Calix[4]crown in dual sensing functions with FRET

Article abstract of DOI:10.1016/j.tetlet.2005.09.117

A new calix[4]crown chemosensor based on dual sensing probes reveals Pb²⁺ ion selectivity over other metal ions, which arises from a hypsochromic shift of azo units in UV spectrum as well as a fluorescence enhancement of pyrenyl parts in fluore

Full text of DOI:10.1016/j.tetlet.2005.09.117

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8163–8167
Calix[4]crown in dual sensing functions with FRET
Seoung Ho Lee,a Sung Kuk Kim,a Ju Han Bok,a Suh Hyun Lee,a Juyoung Yoon,b
Kilsung Leec and Jong Seung Kima,*
aDepartment of Chemistry, Dankook University, Seoul 140-714, Republic of Korea
bDepartment of Chemistry, Ewha Womans University, Seoul 120-750, Republic of Korea
cCheil Industries Inc, Uiwang-si, Gyeonggi-do, 437-711, Republic of Korea
Received 22 August 2005; revised 14 September 2005; accepted 20 September 2005
Available online 10 October 2005
Abstract—A new calix[4]crown chemosensor based on dual sensing probes reveals Pb2+ ion selectivity over other metal ions, which
arises from a hypsochromic shift of azo units in UV spectrum as well as a fluorescence enhancement of pyrenyl parts in fluorescence
spectrum via a suppressed FRET.
ꢀ 2005 Published by Elsevier Ltd.
The design of chemosensors able to selectively recognize
and sense specific analytes has attracted considerable
interests due to their importance in biological and envi-
ronmental settings.1,2 The main issue in designing effec-
tive sensor is to easily convert molecular recognition
into photochemical changes with a high selectivity and
sensitivity. For the chemosensors, it is well known that
the photochemical changes in the sensing modules
are based on the photo-induced electron transfer
(PET), fluorescence resonance energy transfer (FRET),
perturbation of optical transitions, and polarizabilities,
excimer/exciplex formation, modification of redox
potentials in ground or excited states, and photoregu-
lation of binding properties.3–7
form a complex with Pb2+ ion, provides a quenched
fluorescence.16
The FRET is defined as an excited-state energy inter-
action between two fluorophores in which an excited
donor (D) energy is transferred to an acceptor (A) part
without any photon-emission.4,17 So, the FRET is
required to have a certain degree of spectral overlap
between the emission spectrum of the donor and the
absorption spectrum of the acceptor (quencher).
Taking the dual sensing system (both the above chromo-
genic and fluoreogenic) into account with the FRET, we
have developed calixcrown molecules with a diazo-
group giving a visual color change as well as with a
pyrenyl group providing a fluorescence change.
Chromogenic and fluorogenic calixarenes have received
increasing attention and become promising candidates
for sensing probes because they are in a certain pre-
organized framework to easily accommodate metal ions
or neutral molecules, exhibiting a selective change in the
UV/vis and fluorescence spectra.7–14 It was reported
that the absorption band of (azo)calix[4]crown hypso-
chromically moves by the addition of metal ions due
to an electrostatic interaction between the oxygen atom
of diazo-phenoxy group and the metal ion.15 We also re-
cently reported that calix[4]crowns (1) as a PET-utilizing
chemosensor, in which the amide groups selectively
Synthetic pathway for 2 is outlined in Scheme 1. Refer-
ence materials 1 and 3–6 (Fig. 1 and Scheme 1) were pre-
pared by the adaptation of the published procedures.5,15
The reaction of azo-coupled calix[4]monocrown-6 (6)
with 2.2 equiv of N-(1-pyrenylmethyl)chloroacetamide
(5) in the presence of K2CO3 as a base with a catalytic
amount of NaI gave 2 in moderate yield with a cone
conformation retained.18
Compound 1 shows a Pb2+ ion selectivity over other
metal ions in terms of decreasing fluorescence, which is
due to a complexation of crown oxygen atoms with
the aid of two facing amide oxygen atoms to cause a
reverse PET and a heavy metal ion effect.16 Compound
2 bearing additional diazo-phenyl moieties to 1 also
Keywords: Calixarenes; Fluorescence; Metal ion complexation.
*
Corresponding address. Tel.: +82 2 799 1351; fax: +82 2 797 3277;
e-mail: jongskim@dankook.ac.kr
0040-4039/$ - see front matter ꢀ 2005Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2005.09.117

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S. H. Lee et al. / Tetrahedron Letters 46 (2005) 8163–8167
O2N
NO2
O2N
NO2
N
N
N
N
N
N
N
N
a
+
5
O
O
O
O
O
O
H
O
H
O
O
O
O
O
O
O
NH
HN
O
O
O
O
2
6
a
4
+
5
3
Scheme 1. Synthetic scheme for 2 and 3. Reagents and conditions: (a) K2CO3, NaI, CH3CN, reflux for 2 days.
O2N
NO2
N
N
N
N
O
O
O
O
O
O
O
O
O
O
O
O
O
NH
HN
O
O
O
O
O
HN
NH
O
O
2
1
NO2
NO2
N
O
N
O
Cl
N
H
N
N
3
5
4
O
NH
OH
Figure 1. Chromo- and fluorogenic compounds.
selectively detects Pb2+ ion over other metal ions in the
acetonitrile solution. As seen in Figure 2, 2 displays two
distinctive UV bands, a pyrenyl part and a diazo-phenyl
unit, with maxima at 344 and 365nm, respectively,
which is confirmed by those of reference materials 4
and 5.19 Addition of Pb2+ ion into the solution of 2
induced a blue-shifted absorption spectrum of the
diazo-phenoxy unit, which is attributable to a pheno-
menon that the phenolic oxygen atoms of the crown
loop are positively polarized when the metal ion is
bound, as a result, the excited state in electron transition
becomes destabilized (Fig. 3).15,20 Enhanced absorption

S. H. Lee et al. / Tetrahedron Letters 46 (2005) 8163–8167
8165
1.0
0.8
0.6
0.4
0.2
0.0
240
5
200
160
4
+
5
5
4
120
2
3
80
40
0
2
360
390
420
450
480
510
540
300
330
360
390
420
450
480
Wavelength (nm)
Wavelength (nm)
Figure 2. UV/vis absorbance spectra of 2, 4, and 5 in CH3CN.
Conditions: 2 (0.01 mM)/CH3CN; 4 (0.02 mM); and 5 (0.02 mM)/
CH3CN.
Figure 4. Fluorescence emission spectra of 2–5 (6.0 lM, excitation at
344 nm) in CH3CN.
cate that the intermolecular FRET quenching effect from
pyrenyl group to diazo-phenyl moiety is absolutely
excluded. Instead, the intramolecular FRET is much
more predominant to govern the fluorescence changes.
1.2
1.0
0.8
With those reasons it is quite understandable for 2 to
reveal a significant spectral overlap between the fluores-
cence emission band of pyrene units as a donor and
the absorption band of diazo-phenyl units as an accep-
tor (quencher) to display a notable quenched fluores-
cence emission. Surprisingly, upon the addition of
2 + Pb2+ 10 eq
0.6
2
0.4
0.2
0.0
300
330
360
390
420
450
480
Wavelength (nm)
Figure 3. Wavelength changes of 2 upon the addition of Pb2+ ion.
Conditions: 2 (0.01 mM)/CH3CN; Pb2+ ion (10 equiv)/CH3CN.
band in 2-Pb2+ (10 equiv) is not due to an electronic
transition between two components (pyrene and diazo-
phenyl) but due to a spectral overlap between absorp-
tion band of the pyrene units and a blue-shifted band
of the azo units, which is also evidenced by the measure-
ment of the spectral changes for 1 and 1-Pb2+ (10 equiv)
where no change in the absorption band is indicated. So,
it is noteworthy that the electronic coupling in the
ground state between the diazo-phenoxy unit and the
pyrenyl part in the 2-Pb2+ complexation is ignorable.
The fluorescence spectra of 2–5 in CH3CN (6.0 lM,
k
ex = 344 nm) are shown in Figure 4. In order to obtain
an insight into the intramolecular or the intermolecular
FRET in 2, we newly synthesized 3 as a reference, which
consists of both functional groups of chromogenic 4 and
fluorogenic 5. As expected, the fluorescence intensity of
3 is weaker than that of 5. Besides, no difference in the
fluorescence spectra between the mixture (4 and 5) and
5 only were observed. Those observations strongly indi-
Figure 5. Fluorescence emission change of 2 upon the addition of Pb2+
ion. Conditions: 2 (6.0 lM, excitation at 344 nm)/CH3CN; Pb2+ ion
(10 equiv)/CH3CN. Inset: titration curve I À I0 (386 nm) as a function
of [Pb2+]/[2].

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S. H. Lee et al. / Tetrahedron Letters 46 (2005) 8163–8167
Pb2+ ion and irradiation at 344 nm, the fluorescence of 2
was observed to revive although the Pb2+ ion is known
as a quenching metal ion as shown in Figure 5, whereas
3 without ionophoric part for the lead ion did not
change in the fluorescence spectrum. It is obviously
due to the less overlapped bands between the donor
(emission) and the acceptor (absorption) caused by a
hypsochromical shift of diazo units by the metal ion
complexation, resulting in a diminished FRET effect
(Fig. 6). According to the fluorescence emission changes
in metal ion titration, we could obtain the association
constant21 of 2 (Ka = 4.0 · 106 MÀ1) for Pb2+ ion. Fig-
ure 6 shows luminosity changes of 1 (a) and 2 (b) upon
Pb2+ ion complexation where the luminosity of 2
decreases compared to that of 1 by the FRET, but
increases by the addition of Pb2+ ion. In addition, the
Pb2+ ion selectivity was also observed by the selective
color change of 2 from pale green to colorless (Fig. 7c).
Acknowledgments
This work was supported in part by the SRC program
of the Korea Science and Engineering Foundation
(KOSEF) through the Center for Intelligent Nano-Bio
Materials at Ewha Womans University (Grant No.:
R11-2005-008-02001-0).
References and notes
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vergne, J. P., Czarnik, A. W., Eds.; NATO ASI series;
Kluwer Academic: Dordrecht, 1997; (b) de Silva, A. P.;
Gunaratne, H. Q.; Gunnlaugsson, N. T. A.; Huxley, T.
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2941; (b) Rurack, K.; Kollmannsberger, M.; Resch-
Genger, U.; Daub, J. J. Am. Chem. Soc. 2000, 122, 968.
Consequently, the less fluorescent 2 caused by the FRET
revives its fluorescence by the Pb2+ ion complexation.
Compound 2 might be useful as a selective sensor for
Pb2+ ion in a dual sensing system, a visual color change
as well as a fluorescence change including the FRET
concept upon the Pb2+ ion complexation.
´
3. Brousmiche, D. W.; Serin, J. M.; Frechet, J. M. J.; He, G.
S.; Lin, T.; Chung, S. J.; Prasad, P. N. J. Am. Chem. Soc.
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Ono, A.; Togashi, H. Angew. Chem., Int. Ed. 2004, 43, 4300.
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M.; van Veggel, F. C. J. M.; Reinhoudt, D. N. J. Am.
Chem. Soc. 2000, 122, 6112.
1.2
6. Beer, P. D. Acc. Chem. Res. 1998, 31, 71.
7. (a) Ji, H.-F.; Brown, G. M.; Dabestani, R. Chem.
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H.-F.; Dabestani, R.; Brown, G. M.; Hettich, R. L. J.
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Fluorescence spectrum of 1
1.0
0.8
8. (a) Gutsche, C. D. In Calixarenes, Monographs in Supra-
molecular Chemistry; Stoddart, J. F., Ed.; Royal Society of
Chemistry: Cambridge UK, 1989; Vol. 1; (b) Calixarenes:
A Versatile Class of Macrocyclic Compounds; Vicens, J.,
Bo¨hmer, V., Eds.; Kluwer: Dordrecht, 1991; (c) Bo¨hmer,
V. Angew. Chem., Int. Ed. 1995, 34, 713.
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Y.; Vicens, J. J. Org. Chem. 2000, 65, 2386; (b) Kim, J. S.;
Lee, W. K.; No, K.; Asfari, Z.; Vicens, J. Tetrahedron
Lett. 2000, 41, 3345.
0.6
UV/vis spectrum of 2
0.4
UV/vis spectrum
of 2 + Pb2+ 10 eq
0.2
0.0
300
330
360
390
420
450
480
10. (a) Aoki, I.; Sakaki, T.; Shinkai, S. J. Chem. Soc., Chem.
Commun. 1992, 730; (b) Jin, T.; Ichikawa, K.; Koyama, T.
J. Chem. Soc., Chem. Commun. 1992, 499.
Wavelength (nm)
Figure 6. Changes of spectral overlap for FRET upon Pb2+ ion
complexation. Conditions: 1 (6.0 lM, excitation at 344 nm)/CH3CN; 2
(0.01 mM)/CH3CN; Pb2+ ion (10 equiv)/CH3CN.
´
11. (a) Metivier, R.; Leray, I.; Valeur, B. J. Chem. Soc., Chem.
´
Commun. 2003, 996; (b) Metivier, R.; Leray, I.; Valeur, B.
Chem. Eur. J. 2004, 10, 4480.
12. Leray, I.; OÕReilly, F.; Habib Jiwan, J.-L.; Soumillion,
J.-Ph.; Valeur, B. Chem. Commun. 1999, 795.
13. Ji, H.-F.; Dabestani, R.; Brown, G. M. J. Am. Chem. Soc.
2000, 122, 9306.
14. (a) Kim, J. S.; Shon, O. J.; Rim, J. A.; Kim, S. K.; Yoon,
J. J. Org. Chem. 2002, 67, 2348; (b) Kim, J. S.; Noh, K. H.;
Lee, S. H.; Kim, S. K.; Kim, S. K.; Yoon, J. J. Org. Chem.
2003, 68, 597; (c) Kim, S. K.; Lee, S. H.; Lee, J. Y.;
Bartsch, R. A.; Kim, J. S. J. Am. Chem. Soc. 2004, 126,
16499; (d) Lee, J. Y.; Kim, S. K.; Jung, J. H.; Kim, J. S. J.
Org. Chem. 2005, 70, 1463.
15. (a) Kim, J. Y.; Kim, G. C.; Kim, C. R.; Lee, S. H.; Lee, J.
H.; Kim, J. S. J. Org. Chem. 2003, 68, 1933; (b) Lee, S. H.;
Kim, J. Y.; Ko, J.; Lee, J. Y.; Kim, J. S. J. Org. Chem.
2004, 69, 2902.
16. Lee, S. H.; Kim, J. Y.; Kim, S. K.; Lee, J. H.; Kim, J. S.
Tetrahedron 2004, 60, 5171.
Figure 7. Luminosity changes of (a) 1 (0.02 mM/CH3CN) and (b) 2
(0.02 mM/CH3CN) with Pb2+ ion (10 equiv), respectively. Visible
color change of (c) 2 (0.02 mM/CH3CN) upon the Pb2+ ion addition
(10 equiv).

S. H. Lee et al. / Tetrahedron Letters 46 (2005) 8163–8167
8167
17. Lakowicz, J. R. Principles of Fluorescence Spectroscopy,
2nd ed.; Plenum: New York, 1999.
18. 5,17-Bis[(4-nitrophenyl)(azo)phenyl]-26,28-bis[(N-(1-pyren-
ylmethyl)aminocarbonyl)-methoxy]-25,27-calix[4]mono-
crown-6 (2). Yield (36%). Mp: 186–188 ꢁC. IR (KBr pellet,
cmÀ1): 3300 (–NH), 1650 (CO), 1521, 1343 (NO2); 1H
4-[(4-Nitrophenyl)(azo)]phenol (4). A solution of phenol
(2.00 g, 21.3 mmole) in tetrahydrofuran (300 mL) was
treated with 4-nitrobenzenediazonium tetrafluoroborate
(5.54 g, 23.4 mmole). The reaction mixture was stirred for
30 min at 0 ꢁC and pyridine was added dropwise. The
reaction mixture was stirred for the additional 48 h at 0 ꢁC
and treated with 10% aqueous HCl solution (300 mL) and
extracted with CH2Cl2 (300 mL). The organic layer was
washed with 10% aqueous HCl solution (2 · 300 mL) and
dried over MgSO4. Removal of the organic solvent in
vacuo afforded a reddish solid. Column chromatography
using CHCl3/acetone (4:1) as eluent (Rf = 0.45) on silica
gel gave 4. Yield (35%). Mp: 168–170 ꢁC. IR (KBr pellet,
cmÀ1): 3428 (OH), 1505, 1336 (NO2); 1H NMR (400 MHz;
NMR (400 MHz; CDCl3): d 8.38 (d, 4H, NO2Ar–Hortho
J = 8.0 Hz), 8.26–7.83 (m, 24H, pyrene, NO2Ar–Hmeta
,
,
CONHCH2pyrene), 7.59 (s, 4H, N2Ar–Hortho), 6.25(s, 6H,
Ar–H), 5.18 (s, 4H, NHCH2pyrene), 5.10 (s, 4H,
ArOCH2CO), 4.44 (d, 4H, ArCH2Ar, J = 13.3 Hz), 3.68
(s, 4H, OCH2CH2O), 3.36 (s, 4H, OCH2CH2O), 3.18 (s,
4H, OCH2CH2O), 3.09 (s, 4H, OCH2CH2O), 3.04 (d, 4H,
ArCH2Ar, J = 13.4 Hz); 13C NMR (CDCl3): d 169.6,
160.9, 156.9, 155.7, 149.0, 148.5, 138.0, 133.0, 132.7, 131.9,
131.4, 128.8, 128.7, 128.6, 128.2, 128.0, 126.8, 126.0, 125.9,
125.4, 125.3, 125.0, 124.9, 124.3, 123.8 (pyreneCH, ArCH,
CO), 74.2, 73.3, 70.9, 70.8, 70.7, 70.5(O CH2CH2O,
ArOCH2CO), 42.1 (NCH2pyrene) 32.2 (ArCH2Ar) ppm.
FAB MS m/z (M+): calcd, 1467.57, found, 1467.60. Anal.
Calcd for C88H74N8O14: C, 72.02; H, 5.08. Found: C,
72.08; H, 5.16.
CDCl3): d 9.43 (s, 1H, ArOH), 8.44 (d, 2H, NO2Ar–Hortho
,
J = 8.8 Hz), 8.08 (d, 2H, NO2Ar–Hmeta, J = 8.8 Hz), 7.96
(s, 2H, N2Ar–Hortho, J = 8.8 Hz), 7.08 (s, 2H, N2Ar–Hmeta
,
J = 8.7 Hz); 13C NMR (CDCl3): d 161.7, 155.9, 148.2,
146.1, 125.6, 124.6, 122.8, 115.8 (ArCH) ppm. FAB MS
m/z (M+): calcd, 243.22, found, 243.00. Anal. Calcd
for C12H9N3O3: C, 59.26; H, 3.73. Found: C, 59.21; H,
3.74.
4-[(4-Nitrophenyl)(azo)]-[N-(1-pyrenylmethyl)amino-
carbonyl]methoxybenzene (3). Yield (82%). Mp: 154–
156 ꢁC. IR (KBr pellet, cmÀ1): 3300 (–NH), 1650 (CO),
1521, 1343 (NO2); 1H NMR (200 MHz; CDCl3): d 8.35(d,
19. The perchlorate salts of Li+, Na+, K+, Rb+, Cs+, Ag+,
Ca2+, Mg2+, Pb2+, Zn2+, Al3+, and In3+ ions (stock
solutions = 1.0 mM in CH3CN) were tested to evaluate
the metal ion binding properties of 2 (stock solu-
tion = 0.6 mM in CH3CN). For all fluorescence measure-
ments, the excitation was made at 344 nm to give
fluorescence intensity at room temperature.
20. Kim, J. S.; Shon, O. J.; Lee, J. K.; Lee, S. H.; Kim, J. Y.;
Park, K. M.; Lee, S. S. J. Org. Chem. 2002, 67, 1372.
21. (a) Association constants were obtained using the com-
puter program ENZFITTER, available from Elsevier-BIO-
SOFT, 68 Hills Road, Cambridge CB2 1LA, United
Kingdom; (b) Connors, K. A. Binding Constants; New
York: Wiley, 1987.
2H, NO2Ar–Hortho
, J = 7.8 Hz), 8.27–7.81 (m, 13H,
pyrene, NO2Ar–Hmeta, N2Ar–Hortho), 6.96 (d, 2H, N2Ar–
Hmeta, J = 7.6 Hz) 6.92 (s, 1H, CONHCH2pyrene), 5.28
(d, 2H, NHCH2pyrene, J = 5.6 Hz), 4.67 (s, 2H, ArOCH2-
CO) ppm; 13C NMR (CDCl3): 167.1, 160.1, 155.7, 148.4,
147.6, 131.2, 130.7, 130.2, 127.1, 128.4, 127.7, 127.3, 127.2,
126.2, 125.5, 125.4, 125.1, 124.8, 124.7, 124.5, 123.2, 122.5,
115.1, 67.5, 41.6 ppm. FAB MS m/z (M+): calcd, 514.53,
found, 514.02. Anal. Calcd for C31H22N4O4: C, 72.36; H,
4.31. Found: C, 72.31; H, 4.36.