A chiral indolocarbazole foldamer displaying strong circular dichroism responsive to anion binding

Article abstract of DOI:10.1039/c3cc45989f

A chiral foldamer that consists of three indolocarbazoles and chiral amide residues folds into a helical conformation with the orientation bias, thus displaying characteristic CD signals. The X-ray crystal structure of its chloride complex was found to be a left-handed (M-) helix which stacks to give one-dimensional columnar arrays.

Full text of DOI:10.1039/c3cc45989f

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A chiral indolocarbazole foldamer displaying strong
circular dichroism responsive to anion binding†
Cite this: DOI: 10.1039/c3cc45989f
Dan A Kim, Philjae Kang, Moon-Gun Choi and Kyu-Sung Jeong*
Received 6th August 2013,
Accepted 3rd September 2013
DOI: 10.1039/c3cc45989f
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A chiral foldamer that consists of three indolocarbazoles and chiral
amide residues folds into a helical conformation with the orientation
bias, thus displaying characteristic CD signals. The X-ray crystal
structure of its chloride complex was found to be a left-handed
(MÀ) helix which stacks to give one-dimensional columnar arrays.
A number of synthetic oligomers, so-called foldamers, have
been prepared by successive linking of building monomers that
bear appropriate functional groups for elongation, folding, and
other designed functions.1 Some of them contain a binding
cavity for ions and molecules, thus functioning as synthetic
receptors.2,3 Moreover, some are utilised as molecular switches
based on the reversible control of folding and unfolding states
or left- and right-handed helicity.4 In this context, we prepared a
series of biindoles and indolocarbazoles that existed in extended
conformations but adopted compact helical conformations upon
anion binding.5 Herein, we describe the folding and chiroptical
properties of a chiral indolocarbazole foldamer 1 which can fold
into a helical conformation by intramolecular hydrogen bonds
(Scheme 1). In particular, the local chirality of amide units at
Scheme 1 Unfolded and folded structures of 1.
ends is effectively transferred to the folding process, rendering CH2Cl2, respectively), suggesting that 1 exists in a helically
the biased formation of two diastereomeric helices to exhibit folded conformation. In more polar solvents such as acetonitrile
characteristic circular dichroism (CD) signals which are sensitive and dimethyl sulfoxide (DMSO), the CD signals are nearly
to the nature of solvents and anions.
negligible. In addition, the specific rotation ([a]D) of 1 was
Foldamer 1 was synthesized by repeating Sonogashira reaction6 measured at 24 (Æ1) 1C, and the magnitudes highly depend on
and the details are given in the ESI.† The folding properties of 1 the nature of solvents (Table S1, ESI†). The [a]D values are large
were revealed by CD spectroscopy, known as a powerful method to in toluene (À7651), CH2Cl2 (À5141) and CHCl3 (À5561) while
provide valuable information on the helical array of the interacting they are much smaller in more polar solvents, acetone (À0.31)
chromophores.7 The CD spectra of 1 (3.0 Â 10À5 M) were recorded and DMSO (+6.51). These results strongly support that 1 adopts a
at 24 (Æ1) 1C in several solvents (Fig. 1). In nonpolar solvents helically folded conformation and large magnitudes of the CD
such as toluene and chlorinated solvents, strong CD signals values and specific rotations in nonpolar solvents result from the
are observed with negative Cotton effects maximised at 366 nm global helical chirality, not from the local chirality of stereogenic
(De = À263, À129 and À117 MÀ1 cmÀ1 in toluene, CHCl3 and amide appendages.
Computer modeling studies (MacroModel 9.1,8 Fig. S1, ESI†)
afford additional evidence for the helical folding of 1. An
energy-minimised structure adopts a helical conformation
which is stabilised by intramolecular hydrogen bonds between
Department of Chemistry, Yonsei University, Seoul 120-749, Korea.
E-mail: ksjeong@yonsei.ac.kr; Fax: +82-2-364-7050; Tel: +82-2-2123-2643
† Electronic supplementary information (ESI) available. CCDC 951836. For ESI
NH protons in the central indolocarbazole and the oxygen
atoms of terminal amides and by p stacking between aromatic
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c3cc45989f
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Table
1
Binding affinities of
1
with anions in 10% (v/v) MeOH–CH3CN
at 23 Æ 1 1C
Aniona
Ka (Æ10%, MÀ1
)
ÀDG (kcal molÀ1
8.23
6.43
5.57
8.62
)
ClÀ
1.2 Â 106
5.6 Â 104
1.3 Â 104
2.3 Â 106
BrÀ
AcOÀ
2À
SO4
a
Anions used as tetrabutylammonium salts.
inverted with opposite Cotton effects. It is worthwhile mentioning
that the patterns and intensities of the CD spectra of the complexes
depend on the nature of solvents (Fig. S3, ESI†), possibly due to
changes in the degree of helicity bias and in the geometrical
array of interacting chromophores, indolocarbazole and ethynyl-
benzamide planes in different environments.
Fig. 1 CD spectra of 1 (3.0 Â 10À5 M, 24 Æ 1 1C) in organic solvents.
planes. The geometry of the hydrogen bonds is, however, far
from ideal in the aspects of the angles (+NHÁ Á ÁO 891 and 1171)
and distances (NÁ Á ÁO 3.0 and 3.1 Å). As a result, the strengths of
the hydrogen bonds are possibly too weak to be negligible in
polar media.
The binding properties of 1 with tetrabutylammonium
anions were examined. First, addition of anions gave rise to
remarkable changes in the CD spectrum of 1 (3.0 Â 10À5 M) in
CH2Cl2 at 24 Æ 1 1C (Fig. 2a). For example, when anions such as
chloride, bromide and acetate were added, the CD spectra were
1
Next, the H NMR signals are somewhat broadened in the
chlorinated solvents such as CD2Cl2 and CDCl3 due to slow
exchange between 1 and its aggregates, but they are sharp and
well resolved in more polar media such as deuterated acetone
and DMSO. Anion binding causes characteristic changes in the
1H NMR spectrum of 1 (Fig. 2c). Three NH signals of the
indolocarbazoles are shifted downfield by Dd = 1.86, 0.98, and
0.22 ppm when tetrabutylammonium chloride is added in
1/1 (v/v) acetone-d6–CD3CN, as a result of hydrogen bonding.
It should be noted that the amide NH signal is not downfield
shifted but rather upfield shifted by Dd = À0.38 ppm, suggesting
that the amide proton does not participate in the hydrogen
bonding with the anion. In addition, the aromatic CHh in the
benzoate plane is noticeably upfield shifted by Dd = À0.97 ppm,
indicative of this proton located just on the strong shielding
region of the indolocarbazole ring current. The UV-visible titra-
tions afford quantitative binding affinities between 1 and tetra-
butylammonium anions in 10% (v/v) MeOH–CH3CN at 23 Æ 1 1C
(Fig. S7, ESI†). As summarized in Table 1, 1 binds anions very
2À
strongly in the order SO4 > ClÀ > BrÀ > AcOÀ. This trend
implies that the binding affinity depends more on how well the
anions fit into the helical cavity by forming complementary
hydrogen bonds, simply than on the basicity of the anions.
The observations in solution are consistent with the crystal
structure of the chloride complex of 1 (Fig. 3 and Fig. S6, ESI†).
Single crystals† were obtained by slow diffusion of hexane into
a 1/2 (v/v) ethyl acetate–CH2Cl2 solution of 1 and tetrabutyl-
ammonium chloride (2 equiv.). Several features are apparent in
the crystal structure. First, 1 folds into a left-handed (MÀ) helix
when complexed with chloride ions. Two indolocarbazole
planes stack each other in a parallel-displaced manner,9 and
terminal benzoates partially stack with the central indolocarbazole
ring. As a result, the CHh in the benzoate is placed directly above
and below the indolocarbazole plane, which agrees well with the
large upfield shift (Dd = À0.97 ppm) of the 1H NMR signal as
mentioned earlier, together with the 1H–1H NOESY experiment
showing characteristic cross peaks between NH1 and Hf and
between He and Hn (Fig. 2b and Fig. S6, ESI†). Second, the chloride
ion is located in the middle of the helical cavity, stabilised by
hydrogen bonds with all six NH protons in the indolocarbazoles
(NÁÁÁClÀ distances 3.22–3.43 Å). However, two amide NH protons
Fig. 2 (a) CD spectra of 1 (3.0 Â 10À5 M, CH2Cl2, 24 Æ 1 1C) in the absence
(black) and presence of the tetrabutylammonium (TBA) anions (1 equiv.),
(b) molecular structures of a complex between 1 and an anion with the NOE
correlations marked with curved double-headed arrows, and (c) partial 1H NMR
spectra (400 MHz, 1/1 (v/v) acetone-d6–CD3CN, 25 1C) of free 1 (bottom) and in
the presence of TBA chloride (1.1 equiv.) (top).
c
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This study was supported by the National Research Founda-
tion of Korea (NRF) grant funded by the Korea government
(MEST) (2013R1A2A2A05005796). Dan A Kim acknowledges the
fellowship of the BK 21-plus program from the Ministry of
Education and Human Resources Development.
Notes and references
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Fig. 3 (a) X-ray crystal structure of the complex between 1 and tetrabutylammonium
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are pointed away from the cavity, not hydrogen bonded with the
chloride but with solvent molecules, ethyl acetate. Instead, two
CHf protons at the para position of carbonyls in benzoates also
participate in weak hydrogen bonds (4.63 Å for CÁ Á ÁClÀ), which
is consistent with large downfield shift (Dd = 0.6 ppm) of the
CHf signal upon chloride binding (Fig. 2c). Third, in the
packing structure, the helically folded complex stacks to afford
one-dimensional (1D) columnar arrays10 with tetrabutylammonium
cations intercalated between the anionic complexes alternatively.
This 1D columnar structure is stabilised mainly by electrostatic
forces between chloride and tetrabutylammonium ions, and the
N+ÁÁÁClÀ distances are equally 5.58 Å for upper and lower ion pairs.
Noticeably, the CH protons in the g and d carbons of the tetra-
butylammoniums directly come into contact with indolocarbazole
surfaces. In addition, two of four butyl chains interact with the aryl
plane in the upper complex and the remaining two chains come
into contact with that in the lower one. This observation indicates
that the CHÁÁÁp interaction is an additional force stabilising the 1D
columnar array.
In conclusion, it is demonstrated that the helicity direction
of a foldamer can be effectively controlled by incorporation of
chiral segments at ends. The foldamer described here displays
characteristic CD signals responsive to the solvent polarity as
well as anion binding, which might be further applied to the
development of molecular sensors and switches based on the
chiroptical signal.
´
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c
This journal is The Royal Society of Chemistry 2013
Chem. Commun.