),
3.79 (s, 6H), 3.80 (m, 2H), 6.83 (m, 4H), 7.19 (m, 1H), 7.28 (m, 2H),
7.31 (m, 4H), 7.43 ppm (m, 2H); 31P NMR (CDCl3, 122 MHz): d=
148.46 pm; EI-MS: m/z: 1063 [M+], C50H67N2O5PS8, MW=1062.26; Rf
(hexane/EtOAc 2:1)=0.9.
Synthesis and analysis of oligonucleotides: Cyanoethyl phosphoramidites
from Transgenomic (Glasgow, UK) were used for oligonucleotide synthe-
sis. Oligonucleotides 5 and 6 were obtained from Microsynth (Switzer-
land) and were used without additional purification. Oligonucleotides 7–
9 were prepared byautomated oligonucleotide synthesis bya standard
synthetic procedure (ꢁtrityl-offꢂ mode) on a 394-DNA/RNA synthesizer
(Applied Biosystems). Cleavage from the solid support and final depro-
tection was done bya treatment with 33% aqueous NH at 558C over-
3
night. Oligonucleotides 7–9 were purified byreverse-phase HPLC (Li-
Chrospher 100 RP-18, 5 mm, Merck, Bio-Tek instrument Autosampler
560); eluent A=(Et3NH)OAc (0.1m, pH 7.4); eluent B=80% MeCN
and 20% eluent A; gradient 5–80% B over 20 min at 258C. ESI-MS
(negative-mode, CH3CN/H2O/TEA) of oligonucleotides was performed
with a Sciex QSTAR pulsar (hybrid quadrupole time-of-flight mass spec-
trometer, Applied Biosystems). Oligomers 10[50] and 11–13[22] were syn-
thesized as described.
[28] A. D. Malakhov, M. V. Skorobogatyi, I. A. Prokhorenko, S. V. Gon-
tarev, D. T. Kozhich, D. A. Stetsenko, I. A. Stepanova, Z. O. Shen-
karev, Y. A. Berlin, V. A. Korshun, Eur. J. Org. Chem. 2004, 1298–
1307.
[29] Y. Zheng, H. Long, G. C. Schatz, F. D. Lewis, Chem. Commun. 2005,
4795–4797.
[30] N. Rahe, C. Rinn, T. Carell, Chem. Commun. 2003, 2119–2121.
[31] C. Wagner, H. A. Wagenknecht, Org. Lett. 2006, 8, 4191–4194.
[32] S. Bevers, S. Schutte, L. W. McLaughlin, J. Am. Chem. Soc. 2000,
122, 5905–5915.
[33] W. Wang, W. Wan, H. H. Zhou, S. Q. Niu, A. D. Q. Li, J. Am. Chem.
Soc. 2003, 125, 5248–5249.
Acknowledgements
This work was supported bythe Swiss National Foundation (grants
200020–109482 and 200020–116003).
Keywords: DNA
tetrathiafulvalene
·
fluorescence
·
oligonucleotides
·
[34] U. B. Christensen, E. B. Pedersen, Nucl. Acids Res. 2002, 30, 4918–
4925.
[35] S. M. Langenegger, G. BiankØ, R. Tona, R. Häner, Chimia 2005, 59,
794–797.
[1] F. Wudl, G. M. Smith, E. J. Hufnagel, J. Chem. Soc. Chem.
Commun. 1970, 1453–1454.
Chem. Eur. J. 2008, 14, 5732 – 5736
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5735

R. Häner et al.
[36] H. Kashida, H. Asanuma, M. Komiyama, Angew. Chem. 2004, 116,
6684–6687; Angew. Chem. Int. Ed. 2004, 43, 6522–6525.
[37] W. Wang, A. D. Q. Li, Bioconjugate Chem. 2007, 18, 1036–1052.
[38] F. D. Lewis, X. Liu, Y. Wu, S. E. Miller, M. R. Wasielewski, R. L.
Letsinger, R. Sanishvili, A. Joachimiak, V. Tereshko, M. Egli, J. Am.
Chem. Soc. 1999, 121, 9905–9906.
[39] A. Stutz, S. M. Langenegger, R. Häner, Helv. Chim. Acta 2003, 86,
3156–3163.
[40] G. BiankØ, R. Häner, Nucleosides Nucleotides Nucleic Acids 2007,
26, 949–952.
[41] G. BiankØ, R. Häner, ChemBioChem 2004, 5, 1063–1068.
[42] F. D. Lewis, L. G. Zhang, R. F. Kelley, D. McCamant, M. R. Wasie-
lewski, Tetrahedron 2007, 63, 3457–3464.
[43] M. Nakamura, M. Ueda, S. Watanabe, S. Kumamoto, K. Yamana,
Tetrahedron Lett. 2007, 48, 6159–6162.
[50] N. Bouquin, V. L. Malinovskii, R. Häner, Chem. Commun. 2008,
1974–1976.
[51] See, for example: a) S. J. Pace, P. F. Man, A. P. Patil, K. F. Tan, CNT-
based sensors: devices, processes and uses thereof, PCT Int. Appl.
(2007), WO 2007089550; b) G.-U. Flechsig, T. Reske, Selective La-
beling of single-stranded regions of nucleic acid hybrids in the elec-
trochemical detection of hybrids, Ger. (2007), DE 102005039726.
[52] O. Neilands, V. Liepinsh, B. Turovska, Org. Lett. 1999, 1, 2065–2067.
[53] S. Leroy-Lhez, J. Baffreau, L. Perrin, E. Levillain, M. Allain, M. J.
Blesa, P. Hudhomme, J. Org. Chem. 2005, 70, 6313–6320.
[54] S. L. Beaucage, M. H. Caruthers, Tetrahedron Lett. 1981, 22, 1859–
1862.
[55] High coupling yields were obtained during oligonucleotide synthesis.
Some fragmentation of the oligomers at the site of the tetrathiaful-
valene building block during ammonia deprotection was observed,
however.
[44] V. Looser, S. M. Langenegger, R. Häner, J. S. Hartig, Chem.
Commun. 2007, 4357–4359.
[56] F. M. Winnik, Chem. Rev. 1993, 93, 587–614.
[45] K. Yamana, A. Yoshikawa, H. Nakano, Tetrahedron Lett. 1996, 37,
637–640.
[57] N. Berova, L. Di Bari, G. Pescitelli, Chem. Prod. Chem. Soc. Rev.
2007, 36, 914–931.
[46] H. Asanuma, T. Ito, T. Yoshida, X. G. Liang, M. Komiyama, Angew.
Chem. 1999, 111, 2547–2549; Angew. Chem. Int. Ed. 1999, 38, 2393–
2395.
[58] C. Loosli, C. Y. Jia, S. X. Liu, M. Haas, M. Dias, E. Levillain, A.
Neels, G. Labat, A. Hauser, S. Decurtins, J. Org. Chem. 2005, 70,
4988–4992.
[47] F. D. Lewis, Y. S. Wu, X. Y. Liu, J. Am. Chem. Soc. 2002, 124,
12165–12173.
[48] V. L. Malinovskii, F. Samain, R. Häner, Angew. Chem. 2007, 119,
4548–4551; Angew. Chem. Int. Ed. 2007, 46, 4464–4467.
[49] H. Kashida, M. Tanaka, S. Baba, T. Sakamoto, G. Kawai, H. Asanu-
ma, M. Komiyama, Chem. Eur. J. 2006, 12, 777–784.
[59] S. Delahaye, C. Loosli, S. X. Liu, S. Decurtins, G. Labat, A. Neels,
A. Loosli, T. R. Ward, A. Hauser, Adv. Funct. Mater. 2006, 16, 286–
295.
Received: March 18, 2008
Published online: May13, 2008
5736
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