Double versus single helical structures of oligopyridine-dicarboxamide strands. Part 1: Effect of oligomer length

Article abstract of DOI:10.1016/j.tet.2004.07.078

Oligoamides of 2,6-diaminopyridine and 2,6-pyridinedicarboxylic acid were previously shown to fold into single helical monomers and to hybridize into double helical dimers. A new series of these oligomers comprising 5 to 15 pyridine units, 4-decyloxy resi

Full text of DOI:10.1016/j.tet.2004.07.078

Tetrahedron 60 (2004) 10029–10038
Double versus single helical structures of
oligopyridine-dicarboxamide strands.
Part 1: Effect of oligomer length
*
Hua Jiang, Victor Maurizot and Ivan Huc
´
Institut Europeen de Chimie et Biologie, 2 rue Robert Escarpit, 33607 Pessac, France
Received 25 June 2004; revised 12 July 2004; accepted 28 July 2004
Available online 11 September 2004
Abstract—Oligoamides of 2,6-diaminopyridine and 2,6-pyridinedicarboxylic acid were previously shown to fold into single helical
monomers and to hybridize into double helical dimers. A new series of these oligomers comprising 5 to 15 pyridine units, 4-decyloxy
residues, and benzylcarbamate end groups were synthesized using a new convergent scheme that involves an early disymmetrization of the
diamine and of the diacid. The hybridization of these compounds into double helices was studied by 1H NMR spectroscopy in chloroform
solutions at various temperatures. Somewhat unexpectedly, these studies revealed that dimerization increases with oligomer length up to a
certain point, and then decreases down to undetectable levels for the longest strands. NMR studies show that both double helices and single
helices become more stable when strand length increases. The measured values of enthalpy and entropy of hybridization for oligomers of
various length show that the enthalpic gain constantly decreases with strand length. This can be interpreted as being the result of an increasing
enthalpic price of the spring-like extension thatthe strand undergoesuponhybridization asits lengthincreases. Onthe otherhand, the entropic loss
of hybridization also constantly decreases with strand length. Presumably, the helical preorganization of the monomers increases with strand
length, which allows the longer strands to hybridize with a minimal loss of motional freedom, that is to say at a low entropic price. The
competiton between these two factors results in a maximum of hybridization for the strands having an intermediate length.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
dimensional structures of these molecular duplexes have
not always been characterized in detail but the two strands
are most often supposed to adopt a ladder (or zipper) like
linear conformation. Another common way to direct the
assembly of a molecular duplex or triplex is to use metal
ions1,13 or anions14 as templates around which two or three
strands wind upon establishing selective interactions. This
leads to doubly or triply stranded helical architectures
termed helicates. Less commonly, artificial duplexes based
on inter-strand aromatic–aromatic interactions have also
been described.15
In recent years, much effort has been devoted to the design
and characterization of artificial oligomers capable of
pairing into duplexes through multiple cooperative and
selective interactions.1 These structures are useful tools for
the orchestration of self-assembly and self-organization at a
nanometer level. They also give new insights on the
functions of strand pairing as it occurs in biological systems
as, for example, the duplication of information coded in a
molecular strand through the template directed growth of a
complementary strand.
Oligoamide strands derived from 2,6-diaminopyridine and
2,6-pyridinedicarboxylic acid (AOA’s) belong to the wider
class of aromatic oligoamides which adopt well-defined
folded conformations.16–20 AOA’s self-organize into single
helical conformers stabilized by both attractive and
repulsive interactions involving either the amide hydrogen
or oxygen on the one hand, and the adjacent pyridine
nitrogen and protons on the other hand (Fig. 1). Addition-
ally, the helices gain stability from intramolecular aro-
matic–aromatic interaction.16,18 Remarkably, in non polar
solvents, the single helices of AOA’s can extend like springs
and reversibly assemble, giving rise to double-helical
dimeric complexes (Fig. 1).19,20 These artificial molecular
Artificial molecular duplexes may be stabilized by (self)-
complementary hydrogen bond arrays. They can be directly
inspired by natural hybridization motifs as, for example, the
pairing of nucleobases1–3 or the double stranded b-barrel of
the bacterial peptide Gramicidin D4 which both give rise to
double helical architectures. Several non-natural hydrogen
bond arrays have also been designed.1,5–12 The three
Keywords: Helical structures; Molecular recognition; Pi interactions; Self-
assembly.
* Corresponding author. Tel.: C33-54000-2219; fax: C33-54000-3009;
e-mail: i.huc@iecb.u-bordeaux.fr
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.07.078

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H. Jiang et al. / Tetrahedron 60 (2004) 10029–10038
are labeled according to the number of pyridine rings that
they contain. Thus, diester 1a and diamine 1b are efficiently
disymmetrized at an early stage of the synthesis (Scheme 1).
Diester 1a is monosaponified with 1 equiv of NaOH in 85%
yield. Diamine 1b is deprotonated and converted to its
mono-amine mono-benzylcarbamate 1d in 67% yield. This
compound can be coupled to 4-decyloxy-2,6-pyridine
dicarbonyl chloride or to the acid chloride of 1c to give
protected diamine 3a and protected aminoacid 2a, respect-
ively. These products are quantitatively deprotected at the N
terminus using hydrogenation on Pd/C, and at the C
terminus using NaOH. Trimer 3b can also be prepared by
directly reacting the anion of diamine 1b and diester 1a.
Cycles of deprotection, activation via the acid chloride and
coupling, allow to convert 2a into tetrameric strand 4b and
hexameric strand 6b (Scheme 2). Finally, two dimeric,
tetrameric or hexameric acid chloride units can be attached
to a monomeric or trimeric diamine core to give oligomers
5–15 in moderate yield (Scheme 3).
2.2. Dimerization constants as a function of strand length
The alkoxy chains in position 4 of the pyridines diverge
from the helices and confer all oligomers with high
solubility in chlorinated, aromatic, and alkane solvents.
The ability of strands 5–15 to dimerize was investigated in
Figure 1. Intramolecular hydrogen bonds involved in helical conformations
of pyridine oligoamides and schematic representation of single helix/
double helix equilibrium implying a spring like extension/compression of
the strands. The double headed arrows indicate electrostatic repulsions.
1
CDCl3 (Fig. 2). As shown by the H NMR spectra, single
and double helices undergo slow exchange and give rise to
different signals. The coalescence between these signals is
not reached below the boiling point of chloroform for all
these compounds except 5 for which most of the signals
coalesce between 25 and 35 8C.
duplexes represent an original example of double helices
stabilized by direct interactions between the strands
following a non-natural hybridization motif. In contrast
with helicates,13,14 their winding into double helices takes
place without the help of a template. The double helices of
AOA’s involve extensive interstrand aromatic–aromatic
interactions,19,20 unlike natural double helices, for example,
DNA or Gramicidine D, and their synthetic analogs,2–4
which are based on interstrand hydrogen bonding.
The NMR signals can easily be assigned to the single and
double helices according to the variation of their relative
intensity upon changing temperature or concentration: the
proportion of single helix increases upon heating and upon
diluting. The assignment of the signals can also be deduced
from the fact that single and double helices do not have the
Short double helices of AOA’s comprising five or seven
pyridine units per strand were previously characterized in
1
solution by H NMR spectroscopy, in the solid state by X-
ray crystallography, and by molecular modeling studies.19,20
In this report, we present the synthesis of much longer
chloroform soluble strands and show that, somewhat
counter intuitively, dimerization of AOA’s into double
helices increases with strand length to reach a maximum and
then decreases down to undetectable levels for the longest
strands. This can be interpreted as being the result of two
competing factors: the enthalpic gain of hybridization
decreases as strand length increases, but the entropic loss
of hybridization also decreases as strand length increases.
2. Results and discussion
2.1. Synthesis
A series of oligomers was prepared according to a new
scheme that avoids the low yielding late disymmetrization
steps involved in the previous syntheses.18,19 Using a
convergent strategy, we could produce molecular strands up
to twice as long as the longest chloroform soluble oligomers
that we described previously. In the following, oligomers
Figure 2. Part of the 1H 400 MHz NMR spectra of compound 5–15 at
25 8C, CZ1 mM in CDCl3, showing the resonances of the amides (11–
9 ppm) and the resonnances of the benzylic methylenes (5.4–4.4 ppm).
Signals assigned to single and double helices, and to impurities21 are
labelled by circles, squares, and asterisks respectively.

H. Jiang et al. / Tetrahedron 60 (2004) 10029–10038
10031
Scheme 1. Reagents and conditions: (a) MeOH–dioxane, 0 8C, NaOH (1 equiv), 85% yield; (b) SOCl2, reflux, then 1d, toluene, iPr2EtN, RT, 90% yield; (c)
THF, K78 8C, n-BuLi (1 equiv), ClCO2Bn (1 equiv), 67% yield; (d) toluene, 4-decyloxypyridine 2,6-dicarbonylchloride (0.45 equiv), iPr2EtN, RT, 83% yield;
(e) H2O–dioxane, 25 8C, NaOH (2 equiv), quant. yield; (f) ethyl acetate/AcOH, RT, H2/Pd–C, quant. yield.
same symmetry. The single helices possess a C2 symmetry
axis perpendicular to the helical axis. Each signal is
therefore degenerate and corresponds to the two protons
occupying equivalent positions at each end of the strand.
This symmetry is lost in the double helices in which the two
strands are equivalent, but the extremities of each strand are
in different environments. A double helix thus gives rise to
twice as many signals as the corresponding single helix (see
the spectra of 9–15 in Fig. 2). However, this only holds
below a certain temperature. Sliding motions within the
double helix allow the exchange between the different
environments of each strand. When this becomes fast on the
NMR timescale, a coalescence takes place and the NMR
spectrum of an on-average C2 symmetrical double helix is
seen (see the spectrum of 7 in Fig. 2).
three double-helical turns and is more than 2 nm long with a
molecular weigh of 7700 g molK1
.
Dimerization constants at various temperatures were
calculated by non linear regression analysis of the
proportions of monomer and dimer measured from NMR
signals at different concentrations. The values reported in
Table 1 show that dimerization increases with strand length
to reach a maximum value and that, somewhat counter-
intuitively, it decreases for longer strands. At 25 8C, the
value of Kdim increases with strand length from five to nine
pyridine rings (up to 5200 L molK1 for 9), and decreases by
4 orders of magnitude for longer strands down to
undetectable levels for 15. This trend is even more
pronounced at K19 8C where dimerization is strongly
enhanced (Table 1): Kdim then reaches a maximum of
120,000 L molK1 for compound 7, and dramatically
decreases for longer strands. The effect is still observed,
though less intense, at 49 8C where dimerization is
significantly lowered (Table 1).
The considerable size of these synthetic double helices
should be emphasized. Dimer (13)2, for example, spans over
These results are surprising because the number of
stabilizing inter-strand interactions, and thus the stability
of the double helices were expected to increase with
increasing strand length. Indeed, oligomers often exhibit
positive cooperativity upon hybridizing: not only the overall
binding free energy (KDG8) increases with strand length,
Scheme 2. Reagents and conditions: (a) DMF/MeOH, RT, H2/Pd–C, quant.
yield; (b) acid chloride of 2c, toluene, iPr2EtN, RT, 60–80% yield; (c) H2O–
dioxane, NaOH (2 equiv), RT, quant. Yield.
Scheme 3. Reagents and conditions: SOCl2, reflux, then 1b or 3b, toluene,
iPr2EtN, RT, 20–40% yield.

10032
H. Jiang et al. / Tetrahedron 60 (2004) 10029–10038
Table 1. Values of Kdim (MK1)at various temperatures in CDCl3
Entry
5
7
9
11
13
15
a
25 8C
K19 8C
49 8C
210
1900
—
1500
120,000
170
5200
42,800
750
650
920
500
65
180
45
—
—
—
a
a
b
a
Signal intensity too low.
Broad signals.
b
but also the binding free energy per monomer (KDG8/n).
For instance, this is the case in nucleic acids double helices
and their analogs, and in several synthetic oligomers based
on hydrogen bonding.5,7,11
In single helices, the environment of the protons belonging
to the terminal units of the strand is not expected to depend
much on the length of the strand beyond one helical turn.
However, we observe that the signals of these protons
undergo an upfield shift as strand length increases. For the
signals of benzylic protons, the upfield shift is of almost
0.2 ppm between 7 and 15 (d in Table 2). Similar shifts are
observed for amide (Fig. 2) and aromatic (not shown)
resonances. This reflects an increase of the ring current
effects in the folded helical conformations and shows that
short helices apparently spend more time in an extended
form, whereas long helices apparently remain completely
folded.
To explain these results, we first hypothesized that the
attractive interactions leading to duplex formation in
oligopyridine dicarboxamides may not match over long
strands. However, molecular models of long double helices
built on the basis of the crystal structures of short double
helices19 show no alteration of the double helical motif
(Fig. 3). Moreover even if the longer strands did not match
over their entire length, they should still match along part of
their length in the way short strands do and lead to some
dimerization.
In the single helices, the terminal benzylic methylene
1
protons give rise to two diastereotopic H NMR signals
which appear as doublets at ca. 4.8 and 5.2 ppm. Upon
increasing temperature, these signals coalesce as the
inversion of helix handedness becomes rapid on the NMR
timescale (Fig. 4). The temperatures of coalescence
recorded for 5–15 are reported in Table 2 (Tinv). The values
of Tinv increase very rapidly with strand length: about C258
for every two pyridine rings added to the strand. For
pentamer 5, helix inversion becomes rapid on the NMR
timescale above 10 8C. Tinv is found above the boiling point
of CDCl3 for nonamer 9 and undecamer 11 and even close
to the boiling point of C2D2Cl4 for the longest strands. Thus,
these data give a qualitative but clear indication that the
stability of the single helices with respect to unfolded states
increases rapidly as oligomer length increases.
2.3. Stability of double helices and stability of single
helices
The value of Kdim depends on the free energy difference
between the double and the single helix. A drop in Kdim does
not necessarily reflect a destabilization of the double helix.
It may also result from a more important stabilization of the
single helix. We thus sought for data indicating the effect of
strand length on single helix stability on the one hand, and
on double helix stability on the other hand.
Two independent indicators of single helix stability were
followed by measuring 1H NMR spectra of 5–15 at different
temperatures: first, the extent of ring current effects on the
protons belonging to the terminal units which can be
deduced from the amplitude of the upfield shifts of their
signals; and second the rate of inversion of the helix which is
correlated to the temperature of coalescence of diastereopic
patterns in the spectra.
Figure 4. Part of the 1H 400 MHz NMR spectra of compound 7, CZ1 mM
in CDCl3 at various temperatures, showing the resonances of the amides
(11–9 ppm) and the resonnances of the benzylic methylenes (5.4–4.4 ppm).
Some signals assigned to single helices and to the double helices are
labelled by circles and squares respectively. Arrows indicate coalescences.
Figure 3. Molecular models of the double (top) and single (bottom) helices
of compounds 7, 11, and 15, obtained by prolongation of the patterns found
in the crystal structures of previously described single and double helices,18,19
followed by energy minimization (MM3). Alkoxy chains have been
replaced by hydrogens for clarity.

H. Jiang et al. / Tetrahedron 60 (2004) 10029–10038
10033
Table 2. Physical data for 5–15 in CDCl3: chemical shift of one benzylic signal of the single helices (d); temperatures of coalescence of 400 MHz 1H NMR
signals of diastereotopic protons of the single helice (Tinv) and of both ends of each strand in dissymmetrical degenerate double helices (Tdeg); and estimated
surfaces of the strands involved in p–p overlap in double helices (Sdh per strand) and single helices (Ssh)
a
Tinv (8C)
b
Tdeg (8C)
2
Sdh (A )
2
Ssh (A )
2
˚
˚
˚
Compound
d (ppm)
DZSdh–Ssh (A )
c
5
7
9
11
13
15
—
10
43
36
3
500
760
1020
1290
1550
1820
200
450
710
980
1230
1500
300
310
310
310
320
320
4.86
4.78
4.75
4.71
4.69
65d
49
O55
—
90d
O120d
O120d
e
e
—
a
Coalescence of benzylic protons at 5.2 and 4.8 ppm.
Coalescence of benzylic protons at 4.95 and 4.93 ppm.
Broad signal.
In CD2Cl4.
Signal intensity too low.
b
c
d
e
Two indicators of the stability of the double helices were
also found. We initially expected to be able to measure the
temperature of coalescence between the 1H NMR signals of
the single helix and the signals of the double helix. This
temperature is close to room temperature for pentamer 5,
but it increases so rapidly with strand length that we could
not access to this data for any other strand but heptamer 7
for which it was measured above 100 8C. The coalescence
temperatures of longer strands are above the temperatures
that one can reach with a standard NMR spectrometer. This
result is corroborated by molecular dynamics simulations
that we reported previously19 that suggest that the rate of
duplex dissociation is higher for shorter strands than for
longer strands.
arises from an increase of stabilizing interactions in both
single and double helices, and results in a better helical
organization and a decrease of the rates of dynamic motions
as the length increases. However, these data alone give no
hint why the variation of Kdim as a function of strand length
goes through a maximum instead of following a mono-
tonous increase or a monotonous decrease.
2.4. Enthalpic and entropic factors
Previous studies on the dimerization of oligopyridine
dicarboxamides suggest that the main driving force of
hybridization is interstrand p–p stacking.19,20 The increase
of stability of both single and double helices with increasing
chain length presumably arises from an increase of
intramolecular p–p overlap in the single helices (Ssh in
Table 2) and of intermolecular p–p overlap in the double
helices (Sdh in Table 2). In order to estimate Ssh and Sdh, we
calculated the energy-minimized conformations of the
single and double helices (Fig. 3), and compared the solvent
accessible surfaces of these folded structures with those of
linearly extended strands. As could be expected, the surface
involved in p–p overlap increases linearly with strand
length both in the single (Ssh) and in the double (Sdh) helices.
However, the difference between Sdh and Ssh does not
depend upon chain length and remains constant at ca.
We also assessed the stability of the double helices by
monitoring the sliding motion of the strands relative to one
another within the duplex.19 In double helices, the
extremities of each strand are in a different environment,
and the terminal benzylic methylene protons are not
equivalent and give rise to two pairs of doublets between
5.2 and 4.4 ppm (Figs. 2 and 4). These four doublets are the
signals of two pairs of diastereotopic protons which, in
principle, can exchange upon inversion of the double
helices. However, since the inversion of the double helix
handedness requires dissociation of the strands, the
coalescence between the diastereotopic signals of the
double helix could not be observed in CDCl3 (except for
5, see above). Nevertheless, an equilibrium takes place
between two degenerate states of the double helix allowing
an exchange between the different environments of the
strands.19 When this equilibrium is fast on the NMR
timescale, only two diastereotopic doublets are observed for
the benzylic methylenes protons (Figs. 2 and 4). The
temperatures of coalescence between the signals of these
degenerate double helices (Tdeg in Table 2) thus reflect the
rate of an internal motion within the duplex. These
temperatures also increase regularly with strand length
from K36 8C for pentamer 5a to over 55 8C for undecamer
11a. For longer strands, Tdeg could not be measured because
the amount of double helix at high temperature is too low to
be detected. This indicates slower dynamics in longer
double helices, suggesting that the duplexes become more
stable and that they do hybridize over their entire length.
2
˚
300 A , which is roughly the surface of the cross-section of
one helix.22 This result suggests that, in first approximation,
the enthalpic gain of hybridization associated with p–p
interactions is independent of strand length. One may argue
that the nature of the stacked p-systems differ in the single
and in the double helices,23 and that the overall enthalpic
gain may vary with strand length even though the surface
involved in p-stacking does not increase. But the data show
that this effect, if it exists, is not significant.
On the other hand, hybridization has an enthalpic cost
associated with the extension of the strand and the doubling
of the pitch (Fig. 1) that implies an increase of dihedral
angles and a lengthening of the NH/N intramolecular
hydrogen bonds within each strand of the duplex. This cost
is directly proportional to the number of dihedral angles of
the strand, and therefore increases linearly with strand
length. The sum of an enthalpic cost that increases linearly
with strand length and of an enthalpic gain that does not
depend on strand length should lead to an overall decrease
of the enthalpy of double helix formation as strand length
increases.
In summary of this section, NMR data qualitatively show
that, as could be expected, both double and single helices
increase in stability as their length become longer. This

10034
H. Jiang et al. / Tetrahedron 60 (2004) 10029–10038
We calculated the enthalpy of dimerization from van’t Hoff
plots for compounds 7, 9 and 11, for which Kdim can reliably
be measured over a large temperature range. The results
shown in Table 3 indeed show that the enthalpy of
hybridization constantly decreases as the length of the
oligomer increases. The enthaplic term is very strong for
heptamer 7 (DHZK64G3 kJ molK1) as the increase of the
surface involved in p–p overlap from single to double helix
is large relative to the overall surface of the strand. For
nonamer 9, the enthalpic gain of dimerization is smaller
(DHZK42G4 kJ molK1). For compound 11, the enthalpic
3. Conclusion
In summary, we have presented a new synthetic scheme for
the preparation of AOA’s and studied their hybridization
into double helices as a function of strand length. The fact
that the enthalpic price of spring-like extension that a strand
must undergo during the formation of a double helix is not
compensated by intermolecular p–p interactions explains
that dimerization of AOA’s decreases for longer oligomers.
That Kdim goes through a maximum before decreasing
results from entropic effects that partially compensate for
the decreasing enthalpy of hybridization. These results
suggest that a subtle destabilization of the single helical
monomers might enhance their hybridization into double
helices. Studies on these effects and also on the role of the
side chains, and of terminal residues, are currently under-
way and will be reported in due course.
term reaches very low levels (DHZK5.8G0.4 kJ molK1
)
which reflects the fact the gain in p–p overlap upon
dimerization is largely compensated by the cost of helix
extension.
From these results, it seems reasonable to propose that the
drop of Kdim for longer oligomers results from a drop of the
enthalpic gain of hybridization. It remains to explain why
Kdim goes through a maximum and does not follow a
monotonous decrease. The van’t Hoff plots for compounds
7, 9 and 11 show that the entropy of hybridization follows a
trend opposite to that of the enthalpy. The large DH for 7 is
compensated by a large negative entropic term (DSZK
154G9 J KK1 molK1). The entropic loss during hybridiz-
ation is smaller for 9 (DSZK74G14 J KK1 molK1), and
even has a (small) positive value (DSZ34G1 J KK1 molK
1) for 11. This trend of the entropy of hybridization as a
function of length presumably reflects that the helical
preorganization of the monomers increases with strand
length, which allows the longer strands to hybridize with a
minimal loss of motional freedom, that is to say at a low
entropic price. The positive value of DS for 11 suggests that
other factors are at play, possibly desolvation, which may
contribute favorably to dimerization.
4. Experimental
4.1. General
Solvents (THF, toluene, CH2Cl2) were dried by filtration
over activated alumina on a commercially available setup.
FTIR spectra were recorded on a Brucker IFS 55 FT-IR
Spectrometer 400 MHz 1H and 100 MHz 13C NMR spectra
were recorded on a Bruker 400 Ultrashield spectrometer.
The chemical shifts are expressed in parts per million (ppm)
using the residual solvent peak as an internal standard. The
following notations are used for the 1H NMR spectral
splitting patterns: singlet (s), doublet (d), triplet (t), multi-
plet (m), borad (br). Melting points are uncorrected. Diester
1a and diamine 1b were prepared as described previously.
4.1.1. 4-Decyloxy-2,6-pyridinedicarboxylic acid mono-
methyl ester (1c). Dimethyl 4-decyloxy-2,6-pyridinedicar-
boxylate19 (2.1 g, 6 mmol) was dissolved in 1,4-dioxane
(32 mL) and methanol (8 mL) and the solution was cooled
to 0 8C. Sodium hydroxide (0.24 g, 6 mmol) was added and
the mixture was stirred at 0 8C for 2 h and another 2 h at
ambient temperature. The solution was neutralized with
acetic acid and poured into water (100 mL). The product
was extracted with CH2Cl2 (2!50 mL). The organic phase
was evaporated and dried under vacuum. The product
contaminated with small amounts of starting diester was
used without further purification. Yield 1.7 g (85%) of a
It is worth noting that the large value of DS for 7 results in a
strong temperature dependence of Kdim: by up to three
orders of magnitude over a range of 758 (Table 3 and Fig. 4).
On the other hand, dimerization of the longer strands show
very little temperature dependence (Table 3): only a factor
of 2 over a range of 758.
The hybridization behavior of AOA’s contrasts with that of
most artificial and natural oligomers. The major difference
is that not only the dimers of AOA’s fold into well
organized structures, but also the monomers. For instance,
single stranded DNA, does not generally adopt a stable and
well-defined conformation. However, when this is possible
as, for example, in hairpins or in G-quartets, hybridization
into double helices is impeded.24 A few artificial oligomers
capable of pairing into duplexes reported in the literature
also form stable single stranded structures, and it will be
interesting to see whether these oligomers keep their ability
to hybridize as the strands get longer.
1
white solid. Mp: 91–92 8C. H NMR (CDCl3), d 7.84 (1H,
s), 7,80 (1H, s), 4.15 (2H, t, JZ6.7 Hz), 4.01 (3H, s), 1.84
(2H, m), 1.47 (2H, m), 1,27 (15H, m). TOF-MS (m/z):
338.37 [MCH]C (Calcd for C18H28NO5: 338.20).
4.1.2. (6-Amino-4-decyloxy-pyridin-2-yl)-carbamic acid
benzyl ester (1d). To a solution of 4-decyloxy-2,6-
diaminopyridine 1b19 (1.5 g, 5.65 mmol) in anhydrous
Table 3. Values of Kdim (MK1) at various temperatures for and values of DH and DS 7, 9 and 11
Compound
T (8C)
DH (kJ molK1
)
DS (J KK1 molK1
)
K19
K4
10
25
36
K49
55
7
9
11
120,000
42,800
920
22,000
23,200
750
12,000
10,300
710
1500
5200
650
710
2500
560
170
750
500
140
400
480
K64G3
K42G4
K5.8G0.4
K154G9
K74G14
34G1

H. Jiang et al. / Tetrahedron 60 (2004) 10029–10038
10035
THF at K78 8C (60 mL) was slowly added a 2 M solution of
n-butyllithium in hexane (2.7 mL, 1 equiv) After 15 min,
benzyl chloroformate (934 mL, 1 equiv) was added at once.
The mixture was stirred at K78 8C for 5 h, then at room
temperature for 12 h. The reaction was quenched with a
small amount of water. The solvent was evaporated, and the
residue was dissolved in CH2Cl2. This solution was washed
with water, dried (MgSO4), filtered and evaporated. The
residue was purified by flash chromatography on silica gel
eluting with CH2Cl2/AcOEt. Yield 1.5 g (67%) of an off-
white solid. Mp: 85–87 8C. 1H NMR (CDCl3) d 7.56 (1H, s),
7.36 (5H, m), 6.97 (1H, s), 5.69(1H, s), 5.87 (2H, s), 4.21
(2H, s), 3.95 (2H, t, JZ6.8 Hz), 1.74 (2H, m), 1.27 (14H,
m), 0.89 (3H, t, JZ6.8 Hz). 13C NMR (CDCl3) d 168.65,
158.51, 153.08, 151.57, 135.86, 128.51, 128.25, 128.16,
89.86, 89.22, 67.89, 66.85, 31.85, 29.50, 29.27, 28.94,
25.88, 22.64, 14.08. IR (liquid layer) n (cmK1): 3450, 3343,
3258, 3208, 3201, 2957, 2942, 2920, 2873, 2852, 1743,
1718, 1658, 1611, 1578, 1562, 1468, 1454, 1444, 1440,
1405, 1332, 1321, 1313, 1291, 1241, 1226, 1190, 810, 753,
731. TOF-MS (m/z): 400.35 [MCH]C (Calcd for
C23H34N3O3: 400.26).
chromatography on silica gel eluting with cyclohexane/
EtOAc 10:1 vol/vol. Yield 2.63 g (73%) of a white solid.
Mp: 107–109 8C H NMR (CDCl3), d 10.19 (1H, s), 7.91
1
(1H, d, JZ2.8 Hz), 7.75 (1H, d, JZ2 Hz), 7.68 (1H, d, JZ
2 Hz), 7.32 (6H, m), 5.22 (2H, s), 4.15 (2H, t, JZ6 Hz), 4.07
(2H, t, JZ6.8 Hz), 4.02 (3H, s), 1.82 (4H, m), 1.28 (28H,
m), 0.88 (6H, t, JZ6.8 Hz). 13C NMR (CDCl3): d 169.00,
167.64, 165.01, 161.74, 152.84, 151.27, 150.99, 150.19,
148.45, 135.78, 128.58, 128.11, 111.01, 95.88, 94.84, 69.14,
68.43, 67.08, 52.97, 31.85, 29.48, 29.30, 29, 28.94, 28.68,
25.89, 25.80, 22.65, 14.09. IR (KBr) n (cmK1) 3363, 2919,
2852, 1732, 1713, 1695, 1602, 1580, 1537, 1509, 1444,
1354, 1332, 1262, 1215, 1172, 1151, 1092, 1042. TOF-MS
(m/z): TOF-MS 719.46 [MCH]C (Calcd for C41H59N4O7:
719.44), 741.45 [MCNa]C, 757.42 [MCK]C.
4.2.2. Tetramer 4a. From acid 2c (1.44 g, 2.0 mmol) and
amine 2b (1.0 g, 1.7 mmol). The residue was purified by
flash chromatography on silica gel eluting with cyclohex-
ane/EtOAc 10:1 vol/vol. Yield 1.78 g (82%) of a white wax.
1H NMR (CDCl3) d 10.60 (1H, s), 10.52 (1H, s), 10.50 (1H,
s), 8.42 (1H, br), 7.83 (1H, d, JZ2 Hz), 7.77 (1H, d, JZ
2 Hz), 7.75 (1H, d, JZ2 Hz), 7.64 (1H, s), 7.57 (2H, m),
7.40 (1H, d, JZ2 Hz), 7.11 (5H, m), 7.01 (1H, d, JZ3 Hz),
4.85 (2H, s), 4.15 (2H, t, JZ6.8 Hz), 4.04 (4H, t, JZ6 Hz),
3.97 (2H, t, JZ6.4 Hz), 3.67 (3H, s), 1.82 (8H, m), 1.30
(56H, m), 0.89 (12H, t, JZ6.8 Hz). 13C NMR (CDCl3) d
168.92, 168.14, 167.40, 164.61, 161.74, 161.56, 152.91,
151.30, 150.56, 150.47, 150.27, 147.52, 135.51, 128.22,
127.83, 127.35, 114.75, 111.60, 110.90, 97.21, 96.77, 96.05,
95.16, 69.22, 69.08, 68.54, 68.42, 66.62, 52.83, 31.90,
29.58, 29.55, 29.31, 29.00, 28.78, 25.94, 25.84, 22.68,
14.11. IR (KBr) n (cmK1): 2924, 2854, 1736, 1699, 1580,
1522, 1438, 1338, 1218, 1173, 1108, 1088, 1046, 1018.
TOF-MS (m/z): 1271.76 [MCH]C (Calcd for
C73H107N8O11: 1271.81).
4.1.3. Trimeric diamine 3b. To a solution of 4-decyloxy-
2,6-diaminopyridine (0.5 g, 1.88 mmol) in anhydrous THF
(4 mL) at K78 8C, was added n-butyllithium (2.1 M,
0.942 mL, 1.05 equiv). The mixture was allowed to stand
at K78 8C for 15 min. A solution of dimethyl 4-decyloxy-
2,6-pyridinedicarboxylate (0.278 g, 0.79 mmol, 0.42 equiv)
in THF (3 mL) was added using a canula. The mixture was
stirred at K78 8C for 4 h, then at ambient temperature for
24 h. The reaction was quenched with acetic acid
(1.2 equiv) and then evaporated to dryness. The residue
was purified by flash chromatography on silica gel eluting
with ethyl acetate/cyclohexane 2:1 vol/vol, to afford 3b.
1
Yield 259 mg (40% from the diester) of a yellow wax. H
NMR (CDCl3, ppm) d 9.99 (2H, s), 7.86 (2H, s), 7.35 (2H,
s), 5.66 (2H, s), 5.27 (4H, br), 4.10 (2H, t, JZ6,7 Hz), 3.86
(4H, t, JZ6.7 Hz), 1.70 (6H, m), 1.28 (42H, m), 0.89 (9H,
m). 13C NMR (CDCl3): 168.72, 168.15, 161.38, 158.42,
150.27, 111.52, 91.58, 90.12, 69.16, 68.07, 52.74, 31.87,
29.67, 29.56, 29.38, 29.27, 29.00, 25.91, 25.80, 22.65,
14.08. IR (liquid layer) n (cmK1): 3361, 2924, 2854, 1694,
1613, 1578, 1535, 1448, 1378, 1344, 1175, 1048.
4.2.3. Hexamer 6a. From acid 2c (0.26 g, 0.37 mmol) and
amine 4b (0.35 g, 0.31 mmol). The residue was purified by
flash chromatography on silica gel eluting with toluene/
EtOAc 95:5 vol/vol. Yield 390 mg (69%) of a white wax. 1H
NMR (CDCl3, 36 8C, 1 mM) d 10.86 (1H, s), 10.70 (1H, s),
10.46 (1H, s), 10.26 (1H, s), 10.08 (1H, s), 7.94 (1H, br),
7.89 (1H, br), 7.78 (1H, br), 7.80 (1H, br), 7.72 (2H, br),
7.52 (1H, br), 7.43 (1H, br), 7.34 (3H, br), 7.14 (5H, br),
7.00 (2H, br), 5.10 (2H, s), 4.16 (24H, m), 3.64 (3H, s), 1.88
(6H, br), 1.33 (84H, m), 0.91 (12H, s). 13C NMR (CDCl3) d
168.80, 168.00, 167.78, 167.43, 166.95, 164.5, 164.30,
161.39, 160.62, 151.28, 150.27, 150.18, 149.86, 149.44,
135,51, 134.97, 128.83, 128.15, 127.65, 127.18, 114.88,
114.20, 11.49, 111.22, 111.00, 110.36, 110.11, 97.39, 96.64,
96.56, 95.09, 94.70, 69.10, 68.63, 68.01, 66.10, 52.86,
52.48, 31.95, 29.68, 29.42, 29.06, 25.93, 22.71, 14.13. IR
(KBr) n (cmK1): 3372, 2924, 2854, 1735, 1696, 1583, 1523,
1438, 1339, 1218, 1174, 1121, 1046, 849. TOF-MS (m/z):
1824.06 [MCH]C (Calcd for C105H155N12O15: 1824.17).
4.2. Synthesis of 2a, 4a and 6a. General method for
coupling a monoacid and a monoamine
Under an anhydrous atmosphere, a solution of acid 1c or 2c
(1 mmol) in thionyl chloride (5 mL) was heated to reflux till
evolvement of gas stopped (ca 30–60 min). The excess
thionyl chloride was distilled under reduced pressure, and
azeotroped with dry toluene. The residue was dissolved in
dry toluene (10 mL). To this solution at 0 8C was added a
solution of amine 1d, 2b or 4b (0.9 equiv) in dry toluene
(10 mL), followed by distilled N,N-diisopropylethylamine
(5 equiv). The mixture was allowed to warm to ambient
temperature and stirred overnight. The solvent was removed
and the residue was purified by flash chromatography on
silica gel.
4.3. Synthesis of 2b and 4b. General hydrogenation
procedure
A mixture of benzylcarbamate 2a or 4a (1 mmol) dissolved
in DMF (10 mL) and methyl alcohol (10 mL), and of 10%
Pd/C (10% weigh) was stirred overnight under hydrogen at
4.2.1. Dimer 2a. From acid 1c (2.026 g, 6.0 mmol) and
amine 1d (2 g, 5.0 mmol). The residue was purified by flash

10036
H. Jiang et al. / Tetrahedron 60 (2004) 10029–10038
atmospheric pressure The mixture was filtered through
Celite. The solvents were removed under reduced pressure
to give the product, which was used without further
purification.
diamine were used. All products were purified by flash
chromatography on silica gel eluting with cyclohexane/
EtOAc 95/5 vol:vol.
4.5.1. Pentamer 5. From diameric acid 2c (300 mg,
0.42 mmol)) and monomeric diamine 1b (47 mg,
0.18 mmol). Yield 69 mg (25%) of a white wax. H NMR
(CDCl3, 36 8C, 1 mM, signals of the single helix) d 10.35
(4H, br), 7.85 (4H, br), 7.03 (2H, br, m), 7.15 (10H, br, m),
7.03 (6H, br, m), 5.03 (4H, br, m), 4.08 (10H, br, m), 1.86
(10H, br, m), 1.31 (70H, br, m), 0.91 (15H, br, m). IR (KBr)
n (cmK1): 2924, 2854, 1697, 1586, 1533, 1453, 1339, 1217,
1175, 1045. HR TOF-MS (m/z): 1639.04 [MCH]C (Calcd
for C95H136N11O13: 1639.03).
4.3.1. Synthesis of dimer amine 2b. From dimer 2a (1 g,
1.39 mmol) and 10% Pd/C (100 mg). Yield 810 mg
(quantitative) of 2b as an off-white solid. Mp: 160–
1
1
161 8C. H NMR (CDCl3) d 10.15 (1H, s), 7.92 (1H, d,
JZ2.8 Hz), 7.74 (1H, d, JZ2 Hz), 7.46 (1H,d, JZ2 Hz),
5.83 (1H, d, JZ2 Hz), 4.32 (2H, s), 4.14 (2H,t, JZ6.8 Hz),
4.02 (5H, m), 1.82 (4H, m), 1.28 (28H, m), 0.88 (6H, t, JZ
6.8 Hz). 13C NMR (CDCl3) d 168.61, 167.61, 165.01,
158.84, 151.61, 150.62, 148.10, 114.91, 110.82, 91.36,
90.32, 69.10, 68.00, 52.90, 31.85, 29.54, 29.49, 29.28,
29.02, 28.70, 25.93, 25.80, 22.64, 14.09. IR (KBr) n (cmK1):
3404, 3343, 2920, 2851, 1723, 1702, 1658, 1614, 1597,
1532, 1464, 1382, 1347, 1294, 1254, 1165, 1107, 1040.
TOF-MS (m/z): 585.49 [MCH]C (Calcd for C33H53N4O5:
585.40).
4.5.2. Heptamer 7. From dimeric acid 2c (72 mg,
0.1 mmol) and trimeric diamine 3b (36.5 mg,
0.045 mmol). Yield 34.21 mg (35%) of a white wax. H
1
NMR (CDCl3, 36 8C, 1 mM, signals of the single helix) d
10.60 (2H, s), 10.41 (2H, s), 10.25 (2H, s), 7.88 (2H, s), 7.79
(2H, s), 7.65 (2H, s), 7.49 (2H, s), 7.32 (2H, s), 7.13 (7H, m),
7.03 (7H, m), 7.00 (2H, s), 5.23 (2H, br), 4.89 (2H, br), 4.22
(2H, br), 4.14 (12H, br), 1.88 (14H, br), 1.34 (98H, br, m),
0.91 (21H, br, m). 13C NMR (CDCl3) d 169.25, 168.92,
168.11, 167.91, 167.41, 167.31, 163.82, 161.41, 161.05,
160.92, 151.66, 150.22, 150.06, 149.77, 149.46, 148.79,
135.44, 130.86, 128.78, 128.21, 127.74, 127.17, 126.77,
111.65, 111.41, 111.26, 110.93, 96.96, 96.75, 96.28, 95.63,
94.06, 69.22, 68.07, 66.31, 37.39, 33.68, 32.75, 31.93,
30.17, 29.68, 29.40, 29.05, 27.30, 26.05, 25.93, 22.71,
19.73, 14.13. IR (liquid layer) n (cmK1): 3313, 2957, 2924,
2853, 1735, 1700, 1648, 1616, 1585, 1579, 1560, 1540,
1523, 1458, 1430, 1377, 1349, 1339, 1261, 1218, 1176,
1092, 1052, 1020. TOF-MS (m/z): 2191.27 [MCH]C
(Calcd for C127H184N15O17: 2191.40).
4.3.2. Synthesis of tetramer amine 4b. From tetramer 4a
(0.95 g) and 10% Pd/C (80 mg). Yield 850 mg (quantitat-
1
ive) of 4b as an off-white wax. H NMR (CDCl3) d 10.61
(1H, s), 10.47(1H, s), 10.39 (1H, s), 7.91 (4H, m), 7.73 (1H,
s), 7.70 (1H, s), 7.51(1H, s), 5.81 (1H, s), 4.16 (6H, m),
4.01(2H, t, JZ6 Hz), 3.95 (2H, s), 3.50 (3H, s), 1.84 (8H,
m), 1.29 (56H, m), 0.89 (12H, t, JZ7.4 Hz). TOF-MS (m/z):
1137.87 (Calcd for C65H101N8O9: 1137.77).
4.4. General method for the saponification of methyl
esters
To a solution of ester 2a, 4a, or 6a (1.39 mmol) in 1,4-
dioxane (20 mL) and water (2 mL), was added sodium
hydroxide (111.2 mg; 2 equiv). The resulting solution was
stirred for 2 h at 25 8C, and then neutralized with an excess
of AcOH. The solution was extracted with dichloromethane
(40 mL). The organic phase was washed with water, dried
over MgSO4, filtered and evaporated, to yield the corre-
sponding acid which was used without further purification.
Following this procedure, dimer acid 2c, tetramer acid 4c
and hexamer acid 6c were obtained as off-white solids in
4.5.3. Nonamer 9. From tetrameric acid 4c (103 mg,
0.082 mmol) and monomeric diamine 1b (8.68 mg,
0.033 mmol). Yield 19.2 mg (21%) of a white wax. 1H
NMR (CDCl3, 36 8C, 1 mM, signals of the single helix) d
10.65 (2H, s), 10.40 (2H, s), 10.34 (2H, s), 10.32 (2H, s),
7.90 (2H, d, JZ2 Hz), 7.62 (4H, d, JZ2 Hz), 7.59 (4H, d,
JZ2 Hz), 7.54 (2H, d, JZ2 Hz), 7.58 (2H, s), 7.44 (2H, d,
JZ2 Hz), 7.18 (2H, d, JZ2 Hz), 7.10 (10H, br), 6.87 (2H,
d, JZ2 Hz), 5.18 (2H, d, JZ12.8 Hz), 4.79 (2H, d, JZ
12.8 Hz), 4.10 (18H, br, m), 1.93 (18H, br, m), 1.33 (126H,
br, m), 0.91 (27H, br, m). 13C NMR (CDCl3) d 168.08,
167.91, 167.72, 167.17, 161.18, 160.77, 160.70, 151.55,
150.17, 149.85, 149.67, 149.36, 128.16, 127.71, 127.17,
111.30, 111.11, 95.95, 95.60, 94.20, 69.17, 68.03, 31.92,
29.73, 29.68, 29.35, 29.06, 28.87, 26.11, 25.97, 22.68,
14.13. IR (liquid layer) n (cmK1): 2956, 2923, 2853, 1740,
1699, 1613, 1585, 1523, 1439, 1389, 1261, 1217, 1176,
1092, 1046. HR TOF-MS (m/z): 2744.03 [MCH]C (Calcd
for C160H233N18O21: 2742.77).
1
quantitative yield. Dimer 2c could be characterized by H
NMR but 4c and 6c show very broad spectra due to the
single helix-double helix equilibrium and non-specific
aggregation involving the carboxylic acid group. Complete
conversion was confirmed by thin layer chromatography
and the absence of methyl ester signal on the NMR spectra.
1
4.4.1. Dimer 2c. Mp: 176–177 8C. H NMR (CDCl3) d
10.76 (1H, s), 8.03 (1H, s), 7.96 (1H, d, JZ2.7 Hz), 7.90
(1H, d, JZ2.7 Hz), 7.78 (1H, d, JZ2 Hz), 7.41 (6H, m),
5.25 (2H, s), 4.16 (2H, dd, J1Z6.7 Hz, J2Z6 Hz), 4.09 (2H,
dd, J1Z6.7 Hz, J2Z6 Hz), 1.83 (4H, m), 1.46 (4H, m), 1.28
(24H, s), 0.88 (6H, m). HR TOF-MS (m/z): 705.54 [MCH]C
(Calcd for C40H57N4O7: 705.42).
4.5.4. Undecamer 11. From tetrameric acid 4c (55 mg,
0.044 mmol) and trimeric diamine 3b (17 mg, 0.021 mmol).
Yield 23.4 mg (34%) of a white wax. H NMR (CDCl3,
1
4.5. Synthesis of oligomers 5, 7, 9, 11, 13 and 15. General
method coupling an acid and a diamine
36 8C, 1 mM, single helix, ppm) d 10.45 (4H, s), 10.40 (2H,
s), 10.20 (2H, s), 10.07 (2H, s), 7.80 (2H, d, JZ2 Hz), 7.63
(2H, d, JZ2 Hz), 7.57 (2H, s), 7.55 (2H, d, JZ2 Hz), 7.45
(2H, d, JZ2 Hz), 7.33 (2H, d, JZ2 Hz), 7.28 (5H, br), 7.20
The procedure is the same as for coupling a monoacid and a
monoamine (see Section 4.2), except that only 0.4 equiv of

H. Jiang et al. / Tetrahedron 60 (2004) 10029–10038
10037
(5H, br), 7.14 (2H, d, JZ2 Hz), 7.04 (2H, s), 7.02 (2H, s),
References and notes
6.95 (2H, s), 6.93(2H, s), 6.81 (2H, s), 5.17 (2H, d, JZ
12 Hz), 4.76 (2H, d, JZ12.8 Hz), 4.12 (22H, br, m), 1.91
(22H, br, m), 1.34 (154H, br, m), 0.93 (33H, br, m). 13C
NMR (CDCl3) d 168.03, 167.85, 167.64, 167.55, 167.13,
167.04, 161.24, 161.06, 160.61, 160.52, 151.05, 150.14,
149.94, 149.56, 149.34, 149.24, 149.12, 148.82, 148.61,
135.51, 135.33, 130.92, 128.83, 128.15, 127.70, 127.17,
111.65, 111.46, 111.13, 110.82, 95.93, 95.76, 95.51, 69.11,
67.88, 66.52, 66.05, 32.08, 31.90, 30.12, 29.65, 29.40,
29.33, 29.05, 25.99, 25.80, 22.80, 22.711, 14.14. IR (liquid
layer) n (cmK1): 2924, 2854, 1702, 1611, 1581, 1517, 1438,
1339, 1216, 1175, 1048. TOF-MS (m/z): 3113.38 [MCH–
2(C7H8)]C, 3136.24 [MCNa–2(C7H8)]C, 3152.24 [MCK–
2(C7H8)]C (Calcd for C177H266N23O25: 3114.03).
1. Hill, D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore,
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4.5.5. Tridecamer 13. From hexameric acid 6c (128 mg)
and monomeric diamine 1b (7.0 mg). Yield 31.5 mg (31%)
of a white wax. H NMR (CDCl3, 25 8C, 1 mM, signals of
1
the single helix) d 10.29 (2H, s), 10.28 (2H, s), 10.25 (2H, s),
10.18 (2H, s), 10.14 (2H, s), 10.10 (2H, s), 7.79 (2H, s), 7.47
(2H, s), 7.39 (2H, s), 7.37 (2H, s), 7.17 (10H, br, m), 7.02
(4H, s), 6.98 (4H, br, m), 6.96 (2H, s), 6.88 (2H, s), 6.86
(2H, s), 6.84 (2H, s), 6.77 (2H, s), 5.13 (2H, d, JZ12.8 Hz),
4.72 (2H, d, JZ12.8 Hz), 4.08 (26H, br, m), 1.96 (26H, br,
m), 1.35 (182H, br, m), 0.92 (33H, br, m). 13C NMR
(CDCl3) d 168.86, 168.56, 168.02, 167.62, 167.23, 166.99,
166.90, 161.21, 160.83, 160.62, 160.41, 159.26, 153.74,
151.54, 150.09, 149.86, 149.77, 149.53, 149.40, 149.17,
149.00, 148.66, 148.55, 148.34, 135.68, 135.32, 128.10,
127.91, 127.65, 127.17, 126.53, 111.58, 111.38, 111.11,
110.96, 110.86, 96.55, 95.88, 95.70, 95.568, 95.46, 69.07,
68.50, 67.94, 67.82, 66.46, 31.95, 30.15, 29.82, 29.67,
29.56, 29.41, 29.11, 26.05, 22.73, 14.14. IR (liquid layer) n
(cmK1): 2924, 2854, 1700, 1615, 1585, 1524, 1439, 1389,
1339, 1216, 1175, 1046. TOF-MS (m/z): 3666.66 [MCH–
2(C7H8)]C, 3688.45 [MCNa–2(C7H8)]C (Calcd for
C209H314N27O29: 3666.39).
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4.5.6. Pentadecamer 15. From hexameric acid 6c (90 mg)
and trimeric diamine 3b (16.3 mg). Yield 1.9 mg (2.2%) as
a white wax. 1H NMR (CDCl3, 25 8C, 1 mM, signals of the
single helix) d 10.32 (2H, s), 10.29 (2H, s), 10.25 (2H, s),
10.20 (2H, s), 10.11 (2H, s), 9.98 (2H, s), 9.96 (2H, s), 7.76
(2H, s), 7.46 (2H, s), 7.36 (2H, s), 7.34 (2H, s), 7.20 (5H, s),
7.17 (2H, s), 7.13 (2H, s), 7.08 (5H, s), 7.06 (2H, s), 7.02
(2H, s), 7.00 (2H, s), 6.98 (2H, s), 6.95 (2H, s), 6.88 (4H, br),
6.85 (2H, s), 6.79 (2H, s), 6.75 (2H, s), 5.12 (2H, d, JZ
12.8 Hz), 4.71 (2H, d, JZ12.8 Hz), 4.06 (30H, br, m), 1.86
(30H, br, m), 1.35 (210H, br, m), 0.92 (45H, br, m), IR
(liquid layer) n (cmK1): 2923, 2853, 1701, 1585, 1524,
1439, 1340, 1045. TOF-MS (m/z): 4228.65 [MCH–
2(C7H8)]C, 4240.07 [MCNa–2(C7H8)]C, 4256.03 [MC
K–2(C7H8)]C (Calcd for C241H362N31O33: 4218.76).
`
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16. For a review see: Huc, I. Eur. J. Org. Chem. 2004, 17–29.
17. For recent examples: Odriozola, I.; Kyritsakas, N.; Lehn, J.-M.
Chem. Commun. 2004, 62–63. Wu, Z.-Q.; Jiang, X.-K.; Zhu,
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Acknowledgements
This work was supported by the Centre National de la
´
Recherche Scientifique, the Region Aquitaine (predoctoral
fellowship to V. M.), the University of Bordeaux I and by
18. Berl, V.; Huc, I.; Khoury, R. G.; Lehn, J.-M. Chem. Eur. J.
2001, 7, 2798–2809. Huc, I.; Maurizot, V.; Gornitzka, H.;
´
Leger, J.-M. Chem. Commun. 2002, 578–579. Dolain, C.;
`
the Ministere de la Recherche (postdoctoral fellowship to
H. J.).
Maurizot, V.; Huc, I. Angew. Chem., Int. Ed. 2003, 42,
2738–2740.

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H. Jiang et al. / Tetrahedron 60 (2004) 10029–10038
19. Berl, V.; Huc, I.; Khoury, R. G.; Krische, M. J.; Lehn, J.-M.
Nature 2000, 407, 720–723. Berl, V.; Huc, I.; Khoury,
R. G.; Lehn, J.-M. Chem. Eur. J. 2001, 7, 2810–2820.
double helices varies but the quantity of ‘impurity’ is
proportional to neither of them: it remains proportional to
the total concentration of single and double helices.
22. The surface involved in p–p stacking in a double helical dimer
is similar to that involved in two stacked single helical
monomers. It differs from the surface involved in p–p
stacking in two dissociated monomers by twice the cross-
section of the helix.
´
Maurizot, V.; Leger, J. -M.; Guionneau, P.; Huc, I. Russ. Chem.
Bull. 2004, in press.
20. Acocella, A.; Venturini, A.; Zerbetto, F. J. Am. Chem. Soc.
2004, 126, 2362–2367.
21. Final products were purified by chromatography at least three
times on TLC or radial chromatography prior to NMR studies.
The impurities can be characterized as such and not as being
other conformations/aggregates of the oligomers because: (i)
TLC reveals their presence; (ii) the line shape of their signals
remains sharp at any temperature even when the rest of the
spectrum broadens due to coalescence phenomena; (iii) when
the concentration is varied, the proportions of single and
23. Crystal structures show that pyridine rings are sandwiched
between amide functions in the single helices, whereas they
are sandwiched between other pyridine rings in the double
helices, see Ref. 19.
24. Blackburn, G. M., Gait, M. J., Eds.; Nucleic Acids in
Chemistry and Biology; 2nd ed.; Oxford University Press:
Oxford, 1996.