Conformation of S-shaped aromatic imide foldamers and their induced circular dichroism

Article abstract of DOI:10.1016/j.tetlet.2007.12.034

Conformation of aromatic foldamers possessing three aromatic rings in a sequence of anthracene-phenylene-anthracene linked with iminodicarbonyl was examined. Their folding structures were confirmed by single crystal X-ray analysis. Two conformations, straight-zigzag and helically-zigzag conformations, were found depending on the substituents at the imide nitrogen atom. Induced circular dichroism originated in the interaction of the upper and bottom anthracene moieties was observed both in solution and in the solid state.

Full text of DOI:10.1016/j.tetlet.2007.12.034

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Tetrahedron Letters 49 (2008) 1223–1227
Conformation of S-shaped aromatic imide foldamers and
their induced circular dichroism
a,
a
a
b
b
*
Shigeo Kohmoto , Hiroshi Takeichi , Keiki Kishikawa , Hyuma Masu , Isao Azumaya
a Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
b Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan
Received 13 October 2007; revised 5 December 2007; accepted 7 December 2007
Available online 14 December 2007
Abstract
Conformation of aromatic foldamers possessing three aromatic rings in a sequence of anthracene–phenylene–anthracene linked with
iminodicarbonyl was examined. Their folding structures were confirmed by single crystal X-ray analysis. Two conformations, straight-
zigzag and helically-zigzag conformations, were found depending on the substituents at the imide nitrogen atom. Induced circular dichro-
ism originated in the interaction of the upper and bottom anthracene moieties was observed both in solution and in the solid state.
Ó 2007 Elsevier Ltd. All rights reserved.
Folding structures are commonly observed in biomole-
cules and numerous studies have been carried out on pro-
teins related to this. As artificial folding structures1 we
are interested in aromatic foldamers since an array of line-
arly combined aromatic moieties can be created. In this
columnar array, aromatic moieties are forced to face each
other in a p–p stacking mode, which results in a unique
optical property. Aromatic foldamers with dynamic behav-
iors, such as photoswitchable2 and solvocontrollable3 ones,
have been developed recently. Aromatic foldamers can be
categorized into two types depending on their shapes,
namely, helical and zigzag types. Most of them belong to
a helical type as a mimic of peptides with mainly amide4
or urea linkers.5 An ethynyl linker is also used for helical
type foldamers.6 For zigzag type foldamers, several func-
tionalities, amide,7 sulfonamide,8 urea,9 guanidine,10 and
methylene,11 are utilized as linkers. In some cases, zigzag
type foldamers were formed in charge transfer duplex.12
Concerning the way of zigzag folding, there are two types
of folding, straight-zigzag and helically-zigzag types. In a
straight-zigzag type, aromatic moieties are oriented toward
the same direction and each aromatic moiety is stacked
right above or below the neighboring one. On the contrary,
folding occurs helically in a way that aromatic moieties are
rotationally oriented in a helically-zigzag type. Recently,
we have shown that iminodicarbonyl is also a potential
linker for the construction of aromatic zigzag type folda-
mers.13 Due to the intrinsic nature of the iminodicarbonyl
linker, electrostatic dipole repulsion of the two carbonyl
moieties, two substituents have a tendency to locate paral-
lel to each other. In our work the straight-zigzag type fold-
ing structure was found in the foldamer where aromatic
moieties were aligned in a sequence of a naphthalene–
anthracene–naphthalene13b while the helically-zigzag
folding structure was observed in a naphthalene–naphtha-
lene–naphthalene system.13a They were confirmed by single
crystal X-ray analysis. To induce CD, it is essential to have
a helically folded structure. An advantage of an iminodi-
carbonyl linker is an easy introduction of a chiral group
on the imide nitrogen atom, which could result in the
formation of folded and helically chiral structure. In this
letter, we report on our latest findings on the folding
conformation of the S-shaped aromatic imide foldamers
and their induced CD spectra.
Three S-shaped aromatic imide foldamers 1, 2, and 3
possessing i-propyl, (S)-1-phenylethyl, and (S)-1-(1-naph-
thyl)ethyl as substituents at the imide nitrogen atom,
*
Corresponding author. Tel.: +81 290 3420; fax: +81 290 3422.
E-mail address: kohmoto@faculty.chiba-u.jp (S. Kohmoto).
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.12.034

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S. Kohmoto et al. / Tetrahedron Letters 49 (2008) 1223–1227
˚
respectively, were prepared (Fig. 1). Synthetic procedures
of them are cited in Supplementary data. All of them gave
crystals suitable for single crystal X-ray analysis. A
straight-zigzag type folded conformation was found in 1
(Fig. 2). The distance between the anthracene and the phe-
is 3.80 A. The intramolecular distances between the two
˚
anthracene rings are 6.76 and 6.85 A for conformers A
and B, respectively. The distances are shorter than that
of 1. The torsion angles between the axes of two anthracene
rings are 70° for both conformers. The angles created by
the two anthracene ring planes are 12° and 8° for the con-
formers A and B, respectively.
˚
nylene rings is 3.61 A and that between the two anthracene
˚
rings is 7.21 A. There is a center of symmetry in this mole-
cule. Therefore, the two anthracene rings are perfectly par-
allel to each other. Three aromatic rings are well stacked.
In contrast to 1, a helically-zigzag folding conformation
was observed in the crystal structure of 2 (Fig. 3). Although
the compound has a chiral auxiliary, a pair of helically-zig-
zag diastereomeric conformers exists in a unit cell of the
crystal. They are stacked in an alternative way to form a
columnar structure in which an array of aromatic rings
are created.14 There are two ways of helicities to be desig-
nated in respect to the short and long axes of the two
anthracene rings. So the molecule has two helicities
depending on this designation. The distances between the
anthracene and the phenylene rings in the conformers are
Different crystal structure was observed for foldamer 3
with bulky substituent at the imide nitrogen atom. It gave
a chiral crystal (space group: P21) with a single helically-
zigzag conformer in it as shown in Figure 4. The intramo-
˚
lecular distances between the two anthracene rings (6.79 A)
are similar to that of 2. The torsion angle between them is
69° which is also similar to that of 2. Two anthracene rings
are not exactly parallel. The angle between their ring planes
is 10°.
All the compounds have S-shaped folding structures,
but the way of folding is different. A straight-zigzag type
folding is not suitable to show induced CD. No exciton
coupling is expected for this folding since two anthracene
rings are aligned perfectly parallel with the torsion angle
of 0°. To confirm that two anthracene rings are the origin
of induced CDs and also the chiral auxiliary at the imide
nitrogen atom is not the direct source of them, structurally
similar concave-shaped molecules 4 and 5 were synthesized.
Single crystal X-ray structure of 5 showed that the mole-
cule is structurally equivalent to the half of the molecule
of 3 (Fig. 5). The distance between the centroids of the
˚
slightly different. They are in the range 3.35–3.65 A. The
intermolecular distance between the two anthracene rings
O
O
O
R
R
N
N
N R
O
O
O
˚
anthracene and phenyl rings is 3.55 A, which is similar to
O
that of 3. Figure 6 shows the CD spectra of 2, 3, 4, and 5
in CH3CN. Only 3 has a relatively large CD signal in the
region over 350 nm. The M-helicity indicated by the sign
of Cotton effect (–) in this region agrees to the helicity in
respect to the short axes of the anthracene rings observed
in its single crystal X-ray structure. The band at 337 nm
might be the intrinsic CD originated in the chiral (S)-1-
(1-naphthyl)ethyl group. The concave shaped imide 5 with
the same chiral group showed the CD signal only in the
similar shorter wavelength region due to the intrinsic CD
of this chiral group. The lack of induced CD in a longer
wavelength region in 5 indicates that the induced CD in 3
could be originated in the exciton coupling of anthra-
cene–anthracene chromophores in their short axes. In con-
trast to 3, imide 2 showed a very weak intensity CD signal.
We expected no induced CD for 2 since its single crystal X-
ray analysis showed that the compound had two helical
conformers in an equi-amount in its crystal. Therefore,
the cancellation of CD by both helical conformers took
place. However, they are not enantiomers. Their geome-
tries are quite similar but not exactly the same. The CD
spectrum of 2 exhibited that its spectral shape was almost
the mirror image of that of 3 though its intensity was fairly
small. The results suggest that the P-helical conformer in
respect to the short axes of the anthracene moieties might
have a slightly larger signal intensity than that of the
conformer with M-helicity. Almost no CD signal was
observed for 4. There is no significant solvent effect on
N
R
O
1: R = i-Pr
2: R == (S)-1-phenylethyl
3: R == (S)-1-(1-napphhthyyll))eetthhyyll
straigght-zigzag connfformation
O
O
O
O
R
R
R
R
N
O
N
N
O
N
O
O
P-helicity
M-helicity
helically-zigzag cconforrmation
Fig. 1. Three possible conformations of S-shaped aromatic imide folda-
mers. Helicities presented here are based on the long axes of the two
anthracene rings.

S. Kohmoto et al. / Tetrahedron Letters 49 (2008) 1223–1227
1225
Fig. 2. Single crystal X-ray structure of 1 showing straight-zigzag conformation, a side view (a) and a top view (b). For clarity the hydrogen atoms are
˚
omitted. Distances between the centroids of aromatic rings are presented in A. The distance (centroid–centroid) between the two anthracene rings is
˚
7.21 A.
Fig. 3. Single crystal X-ray structure of 2 showing two helically-zigzag folding conformers, a side view (a) and a top view (b). For clarity the hydrogen
˚
atoms are omitted. Distances between the centroids of the aromatic rings are presented in A. Green and red arrows indicate the helicity in respect to the
long and short axes of the anthracene rings, respectively.
Fig. 4. Single crystal X-ray structure of 3 showing a helically-zigzag conformation, the side view (a) and the top view (b). For clarity hydrogen atoms are
˚
˚
omitted. Distances between the centroids of aromatic rings are presented in A. The distance (centroid–centroid) between two anthracene rings is 6.74 A.
Green and red arrows indicate the helicity in respect to the long and short axes of the anthracene rings, respectively.

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S. Kohmoto et al. / Tetrahedron Letters 49 (2008) 1223–1227
O
N
R
O
4: R = (S)-1-phenylethyl
5: R = (S)-1-(1-naphthyl)ethyl
a
b
3.55
Fig. 7b. CD spectra of 2 and 3 in the solid state.
state (Fig. 7b). The solid-state CD spectra were recorded
on their KBr pellets. The pellets were prepared by grinding
ca. 1 mg of imide and ca. 10 mg of dry KBr powder
followed by pressing under vacuum. Their signs are the
same as those in solution. The results indicated that the
helical chirality of 3 in the crystalline state was retained
even in solution after dissolving it. The CD signal of 2
was weak with the same sign as in solution opposite to that
of 3.
Fig. 5. Single crystal X-ray structure of 5 showing a concave-shaped
folding conformation, the side view (a) and the top view (b). For clarity
the hydrogen atoms are omitted and the distance between the centroids of
˚
aromatic rings are presented in A.
The S-shaped conformations of 1–3 in solution were
1
confirmed from their H NMR spectra and NOE experi-
ments. The assignments of the protons in 1H NMR spectra
were carried out based on their HH–COSY spectra. Table
1 shows the chemical shifts of the protons Ha–Hf of the
main chain aromatic rings. Strong shielding was observed
Table 1
1H NMR chemical shifts (d) of the main chain aromatic ring protons of
the S-shaped foldamers in CDCl3
Fig. 6. CD spectra of 2, 3, 4, and 5 in CH3CN.
Hi
Hh
Hg
Hj
O
CD. Figure 7a shows the CD spectrum of 3 in four different
solvents, EtOH, CH3CN, CHCl3, and toluene. Similar
tendency was reported on naphthalene-based foldamers.13a
To verify our interpretation of the induced CD in solu-
tion, we examined the CD spectra of 2 and 3 in the solid
Hb
Hc
Hf
R
N
He
O
Hd
Ha
Ha
O
1: R = i-Pr
2: R = (S)-1-phenylethyl
3: R = (S)-1-(1-naphthyl)ethyl
N
R
O
1H
1
2
3
a
b
c
d
e
f
g
h
i
5.46 (s)
7.71 (d, J = 8.5)
7.38 (t, J = 7.0)
7.25 (t, J = 7.0)
7.58 (d, J = 8.0)
7.92 (s)
e
d
c
5.23 (s)
7.61 (d, J = 8.5)
7.30–7.36a
7.20 (t, J = 7.3)
7.30–7.36a
7.82 (s)
7.43–7.54a
7.06 (t, J = 7.3)
7.14 (t, J = 7.5)
7.30–7.36a
4.40 (br s)
8.18 (d, J = 8.0)
7.83 (t, J = 7.4)
7.64–7.74a
8.39 (d, J = 8.5)
7.64–7.74a
6.99–7.04a
6.33 (t, J = 7.6)
6.47 (t, J = 7.7)
7.30 (d, J = 8.4)
j
b
a
Fig. 7a. CD spectra of 3 in four different solvents showing almost no
Overlapped with other peaks. Blue and red arrows show NOEs
significant solvent effects.
observed in 1 and 2, and 3, respectively.

S. Kohmoto et al. / Tetrahedron Letters 49 (2008) 1223–1227
1227
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Acknowledgment
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This work was supported by a Grant-in-Aid for Scien-
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Supplementary data
Supplementary data (preparation of materials, copies of
NMR spectra, and ORTEP of 1, 2, 3, and 5) associated
with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2007.12.034.
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