A modular strategy to artificial double helices

Article abstract of DOI:10.1002/anie.200501028

(Figure Presented) No metal required: Double-helical assemblies can be constructed through hydrogen bonds upon formation of amidinium-carboxylate salt bridges (see schematic representation). The double-helical structures formed including the helix sense a

Full text of DOI:10.1002/anie.200501028

Angewandte
Chemie
Helical Structures
A Modular Strategy to Artificial Double
Helices**
Yoshie Tanaka, Hiroshi Katagiri, Yoshio Furusho,* and
Eiji Yashima*
The fascination of the structure, dynamics, and recognition
properties of naturally occurring helical polymers, such as the
a-helix of peptides and the double helix of DNA structures
have prompted chemists to design and synthesize artificial
helical polymers and oligomers.[1] Although a number of
synthetic polymers and oligomers that fold into single-helical
conformations have been reported, only a few structural
motifs are available for constructing double-helical structures.
The most widely used approach is the utilization of metal-
directed self-assembly, in which ligand-containing strands
form double-, triple-, or quadruple-helical complexes, that is,
helicates;[2] the three-dimensional structures of helicates are
determined by the geometry of the template metal ions.
Hydrogen-bonding-driven self-assembly is another common
approach to constructing supramolecular duplexes.[3] In most
cases, however, their three-dimensional structures have been
characterized as ladder- or zipperlike linear conformations. It
was recently disclosed that some oligoamides give rise to
double-helical assemblies by making use of interstrand
hydrogen-bonding and aromatic–aromatic interactions.[4]
Although the hydrogen-bonding interaction is a readily
available and versatile tool for constructing supramolecular
assemblies,[5] it is still difficult and challenging to design
double helices with predictable structures.[4c] Herein, we
describe the design and synthesis of hydrogen-bonding-driven
double helices by a modular strategy in which intertwined
supramolecular binary complexes are employed.
Our strategy is based on the crescent-shaped m-terphenyl
derivatives (Figure 1). Crescent-shaped molecules, such as
bipyridine and phenanthroline derivatives, have often been
used to construct intertwined supramolecular complexes and
[*] Dr. Y. Tanaka, Dr. H. Katagiri, Dr. Y. Furusho, Prof. E. Yashima
Yashima Super-structured Helix Project
Exploratory Research for Advanced Technology (ERATO)
Japan Science and Technology Agency (JST)
Creation Core Nagoya 101
2266-22 Anagahora, Shimoshidami
Moriyama-ku, Nagoya 463-0003 (Japan)
Fax: (+81)52-739-2081
E-mail: furusho@yp-jst.jp
yashima@apchem.nagoya-u.ac.jp
Prof. E. Yashima
Institute for Advanced Research
Nagoya University
Chikusa-ku, Nagoya 464-8601 (Japan)
Fax: (+81)52-789-3185
[**] We thank Dr. Mikio Yamasaki of Rigaku Cooperation for the X-ray
crystal-structure analysis.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2005, 44, 3867 –3870
DOI: 10.1002/anie.200501028
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Communications
Figure 1. Schematic illustration of the modular strategy for the con-
struction of artificial double-helical assemblies.
interlocked molecules.[6] We chose amidinium–carbox-
ylate salt bridges as the supramolecular junction for the
m-terphenyl derivatives because the charge-assisted
hydrogen bonding between amidines and carboxylic
acids is quite strong even in polar solvents and has a
well-defined geometry.[7] Chiral groups were intro-
duced onto the nitrogen atoms of the amidine moieties
to control the chirality of the double helices. The
formation of the salt bridge leads to a supramolecular
binary complex, in which the two m-terphenyl deriv-
atives are intertwined around the salt bridge (Figure 1).
Connecting the intertwined complexes together should
result in the formation of the double-helical structure.
The chiral diamidine (R)-1 and its antipode (S)-1
were prepared according to Scheme 1.[8] The iodide 3
was obtained by the Hart coupling of m-dichloroben-
zene with 4-trimethylsilylethy-
Scheme 1. Synthesis of diamidines 1: a) nBuLi/THF, À788C; b) 4-
trimethylsilylethynylphenylmagnesium bromide, À788C to RT; c) I2, RT;
d) nBuLi, TMEDA/Et2O, 08C; e) N,N’-bis[(R)-1-phenylethyl]carbodiimide for
(R)-4, N,N’-bis[(S)-1-phenylethyl]carbodiimide for (S)-4/THF, RT; f) nBu4NF/
THF, 08C; g) [PdCl2(PPh3)2], CuI, Et3N/THF, RT. TMEDA=N,N,N’N’-tetra-
methyl-1,2-ethanediamine.
nylphenylmagnesium bromide
followed by quenching with
iodine.[9] Iodide 3 was lithiated
and then treated with N,N’-
bis[(R)-1-phenylethyl]carbodii-
mide[10a] to yield the amidine (R)-
4.[11] (R)-4 was treated with tetra-
n-butylammonium
fluoride
(TBAF) to give the monosilane
(R)-5, which was dimerized by
oxidative coupling using the
Sonogashira reagents to afford
the diamidine (R)-1. The anti-
pode (S)-1 was synthesized in a
similar manner except that N,N’-
bis[(S)-1-phenylethyl]carbodii-
mide was used.[10b] Similarly, the
Scheme 2. Synthesis of dicarboxylic acid 2: a) nBuLi/THF, À788C; b) 4-trimethylsilylethynylphenylmag-
nesium bromide, À788C to RT; c) CO2, RT; d) nBu4NF/THF, 08C; e) [PdCl2(PPh3)2], CuI, Et3N/THF, RT.
dicarboxylic acid 2 was prepared according to Scheme 2.
Carboxylic acid 6 was obtained by Hart coupling using CO2 as
the quencher. The monodesilylation of 6 was achieved by
treatment with TBAF to yield the monosilane 7, which was
subsequently dimerized by oxidative coupling to afford 2.
Complexation of the diamidine (R)-1 with the dicarbox-
showed a simple spectrum, thus indicating the presence of
only one isomer. This result is consistent with the formation of
a salt bridge between (R)-1 and 2, through which the
geometry around the amidine residues is fixed in the
E configuration. The resonances of the NH protons (c’ and
c’’) were observed as two doublets at a low magnetic field of
approximately d = 13.5 ppm, which is indicative of the
formation of a salt bridge. The CH3 protons of the amidine
groups (d’ and e’) were also evident. The non-equivalency of
these signals is attributed to the formation of a duplex
between (R)-1 and 2, which was also supported by 2D NMR
spectroscopic and electrospray ionization mass spectrometry
(ESI-MS) studies.[8] The association constant of 1 and 2 at
1
ylic acid 2 was first investigated by H NMR spectroscopy
(Figure 2). The 1H NMR spectrum of 1 in CDCl3 was
complicated at 258C, because of the presence of several
=
conformers originating from the E–Z isomerism of the C N
À
double bonds and the restricted rotation about the C C bond
between the amidine and the m-terphenyl groups.[11] In
contrast, the 1H NMR spectrum of the complex (R)-1·2
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Figure 3. Stereoview of the crystal structure of (R)-1·2. The hydrogen
atoms and included solvents are omitted for clarity. The intermolecular
hydrogen bonds between N and O are shown by dashed lines.
370 nm in CHCl3, whereas (R)- and (S)-1 exhibited very weak
Cotton effects in this region. The significant enhancement of
the Cotton effects for the complexes 1·2, especially in the
absorption region of the diacetylene linkages (ca. 300–
370 nm), indicates that the single-handed double-helical
structures of (R)- and (S)-1·2 are likely retained in CHCl3.
This presumption was supported by the variable-temperature
1H NMR spectroscopic measurements of (R)-1·2 in CDCl3; no
signals corresponding to the opposite diastereomeric left-
handed double helix were observed, even at temperatures as
low as À608C. Thus, (R)-1·2 seems to adopt a predominantly
right-handed double-helical structure, although the possibility
that the inversion of the double helices is still fast on the
NMR time scale even at À608C can not be ruled out.
Figure 2. Partial 1H NMR (500 MHz, CDCl3, 258C) spectra of a) diami-
dine (R)-1 (7.1 mm) and b) complex (R)-1·2 (0.4 mm). The asterisks
denote the signals for the corresponding Z isomer of (R)-1. “x” indi-
cates impurities.
1
258C in CDCl3 was estimated to be > 106 mÀ1 by H NMR
spectroscopy.[8]
The X-ray structural analysis unambiguously revealed
that the complex (R)-1·2 adopted a right-handed double-
helical structure in the solid state (Figure 3).[8,12] The amidine
and carboxy groups formed two identical salt bridges with two
hydrogen bonds for each and average N···O
distances of 2.73 ꢀ. The two amidinium–
carboxylate salt bridges enabled the two
strands to be held together. All the benzene
rings of the m-terphenyl groups were chir-
ally twisted clockwise by about 48–618, and
the two strands were wound up to form the
right-handed double-helical structure.
It should be noted that (R)-1·2 even exhibited intense
Cotton effects in DMSO, although the intensities were
1
reduced to 67% of those in CHCl3 (Figure 4). The H NMR
Circular dichroism (CD) measurements
were then performed to examine if the
complexes (R)- and (S)-1·2 maintained
their single-handed double-helical struc-
tures in solution (Figure 4). Both enantio-
mers of 1·2 showed intense mirror-image
CD signals between approximately 260 and
Figure 4. a) UV/Vis spectra (0.1 mm, 208C) of amidine (R)-1 in CDCl3 (blue), and complex (R)-1·2 in
CDCl3 (red) and in DMSO (green). b) CD spectra (0.1 mm, 208C) of (R)-1 (blue), (S)-1 (light blue),
(R)-1·2 (red), and (S)-1·2 (pink) in CDCl3, and (R)-1·2 in DMSO (green).
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[5] L. J. Prins, D. N. Reinhoudt, P. Timmerman, Angew. Chem. 2001,
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[6] Molecular Catenanes, Rotaxanes and Knots (Eds.: J.-P. Sauvage,
C. Dietrich-Buchecker), Wiley-VCH, Weinheim, 1999.
spectrum of 1·2 showed that 60% of the complex 1·2 retained
its duplex structure, whereas the rest of 1·2 underwent
dissociation into 1 and 2 in [D6]DMSO (0.1 mm, 258C).[8] In
sharp contrast, (R)-4·6, a simple model for (R)-1·2, showed a
weak CD spectrum similar to that of (R)-4 in DMSO.[8] In fact,
it was shown by 1H NMR spectroscopic analysis that 4·6
dissociated into 4 and 6 in [D6]DMSO.[8] Consequently, the
complexation of 1·2 was more stable than that of the simpler
4·6.
In summary, we have successfully prepared the first
artificial single-handed double helices through formation of
salt bridges between chiral diamidines ((R)- and (S)-1) and
the achiral dicarboxylic acid 2. Both single-handed double
helices are stable in the solid state as well as in solution. The
modular strategy, we believe, can act as a new design rationale
for the formation of hydrogen-bond-driven double helices in
which the three-dimensional structures including the helix
sense are predictable.
[7] For recent examples of amidinium–carboxylate salt bridges, see
a) J. Otsuki, K. Iwasaki, Y. Nakano, M. Itou, Y. Araki, O. Ito,
Chem. Eur. J. 2004, 10, 3461 – 3466; b) G. Cooke, F. M. A.
Duclairoir, A. Kraft, C. Rosair, V. M. Rotello, Tetrahedron Lett.
2004, 45, 557 – 560; c) N. H. Damrauer, J. M. Hodgkiss, J.
Rosenthal, D. G. Nocera, J. Phys. Chem. B 2004, 108, 6315 –
6321; d) F. Corbellini, L. Di Constanzo, M. Cregs-Calama, S.
Geremia, D. N. Reinhoudt, J. Am. Chem. Soc. 2003, 125, 9946 –
9947; e) A. Kraft, L. Peters, H. R. Powell, Tetrahedron 2002, 58,
3499 – 3505; f) G. Wulff, R. Schꢂnfeld, Adv. Mater. 1998, 10, 957 –
959.
[8] See the Supporting Information for details of the synthesis,
structures, and characterization of compounds 1–7.
[9] A. Saednya, H. Hart, Synthesis 1996, 1455 – 1458.
[10] a) R. R. Hiatt, M.-J. Shaio, F. Georges, J. Org. Chem. 1979, 44,
3265 – 3266; b) R. Chinchilla, C. Nꢁjera, P. Sꢁnchez-Agullꢃ,
Tetrahedron: Asymmetry 1994, 5, 1393 – 1402.
[11] a) R. T. Boerꢄ, V. Klassen, G. Wolmershꢅuser, J. Chem. Soc.
Dalton Trans. 1998, 4147 – 4154; b) J. A. R. Schmidt, J. Arnold,
Chem. Commun. 1999, 2149 – 2150; c) J. A. R. Schmidt, J.
Arnold, J. Chem. Soc. Dalton Trans. 2002, 2890 – 2899.
Received: March 22, 2005
Published online: May 18, 2005
[12] Crystal data for (R)-1·2 (C141H140N4O9Si4): Mr = 2147.03, crystal
Keywords: chirality · helical structures · hydrogen bonds ·
salt bridges · supramolecular chemistry
.
dimensions 0.30 ꢆ 0.24 ꢆ 0.14 mm3, orthorhombic, space group
P212121, Z = 4, 1calcd = 1.132 gcmÀ3
,
m(CuKa) = 8.92 cmÀ1
,
F(000) = 4568, 2qmax = 136.48 were a = 13.6965(5), b =
22.7967(11), c = 40.3486(17) ꢀ, and V= 12598.2(9) ꢀ3. A total
of 124842 reflections were collected, of which 22862 reflections
were independent (Rint = 0.044). The structure was refined to
final R1 = 0.072 for 15968 data [I > 2s(I)] with 1430 parameters
and wR2 = 0.2360 for all data, GOF = 1.039, and residual
electron density max./min. = 0.49/À0.32 eꢀÀ3. CCDC-266647
contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
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