A catenated anion receptor based on indolocarbazole

Article abstract of DOI:10.1016/j.tetlet.2010.06.023

A catenated anion receptor 7 comprising two indolocarbazole units was prepared by olefin ring-closing metathesis using Grubbs' catalyst. Receptor 7 possesses a cage-like cavity where anions are encapsulated by forming four hydrogen bonds in the order of C

Full text of DOI:10.1016/j.tetlet.2010.06.023

Tetrahedron Letters 51 (2010) 4240–4242
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Tetrahedron Letters
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A catenated anion receptor based on indolocarbazole
*
Min Kyung Chae, Jae-min Suk, Kyu-Sung Jeong
Department of Chemistry, Yonsei University, Seoul 120-749, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A catenated anion receptor 7 comprising two indolocarbazole units was prepared by olefin ring-closing
metathesis using Grubbs’ catalyst. Receptor 7 possesses a cage-like cavity where anions are encapsulated
Received 20 April 2010
Revised 2 June 2010
Accepted 7 June 2010
Available online 11 June 2010
by forming four hydrogen bonds in the order of ClÀ > AcOÀ > N3 > H2PO4 > BrÀ > HSO4 > IÀ ꢀ NO3 in
À
À
À
À
1% H2O/acetone.
Ó 2010 Elsevier Ltd. All rights reserved.
Interlocked molecules such as catenanes and rotaxanes have
been intensively studied over the past two decades to develop
molecular-level machines and devices.1 The syntheses of these
molecules have been successfully achieved by utilizing external
templates such as metal cations. In recent years, Beer and cowork-
ers have nicely demonstrated that anions can also serve as effective
templates for the preparation of pseudorotaxanes, rotaxanes, and
catenanes.2,3 Moreover, the anionic templates can be easily re-
moved to give interlocked molecules with empty sites for anion
binding, reminiscent of imprinted polymers. Due to the interlocked
nature of the two molecular components, these receptors are able
to bind anions with high stability and selectivity compared to the
corresponding 2:1 complexes.
Indolocarbazole derivatives with two preorganized NH protons
have been used as versatile building blocks for the construction of
anion receptors. Beer and coworkers reported for the first time that
indolocarbazoles strongly bound anions by two hydrogen bonds in
acetone.4 Utilizing this scaffold, the same group described a variety
of anion-binding interpenetrated and interlocked structures.2,3,5
Our group has also employed indolocarbazole derivatives in the
preparation of molecular clefts, macrocycles, and foldamers that
bind anions with high affinities and selectivity in organic solvents
or in water.6 Herein, we prepared for the first time an indolocar-
bazole-based catenane 7 which contains a cage-type cavity with
four NH protons capable of hydrogen bonding with an anion.
Among the anions examined here, receptor 7 binds chloride most
strongly with an association constant (Ka) of 1.4 Â 105 MÀ1 in 1%
H2O/acetone.
ing to the procedures described previously.6 The Suzuki coupling of
4 and 5 provided compound 6 in 58% yield.8 Ring-closing metath-
esis9 of 6 with Grubb’s catalyst was carried out in the presence of
tetrabutylammonium chloride (0.5 equiv) to give a mixture of cyc-
lic products which was directly subjected to catalytic hydrogena-
tion (H2, Pd/C) to yield the desired receptor 7 (26% yield for two
steps),10 together with a monocyclic product 8 (14% yield for two
steps)10 used as a reference molecule. Here, the yield of 7 was
slightly lower in the absence of tetrabutylammonium chloride,
but the reaction conditions were not optimized.
1H NMR spectra of 7 and 8 are similar to each other in chemical
shifts and splitting patterns, but there are two important differ-
ences. First, the chemical shift of the NH protons of 7 is 10.5 ppm
in CDCl3 at room temperature while that of 8 is 9.6 ppm under
the same conditions. This downfield shift (Dd = 0.9 ppm) in 7 is
possibly attributed to intramolecular hydrogen bonds between
the indole NHs of one ring and the phenolic oxygen atoms of the
other, as demonstrated by computer modeling (Fig. 1a). Second,
the aromatic proton (Ha) in the phenolic arms of 7 appears as a
broad singlet at 7.0 ppm without splitting, while that of 8 reso-
nances at 7.2 ppm as a well-resolved sharp doublet (J = 8.4 Hz).
These observations agree well with the stacked arrangement of
four phenolic rings in the energy-minimized structure of
7
(Fig. 1), which may interfere with the free rotation of the phenolic
C–O bond, thus giving rise to signal broadening. In addition, the
ring current of stacked aromatic rings must be responsible for
the upfield shift (
D
d = À0.2 ppm) of the CHa signal of 7 relative to
that of reference 8. Together with 1H NMR observations mentioned
here, mass spectroscopy clearly supports the structure of catenane
7 (m/z for C128H164N4O24 calcd 2142.17, found 2142.10).
The synthesis of 7 is outlined in Scheme 1. Mono-allylation (48%
yield) of triethylene glycol (1) followed by bromination (90% yield)
afforded compound 2. The substitution reaction of 2 with 4-bro-
mophenol/K2CO3 gave compound 3 (90% yield) which was con-
verted into boronic acid 4 in 87% yield.7 On the other hand, an
indolocarbazole 5 was prepared from 4-aminobenzoic acid accord-
The binding properties of 7 with anions were revealed in 1% (v/
v) H2O/acetone at 24 1 °C using 1H NMR and fluorescence spec-
troscopy. Addition of chloride ion as a tetrabutylammonium salt
gave a new set of 1H NMR signals corresponding to the chloride
complex of 7 (Fig. 2). The 1H NMR signals of the complex increase
at the expense of unbound signals with increasing the amount of
chloride. In the complex, the NH signal was largely downfield
* Corresponding author. Tel.: +82 2 2123 2643; fax: +82 2 364 7050.
E-mail address: ksjeong@yonsei.ac.kr (K.-S. Jeong).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.06.023

M. K. Chae et al. / Tetrahedron Letters 51 (2010) 4240–4242
4241
c
O
O
O
O
a, b
Y
O
O
O
OH
Br
O
HO
O
3 Y = Br
d
1
4 Y = B(OH)2
2
R
O
O
O
O
CO2H
NH2
O
O
R
R
N
N
H
e
N
H
N
H
f
4
5
+
I
I
H
5
O
O
R= CO2(CH2)7CH3
R
6
R
R
O
O
O
O
O
O
O
O
O
O
O
R
O
N
O
O
N
N
H
H
H
H
HN
HN
(CH2)4
O
(CH2)4
O
(CH2)4
O
O
N
R
O
O
O
O
O
O
Hb
7
Ha
R
R
8
Scheme 1. Synthesis of 7 and 8. Reagents and conditions: (a) allyl bromide, t-BuOK, THF, rt, 48%; (b) CBr4, THF, rt, 85%; (c) 4-bromophenol, K2CO3, DMF, 80–84 °C, 90%; (d)
B(OMe3)3, n-BuLi, TMEDA, THF, À78 °C to rt, 87%; (e) Pd(PPh3)4, saturated aqueous Na2CO3, DME, 80–82 °C, 58%; (f) Grubb’s first catalyst, TBACl (0.5 equiv), CH2Cl2, rt, then Pd/
C, H2, EtOAc, 7 (25% yield for two steps) and 8 (14% yield).
c
b
a
ppm
13
12
11
10
9
8
7
Figure 2. Partial 1H NMR spectra (400 MHz, 1% H2O/acetone-d6, rt) of 7 in the
presence of Bu4N + ClÀ: (a) 0, (b) ꢁ0.5 equiv, and (c) 1 equiv.
The association constants between 7 and anions were deter-
mined by fluorescence titrations in 1% (v/v) H2O/acetone at
24 1 °C (Fig. 3). Excitation of the indolocarbazole unit at
350 nm gave rise to an emission band in between 470 nm and
550 nm, showing the maximum intensity at 404 nm. Unlike most
anion receptors showing fluorescent quenching by anion binding,
receptor 7 displays an enhancement upon anion binding. As a rep-
resentative example, the emission increases by approximately
threefold when tetrabutylammonium chloride (ꢁ6 equiv) was
added to a solution of 7 (1.0 Â 10À5 M). The association constants
(Ka’s) were estimated by nonlinear least squares fitting analysis11
with a 1:1 binding isotherm, and the results are summarized in Ta-
ble 1. Job’s plots12 proved 1:1 binding modes of 7 with all anions.
The chloride ion binds to 7 most strongly with the association con-
stant of 1.4 Â 105 MÀ1 which is approximately 20-fold higher than
that (7.3 Â 103 MÀ1) of 8 with chloride under the same conditions,
suggesting that four indole NHs of 7 simultaneously participate in
hydrogen bonding with the same chloride. The magnitudes of the
Figure 1. Energy-minimized structures (MacroModel 9.1, MMFFs force field, in
CHCl3) of (a) unbound 7 and (b) complex 7ÁClÀ where the ester side chains are
replaced by hydrogen atoms. Hydrogen bonds are shown as dotted lines, and
hydrogen atoms except NH protons are omitted for clarity.
shifted by
D
d = ꢁ2 ppm as a result of hydrogen bonds. Moreover,
the CHa signal becomes sharpened, suggesting that anion binding
may lock the rotation of the phenolic ring. It should be mentioned
that reference 8 afforded time-averaged signals upon binding the
chloride ion under the same conditions. As shown in Figure 1b,
the energy-minimized structure of complex 7ÁClÀ demonstrates
that the chloride ion is encapsulated in the cavity surrounded by
four phenolic planes by simultaneously forming four hydrogen
bonds with the convergent indole NHs.

4242
M. K. Chae et al. / Tetrahedron Letters 51 (2010) 4240–4242
I0/I
1.1
I0/I
1.0
References and notes
1. (a) Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart, J. F. Angew. Chem., Int. Ed. 2000,
39, 3348–3391; (b) Pease, A. R.; Jeppesen, J. O.; Stoddart, J. F.; Luo, Y.; Collier, C.
P.; Heath, J. R. Acc. Chem. Res. 2001, 34, 433–444; (c) Collin, J.-P.; Dietrich-
Buchecker, C.; Gaviña, P.; Jimenez-Molero, M. C.; Sauvage, J.-P. Acc. Chem. Res.
2001, 34, 477–487.
0.8
0.6
0.4
0.2
0
0.9
0.7
6.0E-06
4.0E-06
2.0E-06
2. For reviews, see: (a) Beer, P. D.; Sambrook, M. R.; Curiel, D. Chem. Commun.
2006, 2105–2117; (b) Chmielewski, M. J.; Davis, J.; Beer, P. D. Org. Biomol. Chem.
2009, 7, 415–424; (c) Mullen, K. M.; Beer, P. D. Chem. Soc. Rev. 2009, 38, 1701–
1713.
3. (a) Wisner, J. A.; Beer, P. B.; Drew, M. G. B.; Sambrook, M. R. J. Am. Chem. Soc.
2002, 124, 12469–12476; (b) Sambrook, M. R.; Beer, P. D.; Wisner, J. A.; Paul, R.
L.; Cowley, A. R. J. Am. Chem. Soc. 2004, 126, 15364–15365; (c) Sambrook, M. R.;
Beer, P. D.; Wisner, J. A.; Paul, R. L.; Cowley, A. R.; Szemes, F.; Drew, M. G. B. J.
Am. Chem. Soc. 2005, 127, 2292–2302; (d) Curiel, D.; Beer, P. D. Chem. Commun.
2005, 1909–1911; (e) Ng, K.-Y.; Cowey, A. R.; Beer, P. D. Chem. Commun. 2006,
3676–3678; (f) Huang, B.; Santos, S. M.; Felix, V.; Beer, P. D. Chem. Commun.
2008, 4610–4612; (g) McConnell, A. J.; Serpell, C. J.; Thomson, A. L.; Allan, D. R.;
Beer, P. D. Chem. Eur. J. 2010, 16, 1256–1264.
0
0.5
1.0
Mole fraction of
8
0.5
0
2
4
6
8
400
450
500
550
Wavelength (nm)
Equivalent of Guest
Figure 3. (a) Fluorescence spectral changes (excitation: 350 nm) of 7 (1.0 Â 10À5
M
in 1% H2O/acetone-d6) upon addition of Bu4N+ClÀ at 24 1 °C, (b) experimental
(filled squares) and theoretical plots of titration curves and Job’s plot (inset).
4. Curiel, D.; Cowley, A.; Beer, P. D. Chem. Commun. 2005, 236–238.
5. (a) Chmielewski, M. J.; Zhao, L.; Brown, A.; Curiel, D.; Sambrook, M. R.;
Thompson, A. L.; Santos, S. M.; Felix, V.; Davis, J. J.; Beer, P. D. Chem. Commun.
2008, 3154–3156; (b) Zhao, L.; Mullen, K. M.; Chmielewski, M. J.; Brown, A.;
Bampos, N.; Beer, P. D.; Davis, J. J. New J. Chem. 2009, 33, 760–768; (c) Zhao, L.;
Davis, J. J.; Mullen, K. M.; Chmielewski, M. J.; Jacobs, R. M. J.; Brown, A.; Beer, P.
D. Langmuir 2009, 25, 2935–2940; (d) Brown, A.; Mullen, K. M.; Ryu, J.;
Chmielewski, M. J.; Santos, S. M.; Felix, V.; Thompson, A. L.; Warren, J. E.; Pascu,
S. I.; Beer, P. D. J. Am. Chem. Soc. 2009, 131, 4937–4952.
6. (a) Chang, K.-J.; Moon, D.; Lah, M. S.; Jeong, K.-S. Angew. Chem., Int. Ed. 2005, 44,
7926–7929; (b) Kwon, T. H.; Jeong, K.-S. Tetrahedron Lett. 2006, 47, 8539–8541;
(c) Kim, N.-K.; Chang, K.-J.; Moon, D.; Lah, M. S.; Jeong, K.-S. Chem. Commun.
2007, 3401–3403; (d) Ju, J.; Park, M.; Suk, J.-m.; Lah, M. S.; Jeong, K.-S. Chem.
Commun. 2008, 3546–3548; (e) Suk, J.-m.; Jeong, K.-S. J. Am. Chem. Soc. 2008,
130, 11868–11869; (f) Juwarker, H.; Suk, J.-m.; Jeong, K.-S. Chem. Soc. Rev. 2009,
38, 3316–3325; (g) Kim, J.-i.; Juwarker, H.; Liu, X.; Lah, M. S.; Jeong, K.-S. Chem.
Commun. 2010, 46, 764–766.
Table 1
Association constants (Ka 15%, MÀ1) of 7 with anions in 1% (v/v) H2O/acetone at
24 1 °Ca
Aniona
Ka (MÀ1
)
DG (kcal/mol)
ClÀ
BrÀ
IÀ
140,000
660
—
7.00
3.83
—
b
AcOÀ
71,000
5700
6.59
5.11
6.09
2.87
—
À
H2ÀPO4
N3
30,000
130
À
HSO4
b
À
NO3
—
a
Titrations were at least duplicated, and anions were used as tetrabutylammo-
nium salts.
7. (a) Wisner, J. A.; Beer, P. D.; Drew, M. G. B.; Sambrook, M. R. J. Am. Chem. Soc.
2002, 124, 12469–12476; (b) Wytko, J. A.; Graf, E.; Weiss, J. J. Org. Chem. 1992,
57, 1015–1018.
b
Too small to be determined.
8. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483; (b) Suzuki, A. Acc.
Chem. Res. 1982, 15, 178–184; (c) Suzuki, A. Pure Appl. Chem. 1994, 66, 213–222.
9. (a) Mohr, B.; Weck, M.; Sauvage, J.-P.; Grubbs, R. H. Angew. Chem., Int. Ed. 1997,
36, 1308–1310; (b) Kidd, T. J.; Leigh, D. A.; Wilson, A. J. J. Am. Chem. Soc. 1999,
121, 1599–1600; (c) Kilbinger, A. F. M.; Cantrill, S. J.; Waltman, A. W.; Day, M.
W.; Grubbs, R. H. Angew. Chem., Int. Ed. 2003, 42, 3281–3285; (d) Grubbs, R. H.;
Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446–452.
association constants are in the order of ClÀ > AcOÀ > N3 > H2
À
PO4 > BrÀ > HSO4 > IÀ ꢀ NO3À, indicative of the binding affinities
À
À
depending on both the shape and basicity of anions.
In conclusion, a catenane-based anion receptor 7 has been syn-
thesized utilizing an indolocarbazole scaffold that possesses two in-
dole NHs capable of forming strong hydrogen bonds with anions.
Among anions, the spherical chloride ion binds most strongly in
the cage-like cavity of 7 by four hydrogen bonds. Owing to the inter-
locked nature, the exchange process between the unbound and the
complex was found to be slow on the 1H NMR time scale, demon-
strating that catenane-based anion receptors increase not only the
thermodynamic stability of the complex but also the kinetic
stability.
10. Spectroscopic data of 7: 1H NMR (400 MHz, CDCl3) d (ppm) 10.50 (s, 2H, NH),
8.88 (s, 4H), 8.13 (s, 4H), 8.08 (s, 4H), 7.63 (br, 8H), 6.84 (br, 8H), 4.29 (m, 4H),
3.50–3.25 (m. 8H), 1.78–1.26 (m, 48H), 0.87 (m, 12H); 13C NMR (100 MHz,
CDCl3) d (ppm) 163.4, 158.4, 140.4, 130.7, 129.8, 126.6, 125.7, 125.1, 124.5,
123.0, 121.9, 121.2, 114.9, 113.1, 77.2, 70.9, 70.7, 70.6, 69.9, 69.4, 67.0, 65.3,
31.8, 29.2, 29.1, 28.8, 26.1, 22.6, 14.1; IR (thin film) 3375, 3052, 2921, 2856,
1708, 1663, 1610, 1556 cmÀ1; MALDI-TOF (m/z) [M]+ calcd for C128H164N4O24
2141; found 2142.10. Spectroscopic data of 8: 1H NMR (400 MHz, CDCl3): d
(ppm): 9.57 (s, 2H, NH), 8.85 (s, 2H), 8.09 (s, 4H), 7.62 (d, 4H, J = 8.8 Hz), 7.17
(d, 4H, J = 8.4 Hz), 4.40 (m, 4H), 4.30 (m, 4H), 3.93 (m, 4H), 3.67–3.47 (m, 32H),
1.77–1.26 (m, 24H), 0.86 (m, 6H); 13C NMR (100 MHz, CDCl3): d (ppm) 168.0,
158.0, 139.6, 129.9, 128.8, 125.9, 125.3, 124.4, 124.0, 121.4, 120.8, 114.5, 112.8,
70.6, 70.2, 69.6, 69.0, 66.8, 64.8, 31.3, 28.8, 28.7, 28.2, 25.9, 22.1, 13.6; IR (thin
film) 3371, 2929, 2856, 1704, 1663, 1610, 1561 cmÀ1; MALDI-TOF (m/z) [M]+
calcd for C64H82N2O12 1071; found 1071.95.
Acknowledgments
11. Macomber, R. S. J. Chem. Educ. 1992, 69, 375–378.
This work was financially supported by the Center for Bioactive
Molecular Hybrids (CBMH). J.-m.S. acknowledges the fellowship of
the BK 21 program from the Ministry of Education and Human Re-
sources Development.
12. (a) Connors, K. A. Binding Constants; John Wiley & Sons: New York, 1987; (b)
Schneider, H.-J.; Yatsimirsky, A. K. Principles and Methods in Supramolecular
Chemistry; John Wiley & Sons: New York, 2000. p 148.