Sequence- and chain-length-specific complementary double-helix formation

Article abstract of DOI:10.1021/ja806194e

The artificial sequential strands consisting of two, three, or four m-terphenyl groups joined by diacetylene linkers with complementary binding sites, either the chiral amidine (A) or achiral carboxyl (C) group, were synthesized in a stepwise manner. Using circular dichroism and ¹H NMR spectroscopies along with liquid chromatography, we showed that, when three dimeric molecular strands (AA, CC, and AC) or six trimeric molecular strands (AAA, CCC, AAC, CCA, ACA, and CAC) were mixed in solution, the complementary strands were sequence-specifically hybridized to form one-handed double-helical dimers AA-CC and (AC)₂ or trimers AAA-CCC, AAC-CCA, and ACA-CAC, respectively, through complementary amidinium-carboxylate salt bridges. Upon the addition of CCA to a mixture of AAA, AAC, and ACA, the AAC-CCA double helix was selectively formed and then isolated from the mixture by chromatography. Moreover, the homo-oligomer mixtures of amidine or carboxylic acid from the monomers to tetramers (A, AA, AAAA, C, CC, and CCCC) assembled with a precise chain length specificity to form A-C, AA-CC, and AAAA-CCCC, which were separated by chromatography.

Full text of DOI:10.1021/ja806194e

Published on Web 09/30/2008
Sequence- and Chain-Length-Specific Complementary
Double-Helix Formation
Hiroshi Ito,† Yoshio Furusho,*,†,‡ Toshihide Hasegawa,† and Eiji Yashima*,†,‡
Yashima Super-structured Helix Project, ERATO, Japan Science and Technology Agency (JST),
and Department of Molecular Design and Engineering, Graduate School of Engineering,
Nagoya UniVersity, Nagoya 464-8603, Japan
Received August 7, 2008; E-mail: furusho@apchem.nagoya-u.ac.jp (Y.F.); yashima@apchem.nagoya-u.ac.jp (E.Y.)
Abstract: The artificial sequential strands consisting of two, three, or four m-terphenyl groups joined by
diacetylene linkers with complementary binding sites, either the chiral amidine (A) or achiral carboxyl (C)
group, were synthesized in a stepwise manner. Using circular dichroism and 1H NMR spectroscopies along
with liquid chromatography, we showed that, when three dimeric molecular strands (AA, CC, and AC) or
six trimeric molecular strands (AAA, CCC, AAC, CCA, ACA, and CAC) were mixed in solution, the
complementary strands were sequence-specifically hybridized to form one-handed double-helical dimers
AA·CC and (AC)2 or trimers AAA ·CCC, AAC ·CCA, and ACA ·CAC, respectively, through complementary
amidinium-carboxylate salt bridges. Upon the addition of CCA to a mixture of AAA, AAC, and ACA, the
AAC·CCA double helix was selectively formed and then isolated from the mixture by chromatography.
Moreover, the homo-oligomer mixtures of amidine or carboxylic acid from the monomers to tetramers (A,
AA, AAAA, C, CC, and CCCC) assembled with a precise chain length specificity to form A·C, AA·CC, and
AAAA·CCCC, which were separated by chromatography.
Introduction
of synthetic strands that fold into a single helix have been
reported,1,2 only a few structural motifs are available for double
The double helix of DNA is exquisite from the standpoint of
structures and functions that rely on its one-handedness and
complementarity of the strands, motivating chemists to develop
synthetic helical polymers and oligomers.1-9 While a number
helices other than the DNA analogues.2-9 Most of these,
however, lack the important feature of DNA, the complemen-
tarity of the strands. The sequence-specific duplex formation
of DNA is the most essential process for self-replication and
protein synthesis. The first step toward breaking the monopoly
of nature may be the construction of double helices with a
† JST.
‡ Nagoya University.
(1) For reviews on synthetic polymers and oligomers with single-helical
conformations, see: (a) Rowan, A. E.; Nolte, R. J. M. Angew. Chem.,
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2008 American Chemical Society

Complementary Double-Helix Formation
A R T I C L E S
-oligocarboxylic acids through specific double-helix formation.
In seeking to understand the principles that underlie the precise
discrimination behavior of biological molecules such as DNA,
chemists have developed a variety of molecular and supramo-
lecular systems endowed with a self-sorting ability.11-15 In most
cases, their self-sorting has been achieved by the formation of
(supramolecular) macrocyclic species,11 while quite a few
systems perform self-sorting by reading information on the linear
molecular strands, such as the chain lengths and sequences,
through formation of the multiple-stranded complexes.12-15
Double helices could be taken as a versatile platform having
an advantage in the recognition of the sequence and chain length
between the strands,12,13 as exemplified by the seminal examples
of the self-sorting of double-stranded Cu(I) helicates,12a since
the geometrical feature that the two strands are intertwined with
each other in close proximity is likely to work in favor of the
precise recognition of the structures of the molecular strands.
Our double-helical oligomers are capable of discriminating
structural information on the molecular strands, such as chain
lengths and sequences through double-helix formation driven
by the complementary amidinium-carboxylate salt bridge that
are reminiscent of the complementary nucleic acid base pairs
in DNA. Furthermore, the thermodynamically stable salt bridges
enable the separation of the self-sorting mixture by chroma-
tography, as opposed to other dynamic complexes that require
the aid of covalent bonds, such as the disulfide bond, for
separation and isolation.14a,15a
Figure 1. Structures of m-terphenyl-based molecular strands bearing
amidine and/or carboxyl groups and an illustration of double-helical
oligomers consisting of complementary molecular strands stabilized by
amidinium-carboxylate salt bridges. “A” and “C” denote the monomer
units bearing the chiral amidine and achiral carboxyl groups, respectively.
controlled helicity consisting of complementary and sequential
strands. Taking advantage of the high stability and well-defined
directionality of the amidinium-carboxylate salt bridges,10 we
have recently designed and synthesized a heterostranded double
helix with a controlled helix sense that consists of an optically
active dimeric amidine and a complementary achiral carboxylic
acid strand with m-terphenyl backbones, the duplexation of
which relies on salt bridge formation (Figure 1).8 The
amidinium-carboxylate salt bridges have also been widely
employed to construct a number of supramolecular diads10a-f
and capsules10g and utilized as supramolecular junctions for
crystal engineering,10h molecular imprinting,10i and autocatalytic
systems,10j owing to the high association constants and well-
defined geometry of the charge-assisted, double hydrogen
bonding and the high tolerance toward various functional groups.
Results and Discussion
Synthesis of Oligomeric Strands. Molecular strands consisting
of two, three, or four m-terphenyl groups joined by diacetylene
linkers with complementary binding sites, either the chiral
amidine (A) or achiral carboxyl (C) group, were synthesized in
a stepwise manner according to Schemes 1-3. In our previous
study,8a we synthesized the complementary dimer strands
without side chains (AA ·C′C′, C′ ) C (R ) H) in Figure 1)
and investigated their double-helix formation. However, an
increase in the chain lengths of the double helices resulted in a
drastic solubility decrease in most common solvents, which was
improved by introducing a side chain onto the “tail” of the
carboxylic acid units.8f We employed the carboxylic acid unit
with a 1-octynyl chain as a solubility enhancer throughout this
study. In addition to the solubility, the use of less polar solvents
We now report the sequence-specific binding of complemen-
tary molecular strands with sequential information along with
the chain length discrimination of homo-oligoamidines and
(10) For examples of applications of amidinium-carboxylate salt bridges
in supramolecular chemistry, see: (a) Otsuki, J.; Kanazawa, Y.; Kaito,
A.; Islam, D.-M. S.; Araki, Y.; Ito, O. Chem.sEur. J. 2008, 14, 3776–
3784. (b) Otsuki, J.; Iwasaki, K.; Nakano, Y.; Itou, M.; Araki, Y.;
Ito, O. Chem.sEur. J. 2004, 10, 3461–3466. (c) Rosenthal, J.;
Hodgkiss, J. M.; Young, E. R.; Nocera, D. G. J. Am. Chem. Soc. 2006,
128, 10474–10483. (d) Damrauer, N. H.; Hodgkiss, J. M.; Rosenthal,
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G.; Duclairoir, F. M. A.; Kraft, A.; Rosair, G.; Rotello, V. M.
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H. R. Tetrahedron 2002, 58, 3499–3505. (g) Corbellini, F.; Di
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Chem. Soc. 2003, 125, 9946–9947. (h) Fe´lix, O.; Hosseini, M. W.;
De Cian, A.; Fischer, J. Angew. Chem., Int. Ed. Engl. 1997, 36, 102–
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Terfort, A.; von Kiedrowski, G. Angew. Chem., Int. Ed. Engl. 1992,
31, 654–656.
1
with a low viscosity such as CDCl3 gives rise to H NMR
spectra with high resolution, compared to those measured in
(12) For narcissistic self-sorting of double- or triple-helical metal complexes,
see: (a) Kra¨mer, R.; Lehn, J.-M.; Marquis-Rigault, A. Proc. Natl. Acad.
Sci. U.S.A. 1993, 90, 5394–5398. (b) Caulder, D. L.; Raymond, K. N.
Angew. Chem., Int. Ed. Engl. 1997, 36, 1440–1442. (c) Albrecht, M.;
Schneider, M.; Ro¨ttele, H. Angew. Chem., Int. Ed. 1999, 38, 557–
559. (d) Hutin, M.; Cramer, C. J.; Gagliardi, L.; Shahi, A. R. M.;
Bernardinelli, G.; Cerny, R.; Nitschke, J. R. J. Am. Chem. Soc. 2007,
129, 8774–8780. (e) Sarma, R. J.; Nitschke, J. R. Angew. Chem., Int.
Ed. 2008, 47, 377–380.
(11) For examples of self-sorting through (supramolecular) macrocycle
formation, see: (a) Rowan, S. J.; Hamilton, D. G.; Brady, P. A.;
Sanders, J. K. M. J. Am. Chem. Soc. 1997, 119, 2578–2579. (b) Jolliffe,
K. A.; Timmerman, P.; Reinhoudt, D. N. Angew. Chem., Int. Ed. 1999,
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Ko, D. M.; Nakamura, T.; Tsuda, A.; Osuka, A.; Kim, D. J. Am. Chem.
Soc. 2004, 126, 16187–16198. (e) Kamada, T.; Aratani, N.; Ikeda,
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7670–7678. (f) Saur, I.; Scopelliti, R.; Severin, K. Chem.sEur. J. 2006,
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2008, 73, 701–706.
(13) For sequence-selective double-helical metal complex formation, see:
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Soc. 2006, 128, 12628–12629. (b) Schmittel, M.; Kalsani, V.; Kishore,
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11545.
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Scheme 1. Synthesis of the Self-Complementary Dimer AC
Scheme 2. Synthesis of Trimers AAA, AAC, CCA, CCC, ACA, and CACa
a Reagents and conditions: (a) TBAF/THF; (b) PdCl2(PPh3)2, CuI, Et3N-CHCl3.
polar solvents such as DMSO-d6 and D2O. The self-comple-
mentary novel dimeric strand consisting of a chiral amidine and
an achiral carboxyl unit, AC, was synthesized by Glaser-type
coupling16 of the monosilylamidine, A-H,8a and the monosi-
lylated carboxylic acid, C-H,8f using a palladium catalyst
(Scheme 1). The reaction, the progress of which was monitored
by TLC, was terminated after both A-H and C-H had been
completely consumed. AC was obtained in 34% yield along
with the homocoupling side products of AA and CC. The yield
of AC is moderate, considering that the reaction is nonselective,
giving the cross-coupling product with a theoretical maximum
yield of 50%. The six trimeric strands consisting of m-terphenyl
groups joined by diacetylene linkers with complementary
binding sites, either the chiral amidine or achiral carboxyl group,
namely, AAA, CCC, AAC, CCA, ACA, and CAC, were
synthesized in a stepwise manner (Scheme 2). The monosilylated
amidine dimer, AA-H, was obtained from AA8a by treatment
with tetrabutylammonium fluoride (TBAF) in THF. AAA and
AAC were prepared by Glaser-type coupling between AA-H
and A-H or C-H, respectively. Similarly, the carboxylic acid
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Complementary Double-Helix Formation
A R T I C L E S
Figure 2. (A) CD and absorption spectra of (AC)2 (a, green), AA ·CC (b, black), AA (c, blue), and CC (d, red) in CDCl3 (0.10 mM, 25 °C, cell length 0.1
cm). (B) 1H NMR spectra of (AC)2 (a, green) and AA ·CC (b, black) in CDCl3 (0.10 mM, 25 °C).
Scheme 3. Synthesis of Tetramers AAAA and CCCC
dichroism (CD), and electron-spray ionization mass (ESI-MS)
spectroscopies (Figure 2 and the SI). The CD spectrum of (AC)2
exhibited intense Cotton effects in the absorption region of
250-370 nm, suggesting a helix sense bias induction, as
reported for the analogous complementary heterostranded
double-helix dimer AA ·C′C′ without the 1-octynyl groups.8a
(AC)2 appears to have a right-handed double helix on the basis
of the X-ray structure of the heterostranded double helix
AA·C′C′, although the CD spectra of the two double helices
(AC)2 and AA·CC have spectral patterns slightly different from
each other, especially at around 270 nm, reflecting the difference
in their sequences.
The complementary homotrimers AAA and CCC formed the
dimer bearing two 1-octynyl chains, CC, was treated with TBAF
corresponding double helix AAA·CCC in CDCl3 through salt
to afford the monosilylated acid dimer, CC-H, which was
bridge formation. The other complementary heterotrimers, AAC
further allowed to react with A-H and C-H under Glaser-
type coupling conditions to yield CCA and CCC, respectively.
The trimeric strands with an alternate sequence, ACA and CAC,
and CCA, and ACA and CAC, also formed the double helices
AAC·CCA and ACA ·CAC, respectively, with the aid of salt
bridge formation. Similarly to the dimeric double helices, intense
were also synthesized by Glaser-type coupling reactions between
CD signals were observed for the trimeric double helices in
H-C-H and A-H, and H-A-H and C-H, respectively. The
six trimeric strands were obtained in moderate yields (17-52%),
the absorption region of 250-370 nm, indicating that they
adopted a preferred right-handed double helix with an excess
due to the nonselective nature of the coupling reaction. The
one-handedness (Figure 3A-C). The CD spectra of the three
homotetramers of amidine and carboxylic acid, AAAA and
CCCC, were obtained from AA-H and CC-H, respectively,
in good yields by Glaser-type homocoupling (Scheme 3). All
double helices also have spectral patterns slightly different from
each other, especially in the region of 250-300 nm, due to the
difference in their sequences.
The complementary homotetramers AAAA and CCCC also
assembled into the double helix AAAA ·CCCC through the
the oligomers were purified by column chromatography and
characterized and identified using 1H and 13C NMR spec-
troscopies, elemental analyses, and mass measurements (see the
formation of four salt bridges. Similarly to the cases of the
Supporting Information (SI)).
homodimers and -trimers, AAAA ·CCCC showed intense Cotton
Complementary Double-Helix Formation. AC formed a self-
effects in the region above 250 nm, which indicated excess right-
complementary homostranded double helix, (AC)2, through salt
bridge formation in CDCl3, as confirmed by 1H NMR, circular
handed double-helix formation (Figure 3D).
Sequence-Specific Double-Helix Formation. When the three
dimeric strands AA, CC, and AC were mixed together in
CDCl3, the CD and H NMR spectra immediately changed
(16) Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem., Int. Ed.
2000, 39, 2632–2657.
1
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Ito et al.
Figure 3. CD and absorption spectra of AAA (a, blue), CCC (b, red), and AAA ·CCC (c, black) (A), AAC (a, blue), CCA (b, red), and AAC ·CCA (c,
black) (B), ACA (a, blue), CAC (b, red), and ACA ·CAC (c, black) (C), and AAAA (a, blue) and AAAA ·CCCC (b, black) (D) in CDCl3 (50 µM, cell length
0.1 cm) at 25 °C.
Figure 4. (A) CD and absorption spectra of AA ·CC (a, red), (AC)2 (b, green), and a mixture of AA, CC, and (AC)2 (c, black, after mixing in this order)
in CDCl3 at 25 °C (50 µM for each, cell length 0.1 cm), and the simulated CD and absorption spectra for a mixture of separately prepared double-helical
dimers (d, dashed orange). (B) CD and absorption spectra of a mixture of AA, CC, and (AC)2 (c, black, after mixing in this order) and an equimolar mixture
of AA + AC and CC + AC (e, dashed blue, after mixing in this order) in CDCl3 at 25 °C (50 µM for each, cell length 0.1 cm).
and became precisely identical to the simulated spectra
obtained by the summation of each double helix AA · CC and
(AC)2 (Figures 4A and S3 (SI)), indicating that the molecular
strands sequence-specifically hybridized to form the corre-
sponding one-handed double helices through the comple-
mentary amidinium-carboxylate salt bridges. The CD and
1H NMR spectra of the mixture did not change at all
regardless of the orders of addition of the dimeric strands
(Figures 4B and S3 (SI)). For comparison, we mixed an
equimolar amount of AA and AC, which are not comple-
mentary to each other, in CDCl3, forming the self-
complementary double helix (AC)2 together with AA re-
maining as a single strand without any other chemical species,
as evidenced by the identical experimental and simulated CD
combination of CC and AC resulted in the formation of a
mixture of (AC)2 and CC · AC along with the free CC, as
suggested by the CD and 1H NMR spectra, which are
different from the simulated spectra for the mixture of (AC)2
and the free CC (Scheme 4B and Figures S2A and S2B (SI)).
Since the chain exchange between (AC)2 and CC · AC is slow
on the 1H NMR time scale, they gave separated signals, from
which the ratio of (AC)2 to CC · AC was estimated to be 1:1
(Figure S2C (SI)). The formation of CC · AC was presumably
promoted by the dimerization of the carboxylic groups,
though it is much smaller (∼102 M-1 in CHCl3)17 than that
of the amidinium-carboxylate salt bridges (>106 M-1 in
CDCl3).10i
1
and H NMR spectra (Scheme 4A and Figure S1 (SI)). The
(17) I’haya, Y.; Shibuya, T.-i. Bull. Chem. Soc. Jpn. 1965, 38, 1144–1147.
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A R T I C L E S
Figure 5. (A) CD and absorption spectra of AAA ·CCC (a, blue), AAC ·CCA (b, green), ACA ·CAC (c, red), and an equimolar mixture of AAA, AAC,
ACA, CCC, CCA, and CAC (d, black, after mixing in this order; the sample had been allowed to stand for 36 h) in CDCl3 (2 × 10-6 M, 25 °C) and the
simulated CD and absorption spectra for an equimolar mixture of separately prepared double-helical trimers AAA ·CCC, AAC ·CCA, and ACA ·CAC (e,
dashed orange) in CDCl3 at 25 °C (2.0 µM for each, cell length 1 cm). (B) Time course of CD and absorption spectral changes of an equimolar mixture of
AAA, AAC, ACA, CCC, CCA, and CAC in CDCl3 (2.0 µM for each, 25 °C) after mixing in this order.
Scheme 4. Schematic Illustrations of the Duplex Formation between the Dimeric Strands That Are Not Complementary to Each Other
When equimolar amounts of the six trimers AAA, CCC,
AAC, CCA, ACA, and CAC were mixed together in CDCl3,
the CD spectrum gradually changed with time (Figure 5B). After
36 h, the mixture reached equilibrium, and the resultant CD
spectrum became precisely identical to the simulated CD
spectrum obtained by the summation of each double helix
AAA·CCC, AAC·CCA, and ACA ·CAC (Figure 5A), indicat-
ing that the six molecular strands sequence-specifically hybrid-
ized to form the corresponding double helices through the
complementary amidinium-carboxylate salt bridges. As in the
case of the dimeric double helices, the addition order of the
strands did not affect the sequence-specific sorting of the trimeric
strands during double-helix formation. The 1H NMR spectrum
of an equimolar mixture of the six trimeric strands also supports
the perfect sorting of the six trimeric strands (Figure S5 (SI));
the 1H NMR spectrum was identical to the simulated spectrum
obtained by the summation of those of the separately prepared,
three double helices with a complementary sequence. It should
be mentioned here that some trimeric strands with “partially”
self-complementary sequences, such as AAC, ACA, CAC, and
CCA, formed a partial double helix in a staggered fashion
through the salt bridges, showing weak, but distinct Cotton
(18) Some trimer strands also formed double helices with partially
complementary sequences (AAA and CAC, AAA and CCA, AAC
and ACA, AAC and CAC, AAC and CCC, ACA and CCA, ACA
and CCC, and CAC and CCA), exhibiting apparent Cotton effects.
However, the CD intensities, CD patterns, and/or stabilities of the
double helices obtained by dilution CD measurements are different
from those of the fully complementary pairs. The duplex formation
between the partially complementary strands is too complicated to be
fully understood, because of the presence of the concentration
dependence as well as the self-dimerization, whereas the double helices
of the fully complementary pairs are highly stable and did not exhibit
either concentration dependence or self-dimerization over a range of
1-50 µM.
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A R T I C L E S
Ito et al.
Figure 6. (A) UV (328 nm) detected HPLC chromatograms of AAA ·CCC
(a, blue, 29 µM, 7.0 µL), AAC·CCA (b, green, 33 µM, 6.0 µL), ACA·CAC
(c, red, 27 µM, 7.3 µL), and an equimolar mixture of six strands, AAA,
AAC, ACA, CCC, CCA, and CAC (d, black, 10 µM for each, 10 µL, after
mixing in this order; the sample had been allowed to stand for 36 h). (B)
Sequence-selective double-helix formation and its isolation: time-dependent
changes in the HPLC chromatogram of an equimolar mixture of four trimers,
AAA, AAC, ACA, and CCA (CCA was added 12 h after AAA, AAC, and
ACA were mixed in CHCl3), 0-9 h after mixing in CHCl3 at 25 °C. HPLC
conditions: column, TSKgel Silica-60 (Tosoh, 0.46 (L) × 25 cm); eluent,
CHCl3/hexane (1:1, v/v); flow rate, 1.0 mL/min; column temperature, 30
°C.
Figure 7. CD and absorption spectra of A ·C (a, red, 150 µM), AA ·CC
(b, green, 75 µM), AAAA ·CCCC (c, blue, 37.5 µM), and a mixture of
AAAA (12.5 µM), CC (25 µM), A (50 µM), CCCC (12.5 µM), AA (25
µM), and C (50 µM) (d, black, after mixing in this order) in CDCl3 at 25
°C (cell length 1 cm) and the CD and absorption spectra simulated for a
mixture of separately prepared double helices A ·C (50 µM), AA·CC (25
µM), and AAAA ·CCCC (12.5 µM), (e, dashed orange).
effects with CD patterns different from those of the double
helices with the “perfectly” complementary sequences (Figure
S4 (SI)).18
This sorting by sequence was further evidenced by high-
performance liquid chromatography (HPLC). The mixture of
the six strands was then subjected to HPLC using a silica gel
column with CHCl3/hexane (1:1, v/v) as the eluent (Figure 6A).
ThethreedoublehelicesAAA ·CCC,AAC ·CCA,andACA ·CAC
were sequence-specifically eluted without dissociation by virtue
of the strong salt bridges, being separated and eluted in this
order as supported by the identical elution times of each
separately prepared double helix. Under this normal-phase
condition, each trimer itself was strongly adsorbed on the
column and could not be eluted at all. This drastic change in
the elution behavior is attributed to the salt bridges, resulting
in masking the highly polar amidine and carboxyl groups with
the less polar m-terphenyl backbones via duplex formation.
When an equimolar mixture of the three trimeric strands
AAA, AAC, and ACA was injected into the HPLC instrument,
no strand was eluted under the same normal-phase condition
(CHCl3/hexane (1:1, v/v)) due to no complementary pairing.
However, a single peak emerged, and its intensity increased
with time upon the addition of CCA to the mixture, which is
the strand complementary to AAC (Figures 6B and S6 (SI)).
The peak was identified as the double helix AAC·CCA by its
retention time and CD spectrum (Figure S10 (SI)). The other
two strands, AAA and ACA, adsorbed on the stationary phase
under the stated conditions, were eluted after the eluent was
changed to that containing 30 vol % THF (Figure S9 (SI)). Thus,
the AAC strand was successfully extracted from the mixed
strands by its complementary strand, CCA, due to the sequence-
specific binding through salt bridge formation. Similarly, the
CCC sequence-selectively bound its complementary strand,
AAA, in a mixture of AAA, CAC, CCA, and CCC, and ACA
complexed selectively with CAC in a mixture of ACA, CAC,
CCA, and CCC (Figures S7 and S8 (SI)).
Figure 8. SEC chromatogram of a mixture of AAAA (12.5 µM), CC (25
µM), A (50 µM), CCCC (12.5 µM), AA (25 µM), and C (50 µM) in CDCl3
at 25 °C (after mixing in this order) (column, JAIGEL-1H and -2H (JAI, 1
(L) × 60 cm); eluent, CHCl3; flow rate, 3.8 mL/min).
discriminate chain lengths, and only a few examples have been
reported to date.12,13 Therefore, it is of great interest to
investigate the chain-length discrimination ability of our salt-
bridge-based double-helical oligomers. Upon mixing A, C, AA,
CC, AAAA, and CCCC in CDCl3, the absorption, CD, and 1H
NMR spectra quickly became exactly the same as those
simulated for a mixture of A·C, AA·CC, and AAAA·CCCC,
irrespective of the addition order (Figures 7 and S11 (SI)),
indicating that the oligomers formed double helices, with their
complementary strands having the same chain lengths. Further-
more, when the mixture was subjected to SEC using polystyrene
gel columns with CHCl3 as the eluent, the mixture was eluted
without dissolution as in the case of the complementary trimers,
because of the stable salt bridges, and the SEC chromatogram
of the mixture showed three separated peaks that were assigned
to AAAA ·CCCC, AA ·CC, and A ·C from those with the shorter
retention times (Figure 8).
Conclusions
Chain-Length-Specific Double-Helix Formation. The chain
length, or the number of repeating units, is another kind of
intrinsic information about oligomeric molecular strands. As
with the sequence discrimination, it is not a very easy task to
We have synthesized a series of dimeric, trimeric, and
tetrameric strands consisting of m-terphenyl backbones linked
by diacetylene linkers with chiral amidine and/or achiral
carboxylic acid units as the complementary binding sites. The
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14014 J. AM. CHEM. SOC. VOL. 130, NO. 42, 2008

Complementary Double-Helix Formation
A R T I C L E S
trimeric strands with various sequences sequence-specifically
formed double helices with the molecular strands bearing their
complementary sequences. A mixture of homo-oligomers of
amidines and carboxylic acids spontaneously yielded double
helices consisting of the complementary strands with the same
lengths. Thus, our salt-bridge-based double helices have the
capability of precisely discriminating the sequences and chain
lengths of molecular strands through complementary double-
helix formation. In addition, the highly stable salt bridges enable
the separation and isolation of the double helices without
dissolution by chromatography, contrary to the other supramo-
lecular self-sorting systems that may not be separable without
the aid of covalent bonds. Our results provide the first artificial
designer molecules having a dynamic self-sorting ability with
respect to sequences and chain lengths that are separable due
to the strong salt bridges, which may lead to the first step toward
a totally artificial self-replication system.
Acknowledgment. This work was supported in part by a Grant-
in-Aid for Scientific Research (S) from the Japan Society for the
Promotion of Science (JSPS) and JST.
Supporting Information Available: Full experimental details
of the double-helix formation of the dimeric, trimeric, and
tetrameric strands. This material is available free of charge via
the Internet at http://pubs.acs.org.
JA806194E
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