Synthesis and cation binding properties of fluorescent calix[4]arene derivatives bearing tryptophan units at the lower rim

Article abstract of DOI:10.1080/10610278.2010.521832

The fluorescent peptidocalixarenes, 5,11,17,23-tetra-tert-butyl-25,26,27, 28-tetrakis(O-methyl-L-tryptophanylcarbonylmethoxy) calix[4]arene (1) and 5,11,17,23-tetra-tert-butyl-25,27-di(O-methyl)-26,28-bis(O-methyl-L- tryptophanylcarbonylmethoxy) calix[4]arene (2), were prepared by introducing tryptophan subunits at a lower calixarene rim. Coordination abilities of 1 and 2 towards Eu(III) and alkali metal cations were studied by spectrophotometric, spectrofluorimetric, conductometric and potentiometric titrations in acetonitrile at 25°C. Rather strong complexation was observed for smaller alkali metal cations Li⁺ and Na⁺ (logK_Li1 > 6, log K_Li2 > 6, log K_Na1 = 8.25, logK_Na2 = 6.94), and moderate for K⁺ (logK_K1 = 5.09, log K _K2 = 4.09). Larger Rb⁺ and Cs⁺ cations did not fit in the ion binding site of 1 so no complexation was detected, whereas the more flexible ligand 2 accommodated Rb⁺ cation (logK_Rb2 = 3.44). The fluorescence of 1 (λ_ex = 280 nm, λ_em = 340 nm) was remarkably quenched by Eu(III). Stability constant of 1:1 (Eu³⁺:1) complex determined spectrofluorimetrically amounted to log K_Eu1 = 6.16.

Full text of DOI:10.1080/10610278.2010.521832

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Synthesis and cation binding properties of fluorescent
calix[4]arene derivatives bearing tryptophan units at
the lower rim
a
a
a
b
a
Nives Galić , Nataša Burić , Renato Tomaš , Leo Frkanec & Vladislav Tomišić
a
Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a,
0000, Zagreb, Croatia
1
b
Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička 54,
10000, Zagreb, Croatia
Published online: 15 Apr 2011.
To cite this article: Nives Galić , Nataša Burić , Renato Tomaš , Leo Frkanec & Vladislav Tomišić (2011) Synthesis and cation
binding properties of fluorescent calix[4]arene derivatives bearing tryptophan units at the lower rim, Supramolecular
Chemistry, 23:5, 389-397, DOI: 10.1080/10610278.2010.521832
To link to this article: http://dx.doi.org/10.1080/10610278.2010.521832
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Supramolecular Chemistry
Vol. 23, No. 5, May 2011, 389–397
Synthesis and cation binding properties of fluorescent calix[4]arene derivatives bearing
tryptophan units at the lower rim
a
Nives Gali c´ *, Nata sˇ a Buri c´ , Renato Toma sˇ , Leo Frkanec and Vladislav Tomi sˇ i c´
a
a
b
a
a b
Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia; Department of Organic
Chemistry and Biochemistry, Ruder Bo sˇ kovi c´ Institute, Bijeni cˇ ka 54, 10000 Zagreb, Croatia
(
Received 16 June 2010; final version received 15 August 2010)
The fluorescent peptidocalixarenes, 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis(O-methyl-L-tryptophanylcarbonyl-
methoxy)calix[4]arene (1) and 5,11,17,23-tetra-tert-butyl-25,27-di(O-methyl)-26,28-bis(O-methyl-L-tryptophanylcarbo-
nylmethoxy)calix[4]arene (2), were prepared by introducing tryptophan subunits at a lower calixarene rim. Coordination
abilities of 1 and 2 towards Eu(III) and alkali metal cations were studied by spectrophotometric, spectrofluorimetric,
conductometric and potentiometric titrations in acetonitrile at 258C. Rather strong complexation was observed for smaller
alkali metal cations Li and Na (log KLi1 . 6, log KLi2 . 6, log KNa1 ¼ 8.25, log KNa2 ¼ 6.94), and moderate for Kþ
þ
þ
þ
þ
(
log KK1 ¼ 5.09, log K ¼ 4.09). Larger Rb and Cs cations did not fit in the ion binding site of 1 so no complexation was
K2
þ
detected, whereas the more flexible ligand 2 accommodated Rb cation (log KRb2 ¼ 3.44). The fluorescence of 1
3þ
(
l
ex ¼ 280 nm, lem ¼ 340 nm) was remarkably quenched by Eu(III). Stability constant of 1:1 (Eu :1) complex determined
spectrofluorimetrically amounted to log K ¼ 6.16.
Eu1
Keywords: calixarenes; alkali metal cations; Eu(III); stability constants; fluorescence
1
.
Introduction
alkaline-earth cations (2d, 11). Recently, we have reported
on the cation binding affinities of the calix[4]arene tetra(O-
N-acetyl-D-phenylglycine methyl ester]) derivative which
Calixarenes have received a great deal of attention as host
molecules in supramolecular chemistry (1). An important
feature of these compounds is their synthetic flexibility.
Chemical modification of lower or upper calixarene rims
by introducing groups with different binding abilities
enables them to form inclusion complexes with a wide
variety of guest species. Depending on the appended
groups and the number of repeating phenolic units (usually
four or six), which defines a macrocycle cavity size,
functionalised calixarenes are suitable receptors for alkali
[
þ
þ
was shown to be an efficient binder for Li and Na cations
in acetonitrile (12). In view of the fact that tryptophan is a
fluorescent amino acid, in the present paper, we report on
the synthesis and binding abilities of two novel fluorescent
calix[4]arene derivatives containing two and four trypto-
phan subunits at the lower rim. The binding properties of
these compounds towards Eu(III) and alkali metal cations
were examined by spectroscopic and electrochemical
methods.
(
1g, 2), alkaline-earth (1g, 2c–e, 3), transition and heavy
metal cations (1g, 2d, 4), anions (5), neutral (6) and chiral
molecules (7). Complex formation was investigated using
different spectroscopic techniques including NMR,
UV–vis, vibrational and luminescence spectroscopy (8).
Due to its high sensitivity, spectrofluorimetry received
a considerable attention. Fluorimetric determination of
cations based on calixarene derivatives with anthracene,
naphthalene, pyrene and dansyl groups as fluorophore
units are well compiled in the recent review articles (9).
Two-armed calix[4]arene derivatives bearing tryptophan
units were proposed as enantioselective fluorescent
sensors for chiral carboxylates (10).
2
.
Results and discussion
2.1 Synthesis
The synthesis of peptidocalixarenes 1 and 2 in four reaction
steps is shown in Scheme 1. The stepwise route (11b, 13)
via the calix[4]arene tetraacetic acid, its chloride and L-
tryptophan methyl ester hydrochloride (Et N, CH Cl )
3
2
2
gave 1 in 55.0% yield. Calix[4]arene 1,3-OMe derivative 2
with two 2,4-O-(CH COTrpCOOMe) strands was prepared
2
from a 1,3-dimethyl-2,4-(CH COOEt) derivative and its
2
acid chloride and coupled with L-tryptophan methyl ester
hydrochloride. Compound 2 was obtained in 63.5% yield.
Calixarene derivatives were characterised by spectroscopic
Calix[4]arene derivatives with oxygen donor atoms,
such as calixarene esters, ketones, amides (including
peptidocalixarenes), can selectively bind alkali and
1
methods and high-resolution mass spectrometry. The H
*Corresponding author. Email: ngalic@chem.pmf.hr
ISSN 1061-0278 print/ISSN 1029-0478 online
q 2011 Taylor & Francis
DOI: 10.1080/10610278.2010.521832
http://www.informaworld.com

3
90
N. Gali c´ et al.
NH
4
O
NH
(ii)
(iv)
NH3+Cl–
OMe
4
(vi)
4
(v)
+
O
4
O
4
O
NH
OH
+
O
O
O
O
OMe
EtO
Cl
I
II
III
1
2
IV
O
S
O
OCH3
(i)
(iii)
(iv)
2
O
OMe
(v)
O
2
OH
OMe
EtO
V
VI
NH
2
O
OMe
NH
2
+
–
(vi)
O
OMe
+
2
NH3 Cl
O
NH
O
O
OMe
Cl
O
OMe
VII
III
2
Scheme 1. Syntheses of compounds 1 and 2. Reagents and conditions: (i) K CO , MeCN, D; (ii) Ethyl bromoacetate, K CO , acetone,
3
2
3
2
D; (iii) Ethyl bromoacetate, NaH, THF (Ar), 08C ! D; (iv) NaOH, EtOH/H
2
O; (v) SOCl
2
and (vi) Et
3
N, CH
2
Cl
2
(Ar), 08C ! r.t.
NMR spectrum of 1 in CHCl showed two singlets due to
3
NH protons (d ¼ 7.37 ppm) also indicated the presence of
intramolecular NH· · ·OvC hydrogen bonds (11b).
A complete assignment of signals corresponding to indole
ring protons (see Section 3) was enabled by 2D (COSYand
tert-butyl groups (d ¼ 1.05 ppm) and calixarene aromatic
protons (d ¼ 6.63 ppm), a pattern characteristic of cone
conformation and C symmetry of tetrasubstituted
4
1
calix[4]arene (10, 12). Four sets of doublets due to the
bridging methylene protons (d ¼ 2.87 and 4.21 ppm) and
NOESY) H NMR spectra. Contrary to 1, in the chloroform
solution at room temperature, disubstituted calix[4]arene 2
existed as a mixture of all possible conformational isomers.
This was concluded on the basis of the much more complex
ArOCH protons (d ¼ 4.31 and 4.46 ppm) indicated the
2
structural rigidity and possible intramolecular hydrogen
1
bonding interactions (13). A rather high chemical shift of
H NMR spectrum which showed the splitting of signals

Supramolecular Chemistry
4c). Obviously, two ZOCH groups at a lower rim were
391
(
3
(a)
not bulky enough to prevent conformational interconver-
sion by rotation through the calixarene cavity.
1.0
0.8
0.6
2
.2 Cation complexation studies
A
The hypochromic effect on the UV spectrum of the
acetonitrile solution of 1 was observed upon addition of
LiClO , NaClO , KClO and Eu(NO ) (Figures 1(a) and
0.4
0.2
4
4
4
3 3
2
(a)). In addition, a neat isosbestic point at 266 nm
appeared in the case of the titration with Eu(III) (Figure
(a)). In the titrations of 1 with lithium, sodium and
0
.0
2
2
40
260
280
300
320
europium cations, a linear relationship of absorbance vs.
the amount of cation added was observed up to the ratio
n(cation)/n(1) < 1, followed by a break in the titration
curve (Figures 1(b) and 2(b)). These findings revealed a
formation of 1:1 complexes and rather strong complexa-
tion (corresponding stability constants could only be
estimated, Table 1). It should be noted that since the
Wavelength/nm
(
b)
1.04
1.02
1.00
0.98
0.96
0.94
A281
(a)
1.5
1.0
0.5
A
0.0
0.5
1.0
1.5
2.0
n(Eu3+)/n(1)
Figure 2. (a) Spectrophotometric titration of 1 (c ¼ 4.2 £
2
5
23
mol dm ) with Eu(NO ) in acetonitrile. l ¼ 1 cm;
23
1
0
3
3
3
þ
q ¼ (25.0 ^ 0.1)8C; c(Eu ) ¼ 0 (top curve)–5.38 £
2
5
0.0
1
dilution. (b) Dependence of absorbance at 281 nm on the
0
mol dm
(bottom curve); the spectra are corrected for
240
260
280
300
320
Wavelength/nm
n(Eu(NO ) )/n(1) ratio.
3
3
(b)
3
þ
Eu(NO ) absorbed in the same spectral region as a Eu1
3
3
1.44
1.42
1.40
1.38
1.36
1.34
complex, the increase in absorbance after the break in the
titration curve was recorded (Figure 2(b)).
Although observable, the absorbance changes in the
titration of 1 with KClO were insufficient to enable their
4
A281
reliable quantitative processing. The addition of RbNO3
and CsNO into the ligand solution did not cause any
3
significant changes in its UV spectrum, indicating that
under conditions used no observable complexation took
place.
The results of spectrophotometric titrations of 2 with
lithium and sodium cations were similar to those of 1.
A rather strong complexation and formation of 1:1
complexes were observed (Table 1). The spectral changes
0
.0
0.5
1.0
1.5
2.0
+
n(Na )/n(1)
þ
þ
Figure 1. (a) Spectrophotometric titration of
(
1
recorded in the titrations of 2 with K and Rb were too
small for the quantitative analysis, although they definitely
indicated the complexation of these cations with ligand 2.
Almost no change in the UV spectrum of 2 was observed
upon addition of CsNO3 into the acetonitrile ligand
2
5
23
c ¼ 6.04 £ 10 mol dm ) with NaClO in acetonitrile.
4
þ
l ¼ 1 cm; q ¼ (25.0 ^ 0.1)8C; c(Na ) ¼ 0 (top curve)–1.02 £
2
0
4
23
1
mol dm
(bottom curve); the spectra are corrected for
dilution. (b) Dependence of absorbance at 281 nm on the
n(NaClO )/n(1) ratio.
4

3
92
N. Gali c´ et al.
Table 1. Stability constants of complexes of europium and
alkali cations with 1 and 2 in acetonitrile at 258C.
(a)
3
3
2
50
00
50
2
log(K/mol dm ) ^ s
1
3
Cation
1
2
þ
a
a
Li
Na
.6
.6
þ
b
200
8.25 ^ 0.01
5.09 ^ 0.03
6.94 ^ 0.01
4.09 ^ 0.02
3.44 ^ 0.03
þ
c
K
Rb
1
50
00
þ
d
–
þ
d
d
Cs
Eu
–
6.16 ^ 0.02
–
1
3
þ
e
d
–
5
0
a
Estimated by spectrophotometry and conductometry.
Potentiometric determination.
Conductometric determination.
b
c
d
0
2
00
250
300
350
400
450
þ
þ
3þ
Addition of Rb , Cs and Eu salts into the calixarene solution had no
Wavelength/nm
significant effect on the absorbance and emission of 1 and 2. Likewise, in
conductometric titrations of Rb and Cs solutions, no significant
changes in conductivity were observed.
þ
þ
(b)
e
Spectrofluorimetric determination.
500
þ
solution. Besides, contrary to Eu1 , the formation of the
þ
400
Eu2 complex was not detected.
Excited at 280 nm, both calixarene derivatives emitted
at 340 nm (Figure 3(a)). The fluorescence was associated
with the tryptophan subunits of the investigated com-
pounds. Thus, the shapes of the excitation and emission
spectra of both compounds were basically the same.
The tetrasubstituted calixarene 1 emitted strongly whereas
compound 2, bearing only two tryptophan subunits,
emitted moderately under the same experimental con-
ditions. The influence of europium and alkali metal cations
on the emission spectra of 1 and 2 was examined at fixed
molar ratio, n(metal ion):n(calixarene) ¼ 5. The addition
3
2
1
00
00
00
0
0
1
2
3
4
5
1
05 c(calixarene)/mol dm−3
Figure 3. (a) Excitation and emission spectra of 1 (—) and 2 (---)
þ
þ
26
23
of Rb and Cs salts did not show any significant effect on
the ligands emission. The other alkali metal cations,
in acetonitrile. c(1) ¼ c(2) ¼ 5 £ 10 mol dm . (b) Dependence
ofrelative fluorescenceintensity onthe concentration of 1 (B) and 2
(†). lex ¼ 280 nm; lem ¼ 340 nm; slit width ¼ 4 nm.
þ
þ
þ
i.e. Li , Na and K , affected the calixarene fluorescence,
but the changes in the intensity were less than 15%.
The addition of europium nitrate into the acetonitrile
solution of 1 resulted in fluorescence quenching of almost
þ
90%. For this reason, the complexation of europium was
studied in more details, and the spectrofluorimetric
n(1)/n(M ) < 1 (Figure 5). A decrease in molar
conductivity was due to a lower electric mobility of the
þ
titration of 1 with Eu(NO ) in acetonitrile was carried
3
larger M1 complex compared to the free cation, and was
þ
3
out (Figure 4). By processing the fluorimetric data, the
3
also observed for K (Figure 6). The latter data were
analysed by non-linear least-squares regression, and the
calculated stability constant is given in Table 1. During the
þ
stability constant of 1:1 Eu1 complex was obtained
Table 1). The addition of Eu(III) nitrate into the
(
acetonitrile solution of 2 did not cause any significant
effect on the calixarene emission spectrum, indicating that
no complexation took place under the experimental
conditions used. This result was in accordance with the
one obtained by UV–vis spectrometry.
titrations of acetonitrile solutions of RbNO and CsNO
3 3
with 1, almost no changes in molar conductivities
were observed.
þ
þ
The addition of 2 in the Li and Na perchlorate
solutions revealed the formation of 1:1 complexes. A linear
decrease in molar conductivities and a break in the titration
In order to examine the findings obtained by spectro-
metric methods, conductometric titrations of alkali metal
cations in acetonitrile solutions with calixarene derivatives
þ
curves at the molar ratio n(2)/n(M ) < 1 were recorded
(Figure 7(a) and (b)). Changes in molar conductivity upon
þ
þ
were also performed. For Li and Na perchlorate
solutions, an almost linear decrease in molar conduc-
tivities upon addition of 1 was observed. A break in the
titration curve was recorded at the molar ratio
addition of 2 in KClO and RbNO solutions are displayed
4
3
in Figure 8(a) and (b). By processing these data in the same
þ
þ
manner as for 1, stability constants of the K2 and Rb2
complexes were calculated (Table 1). No changes in molar

Supramolecular Chemistry
393
(a)
180
170
160
150
140
130
3
2
2
1
1
00
50
00
50
00
/
5
0
0
300
350
400
450
Wavelength/nm
0.0
0.5
1.0
1.5
2.0
1
04 c(1)/mol dm−3
(b)
3
2
2
1
1
00
50
00
50
00
4
Figure 6. Conductometric titration of KClO with 1 in
þ
24
23
acetonitrile. c(K ) ¼ 1.02 £ 10 mol dm
;
c(1) ¼ 8.4 £
2
4
23
10 mol dm ; q ¼ (25.0 ^ 0.1)8C; B experimental; —
calculated.
(a)
165
160
155
150
5
0
0
0
2
4
6
8
06 c(Eu3+)/mol dm–3
145
40
135
1
1
Figure 4. (a) Spectrofluorimetric titration of 1 (c(1) ¼ 3.2 £
26
10
23
mol dm ) with Eu(NO
3þ
3
)
3
in acetonitrile. c(Eu ) ¼ 0 (top
26
23
curve)–8.75 £ 10 moldm (bottom curve). (b) Dependence of
3
þ
130
relative fluorescence intensity on the Eu
concentration.
lex ¼ 280 nm; l ¼ 340 nm; slit width ¼ 4 nm; B experimental;
em
0.0
0.5
1.0
n(2)/n(Li+)
1.5
2.0
—
calculated.
(b)
170
160
150
140
130
120
180
170
160
150
140
130
/
0.0
0.5
1.0
n(2)/n(Na+)
1.5
2.0
0.0
0.5
1.0
n(1)/n(Na+)
1.5
2.0
4 4
Figure 7. Conductometrictitration of (a) LiClO and (b) NaClO
þ
þ
24
23
Figure 5. Conductometric titration of NaClO with 1 in
4
acetonitrile; c(Na ) ¼ 2.01 £ 10 mol dm ;q ¼ (25.0 ^ 0.1)8C.
with 2 in acetonitrile. c(Li ) ¼ c(Na ) ¼ 2.02 £ 10 mol dm
q ¼ (25.0 ^ 0.1)8C.
;
þ
24
23

3
94
N. Gali c´ et al.
(a) 180
(a) 8.0
7
7
6
.5
.0
.5
175
170
165
160
155
150
145
6.0
5.5
5.0
4.5
4.0
.5
3
0
.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4
0
1
2
3
4
5
n(1)/n(Na+)
1
04 c(2)/mol dm−3
(b)
(b)
7.0
6.5
178
176
174
172
170
168
166
164
162
160
158
6
.0
5.5
.0
4.5
.0
5
4
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8
n(2)/n(Na+)
0
1
2
3
4
5
6
7
1
04 c(2)/mol dm−3
4
Figure 9. Potentiometric titration of NaClO with (a) 1 and (b) 2
3
23
in acetonitrile. V ¼ 30.3 cm ; I ¼ 0.01 mol dm (Et NClO );
0
c
4
4
23
Figure 8. Conductometric titration of (a) KClO and (b)
4
24
q ¼ (25.0 ^ 0.1)8C; (a) c(1) ¼ 8.363 £ 10 mol dm
þ
24
23
,
RbNO
3
with 2 in acetonitrile. c(K ) ¼ 1.01 £ 10 mol dm
;
;
þ
24
(Na ) ¼ 1.07 £ 10 mol dm
23
24
þ
24
23
23
23
c
0
;
(b) c(2) ¼ 6.06 £ 10
c(Rb ) ¼ 1.02 £ 10 mol dm ; c(2) ¼ 2.0 £ 10 mol dm
2
3
þ
24
23
mol dm , c
calculated.
0
(Na ) ¼ 1.01 £ 10 mol dm . B experimental;
q ¼ (25.0 ^ 0.1)8C; B experimental; — calculated.
—
conductivity were observed during the titration of CsNO3
in the acetonitrile solution with 2.
to comprise four ether and four amide carbonyl oxygen
atoms of the substituents at the lower rim. Accordingly, the
binding site of compound 2 possesses two carbonyl
oxygen atoms less, but, on the other hand, it is more
flexible.
þ
þ
The stability constants of the Na1 and Na2
complexes in acetonitrile were too high for spectro-
photometric and conductometric determination. For this
reason, direct potentiometry using a sodium-selective
glass electrode was applied. Potentiometric titrations of
The above considerations are reflected in the results
presented in Table 1. As can be seen, the affinity of 1
NaClO with 1 and 2 are shown in Figure 9(a) and (b),
4
þ
þ
towards Na and K cations is considerably larger than
that of 2, the difference being more pronounced in the case
of sodium. This is expected because both cations prefer
coordination with eight oxygen atoms (four carbonyl and
respectively. A steep p[Na] jump occurred at the 1:1
þ
þ
n(1):n(Na ) and n(2):n(Na ) ratios, which was in
accordance with the results obtained by the other
techniques. However, the p[Na] jump was steeper in the
þ
þ
þ
case of ligand 1, indicating the larger stability of the Na1
þ
four ether), but Na fits better than K into the binding site
formed by these atoms (as is the case of ligand 1). This
leads to the greater difference between the stability
complex compared to Na2 . The stability constants of
these complexes obtained by processing potentiometric
data using Hyperquad program are given in Table 1.
By comparison with the analogous peptidocalix[4]ar-
enes (11b, 12–14), the cation binding site of 1 is expected
þ
þ
þ
þ
constants of Na1 and Na2 complexes compared to K1
þ
þ
and K2 (Table 1). As a consequence, the Na /K
selectivity of 1 expressed as the KNa1/KK1 ratio is about

Supramolecular Chemistry
395
1400, whereas the corresponding selectivity of 2 is lower
and amounts to approximately 700. Since no complexation
a Varian Cary 5 double-beam spectrometer. Fluorescence
spectra were measured on a Perkin-Elmer LS55B spectro-
fluorimeter. Conductometric measurements were per-
formed using a Metrohm 712 conductometer. A Metrohm
713 pH meter was used for potentiometric measurements.
A sodium-selective glass electrode (Metrohm) was used
þ
þ
of Rb and Cs ions with 1 was observed, it can be
concluded that these (larger) cations are not compatible
with the ion binding site of the investigated tetrasub-
stituted calix[4]arene. However, the binding site of the 1,3
disubstituted ligand 2 is flexible enough to accommodate
as the indicator electrode and Ag/AgCl (Metrohm) filled
23
with 0.01 mol dm Et NCl as the reference electrode.
þ
the Rb cation (Table 1).
Compound 1 binds Eu(III) rather strongly, whereas the
complexation of Eu(III) with 2 cannot be observed
4
Commercially available reagents were used as received.
The salts used for titrations in acetonitrile (Merck, Uvasol)
were LiClO , NaClO , KClO , RbNO , CsNO and
(Table 1). This finding could be accounted for by
considering that europium prefers higher coordination
4
4
4
3
3
Eu(NO ) ·5H O (Merck, p.a.). Compounds I (17), II
3 3 2
numbers (the most common are 8 and 9 (15)) which can be
(18), III (19), IV (20), V (21), VI and VII (22) used in the
synthesis of 1 and 2 (Scheme 1) were prepared according to
the procedures described in the literature.
3
achieved in the complex Eu1 , while compound 2 offers
þ
only six coordinating atoms (see above). Although quite
3
þ
high, the stability constant of Eu1
orders of magnitude lower than that of the Na1 complex.
is more than two
þ
3
This could seem surprising since ionic radii of Eu and
þ
þ
3.2 Synthesis of 5,11,17,23-tetra-tert-
butyl-25,26,27,28-tetrakis(O-methyl-L-
tryptophanylcarbonylmethoxy)calix[4]arene (1)
Na are similar (107 and 118 pm for coordination number
8
, respectively (16)), and the europium cation is much
more charged. Therefore, apart from the electronic
structure of the cations examined, one would expect
KEu1 to be even larger than KNa1. The observed difference
in complex stabilities can be partly explained by taking
L-Tryptophane methyl ester hydrochloride (0.98 g,
3
3.85 mmol) was suspended in dry CH Cl (40 cm ) and
cooled (2108C). After the addition of triethylamine
2
2
3
þ
3
(1.1 cm , 7.88 mmol), the mixture was stirred for 30 min
into account that Eu with higher charge number and
þ
similar ionic radius is more strongly solvated than Na .
under argon. Acid chloride of calix[4]arene tetraacetic
acid (the cone conformer; 834.0 mg, 0.873 mmol) in dry
Therefore, the replacement of solvent molecules by the
coordination sites of the ligand during the complexation
process is less favourable in the case of reaction of 1
with Eu(III).
3
CH Cl (40 cm ) was added at once by a syringe. After 1 h,
2
2
the mixture was warmed up to room temperature, stirred
for additional 18 h and then extracted with NaOH
2
3
23
The most attractive feature of the tetrasubstituted
calix[4]arene tryptophan derivative 1 is its prominent
fluorescence which is significantly altered by the presence
of the europium cation (Figure 4), making such system
interesting as a potential fluorimetric sensor for Eu(III).
(c ¼ 1 mol dm ), water, HCl (c ¼ 1 mol dm ), brine
and water. The organic layer was dried with anhydrous
MgSO . After filtration and evaporation of the solvent, the
4
product was recrystallised from CH Cl –light petroleum
2
2
to give
1
(890 mg, 55%). R ¼ 0.53 (MeOH–
f
2
D
21
5
CH Cl ¼ 10:90); Mp 138–1418C; ½aꢀ ¼ þ228
2
2
2
3
(
(
(
g ¼ 1 g dm , CH Cl ); IR (KBr) n
1
CONH, amide II), 1195 (COC); H NMR (300 MHz,
(cm ) ¼ 3417
2
2
max
NH), 1740 (COOMe), 1668 (CONH, amide I), 1538
3
.
Experimental
3
.1 General
CDCl ): d ¼ 1.05 (36H, s, t-Bu), 2.87 (4H, d, J ¼ 13.17,
3
H
Melting points were determined with a Kofler apparatus.
Optical rotations were measured on an AA-10 automatic
polarimeter (Optical Activity Ltd, Ramsey, UK). IR spectra
were acquired with a Bruker Vector 22 Fourier Transform
ArCH Ar), 3.29 (8H, d, J ¼ 2.28, CH -ArTrp), 3.52
3 2ax
2
eq
2
(12H, s, COOCH ), 4.21 (4H, d, J ¼ 12.99, ArCH Ar),
4.31 (4H, d, J ¼ 14.19, OCH CO), 4.46 (4H, d,
2
A
J ¼ 14.19, OCH CO), 4.87 (4H, d, J ¼ 6.42,
2
B
1
13
spectrometer. H and C NMR spectra were recorded in
CDCl with Bruker Avance 300 MHz. COSY and NOESY
NC * HCO), 6.63 (8H, s, ArH), 6.86 (4H, d, J ¼ 1.14,
ArTrp-H2), 7.04 (4H, t, ArTrp-H5), 7.14 (4H, t, ArTrp-
H6), 7.24 (4H, d, J ¼ 8.04, ArTrp-H7), 7.37 (4H, d,
J ¼ 7.02, CONH), 7.47 (4H, d, J ¼ 7.68, ArTrp-H4), 8.38
3
spectra were recorded to enable a complete assignment of
signals. Mass spectra were obtained on a MALDI-
TOF/TOF analyser (Applied Biosystems, Inc., Foster
City, CA, USA) equipped with a 200 Hz, 355 nm Nd:YAG
laser. The spectra were recorded in the CHCA MALDI
matrix by averaging 1600 laser shots covering a mass range
of m/z 700–2500. The ions from trypsin autolysis were
used for internal calibration in positive ion mode (m/z
1
3
(4H, s, ArNHTrp) ppm. C NMR (75 MHz, CDCl ):
3
d ¼ 27.18 (CH -Trp), 30.86 (Ar-CH -Ar), 31.38
C
2
2
(C(C H ) ), 33.84 (C(CH ) ), 52.32 ( * CH), 52.97
3
3
3 3
(COOC H ), 73.55 (OC H CO), 109.94 (ArTrp-C3),
2
3
111.37 (ArTrp-C7), 118.38 (ArTrp-C4), 119.47
(ArTrp-C6), 121.97 (ArTrp-C5), 123.33 (ArTrp-C2),
125.45 (ortho-Ar-C), 125.66 (ortho-Ar-C), 127.50
8
42.5094 and 2211.1040). UV spectra were obtained with

3
96
N. Gali c´ et al.
2
6
23
(
ArTrp-C3a), 132.57 (meta-Ar-C), 132.87 (meta-Ar-C),
36.07 (ArTrp-C7a), 145.24 (Ar-C-t-Bu), 152.57 ( para-
Ar-C), 169.89 (CONH), 172.70 (COOMe) ppm. HR-MS:
c ¼ 3.2 £ 10 mol dm ) placed in the measuring
1
1
quartz cell.
The obtained spectrometric data were processed using
SPECFIT program (23).
þ
1
1
703.8030 (M þ Na) (calcd for C100H112N O Na
8
16
703.8089).
The influence of alkali metal cations on the
emission spectra of 1 and 2 was studied at fixed molar
þ
26
23
ratio, n(M )/n(calixarene) ¼ 5 (c ¼ 4 £ 10 mol dm
,
1
2
5
23
c ¼ 2 £ 10 mol dm , l ¼ 280 nm, l ¼ 340 nm,
3.3 Synthesis of 5,11,17,23-tetra-tert-
butyl-25,27-di(O-methyl)-26,28-bis(O-methyl-L-
tryptophanylcarbonylmethoxy)calix[4]arene (2)
2
ex
em
slit width ¼ 4 nm).
3
Triethylamine (0.68 cm , 4.9 mmol) was added to the
cooled (2108C) solution of L-tryptophane methyl ester
hydrochloride (668.4 mg, 2.62 mmol) in dry CH Cl
3
.5 Conductometry
Conductometric titrations were carried out in acetonitrile
21
at (25.0 ^ 0.1)8C. The cell constant (0.849cm ) was
23
determined using 0.1 mol dm aqueous KCl solution. The
2
2
3
(
of VII (940 mg, 1.093 mmol) in dry CH Cl (20 cm ), the
50 cm ) and stirred for 30 min under argon. Upon addition
3
2
2
3
24
23
ice-cooled mixture was stirred for several hours, and then
for additional 15 h at room temperature. After filtration,
alkalisaltsolution(V
0
23
¼ 20.0cm ,c
0
< 1 £ 10 mol dm
24
or 2 £ 10 mol dm ) was titrated with the ligand solution
23
23
(c < 1 £ 10 mol dm
23
23
23
the filtrate was extracted with NaOH (c ¼ 1 mol dm ),
or 2 £ 10 mol dm ) in a
23
water, HCl (c ¼ 1 mol dm ), brine and water. After
closed, thermostated titration vessel. The measured conduc-
tivities were corrected for the conductivity of the solvent.
drying with anhydrous MgSO and evaporation of the
4
organic solvent, the residue was recrystallised from the
MeOH–H O mixture to give 2 (850 mg, 63.5%).
2
R ¼ 0.30 (MeOH–CH Cl ¼ 5:95); Mp 130–1328C;
3.6 Potentiometry
f
2
2
23
2
D
5
½
aꢀ ¼ þ258 (g ¼ 1 g dm , CH Cl ); IR (KBr) n
þ
þ
2
2
max
The stability constants of Na1 and Na2 complexes in
acetonitrile were determined at (25.0 ^ 0.1)8C by
3
potentiometric titration of 30.3 cm NaClO4 solution
2
1
(
amide I), 1519 (CONH, amide II), 1208 (COC); H NMR
cm ) ¼ 3416 (NH), 1745 (COOMe), 1681 (CONH,
1
(
t-Bu), 2.95–4.44 (28H, m, br m, CH , CH , OCH ,
300 MHz, CDCl ): d ¼ 0.79 (18H, s, t-Bu), 1.35 (18H, s,
24
23
3
H
(
(
c < 1 £ 10 mol dm ) with the solution of 1 or 2
0
23
23
eq
ax
A
c < 1 £ 10 mol dm ) in a thermostated titration
23
OCH , OCH , OOCH , CH -ArTrp), 5.13 (2H, q,
B
3
3
2
vessel. The ionic strength of all solutions was set to
NC * HCO), 6.34–6.48 (8H, m, br m, Ar-H), 6.88–7.60
12H, m, ArTrp-H, CH -ArTrp), 8.17 (2H, s, ArTrp-NH)
0.01 mol dm by Et NClO . The cell was calibrated by
the incremental addition of NaClO4 solution
4 4
(
2
1
3
ppm. C NMR (75 MHz, CDCl ): d ¼ 27.50 (CH -Trp),
23
0.01 mol dm ) to 30.0 cm of 0.01 mol dm solution
3
23
3
C
2
(
of Et NClO . The potentiometric data were analysed using
HYPERQUAD program (24).
3
3
1.02 (C(C H ) ), 31.72 (C(C H ) ), 31.07 (Ar-CH -Ar),
3 3 3 3 2
4
4
3.58 (C(CH ) ), 34.18 (C(CH ) ), 52.43 ( * CH), 52.83
3
3
3 3
(
COOC H ), 60.09 (ArOCH ), 74.06 (OC H CO), 110.16
3 3 2
(
ArTrp-C3), 111.30 (ArTrp-C7), 118.46 (ArTrp-C4),
19.77 (ArTrp-C6), 122.26 (ArTrp-C5), 122.54 (ArTrp-
C2), 124.66, 124.76, 125.66, 125.76 (ortho-Ar-C), 127.71
ArTrp-C3a), 130.99, 131.03, 135.29, 135.30 (meta-Ar-C),
1
Acknowledgements
This work was supported by the Ministry of Science, Education
and Sports of the Republic of Croatia (Projects 119-1191342-
2960 and 098-0982904-2912). The authors thank Mrs Biserka
Kolar and Ms Marina Katava for their technical assistance.
(
1
1
36.04 (ArTrp-C7a), 145.09, 145,57 (Ar-C-t-Bu), 151.70,
55.09 ( para-Ar-C), 169.15 (CONH), 172.46 (COOMe)
þ
ppm. HR-MS: 1215.6353 (M þ Na)
(calcd for
C H N O Na 1215.6393).
74 88 4 10
References
(
1) (a) Gutsche, C.D. In Calixarenes: An Introduction, 2nd ed.;
The Royal Society of Chemistry: Cambridge, UK, 2008.
3
.4 Spectrophotometry and spectrofluorimetry
(
b) Lehn, J.-M. In Supramolecular Chemistry; VCH:
3
UV titrations of 1 and 2 in acetonitrile (V ¼ 2.0 cm ,
Weinheim, 1995. (c) Asfari, Z., B o¨ hmer, V., Harrowfield,
J., Vicens, J., Eds.; Calixarenes 2001; Kluwer Academic
Publishers: Dordrecht, 2001. (d) Vicens, J.; Harrowfield, J.,
Eds.; Calixarenes in the Nanoworld;, Springer: Dordrecht,
2
5
23
24
23
c ¼ 6 £ 10 mol dm , c ¼ 1 £ 10 mol dm ) were
1
2
performed at (25.0 ^ 0.1)8C by the stepwise addition of
)
2
3
23
Eu(III) or the alkali salt solution (c ¼ 1 £ 10 mol dm
2
007. (e) Danil de Namor, A.F.; Cleverley, R.M.;
Zapata-Ormachea, M.L. Chem. Rev. 1998, 98, 2495–
525. (f) Creaven, B.S.; Donlon, D.F.; McGinley, J. Coord.
directly into the measuring quartz cell (l ¼ 1 cm).
The fluorimetric titration was carried out by the
2
2
5
stepwise addition of Eu(III) nitrate (c ¼ 3.8 £ 10
Chem. Rev. 2009, 253, 893–962. (g) Sliwa, W.; Girek, T.
J. Incl. Phenom. Macrocycl. Chem. 2010, 66, 15–41.
2
3
3
mol dm ) to the calixarene solution (V ¼ 2.0 cm ,

Supramolecular Chemistry
397
(
2) (a) Patra, S.; Suresh, E.; Paul, P. Polyhedron, 2007, 26,
971–4980. (b) Baklouti, L.; Cherif, J.; Abidi, R.;
(9) (a) Kim, J.S.; Quang, D.T. Chem. Rev. 2007, 107,
3780–2799. (b) Valeur, B.; Leray, I. Inorg. Chim. Acta
2007, 360, 765–774.
(10) Qing, G.; He, Y.; Wang, F.; Qin, H.; Hu, C.; Yang, X.
Eur. J. Org. Chem. 2007, 1768–1778.
(11) (a) McMahon, G.; O’Malley, S.; Nolan, K. Arkivoc 2003
(vii), 23–31. (b) Nomura, E.; Takagaki, M.; Nakaoka, C.;
Uchida, M.; Taniguchi, H. J. Org. Chem. 1999, 64,
3151–3156.
(12) (a) Tomi sˇ i c´ , V.; Gali c´ , N.; Berto sˇ a, B.; Frkanec, L.;
ˇ
Simeon, V.; Zini c´ , M. J. Incl. Phenom. Macrocycl. Chem.
2005, 53, 263–268. (b) Po zˇ ar, J.; Preo cˇ anin, T.; Frkanec, L.;
Tomi sˇ i c´ , V. J. Solut. Chem. 2010, 39, 835–848.
ˇ
(13) Frkanec, L.; Vi sˇ njevac, A.; Koji c´ -Prodi c´ , B.; Zini c´ , M.
Chem. Eur. J. 2000, 6, 442–453.
(14) Mareque Rivas, J.C.; Schwalbe, H.; Lippard, S. J. Proc.
Natl Acad. Sci. USA 2001, 98, 9478–9483.
4
Arnaud-Neu, F.; Harrowfield, J.; Vicens, J. Org. Biomol.
Chem. 2004, 2, 2786–2792. (c) Diamond, D.; Nolan, K.
Anal. Chem. 2001, 73, 22A–29A. (d) Ludwig, R.; Dzung,
N.T.K. Sensors 2002, 2, 397–416. (e) Arnaud-Neu, F.;
McKervey, M.A.; Schwing-Weill, M.J. In Calixarenes
2
001; Asfari, Z., B o¨ hmer, V., Harrowfield, J., Vicens, J.,
Eds.; Kluwer Academic Publishers: Dordrecht, 2001;
pp 385–406.
(
(
3) (a) Zhou, H.; Liu, D.; Gega, J.; Surowiec, K.; Purkiss, D.W.;
Bartsch, R.A. Org. Biomol. Chem. 2007, 5, 324–332.
(
2
b) _Ji, H.; Yang, Y.; Xu, X.; Brown, G. Org. Biomol. Chem.
006, 4, 770–772.
4) (a) Sliwa, W. J. Incl. Phenom. Macrocycl. Chem. 2005, 52,
¨
1
Bartsch, R.A.; Gorbunova, M.G.; Tu, C.; Surowiec, M.A.
3–37. (b) Ocak, U.; Ocak, M.; Surowiec, K.;
J. Incl. Phenom. Macrocycl. Chem. 2009, 63, 131–139.
(
Inorg. Chem. 2008, 47, 3549–3558. (d) Othman, A.;
Lee, J.W.; Wu, J.; Kim, J.S.; Abidi, R.; Thu e´ ry, P.;
Strub, J.M.; Van Dorsselaer, A.; Vincens, J. J. Org. Chem.
(15) Cotton, F.A.; Wilkinson, G.; Murillo, C.A.; Bochmann, M.
In Advanced Inorganic Chemistry, 6th ed.; Wiley, 1999;
pp 1108–1129.
(16) Lide, D.R., Ed.; CRC Handbook of Chemistry and Physics,
82nd ed.; CRC Press, Boca Raton, FL, 2001; pp 12-14 and
12–15.
c) Buie, N.M.; Talanov, V.S.; Butcher, R.J.; Talanova, G.G.
2007, 72, 7634–7640.
(
5) (a) Hamdi, A.; Abidi, R.; Vicens, J. J. Incl. Phenom.
Macrocycl. Chem. 2008, 60, 193–196. (b) Okunola, O.A.;
Seganish, J.L.; Salimian, K.J.; Zavaliy, P.Y.; Davis, J.T.
Tetrahedron 2007, 63, 10743–10750. (c) Sun, X.H.; Li, W.;
Xia, P.F.; Luo, H.; Wei, Y.; Wong, M.; Cheng, Y.; Shuang, S.
J. Org. Chem. 2007, 72, 2419–2426. (d) Matthews, S.E.;
Beer, P.D. In Calixarenes 2001; Asfari, Z., B o¨ hmer, V.,
Harrowfield, J., Vicens, J., Eds.; Kluwer Academic
Publishers: Dordrecht, 2001; pp 421–439.
(17) Arnaud-Neu, F.; Collins, E.M.; Deasy, M.; Ferguson, G.;
Harris, S.J.; Kaitner, B.; Lough, A.J.; McKervey, M.A.;
Marques, E.; Ruhl, B.L.; Schwing-Weill, M.J.; Seward,
E.M. J. Am. Chem. Soc. 1989, 111, 8681–8691.
(18) Arnaud-Neu, F.; Barrett, G.; Cremin, S.; Deasy, M.;
Ferguson, G.; Harris, S.J.; Lough, A.J.; Guerra, L.;
McKervey, M.A.; Schwing-Weill, M.J.; Schwinte, P.
J. Chem. Soc. Perkin Trans. 2 1992, 1119–1125.
(19) Brugger, M.; Schreiber, J.; Eschenmoser, A. Helv. Chim.
Acta 1963, 46, 577–586.
(
6) (a) Arduini, A.; Ferdani, R.; Pochini, A.; Secchi, A.;
Ugozzoli, F.; Sheldrick, G.M.; Prados, P.; Gonzalez, J.J.;
de Mendoza, J. J. Supramol. Chem. 2002, 2, 85–88.
(20) Roos, A.T.; Gilman, H.; Beaber, N.J. Org. Synth. Coll. Vol.
1941, 1, 145–147; 1929, 9, 28.
(
b) Wang, J.; Bodige, S.G.; Watson, W.H.; Gutsche, C.D.
(21) Ghidini, E.; Ugozzoli, F.; Ungaro, R.; Harkema, S.; Abu El-
Fadl, A.; Reinhoudt, D.N. J. Am. Chem. Soc. 1990, 112,
6979–6985.
(22) Collins, E.M.; McKervey, M.A.; Madigan, E.; Moran,
M.B.; Owens, M.; Ferguson, G.; Harris J. Chem. Soc.
Perkin Trans. 1 1991, 3137–3142.
J. Org. Chem. 2000, 65, 8260–8263. (c) Arduini, A.;
Pochini, A.; Secchi, A.; Ugozzoli, F. In Calixarenes 2001;
Asfari, Z., B o¨ hmer, V., Harrowfield, J., Vicens, J., Eds.;
Kluwer Academic Publishers: Dordrecht, 2001;
pp 457–475.
(
(
7) (a) Lynam, C.; Jennings, K.; Nolan, K.; Kane, P.;
McKervey, M.A.; Diamond, D.; Anal. Chem. 2002, 74,
(23) (a) Gampp, H.; Maeder, M.; Meyer, C.J.; Zuberb u¨ hler, A.D.
Talanta 1985, 32, 95–101. (b) Gampp, H.; Maeder, M.;
Meyer, C.J.; Zuberb u¨ hler, A.D. Talanta 1985, 32, 257–264.
(c) Maeder, M.; Zuberb u¨ hler, A.D. Anal. Chem. 1990, 62,
2220–2224.
59–66. (b) Sirit, A.; Yilmaz, M. Turk. J. Chem. 2009, 33,
159–200. (c) McIldowie, M.J.; Mocerino M.; Ogden, M.I.
Supramol. Chem. 2010, 22, 13–39.
8) Mohammed-Ziegler, I.; Billes, F. J. Incl. Phenom.
Macrocycl. Chem. 2007, 58, 19–42.
(24) Gans, P.; Sabatini, A.; Vacca, A. Talanta 1996, 43,
1739–1753.