A pyrenyl-appended triazole-based calix[4]arene as a fluorescent sensor for Cd2+ and Zn2+

Article abstract of DOI:10.1021/jo8012918

(Figure Presented) The synthesis and evaluation of a novel calix[4]arene-based fluorescent chemosensor 8 for the detection of Cd ²⁺ and Zn²⁺ is described. The fluorescent spectra changes observed upon addition of various metal ions show that 8 is highly selective for Cd²⁺ and Zn²⁺ over other metal ions. Addition of Cd ²⁺ and Zn²⁺ to the solution of 8 results in ratiometric measurement.

Full text of DOI:10.1021/jo8012918

A Pyrenyl-Appended Triazole-Based Calix[4]arene as a Fluorescent
2
+
2+
Sensor for Cd and Zn
†
†
†
‡
Sun Young Park, Jung Hee Yoon, Chang Seop Hong, Rachid Souane,
,
†
,§
,‡
Jong Seung Kim,* Susan E. Matthews,* and Jacques Vicens*
Department of Chemistry, Korea UniVersity, Seoul 130-701, Korea, IPHC-ULP-ECPM-CNRS, 25 rue
Becquerel, F-67087, Strasbourg C e´ dex, France, and School of Chemical Sciences and Pharmacy,
UniVersity of East Anglia, Norwich NR4 7TJ, U.K.
jongskim@korea.ac.kr; susan.matthews@uea.ac.uk; Vicens@chimie.u-strasbg.fr
ReceiVed June 16, 2008
The synthesis and evaluation of a novel calix[4]arene-based fluorescent chemosensor 8 for the detection
2
+
2+
of Cd and Zn is described. The fluorescent spectra changes observed upon addition of various metal
2
+
2+
2+
2+
ions show that 8 is highly selective for Cd and Zn over other metal ions. Addition of Cd and Zn
to the solution of 8 results in ratiometric measurement.
Introduction
effects, it is important to be able to monitor the presence of
cadmium and zinc quantitatively. As a result, in recent years,
interest in both cadmium and zinc sensors has been extensive.
Cadmium has found extensive uses in the fields of Ni-Cd
batteries, phosphate fertilizers, pigments, and semiconducting
quantum dots and rods. The detrimental effects of cadmium
on human health are, however, being increasingly recognized:
chronic cadmium exposure can cause renal dysfunction, calcium
metabolism disorders, and an increased incidence of certain
forms of cancer, possibly due to direct inhibition of DNA
mismatch repair. In addition, zinc is, after iron, the second most
7
8
1
More generally, the sensing of metal ions with selective
analytical reagents remains a challenge for environmental and
9
biological applications. With the advent of supramolecular
chemistry, the design and synthesis of optically responsive
chemical sensors for specific detection of metal ions has become
2
3
4
abundant transition metal in mammals, where it plays important
roles in various biological processes such as neurotransmission,
signal transduction and gene expression. Due to their toxic
(5) Assaf, S. Y.; Chung, S. H. Nature 1984, 308, 734.
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†
Korea University.
IPHC-ULP-ECPM-CNRS.
University of East Anglia.
‡
§
(
1) (a) Friberg, L.; Elinger, C. G.; Kjeltr o¨ , T. Cadmium; World Health
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Betkhar, R.; Chandiramani, M. Tetrahedron Lett. 2007, 48, 8487. (c) Parkesh,
R.; Lee, R. C.; Gunnlaugsson, T. Org. Biomol. Chem. 2007, 5, 310. (d)
Gunnlaugsson, T.; Lee, T. C.; Parkesh, R. Org. Biomol. Chem. 2003, 1, 3265.
(e) Ngwendson, J. N.; Banerjee, A. Tetrahedron Lett. 2007, 48, 7316. (f) Nolan,
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Bawendi, M. G. J. Am. Chem. Soc. 1993, 115, 8706.
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212 J. Org. Chem. 2008, 73, 8212–8218
10.1021/jo8012918 CCC: $40.75  2008 American Chemical Society
Published on Web 09/26/2008

A Fluorescent Sensor for Cd2 and Zn2+
+
1
0
a growing field of research. A chemical sensor generally
includes two components, a reporter unit, for example a
fluorophore, and an ionophore, which can be either independent
species or covalently linked in one molecule, and additionally
1
1
a mechanism for communication between them. When the
analytes bind to the recognition center, changes occur in the
optical properties (e.g., enhancement or inhibition of absorption
or fluorescence) of the chemosensor. Fluorophores are particu-
larly attractive optical molecules and have recently found
1
2
applications in self-assembled chemosensors, for signal am-
13
plification by allosteric catalysis, in supramolecular analytical
1
4
chemistry, and as fluorescent and photochromic chemosen-
1
5
sors.
The majority of fluorescent chemosensors for cations are
composed of a cation recognition unit (ionophore) together
with a fluorogenic unit (fluorophore) and are thus described
FIGURE 1. Structures of fluorescent sensors 7 and 8.
1
0b
as fluoroionophores. An effective fluorescence chemosen-
sor must convert the event of cation recognition by the
ionophore into an easily monitored and highly sensitive light
19
and isolation by Gutsche et al. in the 70s, the cyclooligo-
20
meric phenols known as calixarenes have received much
interest as basic molecular platforms for the construction of
1
6
signal from the fluorophore. As fluorogenic units, pyrenes
Py) are one of the most useful tools due to their relatively
21
desired molecular architectures. The chemistry of calix-
(
arenes is well developed and their unique topology offers a
wide range of scaffolds enabling them to encapsulate many
1
7
efficient excimer formation and emission. Host molecules
with more than one pyrenyl group exhibit intramolecular
excimer emission by two different mechanisms. One results
from π-π stacking of the pyrene rings in the free state, which
results in a characteristic decrease of the excimer emission
intensity and a concomitant increase of monomer emission
intensity. The other mechanism is due to the interaction of
an excited pyrene (Py*) unit with a ground state pyrene (Py)
21
different metal ions. More recently, functionalized calix[4]-
arenes have been incorporated into a large variety of
22
fluorescent ion sensors. In particular Broan reported that a
calixarene containing pyrenyl ester groups forms an intramo-
lecular excimer due to strong π-π interaction between two
23
pyrene units. Additionally we have previously incorporated
pyrene reporter molecules onto single calixarenes as the
pyrene-amide and demonstrated that selective fluorescent
1
8
unit.
2
+
2+
The choice of ionophore is crucial for the development of
an effective sensor and many systems have been developed
including a range of macrocycles. Since their characterization
cation sensors for Cu and Pb could be developed based
2
4
+
2+
on platforms fixed in the cone conformation and K /Pb
on-off switchable sensors when a calix[4]crown fixed in
the 1,3-alternate conformation was used. With tricalix[4]arene
1
8b
3
+
systems, featuring three pyrene moieties, Al selectivity has
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2
5
Desvergnes, J. P., Czarnik, A. W., Eds.; Kluwer Academic: Dordrecht, The
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1
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7
J. Org. Chem. Vol. 73, No. 21, 2008 8213

Park et al.
SCHEME 1. Syntheses of 2 and 3
SCHEME 2. Syntheses of 7 and 8
capability of 8 for cadmium and zinc ions, over a wide range
of competing cations, with respect to ratiometric fluorescent
signals is described.
preparation of calix[4] sugars through azide functionalized
4
2
calix[4]arene intermediates. More relevant to this work are
2
+
the reports of Chung and co-workers who have developed Ca
2+
and Pb chromogenic selective sensors through the introduction
of triazole binding sites to the lower rim of calix[4]arene and
4
3
Results and Discussion
on-off switchable fluorescent sensors based on a calix[4]crown
2
7
28
Since the observation by Sharpless and Meldal that the
2
9
Huisgen 1,3-dipolar cycloaddition of alkynes and azides to
give 1,2,3-triazoles can be catalyzed by Cu(I) to give exclusively
the 1,4-disubstituted steroisomer the use of “click” chemistry
as a straightforward linking strategy has been exploited in a
(
27) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew.
Chem., Int. Ed. 2002, 41, 2596.
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057.
(
3
(
29) Huisgen, R.; Szeimies, G.; Mobius, L. Chem. Ber. 1967, 100, 2494.
30
31
wide variety of areas including bioconjugation, drug design,
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3
0,32
Moorhouse, A. D. Chem. Soc. ReV. 2007, 36, 1249.
and materials chemistry.
In addition the properties of the
(
31) Angell, Y. L.; Burgess, K. Chem. Soc. ReV. 2007, 36, 1674.
linker in multivalent derivatives can be exploited for the binding
of cations, a property first identified and developed for the
accelerated catalysis of the “click” reaction itself by in situ
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6, 1369.
3
6
(
33) Chan, T. R.; Hilgraf, R.; Sharpless, K. B.; Fokin, V. V. Org. Lett. 2004,
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928.
3
3
formation of copper complexes. More recently triazole-based
3
4
phosphine catalysts for Pd-Suzuki-Miyaura cross-couplings
3
and Zn-triazole functionalized resins for enantioselective phe-
(
35) Bastero, A.; Font, D.; Peric a` s, M. A. J. Org. Chem. 2007, 72, 2460.
35
nylation of aldehydes have been developed. The coordination
chemistry of triazoles has also been investigated through the
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2
+
2+
+
3+
formation of Fe , Ru , Re , and Eu complexes of a range
3
6
of bis-triazoles. These cation binding properties of triazoles
have been shown to be of potential in the radiolabeling of
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D. J.; Lemoine, P.; Viossat, B.; Gautier, A. Eur. J. Inorg. Chem. 2008, 298.
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L.; Astruc, D. Chem. Eur. J. 2008, 14, 50.
3
7
biomolecules and the preparation of platinum-based anti-
3
8
2+
2+
cancer agents. Electrochemical sensing of Pt and Pd has
39
been achieved with triazole functionalized dendrimers whereas
fluorescent probes have been developed for Zn .
(
40) (a) Huang, S.; Clark, R. J.; Zhu, L. Org. Lett. 2007, 9, 4999. (b) David,
4
0
2+
O.; Maisonneuve, S.; Xie, J. Tetrahedron Lett. 2007, 48, 6527.
(
(
41) Ryu, E.-H.; Zhao, Z. Org. Lett. 2005, 7, 1035.
42) (a) Dondoni, A.; Marra, A. J. Org. Chem. 2006, 71, 7546. (b) Marra,
The copper-catalyzed triazole click reaction has, to date, been
little exploited for the functionalization of the calixarene
A.; Moni, L.; Pazzi, D.; Corallini, A.; Bridi, D.; Dondoni, A. Org. Biomol. Chem.
4
1
2
008, 6, 1396. (c) Bew, S. P.; Brimage, R. A.; L’Hermitie, N.; Sharma, S. V.
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scaffold. Since the first report in 2005 on the synthesis of
water-soluble derivatives through the incorporation of polyhy-
droxyl groups and sulfonates most reports have focused on the
(
8
214 J. Org. Chem. Vol. 73, No. 21, 2008

A Fluorescent Sensor for Cd2 and Zn2+
+
4
4
fixed in the 1,3 alternate conformation. Additionally a tris
upper-rim triazole functionalized calix[6]arene has been de-
2
+
45
scribed recently that is able to coordinate Zn .
To prepare the pyrenyl-appended calix[4]arenes we func-
tionalized p-tert-butylcalix[4]arene with terminal alkyne groups
and treated this with an azidopyrene that allows the formation
of intramolecular 1,2,3-triazole cation-binding linkers. The
synthesis of 1,2,3-triazole calixarenes 7 and 8 is shown in
Scheme 2.
To incorporate the reporter unit through a triazole cation
binding site, the azido derivative of pyrene was prepared in a
short synthetic sequence from the commercially available
pyrenemethanol. The alcohol was initially converted to the
bromo derivative 2 in 82% yield, using PBr3 in dry THF.
Subsequently the azide 3 was prepared in 91% yield by
treatment of 2 with sodium azide (Scheme 1). As significant
decomposition of 3 was observed over time, the azido derivative
was freshly prepared and immediately used before each coupling
reaction.
3
FIGURE 2. Fluorescence spectra of 7 and 8 (6.0 µM) in CH CN. The
excitation wavelength is 343 nm.
the triazole-H signal as a singlet within the range 8.00-8.50
ppm for 7 and 7.55 ppm for 8 and the downfield shift of the
OCH2-triazole linker (Supporting Information, Figures S8 and
S11). The cone conformation of 8 was also confirmed by the
determination of its X-ray crystal structure (Supporting Informa-
tion, Figure S14).
The optical properties of both 8, featuring two triazole binding
sites, and 7, which incorporates a single triazole binding site
and an additional carbonyl moiety, known for binding of group
1 metals, were studied. On excitation at 343 nm, the maximum
absorption wavelength of the pyrene in 8 displays both monomer
and excimer emissions at 395 and 476 nm, respectively, whereas
in 7 only a monomer emission is observed at 395 nm (Figure
It is interesting to note that the pyrene azide reporter unit
has not been previously used in the formation of triazole-based
4
6
sensors; however, a very recent report has described the
synthesis of dialkyne pyrene derivatives which have been further
functionalized as phosphoamidites for inclusion into oligonuce-
lotides.
4
7
48
The synthesis of both the mono-4 and dipropargyl 5
derivatives of p-tert-butylcalix[4]arene have previously been
described. A new synthetic route was developed, as part of this
synthesis, which allowed the isolation of both 4 and 5, in
acceptable yields, from a single one-pot reaction by treatment
of p-tert-butylcalix[4]arene with an excess of propargyl bromide
in the presence of 0.86 equiv of potassium carbonate. Elution
of the reaction residue on silica gel with 1:1 cyclohexane/CH2Cl2
as eluent gave 4 (36% yield) and additionally the dialkyne 5
2
). It is notable that the formation of the excimer emission in 8
is caused by an intramolecular interaction between Py (the
ground state pyrene) and Py* (the photoinduced excited state
1
8
pyrene) where two pyrenes are likely to be in parallel, which
is quite constant with the results from X-ray crystal analysis
(
vide supra).
(
23% yield). Data of 4 and 5 were consistent with materials
To obtain an insight into the binding properties of 7 and 8
toward metal ions, we investigated the fluorescence changes
upon addition of the perchlorate salt of a wide range of cations
previously prepared. The introduction of the additional carbonyl
cation binding site in 7 was acheived through selective alkylation
of 5 with 1 equiv of methylbromoacetate in the presence of
K2CO3 to give the intermediate calixarene 6 in 33% yield.
The synthesis of the triazole calix[4]arene 8 was initially
+
+
+
+
+
2+
2+
2+
2+
including Li , Na , K , Rb , Cs , Mg , Ca , Sr , Ba ,
+
2+
2+
2+
2+
2+
Ag , Cu , Zn , Cd , Hg , and Pb in CH3CN. The
fluorescence changes are depicted in Figure 3. Addition of Zn
2+
43
attempted by using previously described conditions involving
2+
or Cd ion to the CH3CN solution of 8 bearing pyrene-triazoles
as a metal ligating group induced a remarked ratiometry where
the monomer emission increases as its excimer emission
declines. By contrast, no significant spectral changes were
observed upon addition of most of the other metal ions; however,
catalysis by CuI in a THF/H2O mixed solvent system stirred at
5
0 °C. While after this time some of the desired material had
been formed, more effective synthesis was achieved through
alteration of the solvent to DMF, in which both reagents were
freely soluble, and acceptable yields were achieved, for both 7
2
+
2+
2+
when other heavy metal ions such as Pb , Hg , and Cu
(
56%) and 8 (57%), after stirring at 90 °C for 2 h. All the
were added to the solution of 8, we unexpectedly observed a
quenched fluorescence in both monomer and excimer emissions
due to heavy metal ion effects. In contrast, 7 bearing only one
pyrene unit, shows no significant spectral changes upon addition
of any of the metal ions used apart from the heavy metal ions
where quenching is again observed. The two triazole units of 8
are thus proven to form an efficient and selective metal ion
binding site, whereas 7, which features only one triazole binding
site, is unable to form effective complexes despite the inclusion
of an additional carbonyl binding site. Furthermore, the geom-
etry of the binding site of the ligand, in which the two N atoms
of triazole rings are arranged distally on the calix[4]arene
scaffold, seems to be ideal in terms of arrangement and size
calixarenes 5-8 were fully characterized by NMR, MALDI-
TOF mass spectrometry, and elemental analysis (Supporting
Information, Figures S5-S13).
The conservation of the original fixed cone conformation of
the calix[4]arene was confirmed by the presence of doublets
for the ArCH2Ar protons at ∼3 and 4 ppm. The formation of
the 1,2,3-triazole rings was apparent from the appearance of
(
44) Chang, K.-C.; Su, I.-H.; Senthilvelan, A.; Chung, W.-S. Org. Lett. 2007,
, 3363.
45) Colasson, B.; Save, M.; Milko, P.; Roithov a´ , J.; Schr o¨ der, D.; Reinaud,
9
(
O. Org. Lett. 2007, 9, 4987.
(
(
46) Werder, S.; Malinovskii, V. L.; H a¨ ner, R. Org. Lett. 2008, 10, 2011.
47) Santoyo-Gonzalez, F.; Antonio Torres-Pinedo, A.; Sanchez-Ortega, A.
4
3
J. Org. Chem. 2000, 65, 4409.
48) Asfari, Z.; Bilyk, A.; Bond, C.; Harrowfield, J.; Koutsantonis, G. A.;
for recognition of transition metal cations.
(
Figure 4 shows the titration profiles of 8 on Cd and Zn2+
2
+
Lengkeek, N.; Mocerino, M.; Skelton, B. W.; Sobolev, A. N.; Strano, S.; Vicens,
J.; White, A. H. Org. Biomol. Chem. 2004, 2, 387.
2
+
addition. When the concentration of Cd is increased up to
J. Org. Chem. Vol. 73, No. 21, 2008 8215

Park et al.
FIGURE 4. Fluorescence spectra of 8 (6.0 µM) in CH
addition of increasing concentrations of (a) Cd(ClO and (b) Zn(ClO
0, 6, 12, 18, 30, 60, 120, 180, 300, 600, 1200, 1800, 3000 µM) with
an excitation at 343 nm.
3
CN upon
)
4 2
4 2
)
FIGURE 3. Fluorescence spectra of (a) 7 and (b) 8 (6.0 µM) upon
(
-
+
+
+
+
+
2+
2+
2+
addition of ClO
4
salts of Li , Na , K , Rb , Cs , Mg , Ca , Sr ,
Ba , Ag , Cu2+, Zn , Cd , Hg , and Pb (100 equiv) in CH
2
+
+
2+
2+
2+
2+
CN.
3
-
4
1
.2 × 10 M, the intensity is increased by 10-fold in monomer
49
emission. The association constants (Ka) of 8 were thus
4
4
-1
2+
determined to be 5.18 × 10 and 1.7 × 10 M for Cd and
2+
[d] 50
2+
Zn , respectively. The quantum yields (Φf
)
of 8, 8-Cd ,
2+
and 8-Zn , referenced to anthracene, were also determined and
found to be 0.229, 0.267, and 0.258, respectively.
To utilize 8 as an ion-selective fluorescence chemosensor for
Cd2 and Zn
+
2+
the effect of competing metal ions was
determined. Compound 8 (6.0 µM) was treated with 20 equiv
2
+
2+
of Cd or Zn in the presence of other metal ions (20 equiv).
2
+
As shown in Figure 6, no interference in detection of Cd and
2+
Zn was observed in the presence of group 1 or group 2 metals
or with silver and lead. However, the quenching effects of
mercury and copper do abolish the ratiometric effect on binding
FIGURE 5. Fluorescence intensities after treatment of 8 in CH
3
CN
with a variety of metal perchlorates, and relative binding abilities of 8
2
+
2+
2+
2+
of Cd and Zn . Thus it is notable that 8 can be used as a
to different metal ions compared to Cd and Zn , respectively. Black
2
+
2+
bar, 6.0 µM of 8 with 20 equiv of metal ion stated. White bar, 6.0 µM
Cd or Zn selective ratiometric fluorescent sensor in the
2
+
2+
of 8 with 20 equiv of metal ion in 20 equiv of Cd (for Cd effect
presence of most competing cations.
2
+
of 40 equiv Cd ). Slant line bar, 6.0 µM of 8 with 20 equiv of metal
1
2+
2+
H NMR spectroscopy of 8, 8-Cd , and 8-Zn in CD3CN
2+
2+
2+
ion in 20 equiv of Zn (for Zn effect of 40 equiv Zn ) (λ ) 376
nm). The responses of the sensor 8 to cadmium and zinc, in the absence
of competing ions, are included as controls: black bar, no metal ion
was undertaken to determine the complexation mode of 8 for
metal cations, which results in the excimer emission changes.
The spectral differences are depicted in Figure 6. Some
2
+
added; white bar, 6.0 µM of 8 with 20 equiv of Cd ; slant line bar,
2
+
1
6.0 µM of 8 with 20 equiv of Zn .
significant spectral changes are observed in the H NMR spectra
on addition of both of the cations. For example, upon interaction
with Cd , Hb (Figure 6) on the triazole ring undergoes a
downfield shift by 0.26 ppm to 7.79 whereas the OCH -triazole
2
2
+
linker proton H is shifted from 4.79 to 4.25 ppm. Similarly, in
c
2
+
the presence of Zn , the Hb peak is downfield shifted by 0.05
ppm and the Hc peak is upfield shifted by 0.19 ppm. These
(
49) Association constants were calculated by using the computer program
ENZFITTER, available from Elsevier-BIOSOFT, 68 Hills Road, Cambridge CB2
2
+
2+
spectral changes suggest that both Cd and Zn are bound
1
LA, United Kingdom.
50) Albini, A.; Fasani, E.; Faiardi, D. J. Org. Chem. 1987, 52, 155.
4
4
(
by the nitrogen atom of the triazole ring. This putative binding
8
216 J. Org. Chem. Vol. 73, No. 21, 2008

A Fluorescent Sensor for Cd2 and Zn2+
+
ions. Binding of Cd2 and Zn2+ ions occurs in a ratiometric
manner through an enhanced monomer and declining excimer
emission spectrum and can be additionally observed through
+
1
changes in both the H NMR and FAB-MS spectra. This work
opens up the possibility of a family of highly selective sensors
for a range of cations based on conformationally tuneable
calixarene platforms, an area we are currently exploring.
Experimental Section
1
-Bromomethylpyrene (2). Phosphorus tribromide (1.75 g, 6.45
mmol) was added to a suspension of commercial 1-pyrenemethanol
1) (1.00 g, 4.30 mmol) in 5 mL of dry THF and stirred at room
temperature for 30 min. The resulting mixture was filtered and the
residue was washed with Et O to yield the desired bromomethyl
(
2
compound (2) as a yellow solid (1.04 g, 82%). Mp 145-146 °C.
1
H NMR (300 MHz) δ 8.31 (1H, d, J ) 10 Hz), 8.15 (3H, m),
1
3
7
1
1
2
1
1
.98 (4H, m), 5.18 (2H, s). C NMR δ 32.46, 123.01, 124.79,
25.04, 125.28, 125.81, 125.83, 126.46, 127.52, 127.88, 128.21,
28.42, 129.24, 130.72, 130.03, 131.38, 132.12. IR V 3037.359,
987.080, 2883.720, 2119.843, 1915.830, 1789.935, 1587.225,
556.438, 1514.198, 1310.830, 1244.134, 1200.661, 1183.767,
083.749, 842.962, 838.874, 826.743 cm- . Electro Spray MS
1
(
C
17
H
11Br ) 295.17) 159.455 [M - Br].
1
-Azidomethylpyrene (3). Sodium azide (164 mg, 2.54 mmol)
was added to a solution of bromomethylpyrene 2 (500 mg, 1.69
mmol) in 3 mL of anhydrous DMF and the suspension was heated
at 60 °C for 6 h. The mixture was then cooled and diluted with
water. The aqueous phase was extracted with Et
phase was dried (Na SO ), and the solvent was evaporated to yield
the azide (3) as a yellow waxy solid (395 mg, 91%). Mp 59-61
2
O, the organic
1
FIGURE 6. The proposed structure for 8 + metal ions, and H NMR
4 2
spectra of 8 in CD CN and in the presence of Cd(ClO and Zn(ClO )
2
4
3
)
4 2
in a 1:1 ratio (full spectra are available in the Supporting Information,
Figures S17 and S18
1
°
C. H NMR (300 MHz) δ 8.14 (4H, m), 7.95 (5H, m), 7.98 (4H,
13
m), 4.95 (2H, s). C NMR δ 53.12, 122.68, 124.66, 125.07, 125.56,
25.63, 126.19, 127.34, 127.46, 127.89, 128.29, 128.40, 129.27,
130.75, 131.24, 131.81. IR V 3041, 2099, 2079, 1601, 1251, 1227,
1
mode is further elucidated by additional changes in the spectra
which point to the metal being bound by the upper part of the
triazole ring with the aid of two facing phenol groups. In
particular, the phenol-Hf is downfield shifted by 0.29 and by
1180 cm- . Electro Spray MS (C17
N], 230.12 [M - 2N], 215.10 [M - 3N].
,11,17,23-Tetra-tert-butyl-25,26,27-trihydroxy-28-pro-
1
11 3
H N ) 257.29) 242.12 [M -
5
2
+
2+
pargylcalix[4]arene (4) and 5,11,17,23-Tetra-tert-butyl-25,27-
dihydroxy-26,28-dipropargylcalix[4]arene (5). p-tert-Butyl-
0
.20 ppm with Cd and Zn , respectively, whereas the Ha
peak proximal to the pyrene does not undergo a significant
change in the presence of the metal cations. This binding mode
is in line with the fluorescence changes observed as the induced
conformational changes of the triazole units by 1:1 complexation
would prevent the two pyrene molecules from maintaining the
π-π interaction necessary for excimer emission, but instead
would force their separation and lead to the increasing monomer
emission of 8, which is observed. It is interesting to note that
the extent of chemical shift changes is in agreement with the
calix[4]arene (3.10 g, 4.78 mmol) and K
were heated at reflux for 1 h in acetone (50 mL). Propargyl bromide
80% in toluene, 0.82 g, 6.89 mmol) was added and the mixture
2 3
CO (0.57 g, 4.12 mmol)
(
refluxed for 18 h. The solvents were evaporated and the residue
partitioned between 10% HCl and CH Cl . The organic layer was
2
2
separated and dried (Na
The residue was purified by column chromatography on silica gel
with 1:1 cyclohexane/CH Cl as eluent to yield the title compound
(1.17 g, 36%) and additionally the dialkyne 5 (0.79 g, 23%).
Analytical data of 4 and 5 were consistent with the materials
2 4
SO ) and the solvents were evaporated.
2
2
4
2
+
2+
association constants (Cd
> Zn ) calculated from the
fluorescence spectrometry results suggesting that Cd is likely
to interact with the triazole group of 8 more strongly than the
4
7,48
prepared in the corresponding references.
,11,17,23-Tetra-tert-butyl-25,27-dihydroxy-26-methyl-
acetate-28-propargylcalix[4]arene (6). 4 (1.00 g, 1.47 mmol) and
CO (203 mg, 1.47 mmol) were heated at reflux in 30 mL of
acetone for 1 h. BrCH CO CH (225 mg, 1.47 mmol) was added
and the mixture was refluxed for 18 h. The solvent was evaporated
and the residue was partioned between 10% HCl and CH Cl . The
organic layer was separated and dried (Na SO ) and the solvents
were evaporated. The residue was purified by column chromatog-
raphy on silica gel with CH Cl as eluent to yield 6 (915 mg, 33%)
as a white solid. Mp 112-114 °C. H NMR (300 MHz) δ 6.97
4H, s), 6.68 (2H, s), 6.67 (2H, s), 6.62 (2H, s), 4.69 (2H, d, J )
2+
5
2
+
Zn cation.
K
2
3
1
The 1:1 binding mode proposed from the H NMR studies is
further confirmed by mass spectrometry in the presence of the
metal cations. The FAB-MS spectra of mixtures of 8 with
cadmium and zinc showed exclusively the formation of 8·Cd
m/z 1351.0 (calcd ) 1352.54) [8·Cd -H ]) and 8·Zn
1302.0 (calcd ) 1302.57) (Supporting Information, Figures S15
and S16).
In summary, the synthesis of a new calix[4]arene fluorescent
chemosensor 8 has been achieved in a short high yielding
synthetic sequence from commercial starting materials. The
inclusion of 1,2,3-triazoles as both spacers and cation-binding
sites coupled with pyrene reporting units onto a rigid calyx[4]arene
2
2
3
2
2
2+
2
4
2
+
+
2+
(
2
2
(
1
(
2
(
(
3
.3 Hz), 4.60 (2H, s), 4.32 (4H, d, J ) 13.2 Hz), 3.77 (3H, s), 3.25
4H, d, J ) 13.2 Hz), 2.45 (1H, t, J ) 2.3 Hz), 1,21 (18H, s), 0.85
13
9H, s), 0.83 (9H, s). C NMR (75 MHz) δ 30.96, 31.69, 32.09,
3.83, 33.87, 52.17, 63.15, 72.38, 96.13, 125.06, 125.57, 125.71,
127.94, 128.09, 132.15, 132.76, 141.58, 150.37, 169.44. MALDI-
TOF MS (758.45) 759.455 [M + H]. Microanalysis Calcd: C, 79.12;
2
+
2+
support provides a highly selective sensor for Cd and Zn
J. Org. Chem. Vol. 73, No. 21, 2008 8217

Park et al.
H, 8.23. Found: C, 78.87; H, 7.96. IR V 3423, 2952, 1757, 1482,
+ H]. IR V 3369, 2950, 2361, 2091, 1687, 1481, 1461, 1390, 1364,
1
360, 1301, 1190, 1123 cm-
1
.
1245, 1169, 1120 cm .
-1
Fluorescence Studies. UV/vis and fluorescence spectra were
recorded with a S-3100 spectrophotometer and a RF-5301PC
spectrophotometer, respectively. Stock solutions (1.00 mM) of the
5
,11,17,23-Tetra-tert-butyl-25,27-dihydroxy-26-methyl-
acetate-28-(1,2,3-triazol-1-methyl pyrene)calix[4]arene (7). Cop-
per iodide (20 mg) was added to 5,11,17,23-Tetra-tert-butyl-25,27-
dihydroxy-26-methylacetate-28-propargylcalix[4]arene (6) (320 mg,
.42 mmol) and azide (3) (275 mg, 1.07 mmol) in anhydrous DMF
15 mL) and the mixture was heated at 90 °C for 2 h. The resulting
solution was cooled and diluted with water. The mixture was
filtered, the residue was washed with water and then taken up in
3
metal perchlorate salts were prepared in CH CN. Stock solutions
of 7 and 8 (0.06 mM) were prepared in CH CN. For all measure-
3
0
(
ments of fluorescence spectra, excitation was at 343 nm with
excitation and emission slit widths at 3.0 nm. UV/vis and
fluorescence titration experiments were performed with 6.0 µM
solutions of 7 and 8 in CH
3
CN and varying concentrations of the
CH
2 2 2 4
Cl and dried (Na SO ). The desired compound 7 (236 mg,
metal perchlorate in CH CN.
3
5
6%) was isolated as a buff solid following column chromatography
1
X-ray Studies. X-ray data for 8 were collected on a Bruker
SMART APEXII diffractometer equipped with graphite monochro-
mated Mo KR radiation (λ ) 0.71073 Å). Preliminary orientation
matrix and cell parameters were determined from three sets of ω
scans at different starting angles. Data frames were obtained at scan
intervals of 0.5° with an exposure time of 10 s per frame. The
reflection data were corrected for Lorentz and polarization factors.
by eluting with 50:1 CH
2
Cl
2 3
/CH OH. Mp 225-227 °C. H NMR
(
2
(
(
(
300 MHz) δ 8.00-8.50 (10H, m), 7.21 (2H, s), 7.05 (2H, d, J )
.5 Hz), 7.00 (2H, d, J ) 2.5 Hz), 6.77 (4H, d, J ) 6.0 Hz), 6.47
2H, s), 5.24 (2H, s), 4.51 (2H, s), 4.21 (2H, d, J ) 12.3 Hz), 4.20
2H, d, J ) 14.1 Hz), 3.64 (3H, s), 3.23 (2H, d, J ) 12.3 Hz), 3.22
1
3
2H, d, J ) 14.1 Hz), 1.30 (18H, s), 0.95 (9H, s), 0.94 (9H, s).
C
NMR (75 MHz) δ 30.93, 31.60, 31.70, 33.81, 33.91, 51.91, 52.16,
5
1
Absorption corrections were carried out with SADABS. The
structures were solved by direct methods and refined by full-matrix
least-squares analysis, using anisotropic thermal parameters for non-
7
1
1
0.25, 71.89, 122.19, 124.97, 125.08, 125.12, 125.25, 125.68,
25.75, 126.19, 127.13, 127.31, 127.52, 127.58, 127.99, 128.03,
28.75, 132.26, 132.65, 141.50, 149.32, 149.67, 150.45, 169.36.
MALDI-TOF MS (1016.31) 1016.53 [M ]. IR V 3439, 2953, 2863,
750, 1682, 1595, 1482, 1462, 1431, 1361, 1299, 1191, 1123 cm .
5
2
+
hydrogen atoms with the SHELXTL program. The SQUEEZE
routine of the PLATON program was employed to calculate the
disorder area of the solvent molecule and get rid of its contribution
to the whole intensity data. Hydrogen atoms were calculated at
idealized positions and refined with the riding models.
-1
1
5
,11,17,23-Tetra-tert-butyl-25,27-dihydroxy-26,28-di(1,2,3-
triazol-1-methylpyrene)calix[4]arene (8). Copper iodide (20 mg)
was added to 5,11,17,23-tetra-tert-butyl-25,27-dihydroxy-26,28-
dipropargylcalix[4]arene (5) (394 mg, 0.54 mmol) and azide 3 (350
mg, 1.36 mmol) in 15 mL of anhydrous DMF and the mixture was
heated at 90 °C for 2 h. The resulting solution was cooled and
diluted with water. The mixture was filtered, then the residue was
Acknowledgment. The authors wish to acknowledge the
financial support of the SRC program (R11-2005-008-02001-
0
(2008) (J.S.K.) and the University of East Anglia (S.E.M.).
washed with water and then taken up in CH
The residue eluted from a column chromatography of silica gel
with 30:1 CH Cl /acetone to give the desired material 6 (388 mg,
2 2 2 4
Cl and dried (Na SO ).
Supporting Information Available: General experimental
1
13
methods, H and C NMR for 2, 3, and 6-8, MS spectra for
2
2
2
+
2+
1
6-8 and 8·Cd and 8·Zn , ORTEP diagram for 8, and
Cartesian coordinates for 8. This material is available free of
charge via the Internet at http://pubs.acs.org.
5
7
6
2
7%) as a cream solid. Mp 198-200 °C. H NMR (300 MHz) δ
.62-8.09 (9H, m), 7.55 (2H, br s), 6.70 (4H, s), 6.61 (2H, s),
.48 (4H, s), 6.00 (4H, s), 4.74 (4H, s), 3.61 (4H, d, J ) 13 Hz),
1
3
.82 (2H, d, J ) 13 Hz), 1.15 (18H, s), 0.74 (18H, s). C NMR
JO8012918
(
75 MHz) δ 30.84, 31.45, 31.67, 33.71, 33.78, 121.94, 124.39,
1
1
1
24.77, 124.87, 125.37, 125.73, 125.81, 126.21, 127.25, 127.33,
27.45, 128.14, 128.84, 130.50, 131.09, 131.92, 132. 43, 141.28,
47.04, 149.43, 149.98. MALDI-TOF MS (1238.64) 1239.60 [M
(
51) Sheldrick, G. M. SADABS, a program for area detector absorption
corrections; University of G o¨ ttingen: G o¨ ttingen, Germany, 1994.
(52) Sheldrick, G. M. SHELXTL, version 5; Bruker AXS: Madison, WI, 1995.
8
218 J. Org. Chem. Vol. 73, No. 21, 2008